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Biomedical subjects

W A Day

Publications and source records attributed to W A Day.

At least 37 records · Page 2Linked to original sources

Phagocytic cells in glomerular cultures from NZB/W mice.

Comparative studies of glomerular cultures from NZB/W and normal control mice aged 2, 4, 6, 8, 10 and 12 months revealed a significant increase in the number of phagocytic cells in cultures from NZB/W mice at all ages. These cells on electron microscopy had the appearance of macrophages and on immunofluorescence showed Fc receptors and reacted with rabbit anti-mouse macrophage serum. The cells appear to be of blood monocyte origin and it is likely that they play a role in the pathogenesis in NZB/W mice of the glomerulopathy associated with clearance of immune complexes.

Animals↗

Macrophages in NZB/NZW mouse glomerular disease.

Glomerular cultures from mice have been established and the various cells associated with them observed microscopically by phase contrast time-lapse cinematography, after histological staining and ultrastructurally with the transmission and scanning electron microscope. The most common cell types were large 80-200 microns diameter irregular polyhedral cells appearing as flattened plate-like structures morphologically, possibly of epithelial origin. Smaller 70-100 microns diameter fusiform cells possibly derived from either endothelium or mesangium were also often seen. A third cell type, small 10-20 microns diameter circular, motile and actively phagocytic was especially noticeable in cultures of hybrid New Zealand Black/New Zealand White mice but was not present in appreciable numbers in control cultures from strains without renal disease. This third cell type appeared to have Fc receptors, stained positively with non-specific esterase and by indirect immunofluorescence with specific rabbit anti-mouse macrophage serum and had the morphological appearance of a macrophage by scanning and transmission electron microscopy. It is concluded that cells of macrophage origin are associated with the immune complex glomerulonephritis in these hybrid mice.

Age Factors↗

Damage of rat liver sinusoidal endothelium by ethanol.

Hepatic blood in normal rats is separated from the space of Disse and hepatocytes by an ultrastructural sieve formed by pores in the sinusoidal endothelium. This sieve has previously been shown to shield hepatocytes from circulating chylomicrons, the largest of the lipoproteins, which transport most triglycerides of dietary origin. In the present paper it has been shown that the chronic ingestion of ethanol leads to a significant enlargement of pores within the sieve, increasing them from a normal median diameter of 100 nm to 120 nm. A decrease in the normal sieving of perfused labelled large and small chylomicrons has also been noted. It is postulated that the decreased shielding of hepatocytes from large chylomicrons may be a factor in the pathogenesis of alcoholic fatty liver.

Animals↗

Biochemical and mitogenic properties of Tamm-Horsfall urinary glycoprotein.

Thirty separate preparations of human Tamm-Horsfall urinary glycoprotein (THP) prepared from pooled urine of normal individuals were assessed for the capacity to stimulate in vitro blast transformation with normal human peripheral blood lymphocytes. Detailed studies were performed on some of these preparations by various biochemical, ultrastructural and in vitro techniques. Heterogeneity amongst the sodium dodecyl sulphate polyacrylamide gel (SDS-PAGE) profiles of several electrophoresis (2D-IEP). Gas liquid chromatographic analysis (GLC) revealed significant amounts of glucose in two of these samples. Ultrastructural studies using direct staining or platinum carbon shadowed specimens confirmed the fibrillar polymeric nature of soluble THP in vitro studies with human peripheral blood lymphocyte populations showed THP to have mitogenic properties towards B cells associated with the production of intracytoplasmic immunoglobulin. THP also stimulated the migration of mouse peritoneal exudate macrophages in a micro macrophages migration assay.

Cell Migration Inhibition↗

Ihibition of rat brain norepinephrine N-methyltransferase in vitro and in vivo by chloro-substituted 1-aminoindans.

Norepinephrine N-methyltransferase from rat brain stem was inhibited in vitro by 1-aminoindans with chlorine substituents on the aromatic ring. The order of inhibitory potency among these compounds was 4.5-dichloro greater than 4-chloro greater than 5-chloro approximately or equal to 5,6-dichloro approximately or equal to 6,7-dichloro greater than 6-chloro greater than 7-chloro. All except the 7-chloro compound were more potent inhibitors than the parent unsubstituted 1-aminoindan. 4,5-Dichloro-1-aminoindan was a competitive inhibitor in kinetic studies with L-norepinephrine as the variable substrate; its Ki value determined from a Dixon plot was 3.3 x 10(-7) M. At doses of 10-40 mg/kg i.p., this compound inhibited brain stem and hypothalamic norepinephrine N-methyltransferase in vitro and lowered hypothalamic concentrations of epinephrine in rats, effects that lasted for several hours. 4,5-Dichloro-1-aminoindan may be a useful pharmacologic tool for studies of epinephrine-forming neurons in brain.

Animals↗

High perfusion pressure damages the sieving ability of sinusoidal endothelium in rat livers.

Fenestrated endothelium lining liver sinusoids forms an ultrastructural sieve between blood and hepatocytes which at physiological perfusion pressures has previously been shown to shield hepatocytes from large triglyceride-rich chylomicrons. In the study reported in this paper, enlargement of endothelial fenestrae at high perfusion pressures has been confirmed and a concurrent increase in trapping of large chylomicrons by the liver noted. These findings suggest the importance of employing physiological perfusion pressures in studies designed to examine hepatic lipoprotein metabolism and also suggest a possible mechanism in the pathogenesis of fatty change seen in the "nutmeg" liver of chronic venous congestion.

Animals↗

Filtration of chylomicrons by the liver may influence cholesterol metabolism and atherosclerosis.

A fenestrated endothelial lining of sinusoids in rat liver has been shown to separate chylomicrons of different sizes following their injection into the portal vein. This sieving may have physiological importance, since during low dietary fat intake some intestinal lipoproteins are probably small enough to contact liver cells, but during high dietary fat loads most chylomicrons are too large to pass through the filter and must first be degraded to smaller remnants. The liver plays a central role in cholesterol metabolism since it catabolises dietary cholesterol which inhibits synthesis of cholesterol to be circulated as liver-derived very low density lipoproteins (VLDL) and low density lipoproteins. The sieving of chylomicrons, remnants and other lipoproteins by the sinusoidal endothelium of the liver may thus play an important role in lipid transport, affecting the balance of various lipoprotein moieties which in turn may affect the relationship of dietary lipids to various hyperlipidaemias and atherosclerosis.

Animals↗

Tamm-Horsfall protein in the glomerular capsular space.

Tamm-Horsfall protein was detected within the capsular space by immunofluorescence in 7 of 72 consecutive patients on whom renal immunopathological studies were performed. Three patients showed prominent aggregates or crescentic collections affecting 30-50% glomeruli; the remaining four patients showed smaller aggregates between lobules. All patients showed pathological evidence of tubulointerstitial disease. It is suggested that Tamm-Horsfall protein in the capsular space is a sign of intratubular urinary backflow and that Tamm-Horsfall antiserum is a useful addition to the reagents used in the immunofluorescence study of renal biopsies.

Adult↗

Glomerular lesions in argyric NZB/NZW mice.

Glomerular basement membranes showed strong silver labelling on electron microscopy in NZB/NZW mice fed 12 mmol AgNO3 for 6 weeks at ages from 1-7 months. Although some silver granules were seen within mesangial immune deposits following their concurrent deposition, silver was usually deposited in electron-lucent areas around pre-existing deposits, or formed a boundary to an expanded mesangium when immune deposits subsequently developed. Immune deposits in capillary loops occurred on the outer or inner aspect of the zone of silver labelling.

Animals↗

IgA nephropathy: a report on three cases.

Three cases are presented of a recently defined group of patients with renal disease who presented with macroscopic or persisted microscopic haematuria. These patients were found to have deposition of IgA in the glomerulus. They may thus be classified as suffering from an immunologically related glomerulonephritis.

Adult↗

Silver deposition in mouse glomeruli.

Administration of 6 mM silver nitrate in the drinking water of mice resulted in deposition within the glomerular basement membrane of silver granules which were detected on electron microscopy after 12 days. Larger aggregates were detected in the basement membrane and mesangium when silver ingestion was extended to 14 weeks. The silver deposits did not alter significantly over a period of 21 weeks after silver nitrate ingestion was stopped.

Animals↗

Immmune complex glomerular disease in argyric mice.

A mesangiopathic glomerulonephritis with prominent mesangial immunoglobulin deposits was induced in mice by single or multiple intraperitoneal injections of bovine serum albumin. The silver-labelled basement membrane in mice which had ingested 6mM silver nitrate in drinking water proved a useful marker indetermining that the immune deposits were on the intracapillary aspect of the basement membrane.

Animals↗

Norepinephrine N-methyltransferase inhibition by benzamidines, phenylacetamidines, benzylguanidines, and phenylethylguanidines.

Norepinephrine N-methyltransferase (NMT) from rabbit adrenal glands was inhibited by benzylamine and phenethylamine analogs in which the nitrogen was replaced by an amidino or guanidino group. Mono and dichloro derivatives of benzamidines, phenylacetamidines, benzylguanidines, and phenethylguanidines were studied. The two most potent NMT inhibitors among the compounds examined were 2,3-dichlorobenzamidine and 3,4-dichlorophenylacetamidine, with pI50 values of 5.55 and 5.36, respectively. These inhibitors were reversible and were competitive with norepinephrine as the variable substrate. They inhibited NMT from human, rat, and bovine adrenal glands but were slightly less effective against those enzymes than against the rabbit adrenal enzyme. In exercised rats, 2, 3-dichlorobenzamidine had no significant effect on adrenal catecholamine levels. 3,4-Dichlorophenylacetamidine slightly reduced epinephrine levels in the adrenal glands of exercised rats, but the effect may have been due to release rather than inhibition of synthesis, since heart norepinephrine levels were also reduced significantly by that agent (which is from a chemical series known to release catecholamines). Thus, whereas these compounds are reasonably potent inhibitors of NMT in vitro, they apparently are not effective in blocking enzyme activity in vivo.

Acetamides↗

Biochemical pharmacology of some chlorinated 3-phenyl-piperidines in rats.

Chlorinated 3-phenyl-piperidines were administered to rats with the expectation--based on structural similarities--that they might resemble chlorinated amphetamines pharmacologically. The 3-chloro, 4-chloro, and 3,4-dichloro compounds all lowered serotonin and 5-hydroxyindoleacetic acid levels in rat brain, whereas the 2-chloro compound had no effect. The brain levels and half-lives of the four compounds suggested that the compounds might be metabolized by hydroxylation at the 4- position of the phenyl ring. Desmethylimipramine, an inhibitor of amphetamine hydroxylation in the 4- position, markedly elevated brain levels of the 2-chloro compound and to a lesser extent of the 3-chloro compound. The 2-chloro compound did not lower brain serotonin levels even in desmethylimipramine-treated rats, however. The results suggest that some pharmacologic properties of the chlorinated 3-phenyl-piperidines are indeed similar to those of chlorinated amphetamines.

Amphetamine↗