Biomedical subjects

S B Weinstock

Publications and source records attributed to S B Weinstock.

7 recordsLinked to original sources

PubMed1992

Effects of liposome encapsulated hemoglobin on the reticuloendothelial system.

The effects of different doses (4, 10, and 25%) of liposome encapsulated hemoglobin (LEH) were measured on the Reticuloendothelial System (RES) and Kupffer cells (KC) by i) colloidal carbon clearance in the rat in vivo and in the isolated perfused liver, ii) magnetometry, and iii) histological analysis. At the highest dose, in vivo carbon clearance rates (k) were half the rate as in controls at 2 and 12 hours post-treatment. By 24 hours post-treatment clearance rates were at control levels. Empty liposomes (LIP) caused a 2-fold decrease in k at 2 hours only. With both LEH and LIP, the effects were less severe when rats were given the lower doses. Magnetometric studies showed a decrease in KC phagosomal motion in the LEH-treated (25%) rats at 2 and 24 hours that returned to control levels at 2 weeks. Perfused livers from rats treated with a low dose of LEH cleared carbon at the same rate as LIP and Krebs Ringer Bicarbonate (KRB) controls. Histological examination showed minimal tissue damage in all test groups. Thus, LEH and LIP have some short-term deleterious effects on KC and the RES probably due to RES blockade rather than cellular damage.

Animals↗

PubMed1991

Perfluorochemical emulsions decrease Kupffer cell phagocytosis.

One drawback to using perfluorochemical emulsions as blood substitutes is that perfluorochemical particles are cleared from the blood by the reticuloendothelial system, primarily liver and spleen. We measured the impact of two perfluorochemical emulsions on clearance of colloidal carbon (less than 1 microns) and 51Cr-sheep red blood cells (about 8 microns) by the reticuloendothelial system in vivo and in the isolated perfused liver. Male rats were injected with 2 ml/100 gm body wt of Fluosol-DA or Oxypherol-ET for 4 consecutive days. Carbon (1 ml/100 gm body wt) or sheep red blood cells (0.05 ml of 5% vol/vol/100 gm body wt) were then injected intravenously (in vivo) or added to perfusate. Samples were taken at several time points for 1 hr. In the isolated perfused liver, carbon clearance was depressed by 25% 1 day after treatment. Rates returned to control levels by 12 days in Fluosol-DA-treated rats but remained depressed by 67% in Oxypherol-ET-treated rats. Sheep red blood cell (8 microns) clearance was two to five times slower than carbon clearance and depressed by 40% in livers from Fluosol-DA rats 1 day and 12 days after treatment. Added serum did not improve phagocytosis. In vivo carbon clearance remained normal in Fluosol-DA-treated rats but decreased by 74% in Oxypherol-ET-treated rats 1 day after treatment, returning to normal by 12 days. Clearance rates were similar in control rats in vivo and in the perfused liver. We conclude that the isolated perfused liver is a good model to measure liver clearance function. Although low doses of perfluorochemical emulsions may depress Kupffer cell phagocytosis, general reticuloendothelial system function is not significantly compromised.

Carbon↗

PubMed1988

Comparison of particle clearance and macrophage phagosomal motion in liver and lungs of rats.

Magnetic particles and magnetometry were used to noninvasively measure motion of particle-containing organelles in macrophages as well as to monitor the disappearance of particles from tissues. We compared these parameters in the liver (where macrophages are attached to the endothelium) and in the lungs (where macrophages were mobile on epithelial surfaces). Submicrometric magnetic particles were injected intravenously (1.5 mg/kg) into rats; 94% was taken up by the liver. Rats were also instilled intratracheally (1.0 mg/kg) with the same particles. Ultrastructural analyses showed that almost all particles were ingested by macrophages in both organs. Periodically, the retained particles were magnetized and aligned with an external magnet. After the magnet was removed, the decay of the resulting remanent field (relaxation) was followed for 25 min. Relaxation parameters (t1/2 and lambda 0) in the liver were constant from 30 min to 30 days after particle administration, but relaxation in lungs showed a time-dependent increase during the 1st day due to the slower rate of particle phagocytosis. Relaxation in both organs primarily reflects the motion of particle-containing organelles as they are rotated by the cytoskeleton. Relaxation in the lungs may also reflect cell translocation or even changes in alveolar shape. Clearance of particles from the lungs or liver was measured by following B0 (initial magnetic field strength). After correction for growth, the clearance t1/2 was 17.7 and 27.3 days for the lungs and liver, respectively. Bulk transport of particles is probably a more important clearance mechanism in the lungs than in the liver.

Animals↗

PubMed1984

The shunt pathway of mevalonate metabolism in the isolated perfused rat liver.

The shunt pathway of mevalonate metabolism (Edmond, J., and Popják, G. (1974) J. Biol. Chem. 249, 66-71) has been studied in isolated livers from fed rats perfused with physiological concentrations of variously labeled [14C]mevalonates. The measured rates of 14CO2 production were converted to rates of mitochondrial acetyl-CoA production from mevalonate by methods which take into account underestimations of metabolic rates derived from 14CO2 production. Our data confirm that the shunt pathway leads to mitochondrial acetyl-CoA. The apparent negligible rate of mevalonate shunting in liver, previously reported by others, stems from the very low contribution (congruent to 0.1%) of plasma mevalonate to total mevalonate metabolism in the liver. This contribution was assessed from the relative incorporations of 3H2O and [5-14C]mevalonate into sterols. In livers from fed rats, the shunt diverts about 5% of the production of mevalonate. The total rate of mevalonate shunting in the liver is about 200 times greater than in two kidneys. The liver is therefore the main site of mevalonate shunting in the rat.

Acetyl Coenzyme A↗

PubMed1982

Metabolism of plasma mevalonate in rats and humans.

A circadian rhythm in plasma mevalonate was identified in human subjects. This variation, over a 5-fold range, is paralleled by a rhythm in urinary excretion. No such diurnal change in plasma mevalonate was observed in schedule-fed, light-cycled rats, despite the presence of a pronounced rhythm in liver HMG-Coa reductase and sterol synthesis. A linear correlation was found between liver HMG-CoA reductase activity and the rate of hepatic sterol synthesis. Sterol synthesis accounted for 59% of the HMG-CoA reductase activity. A 4-fold increase in plasma mevalonate following bilateral nephrectomy did not feed back on liver HMG-CoA reductase. Turnover rates for circulating R- and S-mevalonate were determined by the kinetics of tritiated tracers. S-Mevalonate exhibited first-order kinetics with a T 1/2 of 19 to 23 min, while R-mevalonate kinetics could be resolved into two phases with half-lives of 9 and 42 min. The renal uptake of circulating mevalonate was measured by the initial rate of increase in plasma mevalonate immediately following bilateral nephrectomy; this was confirmed by determination of the renal arterio-venous difference. This value ranges between 500 and 600 pmol/min for a 250-g rat.

Adult↗

PubMed1981

Urinary clearance and metabolism of mevalonate by the isolataed perfused rat kidney.

The urinary excretion and the incorporation into lipids of R[3-14C]mevalonate was investigated in isolated rat kidneys perfused with physiological concentration sof the substrate (80-500 pmol/ml). The clearance of R[3-14C]mevalonate and of the unnatural enantiomer S[5-14C]mevalonate were compared to the glomerular filtration ratea measured by the clearance of inulin. Evidence is presented that half of R-mevalonate filtered in the glomerulus is reabsorbed in the tubule whereas S-mevalonate is not reabsorbed. The kidney tubule appears to discriminate between the R and S forms of the mevalonate salt. Urinary excretion and incorporation into lipids accounted for 22% and 46%, respectively, of the uptake of R[3-14C]mevalonate from the perfusate. The label of R[3-14C]mevalonate recovered in lipids was distributed among saponifiable (15%), digitonin-precipitable sterols (18%) and squalene + prenols (67%). Sterol synthesis in the kidney appears to be controlled, at least in part, by the level of circulatinga R-mevalonate.

Animals↗

PubMed1978

Glycolysis mutants in Saccharomyces cerevisiae.

Mutants have been isolated in S. cerevisiae with the phenotype of growth on pyruvate but not on glucose, or growth on rich medium with pyruvate but inhibition by glucose. Screening of mutagenized cultures was either without an enrichment step, or after enrichment using the antibiotic netropsin (Young et al. 1976) or inositol starvation (Henry, Donahue and Culbertson 1975). One class of mutants lacked pyruvate kinase (pyk), another class had all the enzymes of glycolysis, and one mutant lacked phosphoglucose isomerase (pgi, Maitra 1971). Partial reversion of pyruvate kinase mutants on rich medium containing glucose gave double mutants now also lacking hexokinase (hxk), phosphofructokinase (fk), or several enzymes of glycolysis (gcr). In diploids the mutations were recessive. pyk, pgi, pfk, and gcr segregated 2:2 from their wild-type alleles. PYK hxk, PYK pfk, and PYK gcr segregrants grew on glucose.

Glucose-6-Phosphate Isomerase↗