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D S Goodman

Publications and source records attributed to D S Goodman.

At least 163 records · Page 9Linked to original sources
PubMed1973

Comparative studies of retinol transport in plasma.

The comparative immunology and biochemistry of plasma retinol transport were studied using radioimmunoassays previously developed for human and for rat retinol-binding protein (RBP). Serum or plasma from 25 species of verebrates, from the mammalian orders Primates, Artiodactyla, Perissodactyla, Carnivora, and Rodentia and from the classes Aves, Amphibia, and Pisces, were assayed. There was a high degree of immunological specificity within a given mammalian order. Sera from seven subhuman primate species tested reacted in the human RBP immunoassay, and sera from four of five rodents reacted in the rat RBP immunoassay. Primate sera failed to react in the rat RBP immunoassay, and rodent sera failed to react in the human RBP immunoassay. Except for a slight reactivity of canine serum in the human RBP immunoassay, other sera showed no immunoreactivity. Using gel filtration, apparent molecular weights were estimated at 60,000-80,000 for the retinol transport systems in whole serum from cow, swine, chicken, and dog. Canine RBP was isolated and partially characterized. Purified canine RBP was generally similar to human and rat RBP with regard to molecular weight (approximately 20,000) and other properties. In plasma, canine RBP circulates as a protein-protein complex of higher apparent molecular weight. The complex remains to be characterized. These data suggest that mammals in general have a retinol transport system similar to the human and rat transport systems but that immunologically important differences in RBP occur among mammalian orders.

Amphibians↗
PubMed1972

Extraction and recombination studies of the interaction of retinol with human plasma retinol-binding protein.

Methods have been developed for the removal of retinol from human plasma retinol-binding protein (RBP), so as to form the retinol-free apoprotein, and for the recombination of apo-RBP with retinol to again form the holoprotein. Retinol is removed from RBP by gently shaking a solution of RBP with heptane under controlled conditions. During the shaking, retinol is gradually extracted from the RBP and into the heptane phase. The reassociation of apo-RBP with retinol is achieved by exposing a solution of apo-RBP to Celite coated with a thin film of retinol, followed by isolation of the RBP by gel filtration on Sephadex G-100. This procedure results in the recombination of apo-RBP with an amount of retinol almost identical with that previously removed by extraction. The two-phase extraction procedure was used to explore some of the factors which affect the interaction of retinol with RBP. The retinol-RBP complex was most stable in the lower portion of the pH range 5.6 to 10. The rate of removal of retinol from the RBP-prealbumin complex (the form in which RBP normally circulates in plasma) was markedly less than the rate of its removal from RBP alone. The interaction of retinol with RBP appears to be stabilized by the formation of the RBP-prealbumin complex. The recombination procedure was employed to examine the specificity of the binding of retinol to RBP, by determining whether compounds other than all-trans-retinol would effectively bind to apo-RBP. Apo-RBP did not bind cholesterol, but displayed a slight affinity for phytol. The affinity of RBP for beta-carotene was minimal, whereas both retinyl acetate and retinal were bound about one-third as effectively as all-trans-retinol. In contrast, retinoic acid bound to apo-RBP almost as effectively as did retinol. Each of two isomers of retinol, 13-cis and 11,13-di-cis-retinol, bound to apo-RBP to some extent. The 13-cis isomer appeared to bind somewhat less effectively than did the 11,13-di-cis isomer. The binding of retinol to RBP is highly but not absolutely specific.

Acetates↗
PubMed1971

The turnover and transport of vitamin D and of a polar metabolite with the properties of 25-hydroxycholecalciferol in human plasma.

Four normal men were injected intravenously with physiological doses (6 mug) of vitamin D(3)-1,2-(3)H. Serial samples of plasma were collected for 50 days. Total lipid extracts were chromatographed on silicic acid columns or thin-layer plates in order to characterize the radioactive components. Labeled vitamin D(3) disappeared rapidly from plasma (initial half-life approximately 12 hr); after 7 days unchanged vitamin D(3) represented less than 1% of circulating radioactivity. Coincident with vitamin D(3) disappearance a more polar labeled metabolite appeared with chromatographic and other properties identical with those of 25-hydroxycholecalciferol. The disappearance of the more polar metabolite was relatively slow with a half-life of 19.6 +/-0.6 days. A similar half-life was seen in a fifth subject, injected with 80 mug of vitamin D(3)-(3)H. Most (approximately 92%) of the plasma total radioactivity was represented by this component throughout the study. Plasma samples collected at various times were adjusted to density (d) 1.21 and were ultracentrifuged to separate plasma lipoproteins from proteins with d > 1.21. In all samples, almost all (mean 94%) of the radioactivity was found in association with proteins of d > 1.21. This observation was confirmed by bioassay, measuring uptake of (45)Ca by intestinal slices. All plasma bioassayable vitamin D was found in association with proteins of d > 1.21; 55% of bioactivity was found in the chromatographic fraction corresponding to 25-hydroxycholecalciferol and 44% in the fractions representing vitamin D(3). Since both vitamin D(3) and its 25-hydroxy metabolite are lipid-soluble sterol derivatives, the finding that these compounds do not circulate in association with the known plasma lipoproteins provides presumptive evidence for the existence of a specific transport protein of d > 1.21. The transport protein for the polar metabolite has been partly characterized by gel filtration on Sephadex G-200 and by electrophoresis on polyacrylamide gel. The protein has an apparent size slightly smaller than plasma albumin (approximate mol wt 50,000-60,000) and an electrophoretic mobility very slightly greater than that of albumin. Studies are in progress to fractionate further and to characterize the transport protein.

Adult↗
PubMed1971

The effects of diseases of the liver, thyroid, and kidneys on the transport of vitamin A in human plasma.

The effects of diseases of the liver, the thyroid, and the kidneys on the retinol-binding protein (RBP)-prealbumin (PA) system responsible for the transport of vitamin A in plasma were examined, using a radial gel diffusion immunoassay for PA and the previously described radioimmunoassay for RBP. Measurements were made on plasma samples from 118 normal subjects, 31 patients with cirrhosis, 5 with chronic active hepatitis, 27 with acute viral hepatitis, 14 patients with hyperthyroidism, 7 with hypothyroidism, and 26 patients with chronic renal disease of varying etiologies. In the patients with liver disease, the levels of vitamin A, RBP, and PA were all markedly decreased and were highly significantly correlated over a wide range of concentrations. Serial samples were available in 19 patients with acute hepatitis; as the disease improved the plasma concentrations of vitamin A, RBP, and PA all increased. In patients with acute hepatitis RBP concentrations correlated negatively with the levels of plasma bilirubin, glutamic-oxaloacetic transaminase, and alkaline phosphatase. In the hyperthyroid patients both RBP and PA concentrations were significantly lower than normal; in hypothyroidism, neither protein showed levels significantly different from normal. In both hyper- and hypothyroidism and in liver disease, the molar ratios of RBP:PA and of RBP:vitamin A were not significantly different from normal.Patients with chronic renal disease had marked abnormalities in the plasma concentrations of RBP and vitamin A and in the molar ratios examined. In renal disease the levels of both RBP and vitamin A were greatly elevated, while the PA levels remained normal. The molar ratios of RBP:PA and of RBP:vitamin A were both markedly elevated. In many patients RBP was present in molar excess as compared with PA. The presence of a relatively large proportion of free RBP, not complexed to PA, in some patients with chronic renal disease was confirmed by gel filtration. The free RBP, present in molar excess, was capable of forming a complex with additional purified PA added to the plasma. The kidneys appear to play an important role in the normal metabolism of RBP.

Adolescent↗
PubMed1970

Radioimmunoassay of human plasma retinol-binding protein.

A radioimmunoassay for human plasma retinol-binding protein (RBP) has been developed utilizing a double antibody precipitation technique. RBP was purified 1500- to 2000-fold by procedures described previously. A specific anti-human RBP antiserum was prepared in rabbits by three once-weekly injections of purified RBP emulsified with Freund's adjuvant. RBP was iodinated with (131)I and the RBP-(131)I was purified by gel filtration on Sephadex G-100 after complex formation with human plasma prealbumin. The RBP-(131)I was completely (> 95%) immunoprecipitable in the presence of an excess of specific antiserum, it was not (< 5%) immunoprecipitable in the absence of specific antiserum, and it could be completely displaced from antibody by excess unlabeled RBP. The standard curve obtained in the immunoassay with normal plasma was identical to that with pure RBP. Duplicate samples differed from their mean by 5 +/-5% (+/-SD). There was a quantitative recovery of pure RBP added in varying amounts to normal plasma. The immunoassay accurately measured RBP in amounts of 10-100 ng per assay tube. There was no significant difference in the immunoreactivity of apo-RBP as compared to holo-RBP. The mean plasma values (+/-SEM) for a group of 76 normal subjects were 47.2 +/-1.6 mug/ml for males and 41.6 +/-1.6 mug/ml for females. Plasma RBP levels were markedly depressed (15 +/-2.3 mug/ml) in 14 patients with acute viral hepatitis. There was a highly significant correlation between the plasma levels of RBP and of vitamin A in both normal subjects and patients with hepatitis. In all subjects plasma RBP was generally saturated with retinol. The data suggest that under normal circumstances RBP circulates almost exclusively as the holoprotein.

Animals↗
PubMed1970

Cholesteryl ester turnover in human plasma lipoproteins during cholestyramine and clofibrate therapy.

The effects of cholestyramine and of clofibrate on the turnover rates of individual cholesteryl esters in whole human plasma and in each of the three classes of plasma lipoproteins have been studied. Four hyperlipidemic patients (two under treatment with each of the two drugs) were injected intravenously with cholesterol-(14)C, and serial plasma samples were collected after 3-4 hr, 8 hr, 24 hr, and 4-5 days. The plasma samples were separated into three classes of lipoproteins by ultracentrifugation. The cholesteryl esters and free cholesterol were isolated from each sample, and the specific radioactivity of the free and esterified cholesterol was determined. The specific radioactivity of each individual cholesteryl ester was then determined for each sample, by separately measuring the distribution of cholesterol mass and of radioactivity among four different cholesteryl ester groups, namely the saturated, mono-, di-, and tetra-unsaturated esters. In all subjects the plasma cholesteryl esters were metabolically heterogeneous, and could be divided into three pools corresponding to the three classes of plasma lipoproteins. High density lipoprotein (d > 1.063) cholesteryl esters showed the greatest fractional turnover rate, and low density lipoprotein (d 1.019-1.063) cholesteryl esters showed the smallest fractional turnover rate. In each subject the cholesteryl ester composition of the three classes of plasma lipoprotein was almost identical. Within each lipoprotein, and in whole plasma, all the different individual cholesteryl esters were found to turn over at the same fractional rate. In all respects these results were similar to those previously obtained with normal subjects. The results suggest that neither drug has a strongly selective effect on the turnover of one particular cholesteryl ester, or on the turnover or composition of the cholesteryl esters in one particular plasma lipoprotein.

Aged↗