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Biomedical subjects

D S Goodman

Publications and source records attributed to D S Goodman.

At least 127 records · Page 7Linked to original sources
PubMed1979

Intracellular binding proteins for retinol and retinoic acid: comparison with each other and with serum retinol-binding protein.

Soluble proteins with binding specificity for either retinol or retinoic acid were isolated from rat testis cytosol. The characteristics of the purified cytosolic protein were compared both with each other, and directly with those of serum retinol-binding protein (RBP). Substantial similarities were observed between the two cytosol retinoid binding proteins, as well as clear differences between each of these proteins and serum RBP. The intracellular binding proteins differed from serum RBP with regard to molecular weight, immuno-reactivity, binding affinity for serum prealbumin, and ultraviolet and fluorescence spectral characteristics. The ultraviolet absorption spectrums of the cytosol binding protein for retinol (CRBP) and of the cytosol binding protein for retinoic acid (CRABP) were almost identical despite differences in the nature of the ligands bound by these two proteins.

Animals↗
PubMed1979

Partial amino acid sequence of human plasma retinol-binding protein. Isolation and alignment of the five cyanogen bromide fragments and the amino acid sequences of four of the fragments.

Studies are reported on the primary structure of human retinol-binding protein (RBP), the specific plasma transport protein for vitamin A. The protein consists of a single polypeptide chain of 186-187 amino acids. RBP was cleaved by cyanogen bromide into five fragments, CB-I (27 residues), CB-11 (25 residues), CB-III (20 residues), CB-IV (15 residues), and CB-V (99-100 residues). The cyanogen bromide fragments were isolated, their compositions were determined, and they were aligned after studies that included the tryptic digestion of maleylated, reduced, and carboxymethylated RBP and subsequent enzymatic digestion of some of the resulting tryptic peptides. The amino acid sequences of four of the five cyanogen bromide fragments were determined, and the sequence of almost two-thirds of the NH2-terminal portion of the RBP molecule was determined as: H2N-GLU-Arg-Asp-Cys-Arg-Val-Ser-ser-Phe-Arg-Val-Lys-Glu-Asn-Phe-Asp-Lys-Ala-Arg-Phe-Ser-Gly-Thr-Trp-Tyr-Ala-Met-Ala-Lys-Lys-Asp-Pro-Glu-Gly-Leu-Phe-Leu-Gln-Asp-Asx-Ile-Val-Ala-Glu-Phe-Ser-Val-Asx-Glx-Gly-Thr-Met-Ser-Ala-Thr-Ala-Gly-Lys-Arg-Val-Arg-Leu-Leu-Asn-Asn-Trp-Asp-Val-Cys-Ala-Asp-Met-Val-Gly-thr-Phe-Thr-Asp-Thr-Glu-Asp-Pro-Ala-Lys-Phe-Lys-Met-Lys-Tyr-Trp-Gly-Val-Ala-Ser-Phe-Leu-Gln-Lys-Gyl-Asn-Asp-Asx-His-Trp-Ile-Val-Asp-Thr-Asx-Thr-Tyr-Tyr-Ala-Val-Glu-Tyr-Cys-Ser-Arg---.

Amino Acid Sequence↗
PubMed1977

Inhibition of lymphocyte proliferation stimulated by lectins and allogeneic cells by normal plasma lipoproteins.

Lipoproteins, isolated by sequential flotation at densities 1.006, 1.019, 1.063, and 1.21, were examined for their ability to inhibit human lymphocytes stimulated by allogeneic cells and by lectins (phytohemagglutinin-P and concanavalin A). All the classes of normal plasma lipoproteins inhibited lymphoproliferation when peripheral blood lymphocytes were cultured in autologous, heterologous, or lipoprotein-deficient plasma (d greater than 1.21). The rank order of inhibitory potency was intermediate density lipoprotein (IDL) greater than very low density lipoproteins (VLDL) greater than low density lipoproteins (LDL) greater than high density lipoproteins (HDL), regardless of the mode of stimulation. The concentrations of IDL, VLDL, and LDL required for complete inhibition of stimulated lymphoproliferation were considerably below the levels of each of these lipoproteins normally found in human plasma. In addition, the concentration of HDL required for 50-90% inhibition was in the range of HDL levels normally found in human plasma. Moreover, at relatively higher concentrations, lipoproteins suppressed the incorporation of [3H]thymidine into DNA below the levels seen with reseting, unstimulated lymphocytes. The results suggest that circulating lymphocytes may normally be highly suppressed by the combined effects of all the endogenous lipoproteins and that the lipoproteins may play important roles in vivo in modulating lymphocyte functions and responses.

Depression, Chemical↗
PubMed1977

Vitamin A and retinol-binding protein metabolism during fetal development in the rat.

Studies were conducted on the metabolism and placental transport of vitamin A and plasma retinol-binding protein (RBP) during fetal development in the rat. Vitamin A accumulated in the conceptus in three phases: an early phase (days 7-9 of gestation) characterized by a high vitamin A concentration; a second phase (days 11-14) where vitamin A and RBP accumulated in parallel; and a third phase of continued vitamin A and RBP accumulation (days 16-20) in which vitamin A was stored in the fetal liver. The early phase of vitamin A accumulation may reflect a mechanism that exists to prepare the conceptus to meet the presumably higher vitamin A requirements of the critical period (days 10-14) of organ differentiation. Fetuses and placentas from retinol-deficient dams showed low levels of RBP through days 16-18 of gestation. A retinol-repletion study suggested, moreover, that the maternal retinol-RBP complex crossed the placenta. The various studies all suggest that vitamin A is transported from dam to fetus, from and after day 11, mainly by transplacental transport of maternal retinol-RBP. Finally, evidence was obtained indicating that the fetal liver begins to synthesize RBP around the 16th day of gestation and that by the 20th day, the fetal liver has a considerable capacity for RBP synthesis.

Animals↗
PubMed1977

Immunological and immunoassay studies of the binding protein for vitamin D and its metabolites in human serum.

This study reports the development of a specific and sensitive radioimmunoassay and a simple and accurate radial immunodiffusion (RID) assay for the human serum-binding protein for vitamin D and its metabolites (DBP). These immunoassays employed a monospecific antiserum that was prepared in rabbits against human DBP. The radioimmunoassay effectively measured DBP in amounts of 1-10 ng, whereas the RID assay measured DBP accurately in amounts of 0.2-0.8 mug. The results obtained with the two immunoassays on the same samples of serum agreed well with each other. Using the RID assay, the mean (+/- SD) serum DBP concentration observed in 35 normal persons was 422 +/- 27 micrograms/ml. Generally similar levels were observed in 66 hyperlipidemic subjects. In molar terms, the mean DBP concentration (approximately 8 microgramsM) was of the order of 50 times the usual serum level of 25-hydroxyvitamin D (25-OH-D) plus vitamin D. Thus, most of plasma DBP circulates as apo-DBP, not containing a bound molecule of 25-OH-D or of vitamin D. DBP and 25-OH-D concentrations were measured in a limited number of patients with hypercalcemia, mild hypocalcemia, and markedly elevated serum 25-OH-D levels due to oral vitamin D supplementation. It was found that major changes can occur in the serum levels of 25-OH-D and of calcium with very little or no associated changes occurring in the serum concentration of DBP, The results suggest that neither serum 25-OH-D nor serum calcium plays an important role in the regulation of the metabolism of DBP. Data were obtained that confirmed and extended an earlier report on the identity of the group-specific component (Gc) protein in plasma with the plasma vitamin D-binding protein. On immunodiffusion against whole serum, the line formed with the anti-DBP antiserum showed a complete reaction-of-identity with the line formed with commercial antiserum against Gc protein. Furthermore, serum that had been depleted of DBP by treatment with Sepharose containing covalently coupled antibodies against DBP was found to be depleted also of immunoreactivity against anti-GC protein antiserum. In addition, the properties of the purified DBP preparation agreed closely with those previously reported by others for Gc protein. Finally, a comparative immunology study showed that sera from several different mammalian orders showed some immunoreactivity against the antihuman DBP antiserum. Thus, proteins immunologically similar to human DBP are present in sera from a number of mammalian species and orders.

Calcium↗
PubMed1976

Vitamin A transport in human vitamin A toxicity.

The plasma retinol transport system was studied in three patients with chronic hypervitaminosis A. The toxic state in each was associated with increased plasma concentrations of total vitamin A, and particularly of retinyl esters. The concentrations of plasma retinol-binding protein and prealbumin were, in contrast, non to retinol-binding protein. These limited clinical data support conclusions from detailed studies with hypervitaminotic rats, which suggest that vitamin A toxicity occurs when excessive amounts of vitamin A are presented to cell membranes in association with plasma lipoproteins, rather than specifically bound to retinol-binding protein. Retinol-binding protein may not only regulate the supply of retinol to tissues but also protect tissues from the surface-active properties of the vitamin.

Adult↗
PubMed1976

Parameters of the three-pool model of the turnover of plasma cholesterol in normal and hyperlipidemic humans.

Long-term studies (32-49 wk) of the turnover of plasma cholesterol were conducted in 24 subjects. Eight subjects were normilipidemic, six had hypercholesterolemia, eight had hypercholesterolemia and hypertriglyceridemia, and two had hypertriglyceridemia alone. 10 of the hyperlipidemic patients had a definite familial disorder. In all subjects (except one for whom complete data were not available), the same three-pool model previously described gave the best fit for the data. The parameters of the three-pool model observed in the normal subjects were compared with the model parameters found in the patients with the different kinds of hyperlipidemia. In addition, single and multiple regression analyses were conducted to explore the relationships between the model parameters and various physiological variables, including age, body size, and serum lipid concentrations. Using this approach, significant differences between groups, or correlations with serum lipid levels were seen for several parameters of the three-pool model: the production rate (PR); the size of the rapidly exchanging pool 1 (M1); all estimates of the size of the most slowly equilibrating pool 3 (M3); and the rate constant k21. The PR in normal subjects (1.14 +/- 0.19 g/day, mean +/- SD) was not significantly different from that found in patients with hypercholesterolemia, with or without hypertriglyceridemia. The major determinant of cholesterol PR was overall body size, expressed either as total body weight or as surface area. The correlations between PR and indices of adiposity (percent ideal weight and excess weight), although statistically significant, were much weaker in this nonobese population. After adjustment for body size variation, cholesterol PR was not correlated with the serum cholesterol concentration but was probably (P less than 0.05) correlated with the triglyceride concentration. When the two patients with very high triglyceride concentrations were excluded, however, no correlation was observed between adjusted PR and triglyceride level. It is probable that hypertriglyceridemic patients represent a heterogeneous population, in which the majority do not show increased cholesterol PR. M1 was correlated with all body size variables, but most strongly with excess weight. After adjusting for the effects of body size, M1 was also correlated and triglyceride. Major differences were found in the relationships between the physiological variables and the sizes of pools 2 and 3. M2 was correlated neither with any of the indices of body size or adiposity, nor with the serum levels of either cholesterol or triglyceride. In contrast, all estimates of M3 were correlated with indices of adiposity (but not of overall body size) and with the serum cholesterol concentration. Thus, the amount of cholesterol in slowly equilibrating tissue sites appears to particularly increase with elevations of the serum cholesterol level. The results also confirm previous data that adipose tissue cholesterol is an important part of pool 3.

Adipose Tissue↗
PubMed1976

The transport of vitamin D and its 25-hydroxy metabolite in human plasma. Isolation and partial characterization of vitamin D and 25-hydroxyvitamin D binding protein.

This study reports the isolation and partial characterization of vitamin D and 25-hydroxyvitamin D binding protein (DBP), the specific transport protein for vitamin D and its 25-hydroxy metabolite in human plasma. DBP was labeled by the addition of a tracer amount of 3H-labeled 25-OH-D3 to the original plasma used for protein fractionation. Previous experiments have shown that such 25-OH-D3 added in vitro binds to the same protein normally responsible for the transport of endogenous 25-OH-D and of vitamin D. The isolation of human DBP was achieved by an extensive sequence of procedures which resulted in a final yield of only approximately 4 mg of purified DBP from a starting volume of 34 liters of plasma. Purified DBP was homogeneous in the analytical ultracentrifuge and showed a single band of protein on analytical polyacrylamide gel electrophoresis. DBP had a sedimentation constant of 3.49s and a mol wt of approximately 52,000. The molecular weight was assessed by sedimentation equilibrium analysis and also by sodium dodecyl sulfate-disc-gel electrophoresis and by gel filtration on a standardized column of Sephadex G-150. The amino acid composition of DBP was determined and was generally consistent with the estimated extinction coefficient (E1cm1% at 280 nm) of about 9.1. The isoelectric point of DBP was estimated as 4.8 from isoelectric focusing experiments. Direct study of the binding capacity of the purified DBP for added 25-OH-D3 showed that the isolated DBP had a high affinity for 25-OH-D3, with an apparent maximum binding capacity of one molecule of 25-OH-D3 per molecule of protein.

Amino Acids↗
PubMed1976

Studies on the transport of vitamin D and of 25-hydroxyvitamin D in human plasma.

A study was conducted to investigate whether human plasma contains one or more than one protein for the transport of vitamin D and of 25-hydroxyvitamin D (25-OH-D). Serum was labeled in vivo with a mixture of radioactive vitamin D3 (derived from orally administered tracer vitamin D3) and of endogenously synthesized labeled 25-OH-D3. Samples of such serum were subjected to several different protein fractionation procedures. Only a single peak of protein-bound radioactivity was observed after each of these procedures. The fraction comprising the ascending and the descending limbs of the single peak of protein-bound radioactivity (after each procedure) were separately pooled. In each instance the ratio of radioactive 25-OH-D3 to radioactive vitamin D3 was found to be almost identical in both the ascending and the descending limbs. Taken together, these findings provide strong evidence that human serum contains only a single binding protein responsible for the normal transport of both vitamin D and 25-OH-D. Plasma labeled in vitro with added 3H-labeled 25-OH-D3 was subjected to gel filtration on Sephadex G-200 and to chromatography on columns of DEAE-cellulose and of SP-Sephadex. After each of these procedures a single peak of protein-bound radioactivity was observed, with elution profiles of protein and of radioactivity that were identical with those observed with in vivo labeled serum. These data indicate that tracer 25-OH-D3 added to plasma in vitro binds to the same plasma protein normally responsible for the transport of vitamin D and of 25-OH-D.

Adult↗