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Biomedical subjects

S K Basu

Publications and source records attributed to S K Basu.

At least 109 records · Page 6Linked to original sources
PubMed1984

HMG CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions.

The rate-limiting enzyme of cholesterol biosynthesis, HMG CoA reductase, is controlled by negative feedback regulation of transcription. We have isolated the reductase gene from a bacteriophage lambda genomic library prepared from hamster UT-1 cells. The 25 kilobase gene is split into 20 exons. The 5' untranslated and promoter regions differ from those of previously characterized genes. The 5' untranslated region encompasses as many as 670 nucleotides; contains up to eight AUG codons upstream of the codon used to initiate translation; and has multiple transcription initiation sites as determined by S1 nuclease mapping and primer extension analysis. The promoter region lacks a characteristic TATA box and CCAAT box; is rich in G + C residues (65%); and contains repeat sequences homologous to the 21 base pair repeats of the SV40 promoter. These unusual features may be relevant to the mechanism of expression of "housekeeping" genes, particularly those that are subject to negative feedback regulation.

Animals↗
PubMed1984

Evaluation of radioprotectors by the Na+ influx study in RBC of lethally irradiated rats.

Sodium homeostasis in adult male albino Sprague Dawley rats has been examined 24 hours after exposure to 11 Gy whole-body gamma irradiation. Rate of influx of 22Na in red blood corpuscles (in vitro) of irradiated rats significantly increased and was modified by the administration of some radioprotective drugs prior to irradiation. Solcoseryl and AET (200 mg/kg) gave excellent protection and the combinations of 5-HTP with AET or MPG rendered better protection than when used alone.

Animals↗
PubMed1983

Independent pathways for secretion of cholesterol and apolipoprotein E by macrophages.

Cholesterol-loaded macrophages secrete cholesterol and apolipoprotein E. The current studies show that this secretion occurs by two independent pathways. In the absence of serum, the cells secrete apolipoprotein E, but not cholesterol. In the presence of monensin (an inhibitor of protein secretion), the cells secrete cholesterol, but little apolipoprotein E. After secretion, apolipoprotein E and cholesterol associate with high-density lipoprotein to form a particle that can deliver cholesterol to the liver by receptor-mediated endocytosis. We conclude that apolipoprotein E does not function to remove cholesterol from macrophages but rather to participate in "reverse cholesterol transport."

Animals↗
PubMed1983

Genetic aspects of myopia among the Shia Muslim Dawoodi Bohras of Udaipur, Rajsthan.

359 sibs from 92 families, where any one member of the family (basic unit of study) was found to be affected, were screened for myopia. Data on age at onset, parity and severity were studied in relation to consanguinity. Significant consanguinity differentials in the manifestation of myopia were seen. Offspring who were the product of a consanguineous mating manifested myopia more frequently as compared to the offspring from the non-consanguineous matings (control group). Males from consanguineous matings were affected in a higher frequency and manifested myopia at early ages. Myopia was found to be birth order-dependent. Pedigree analysis has shown that myopia is not a monogenic trait. The most plausible mode of inheritance of myopia seems to be polygenic with variable expressivity, and shows gene dosage effect.

Birth Order↗
PubMed1983

Role of some radioprotectors on 59Fe uptake in bone marrow after whole-body gamma irradiation to mice.

59Fe uptake in the femur has been studied at four time intervals up to 10 days in mice receiving pretreatment with hydroxytryptophan (HT), AET, MPG and combination of HT and AET or MPG and exposed to 6 Gy whole-body gamma irradiation. MPG or 20 mg/kg dose of AET pretreatment has failed to improve upon the 59Fe uptake depression induced by the gamma irradiation to mice at any of the time intervals. AET (200 mg/kg), HT + AET (20 mg/kg) and HT + MPG treatments though have failed to prevent the initial 59Fe uptake depression induced by the irradiation, have helped a speedy recovery in the iron uptake so that normal level of uptake is obtained on the 7th day. Pretreatment with the HT dose also helps in a speedy recovery as judged on the 7th day and a normal 59Fe uptake is reached in these animals by the 10th day.

5-Hydroxytryptophan↗
PubMed1981

Monensin interrupts the recycling of low density lipoprotein receptors in human fibroblasts.

In cultured human fibroblasts, each LDL receptor mediates the internalization of approximately 100 particles of LDL every 20 hr. We provide evidence that this reutilization of LDL receptors involves the recycling of receptors into and out of the cell and that the carboxylic ionophore monensin blocks the return of the receptors to the surface. In the presence of monensin and LDL, 75% of the receptors disappeared from the cell surface within 15 min and more than 90% disappeared within 60 min. The receptors that left the surface were trapped intracellularly within perinuclear vacuoles, as visualized by indirect immunofluorescence with the use of LDL, monensin caused about 50% of the receptors to be trapped intracellularly within 15 min. The receptors that remained on the surface after monensin treatment could be trapped within the cell if LDL was added subsequently in the continued presence of monensin. Monensin did not decrease surface LDL receptors in fibroblasts from a patient (J.D.) with the internalization-defective form of familial hypercholesterolemia. In these mutant cells, LDL receptors are not localized to coated pits. The current data are interpreted to indicate that: in normal fibroblasts about 50% of surface LDL receptors absence of LDL; the remaining 50% of surface receptors can be induced to recycle by the presence of LDL; and monensin interrupts this recycling by preventing the receptor from returning to the surface, thereby causing the receptors to accumulate within the cell.

Cations, Monovalent↗
PubMed1981

Mouse macrophages synthesize and secrete a protein resembling apolipoprotein E.

Monolayers of mouse peritoneal macrophages were shown to synthesize and secrete a protein that resembles apoprotein E (apoE), a normal constituent of plasma lipoproteins. Synthesis and secretion were studied by incubation of macrophages with L-[35S]methionine and analysis of the 35S-labeled proteins secreted into the culture medium. The 35S-labeled protein resembling apoE showed the following properties: (i) it floated in the ultracentrifuge at a density less than 1.215 g/ml, indicating that it was associated with lipid; (ii) by NaDodSO4/polyacrylamide gel electrophoresis, its Mr of 35,000 was identical to that of authentic apoE obtained from mouse plasma very low density lipoprotein; (iii) its isoelectric point of 5.4 was the same as that of authentic mouse apoE; (iv) it comigrated with authentic mouse apoE after two-dimensional isoelectric focusing/NaDodSO4/polyacrylamide gel electrophoresis; and (v) it was quantitatively precipitated by a monospecific antibody directed against rat apoE. Synthesis and secretion of the apoE-like protein was stimulated 3- to 8-fold when the macrophages were loaded with cholesterol by incubation with either acetylated low density lipoprotein (acetyl-LDL) or beta-migrating very low density lipoprotein from cholesterol-fed rabbits. When the cells were incubated with acetyl-LDL, the apoE-like protein composed approximately 2% of the total 35S-labeled protein synthesized by the cells and approximately 10% of the total 35S-labeled protein secreted into the medium. The current findings suggest a role for apoE in the plasma transport of cholesterol excreted from cholesterol-loaded macrophages.

Animals↗
PubMed1981

Saturation and suppression of hepatic lipoprotein receptors: a mechanism for the hypercholesterolemia of cholesterol-fed rabbits.

Cholesterol-fed rabbits develop a marked in crease in plasma cholesterol levels. Most of the excess plasma cholesterol is contained in beta-migrating very low density lipoprotein (beta-VLDL), a cholesterol-rich particle that contains apoproteins B and E. When 125I-labeled beta-VLDL from cholesterol-fed rabbits was injected intravenously into normal rabbits, the lipoprotein was cleared rapidly from plasma, 80% of the radioactivity appearing in the liver within 4 min. In vitro binding assays showed that this uptake was due to the presence on liver membranes of a high-affinity, low-capacity binding site that resembles the low density lipoprotein receptor previously characterized on extrahepatic tissues. When the 125I-labeled beta-VLDL was injected into cholesterol-fed rabbits, hepatic uptake was reduced by more than 95% and the lipoprotein remained in the plasma. This defective uptake in cholesterol-fed rabbits was due to two factors: (i) saturation of the lipoprotein receptors by the high concentration of endogenous plasma beta-VLDL and (ii) a 60% reduction in the number of hepatic receptors after cholesterol feeding. Of the two factors, saturation of receptors was quantitatively more important. We suggest that, as a result of the saturation and suppression of receptors, the hepatic removal of beta-VLDL in the cholesterol-fed rabbit fails to increase commensurate with the diet-induced increase in beta-VLDL synthesis and profound hypercholesterolemia ensues.

Adrenal Glands↗
PubMed1980

The scavenger cell pathway for lipoprotein degradation: specificity of the binding site that mediates the uptake of negatively-charged LDL by macrophages.

Macrophages isolated from a variety of organs in several animal species exhibit high affinity binding sites that recognize chemically modified proteins. One of these binding sites recognizes human plasma low density lipoprotein (LDL) in which the positive charges on the epsilon-amino groups of lysine have been removed or neutralized by chemical modification, thus giving the protein an enhanced negative charge. Effective treatments include reaction of LDL with organic acid anhydrides (acetylation or maleylation) and reaction with aldehydes, such as treatment with malondialdehyde. After the negatively-charged LDL binds to the surface receptor sites, it is rapidly internalized by the macrophages by endocytosis and hydrolyzed in lysosomes. The liberated cholesterol is reesterified in the cytoplasm, producing massive cholesteryl ester deposition. The binding sites for negatively-charged LDL has been demonstrated so far only on macrophages and other scavenger cells. It is not expressed in cultured fibroblasts, smooth muscle cells, lymphocytes, or adrenal cells. In addition to its affinity for acetylated LDL and malondialdehyde-treated LDL, the macrophage site binds a variety of polyanions. It exhibits a particularly high affinity for certain sulfated polysaccharides (dextran sulfate and fucoidin), certain polynucleotides (polyinosinic acid and polyguanylic acid), polyvinyl sulfate, and maleylated albumin. It is possible that the site that binds negatively-charged LDL may be responsible for the massive accumulation of cholesteryl esters that occurs in vivo in macrophages and other scavenger cells in patients with high levels of circulating plasma LDL.

Acetylation↗