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Biomedical subjects

R Gupta

Publications and source records attributed to R Gupta.

At least 721 records · Page 40Linked to original sources
PubMed1988

Camptothecin-resistant mutants of Chinese hamster ovary cells containing a resistant form of topoisomerase I.

In Chinese hamster ovary cells, stable mutants that exhibit 250- to 350-fold resistance to camptothecin (CptR mutants) have been isolated from mutagen-treated cultures. The CptR mutants exhibited no cross-resistance towards drugs such as colchicine, vinblastine, taxol, or puromycin but showed slightly (2- to 3-fold) enhanced sensitivity towards various drugs that inhibit DNA topoisomerase II (namely teniposide, etoposide, doxorubicin, mitoxantrone, amsacrine, ellipticine), suggesting that the genetic lesion in these mutants was highly specific. In contrast to the wild-type cells, the CptR line was resistant to camptothecin-induced DNA strand breaks as measured by alkaline elution. Biochemical studies revealed that in CptR mutants the cellular activity as well as protein content of DNA topoisomerase I were reduced to about 40-50% of the level in wild-type cells. Normal levels of activity and content were observed for the related enzyme DNA topoisomerase II. Studies with DNA topoisomerase I purified from the wild-type and the mutant cells showed that the enzyme from the CptR cells was markedly resistant to camptothecin as assayed by the drug's effects either on relaxation of supercoiled DNA or on stabilization of the covalent enzyme-DNA intermediate. The presence of a camptothecin-resistant form of DNA topoisomerase I in the mutant cells provides further evidence that this enzyme is the cellular target of camptothecin. Cell hybridization studies between the CptR and CptS cells showed that the hybrids formed between these two cell lines were sensitive to camptothecin. The recessive behavior of the CptR mutation provides a plausible explanation for the reduced topoisomerase I content (about one-half of wild-type cells) of the mutant cells and also for their enhanced sensitivity towards inhibitors of topoisomerase II.

Animals↗
PubMed1988

Species-specific differences in the toxicity of puromycin towards cultured human and Chinese hamster cells.

The toxicity of the protein synthesis inhibitor puromycin towards a number of human and Chinese hamster cell lines has been examined. In comparison to cells of human origin, Chinese hamster cells exhibited about 25-fold higher resistance towards puromycin. These differences appeared to be species related as all the cell lines from any one species showed similar sensitivity towards puromycin. The incorporation of [3H]leucine in the hamster cell lines was accordingly found to be more resistant to the inhibitory effects of puromycin as compared to human cells. Studies on the cellular uptake of [3H]puromycin showed that in comparison to human cells, the drug uptake/binding in the hamster cell lines was greatly reduced. However, protein synthesis in the extracts of hamster and human cells showed no significant differences in sensitivity towards puromycin. These results show that the observed species related differences in cellular toxicity to puromycin are due to differences in the cellular uptake/binding of the drug.

Animals↗
PubMed1988

The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis.

We evaluated the use of the urinary anion gap (sodium plus potassium minus chloride) in assessing hyperchloremic metabolic acidosis in 38 patients with altered distal urinary acidification and in 8 patients with diarrhea. In seven normal subjects given ammonium chloride for three days, the anion gap was negative (-27 +/- 9.8 mmol per liter) and the urinary pH under 5.3 (4.9 +/- 0.03). In the eight patients with diarrhea the anion gap was also negative (-20 +/- 5.7 mmol per liter), even though the urinary pH was above 5.3 (5.64 +/- 0.14). In contrast, the anion gap was positive in all patients with altered urinary acidification, who were classified as having classic renal tubular acidosis (23 +/- 4.1 mmol per liter, 11 patients), hyperkalemic distal renal tubular acidosis (30 +/- 4.2, 12 patients), or selective aldosterone deficiency (39 +/- 4.2, 15 patients). When the data on all subjects studied were pooled, a negative correlation was found between the urinary ammonium level and the urinary anion gap. We conclude that the use of the urinary anion gap, as a rough index of urinary ammonium, may be helpful in the initial evaluation of hyperchloremic metabolic acidosis. A negative anion gap suggests gastrointestinal loss of bicarbonate, whereas a positive anion gap suggests the presence of altered distal urinary acidification.

Acid-Base Equilibrium↗
PubMed1988

Genetic studies among the sedentes and migrant Oraons of eastern India.

A total of 334 Oraons of both sexes from two localities in eastern India were tested for 11 polymorphic and six monomorphic blood genetic markers. The sample comprised 130 sedentes from the Gumla district in Bihar and 204 migrants to the Jalpaiguri district of North Bengal. At the hemoglobin locus one example of HbAS was observed in the Gumla sample, while two cases of HbAS were found in the Jalpaiguri group. The Oraons are a distinct tribe and are characterized by a very low frequency of Hp1, TFC2, and a high frequency of TfD1 and GcIF at the serum protein loci. In the red cell enzyme systems the Oraons have a higher frequency of pa at the acid phosphatase locus and GLO1 at the Glyoxalase I locus. Absence of red cell lactate dehydrogenase and very low HbS and GdB- is also characteristic of the Oraons. A probable new nondeficient slow variant of Gd has been observed in polymorphic frequency in the Oraons of Gumla. There was an excess of homozygotes at the Gc locus. No significant difference in the gene frequency between the two groups of Oraons was observed at any of the loci. Genetic distance estimates using the gene frequency data indicate that the Oraons of the two localities are genetically homogeneous and form one cluster with the Bhils. They are nearer to the Irula and Kurumba tribes of the Nilgiris rather than the other Dravidian tribes, Tamils, or Nayars.

Blood Proteins↗
PubMed1988

4-Dimethylaminoazobenzene interferes with the binding of ribosomes to reticular membranes.

Treatment of chemically degranulated rough endoplasmic reticulum (RER) with 4-dimethylamino-azobenzene (4-DAB) partly damages binding of fresh polyribosomes to both the lighter and heavier fractions of reconstituted RER. Also, treatment of ribosomes with 4-DAB seemed to inhibit their binding to the chemically stripped RER (DRER) appearing both as lighter and heavier rough membrane layers after reconstitution. The interaction of 4-DAB with stripped microsomal fraction and ribosomes might be introducing certain conformational constraints into their proteins, thus crippling the binding of the ribosomes to reticular membranes.

Animals↗
PubMed1988

Oxalate uptake in intestinal and renal brush-border membrane vesicles (BBMV) in vitamin B6-deficient rats.

Acute, subclinical, and chronic pyridoxine deficiency did not modify the oxalate influx in rat intestinal BBMV but elevated the oxalate reabsorption by renal tubular cells. The Na+ and K+ ions did not affect oxalate uptake in either intestinal or renal BBMV. Although thiol group blocking agents did not affect intestinal uptake of oxalate they significantly altered oxalate translocation across the renal tubular cells. Following pyridoxine deficiency the rat kidneys appear to be more specific for inducing oxalate lithiasis as compared to oxalate influx through the intestine.

Animals↗
PubMed1988

Rooting the archaebacterial tree: the pivotal role of Thermococcus celer in archaebacterial evolution.

The sequence of the 16S ribosomal RNA gene from the archaebacterium Thermococcus celer shows the organism to be related to the methanogenic archaebacteria rather than to its phenotypic counterparts, the extremely thermophilic archaebacteria. This conclusion turns on the position of the root of the archaebacterial phylogenetic tree, however. The problems encountered in rooting this tree are analyzed in detail. Under conditions that suppress evolutionary noise both the parsimony and evolutionary distance methods yield a root location (using a number of eubacterial or eukaryotic outgroup sequences) that is consistent with that determined by an "internal rooting" method, based upon an (approximate) determination of relative evolutionary rates.

Archaea↗
PubMed1988

Cross resistance pattern towards anticancer drugs of a human carcinoma multidrug-resistant cell line.

Puromycin-resistant (PurR) mutants/variants of a human carcinoma cell line (HeLa), which show greatly reduced cellular uptake of 3H-puromycin and 3H-daunomycin have been isolated after one- and two-step selections in presence of the drug. The cross-resistance pattern of these mutant cell lines towards numerous anticancer drugs and other inhibitors has been examined. Both the first- and the second-step mutants exhibited increased resistance to a number of antimitotic drugs (viz. vinblastine, vincristine, colchicine, taxol and maytansine), several protein synthesis inhibitors (viz. chalcomycin, bruceantin, harringtonine, homoharringtonine), a large number of DNA interactive compounds (viz. aclacinomycin A, actinomycin D, adriamycin, m-AMSA, chromomycin A3, coralyne sulphoacetate, daunomycin, ellipticine, mithramycin, mitoxantrone, 5-methoxysterigmatocystin, rubidazone, variamycin, VM26 and VP16-213) and a number of other drugs acting via other mechanisms (viz. Baker's antifol, nitidine chloride and rhodamine 123). Whereas the first-step mutants showed stable resistance to these drugs, the second-step lines partially reverted upon growth in non-selective medium. Further, treatment of these mutant lines with non-cytotoxic doses of the calcium channel blocker verapamil reverted or abolished their resistance to the above drugs in a dose-dependent manner. In contrast to the above compounds, the PurR mutants showed no significant cross-resistance to a large number of other drugs which included asaley, AT-125, 5-azacytidine, azaserine, cyclocytidine, cis-platin, cytosine arabinoside, chlorambucil, chlorpromazine, alpha-difluoromethyl ornithine, 5-fluorouracil, ftorafur, gallium nitrate, hydroxyurea, ICRF-159, ICRF-187, imipramine, methotraxate, 6-methylmercaptopurine riboside, mycophenolic acid, melphalan, mitomycin C, methyl GAG, nafoxidine, reumycin, 6-selenoguanosine, 6-thioguanine, tiazofurin, tamoxifen, thalicarpine, tiapamil and verapamil). These cross-resistance data should prove useful in developing suitable drug combinations to which cellular resistance would not develop readily.

Animals↗