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S Kumar

Publications and source records attributed to S Kumar.

At least 1,747 records · Page 97Linked to original sources
PubMed1989

Structure of 3-isoinosine.

3-beta-D-Ribofuranosylhypoxanthine, 3-beta-D-ribofuranosyl-1,6-dihydro-3H-purin-6-one, C10H12-N4O5, Mr = 268.23, monoclinic, P2(1), a = 6.503 (1), b = 24.007 (6), c = 7.392 (2) A, beta = 106.53 (2) degrees, V = 1106.3 (9) A3, Z = 4, Dx = 1.610 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 1.23 cm-1, F(000) = 560, T = 299 K, R = 0.048 and wR = 0.043 for 1602 observed reflections. There are two crystallographically independent molecules in the structure; in both of them the 6-oxo, 7H tautomer is the predominant form. The bond lengths and angles of the two molecules are almost identical and the hypoxanthine moiety is almost planar. The torsional angles of the glycosidic linkage O(4')-C(1')-N(3)-C(4) are -159.3 and -148.8 degrees, both in the anti range. The sugar puckers are 4T3 (C4'-exo/C3'-endo), with P = 46.35 degrees and tau m = 42.30 degrees, and 2E (C2'-endo), with P = 157.24 degrees and tau m = 41.32 degrees. All N and O atoms except N(3) and O(4') participate in a three-dimensional hydrogen-bonding system.

Chemical Phenomena↗
PubMed1989

Interdependence of CD4+ T cells and malarial spleen in immunity to Plasmodium vinckei vinckei. Relevance to vaccine development.

We studied immunity to the blood stage of the rodent malaria, Plasmodium vinckei vinckei, which is uniformly lethal to mice. BALB/c mice develop solid immunity after two infections and drug cure. The following experiments define the basis of this immunity. Transfer of pooled serum from such immune mice renders very limited protection to BALB/c mice and no protection to athymic nu/nu mice. Moreover, B cell-deficient C3H/HeN mice develop immunity to P. vinckei reinfection in the same manner as immunologically intact mice, an observation made earlier. In vivo depletion of CD4+ T cells in immune mice abrogates their immunity. This loss of immunity could be reversed through reconstitution of in vivo CD4-depleted mice with fractionated B-, CD8-, CD4+ immune spleen cells; however, adoptive transfer of fractionated CD4+ T cells from immune spleen into naive BALB/c or histocompatible BALB/c nude mice does not render recipients immune. In vivo depletion of CD8+ T cells did not influence the parasitemia in nonimmune or immune mice. Splenectomy of immune mice completely reverses their immunity. Repletion of splenectomized mice with their own spleen cells does not reconstitute their immunity. We conclude that some feature of the malaria-modified spleen acts in concert with the effector/inducer function of CD4+ T cells to provide protection from P. vinckei. To be consistent with this finding, a malaria vaccine may require a combination of malaria Ag to induce immune CD4+ T cells and an adjuvant or other vaccine vehicle to alter the spleen.

Animals↗
PubMed1989

DNA topology of the ordered chromatin domain 5' to the human c-myc gene.

DNA restriction fragments located 5' to the human c-myc gene display anomalous electrophoretic mobility on polyacrylamide gels. Computer modeling of the c-myc flanking DNA suggests that the slow-moving DNA fragments spanning nucleotides -1690 to -1054 (relative to c-myc promoter P1) and -718 to -452 form large left handed superhelices or curved structures while the fast-moving DNA fragment spanning nucleotides -407 to +78 has an unusually straight structure. These analyses also predict a periodic array of localized regions of bending through the superhelical domains. Micrococcal nuclease digestion of isolated nuclei reveals that the slow-moving DNA fragments exist in an ordered chromatin structure stable to nuclease, whereas the digestion pattern of the fast-moving DNA fragment suggests a less ordered array of nucleosomes or a non-nucleosomal chromatin structure.

Base Sequence↗
PubMed1989

Mutagenicity and tumorigenicity of dihydrodiols, diol epoxides, and other derivatives of benzo(f)quinoline and benzo(h)quinoline.

The mutagenic activities of benzo[f]quinoline, benzo[h]quinoline, and a number of their derivatives, including dihydrodiols, K-region oxides, diol epoxides, and tetrahydroepoxides, were assessed in strain TA 100 of Salmonella typhimurium. The dihydrodiol derivatives of benzo[f]quinoline and benzo[h]quinoline were also tested for tumorigenic activity in newborn mice. Benzo[f]quinoline was metabolically activated in the presence of rat liver S-9 preparation to products mutagenic to the bacterial system to a greater extent than was benzo[h]quinoline. However, trans-7,8-dihydro-7,8-dihydroxybenzo[f]quinoline was less mutagenic compared to trans-7,8-dihydroxy-7,8-dihydrobenzo[h]quinoline in the presence of rat liver homogenate. The data on the mutagenic activity of the dihydrodiol derivatives of benzoquinolines were consistent with the intrinsic mutagenicity of the corresponding epoxide derivatives, in that the bay-region diol epoxides and tetrahydroepoxide of benzo[h]quinoline exhibited considerably higher mutagenic activities compared to those of the corresponding derivatives of benzo[f]quinoline at equivalent doses. The K-region oxides of benzo[f]quinoline and benzo[h]quinoline were significantly less mutagenic than their corresponding bay-region diol epoxide and tetrahydroepoxide derivatives. The demonstration that benzo[f]quinoline is significantly more mutagenic than trans-7,8-dihydro-7,8-dihydroxybenzo[f]quinoline, a precursor to the weakly mutagenic bay-region diol epoxide, suggests that the bay-region diol epoxide formation is not the principal pathway for the metabolic activation of benzo[f]quinoline to a mutagen. On the other hand, the isomeric benzo[h]quinoline appears to exert its mutagenic effect via the formation of its bay-region diol epoxide. These results indicate that the position of a nitrogen heteroatom in phenanthrene (the analogous carbocyclic aromatic hydrocarbon) not only has a marked effect on the mutagenic activities of the diol epoxide derivatives, but also can alter the metabolic activation pathways of the parent hydrocarbon. Benzo[f]quinoline, benzo[h]quinoline, and their dihydrodiol derivatives were not tumorigenic in newborn mice.

Animals↗
PubMed1989

Hyaluronan and angiogenesis.

Remodelling tissues, in both normal and pathological situations, show a greatly increased synthesis and turnover of hyaluronan. An essential part of these processes is new blood vessel formation. Whereas native hyaluronan has been reported to inhibit angiogenesis in vivo, partial degradation products (4-25 disaccharide units) have been found to stimulate angiogenesis in several in vivo systems. Examination of the effect of hyaluronan and its oligosaccharides on cultured cells suggests that these effects are due to the direct action of hyaluronan on endothelial cells. Native HA inhibits endothelial cell proliferation and disrupts cell-cell/cell-substrate interactions at physiological concentration. Angiogenic oligosaccharides induce both endothelial proliferation and migration, possibly via a receptor-mediated mechanism. Thus the metabolic state of hyaluronan could have profound effects on tissue neovascularization.

Animals↗
PubMed1989

The CD of two-chain coiled coils: experiments on tropomyosin and tropomyosin segments in the tyrosine/disulfide spectral region.

CD experiments are reported for several coiled-coil species in the tyrosine/disulfide (approximately 250-350-nm) region. Intact noncross-linked tropomyosin (approximately 3 degrees C) shows a negative nonsymmetric band maximal at 280 nm. This spectrum is the sum over six tyrosines/chain, and has conformational significance, since it disappears on denaturation. Experiments on an excised coiled-coil segment, each of whose chains comprise residues 11-127 of the tropomyosin sequence and only one tyrosine (Y60), reveal that not all tyrosines are alike. The spectrum at 3 degrees C shows a small negative maximum at approximately 285 nm and a substantial, hitherto unknown, positive band at approximately 270 nm, the latter masked in the parent protein by the negative contribution from the other tyrosines. A noncross-linked coiled-coil segment comprising residues 142-281, in which Y60 is absent, shows no such positive band. This peculiarity of Y60 is confirmed by absorbance spectra, with the extinction coefficient of Y60 larger in benign media than the average of the other tyrosines. Intact (3 degrees C) C190 cross-linked tropomyosin is known to yield, besides tyrosine contributions, a positive maximum at approximately 300 nm. Subtracting the corresponding data for noncross-linked tropomyosin shows that the disulfide spectrum itself actually has two equal, partly resolved bands at, respectively, 250 and 280 nm. The existence of a chiral disulfide argues for a relatively rigid, perhaps strained, local coiled coil. A C190 cross-linked segment comprising residues 142-281 shows a chiral disulfide spectrum like tropomyosin's, but another segment, comprising residues 168-284, shows none; thus removal of residues 142-167 causes loss of chirality at C190, over 20 residues away. These spectra thus contain important information on the subtle local differences in coiled-coil structures.

Animals↗
PubMed1989

Cell death by apoptosis in acute leukaemia.

We have previously demonstrated that when freshly isolated childhood T-cell acute lymphoblastic leukaemia cells are incubated in growth medium after isolation from blood, chromatin is rapidly cleaved into nucleosomal sized fragments that are multiples of 200 bp. The fragmentation is similar to that observed in other types of cells undergoing apoptosis or programmed cell death. In this study we describe a more comprehensive approach to the study of DNA fragmentation in leukaemia. Fragmentation was observed in freshly isolated cells from patients with T-cell acute lymphoblastic leukaemia and in one with common acute lymphoblastic leukaemia. Frozen samples of T-cell acute lymphoblastic leukaemia, common acute lymphoblastic leukaemia, and acute myeloid leukaemia cells also showed fragmentation of DNA. However, no fragmentation was evident in normal leukocytes treated under the same conditions. Ultrastructural studies on the isolated leukaemia cells demonstrate that the chromatin cleavage observed biochemically is associated with morphological changes characteristic of apoptosis.

Cell Survival↗
PubMed1989

Methionine-oxidized horse heart cytochrome c. III. Ascorbate reduction and the methionine-80-sulfur-iron linkage.

The ascorbate reduction of the CT-cytochromes--two chemically generated forms of horse heart cytochrome c, FIII and FII, with both methionines, 80 and 65, as methionine sulfoxides, no iron-sulfur linkage, and potentiometric and physiological oxidoreduction properties distinct from those of the native protein and one another (J. Pande et al., 1987)--has been investigated using a stopped-flow technique. The reaction was monitored at 550 nm, and studies were conducted in 10 mM phosphate + 0.17 M NaCl buffer, pH 7.4. Both CT-cytochromes are reduced by triphasic profiles, a faster and an intermediate ascorbate-dependent reaction and a slow, ascorbate-independent process. Both CT-cytochromes contain three molecular forms in slow equilibrium, two reducing directly by reaction with ascorbate and a third through conversion to one of the reducible forms. Like the reaction of the native protein, the ascorbate dependence of both the rapid and the intermediate process is nonlinear, approaching saturation values at high concentrations. The ascorbate profiles of the pseudo-first-order reduction constants are typical of the model for the reduction reaction of the unmodified protein, binding followed by a first-order reduction reaction (Myer et al., 1980; Myer and Kumar, 1984), but with distinct kinetic parameters, the first-order reduction constants and the protein-ascorbate stability constants. It has been concluded that the functional-conformational differences between the two CT-cytochromes are not operational to any significant extent in the reduction reaction with ascorbate. The methionine-80-sulfur-iron linkage of the protein is not a crucial requirement for the ascorbate reduction of the protein. The mechanism of the reaction in the main is also insensitive to the replacement of Met-80-S from heme coordination and/or the associated conformational-oxidoreduction properties of the protein. Of the two aspects of the reaction, the efficiency of the electron-transfer reaction and the stability of the ascorbate dianion-protein complex, the former is dependent on the integrity of the structural-conformational state of the molecule.

Animals↗
PubMed1989

Role of serum complement, immunoglobulins, and cell-mediated immune system in the pathogenesis of spontaneous bacterial peritonitis (SBP).

Spontaneous bacterial peritonitis (SBP) is a common complication of advanced liver disease, which has a reported prevalence of between 4 and 27%. Frequent bacteremias due to inadequate host defense mechanisms, particularly the reticuloendothelial system (RES), with seeding of an ascitic fluid that lacks a normal opsonic activity, is believed to be the principal cause of SBP. Little data exist as to the role of serum levels of complement and immunoglobulins as well as the cell-mediated immune system in the pathogenesis of SBP. The aim of this study was to determine the serum levels of the third and fourth components of complement (C3, C4), total hemolytic complement activity (CH100), and properdin factor B (PFB) and immunoglobulins G, A, and M and various T-cell parameters in individuals admitted to hospital with ascites and advanced liver disease and to determine whether one or more of these factors could be used to predict the development of SBP in patients with advanced liver disease. Fourteen consecutive patients (nine male and five female; age 47.5 +/- 3.1 years, mean +/- SEM) with end-stage liver disease and ascites, who were evaluated for possible liver transplant at the University of Pittsburgh and who developed SBP, comprised the study group. The diagnosis of SBP was determined by positive ascitic fluid culture (three patients) and/or ascitic fluid neutrophil count of greater than 250 cells/mm3 (all patients). The control group consisted of 14 patients, matched for type of liver disease, age, and sex, who did not develop SBP.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascites↗
PubMed1989

Midazolam versus diazepam for combined esophogastroduodenoscopy and colonoscopy.

This study compares the effects of two different benzodiazepines used for conscious sedation during combined upper gastrointestinal endoscopy (EGD) and colonoscopy. Subjects were assessed for their degree of analgesia and amnesia for the procedure, prior experience with endoscopy, and willingness to undergo another similar procedure should such be necessary. The patients were randomized single blind to receive either midazolam or diazepam for their preprocedure sedation. The amount of preprocedure sedation utilized was determined by titration of the dose to achieve slurring of speech. Prior to receiving either agent, the subjects were shown a standard card containing pictures of 10 common objects, were asked to name and remember them, and were told they would be "quizzed" (at 30 min and 24 hr) after being sedated for their recollection as to the objects pictured on the card. Each subject filled out a questionnaire addressing their perceived discomfort during the endoscopic procedure and their memory of the procedure 24 hr after the procedure. Sixty-three percent of the midazolam-sedated subjects reported total amnesia for their colonoscopy vs 20% of diazepam-sedated patients (P less than 0.001). Fifty-three percent of midazolam-sedated patients reported total amnesia of their upper gastrointestinal endoscopy vs only 23% of diazepam-sedated subjects (P less than 0.05). The midazolam-sedated subjects reported experiencing less pain with both upper gastrointestinal endoscopy (P less than 0.05) and colonoscopy (P less than 0.001) than did the diazepam-sedated group. Most importantly, the midazolam group was more willing to undergo another similar endoscopic procedure should they be asked to do so by their physician (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗