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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 217 records · Page 12Linked to original sources
PubMed1990

Effect of warfarin on plasma concentrations of vitamin K dependent coagulation factors in patients with stable control and monitored compliance.

There is a discrepancy in the results of reported studies of levels of vitamin K dependent coagulation factors in patients on warfarin therapy. This may have arisen partly because of the problem of assuring compliance with therapy in outpatients. The plasma concentrations of the vitamin K dependent clotting factors II, VII, IX and X were studied in 23 outpatients whose adherence to prescribed warfarin therapy was determined using a pharmacological indicator of compliance. In these patients, who were shown to have consistently good compliance and stable anticoagulant control over a period of 3-6 months, the activities in plasma of the four coagulation factors were not equally suppressed. Factor IX levels were significantly greater than those of factor VII (P less than 0.0001) which in turn were significantly greater than the levels of factor II (P less than 0.0001) or factor X (P less than 0.0001). There was no significant difference between the levels of factors II and X which were depressed to a similar extent. The proportion of variability of the International Normalized Ratio (INR) explained by linear regression was 51-77% and a model was derived to predict the INR from the mean of the levels of the four clotting factors. The concentrations of the coagulation factors II, VII, IX and X are likely to be highly dependent on the degree of compliance with warfarin therapy which should be taken into account when investigating the behaviour of these factors.

Aged↗
PubMed1990

Generation of a cytotoxic T-lymphocyte response using a Salmonella antigen-delivery system.

We have constructed a general-use vector for the cloning and stable expression of foreign genes in the chromosome of attenuated Salmonella typhimurium. Using this chromosomal expression vector (CEV), we expressed the circumsporozoite (CS) gene of the mouse malaria Plasmodium yoelii in an aroA S. typhimurium strain. Mice immunized with CS-expressing Salmonella recombinants mount a CS-specific cytotoxic T-lymphocyte (CTL) response. This is the first demonstration that attenuated Salmonella can elicit a specific CTL response to a foreign protein in mice. The ability to easily and stably express foreign genes from the Salmonella chromosome and the generation of specific CTL greatly expands the potential of Salmonella as an antigen-delivery system.

Amino Acid Sequence↗
PubMed1990

Effect of liver transplantation on the hypothalamic-pituitary-gonadal axis of chronic alcoholic men with advanced liver disease.

The hormones testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were assayed in blood obtained from men with alcoholic liver disease before and after successful liver transplantation. The frequency and severity of self reported impotence, intercourse, and paternity were assessed before and 18 +/- 3 months post-transplantation. The results obtained were compared with those of age-matched males transplanted within the same month by the same surgical teams for advanced hepatocellular disease other than alcoholism. Little change for any parameter assessed pre- and post-transplantation was noted for the nonalcoholics. In contrast, the FSH, LH, and testosterone levels of the alcoholic men all increased significantly following successful transplantation. These data suggest that the liver disease associated with alcoholism contributes to some of the endocrine effects of alcohol-associated cirrhosis but not all. Because the transplanted alcoholics remain less adequate than controls, it is further suggested that some residual alcohol-induced injury to the hypothalamic-pituitary-gonadal axis persists despite successful liver transplantation.

Follicle Stimulating Hormone↗
PubMed1990

A quantitative animal model of traumatic iridodialysis.

The impact velocities and kinetic energies necessary to create a particular form of ocular injury, traumatic iridodialysis, were quantitatively studied by experimentally traumatizing enucleate porcine eyes. Thicknesses and tensile strengths of porcine and human iris tissue were measured in order to allow for predictions of human results to be made from the animal model. Application of blunt trauma at an impact angle of 30-35 degrees with respect to the iris plane with striking of the eye at the corneolimbal junction was found to optimize tearing of the iris from the root. Using this vector, the minimum velocity for the creation of an iridodialysis at least 6 mm in length in the human eye is predicted to be 14 m/sec for impact with a projectile of 13.4 g with a 6 mm diameter tip.

Animals↗
PubMed1990

Immunization of mice against Plasmodium vinckei with a combination of attenuated Salmonella typhimurium and malarial antigen.

Infection with the blood stage of the malaria parasite Plasmodium vinckei is uniformly lethal in mice. We found that immunization of BALB/c mice with a combination of killed P. vinckei antigens and an attenuated (aroA) Salmonella typhimurium strain induces high levels of protection against challenge with live P. vinckei. This is especially significant because, in our previous studies, immunization of mice with killed P. vinckei antigens and adjuvants such as Bordetella pertussis, complete Freund adjuvant, and saponin failed to induce protective immunity. Immunization with attenuated S. typhimurium alone did not provide any nonspecific immunity. In vivo depletion of CD4+ T cells in the mice immunized with attenuated S. typhimurium and P. vinckei antigens caused the loss of their immunity. Expression of this immunity required the presence of a spleen. These results support our previous hypothesis that a blood stage malaria vaccine may need both induction of CD4+ T cells specific for the parasite and modification of the spleen with a vaccine vehicle. Therefore, attenuated Salmonella strains such as the one used in this study, when expressing recombinant malarial antigens, might fulfill this requirement.

Animals↗
PubMed1990

Bovine pulmonary endothelial cell damage mediated by Pasteurella haemolytica pathogenic factors.

The in vitro effects of Pasteurella haemolytica components on bovine pulmonary endothelial monolayers were investigated to determine the relative role of individual bacterial factors in the pathogenesis of bovine pulmonary pasteurellosis. Bovine pulmonary endothelial monolayers were treated with P. haemolytica bacterial culture supernatant (CS) and P. haemolytica lipopolysaccharide. At 22 h postinoculation, the CS produced severe damage to the endothelial cells, indicated by high 51Cr release, extensive cellular detachment, and morphologic changes characterized by cell contraction, cytoplasmic blebbing, and loss of monolayer confluency. The neutralization of leukotoxin activity of the CS by heat inactivation was ineffective in decreasing the damage to endothelial cells; however, leukotoxin-neutralizing monoclonal antibody slightly diminished the toxic effect. P. haemolytica lipopolysaccharide by itself or as a supplement to CS produced endothelial cell damage similar to that of CS. The preincubation of CS dilutions (10(-1) and 10(-2)) or P. haemolytica lipopolysaccharide with polymyxin B almost completely eliminated cell toxicity. These studies show that P. haemolytica produces a soluble factor that is consistent with bacterial lipopolysaccharide and that is directly toxic to bovine pulmonary endothelial cells in vitro.

Animals↗
PubMed1990

Exclusion of autosomal dominant polycystic kidney disease type II (ADPKD2) from 160 cM of chromosome 1.

Autosomal dominant polycystic kidney disease is a heritable disorder and recent studies have shown genetic heterogeneity, with some, but not all, families showing linkage with markers on chromosome 16p. Members of a large ADPKD family, unlinked to chromosome 16, have been typed for 12 marker loci located on both arms of chromosome 1. Multipoint analysis excluded ADPKD2 from the region between D1S81 (pTHH33) and D1S67 (pHHH106) on the long arm and between Rh and PGM1 on the short arm. This excludes the disease locus from about 61% of chromosome 1.

Chromosomes, Human, Pair 1↗
PubMed1990

Efficacy of enalapril in essential hypertension and its comparison with atenolol.

The effect of enalapril was evaluated in 67 patients with essential hypertension, and its therapeutic efficacy was compared with atenolol in a placebo run-in, single-blind, cross-over trial. Enalapril significantly reduced blood pressure in all grades of essential hypertension. As monotherapy it 'normalized' blood pressure in 88%, 50% and 25% of patients with mild, moderate and severe hypertension respectively. Optimal dose for most of the patients was 20 to 40 mg/day. Comparison with atenolol revealed almost parallel efficacy of the two drugs, although enalapril produced a significantly greater reduction in systolic blood pressure in patients with mild and moderate hypertension (P less than 0.01 in each group). No serious side effects were encountered with either drug. Enalapril, therefore, has a potent and slightly superior antihypertensive effect to that of atenolol, and may be used as a 'first-step' drug in the treatment of hypertensive patients.

Adult↗
PubMed1990

Transcriptional regulation studies of myelin-associated genes in myelin-deficient mutant rats.

To identify and assess the consequences of the mutation in myelin-deficient (md) rats, the myelin proteolipid protein (PLP) gene and its expression were studied in md rats. Southern blots of the PLP gene demonstrated that no major deletions or insertions have occurred in this gene. In addition, the mutation in this gene does not result in a splicing defect in the RNAs, since all exons are represented in md PLP RNAs. These data are consistent with results in another laboratory indicating that a point mutation in the PLP gene in md rats results in a single amino acid alteration in the protein. To elucidate the molecular mechanisms producing reduced levels of PLP, myelin basic protein (MBP) and glycerol phosphate dehydrogenase (GPDH) mRNAs, and their corresponding proteins in md rats, in vitro transcription assays were performed. Transcription of the PLP gene in nuclei isolated from 23-day-old md rat brains was dramatically reduced relative to normal tissue. Thus, the single amino acid alteration in this protein alters the regulation of transcription of this gene. In contrast, the transcriptional activities of the MBP and GPDH genes in md rats were indistinguishable from normal animals. Thus, the lower level of MBP and GPDH mRNA and protein in md rats relative to normal results from a posttranscriptional event.

Animals↗
PubMed1990

The myelin-deficient rat mutant: partial recovery of oligodendrocyte maturation in vitro.

The morphological and immunocytochemical identification and characterization of the myelin-forming cell, the oligodendrocyte, have defined a model system for developmental studies. The myelin-deficient (md) rat mutant lacks myelin in the central nervous system and fails to express the normal developmental increase in oligodendroglial and myelin markers, apparently as a consequence of a point mutation in the proteolipid protein gene. In the present work, we compared the developmental pattern of primary glial cultures derived from newborn md rat brains to those derived from wild-type animals. Brain cell suspensions were prepared from each rat pup and cultured separately. We found by immunocytochemical and enzymatic analyses for the various markers that the developmental cascade of oligodendroglial marker expression is delayed, oligodendrocytes failing to mature compared to normal cultures. However, a partial recovery of marker expression was observed in md-derived cultures as compared to development previously reported in the intact md animals. We suggest that the partial recovery of the sequential expression of oligodendroglial markers may be due to a supportive environment provided to the oligodendrocyte progenitor cell (1) by tissue culture conditions or (2) by the absence of the blood-brain barrier in contrast to its presence in the intact animal.

Animals↗
PubMed1990

Evidence implicating MHC genes in the immunological nonresponsiveness to the Plasmodium falciparum CS protein.

The circumsporozoite (CS) protein is a major candidate vaccine antigen for the sporozoite stage of malaria. Both cytotoxic T cells (CTL) and antibody specific for the CS protein are thought to be important in protection. By examining the immune response in mice and humans we have shown that genes mapping to the major histocompatibility complex (MHC) are important for immune responsiveness. F1 mice between high antibody responders and low antibody responders are high antibody responders, suggesting that in this model immune suppressor genes do not control the immune response. Using synthetic peptides to map epitopes for CTL and helper T cells (which are important for the antibody response) we have shown that the T-cell epitopes are located in the polymorphic region of the protein, and we hypothesize that T cells have indeed selected the variation observed in the CS protein. The success of subunit vaccines will depend on the pattern of variation in different geographical locations, the ability to construct multivalent vaccines containing different variant epitopes from this protein, and on the existence of other sporozoite and liver-stage proteins involved in protection.

Animals↗
PubMed1990

Presence of gamma glutamyl transferase in Mycobacterium smegmatis.

The presence of gamma glutamyl transferase (GGT) has been established in Mycobacterium smegmatis. The 10,000 x g supernatant demonstrated only hydrolase activity and did not exhibit any transpeptidase activity. Most of the transferase activity was recovered in 100,000 x g supernatant demonstrating that GGT is a cytosolic enzyme. Maximum activity of GGT was observed at two days of growth and the activity decreased significantly till the seventh day of growth when mycobacteria was grown as stationary culture. The km for gamma glutamyl-p-nitroanilide was found to be 0.074 mM and Vmax for the reaction approached 11.9 nmol per min per mg protein. L-serine + borate was found to be a competitive inhibitor (Ki 12.05 mM) for GGT activity. The pH optimum for GGT activity was observed between 7.5 to 8.5 and temperature above 35 degrees C rapidly inactivated the enzyme activity. To the best of our knowledge, this is the first report which unequivocally establishes the presence of GGT activity in 10,000 x g supernatant of M. smegmatis.

Cytosol↗
PubMed1990

Value of serum prolactin in differentiating epilepsy from pseudoseizure.

We studied the serum prolactin levels in 35 cases with various types of seizures viz. generalized tonicolonic seizures (GTC), complex partial seizures (CPS), and simple partial seizures (SPS). We also studied 20 cases with pseudoseizure (hysteria) presenting in an epileptiform manner. Twenty two normal healthy subjects were also studied. All the cases were studied both in the postictal and interictal periods. Serum prolactin rose significantly in the postictal periods in patients with GTC and CPS, but patients with SPS or pseudoseizure did not demonstrate this rise. Thus serum prolactin estimation can be of help in differentiating true generalized seizures from pseudoseizure presenting in an epileptiform manner.

Diagnosis, Differential↗