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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 199 records · Page 11Linked to original sources
PubMed1993

Population pharmacokinetics of ceftizoxime in premature newborns.

The population pharmacokinetic parameters of ceftizoxime were determined in 50 premature newborns less than 1 week of age (birth weight = 1.8 +/- 0.6 kg) with a clinical diagnosis of suspected sepsis. Each infant received ceftizoxime 25 mg/kg every 12 h intravenously over 30 min for a total of 6 doses. Serum concentrations of ceftizoxime were assayed by HPLC at 0.5, 1, 2.5 and 11.5 h or at 0.5, 1.5, 4.5 and 11.5 h after the first and the sixth dose. A total of 184 serum concentrations following the first dose and 160 following the sixth dose were fit separately and then collectively to a one-compartment model using NONMEM. The separately estimated parameters were not significantly different between the first and the sixth dose. The final parameter estimates were 27.1 ml/h/kg, 333 ml/kg and 8.5 h for clearance, volume of distribution and half-life, respectively. Other factors including gestational and postnatal age were not associated with alterations in ceftizoxime clearance. That the large variability in clearance was decreased from a coefficient of variation of 80 to 50% warrants dosing premature infants on the basis of body weight. The results of this study suggest that 25 mg/kg ceftizoxime every 12 h appears to be an appropriate dosing regimen for premature neonates.

Ceftizoxime↗
PubMed1993

The mystery ingredients: sweeteners, flavorings, dyes, and preservatives in analgesic/antipyretic, antihistamine/decongestant, cough and cold, antidiarrheal, and liquid theophylline preparations.

OBJECTIVE: Pharmaceutical preparations may contain a variety of excipients ("inert ingredients"). These excipients are generally inactive; however, rare adverse effects caused by excipients have been reported. Information about the excipients in a particular preparation is not readily available. METHODS: The information about sweeteners, flavorings, dyes, and preservatives for the chewable and liquid preparations of over-the-counter and prescription products of antidiarrhea, cough and cold, antihistamine/decongestant, analgesic/antipyretic, and liquid theophylline medications was collected. RESULTS: Information about excipients in 102 chewable and liquid preparations was compiled. An average preparation contained two sweeteners. Saccharin and sucrose were the most common sweeteners found--each was present in 52 preparations--followed by sorbitol, glucose, fructose, and others. For 36 of the 102 preparations, type of flavoring was not specified. In the remaining preparations, cherry was the most common flavoring, followed by vanilla and lemon. Twenty-one different dyes and coloring agents were used. Red dye No. 40 was the most common (42/102), followed by yellow No. 6 (27/102). Of the eight preservatives used, sodium benzoate and methylparabens were present in 42 and 27 of the preparations, respectively. Tables detailing these excipients and adverse effects reported are presented. CONCLUSIONS: The tables should be helpful to physicians in selecting preparations containing different excipients when an adverse reaction occurs. The mandatory labeling of excipients in all pharmaceutical preparations is the only way that physicians and patients can be fully informed.

Analgesics↗
PubMed1993

Effect of sodium valproate on serum amylase in epileptics.

Thirty-eight patients of generalised tonic-clonic seizures of epileptics in the age group of 15-30 years were included in this study. Of these 20 were started sodium valproate afresh and 18 already taking it for more than one year prior to inclusion. Serum amylase and serum valproic acid levels were measured in all of them, initially and at every 3 months interval for 9 months. Though no clinical evidence was present, there was significant increase in serum amylase levels in both the groups which has no correlation with dose or serum valproic acid levels.

Adolescent↗
PubMed1993

Acute non-lymphocytic leukemia with expression of surface antigen CD7--morphological, cytochemical, immunological and ultrastructural features in eight patients.

Of late, there has been an increase in the number of acute leukemias coexpressing markers believed to be restricted to a single lineage. Eight patients with ANLL whose blast coexpressed the T cell associated CD7 antibody were identified among 462 consecutive ANLL cases. Seven had FAB defined AML according to morphocytochemical criteria, whereas one patient was classified as MO on the basis of ultrastructural studies. The incidence of CD7 positivity was particularly significant in the less differentiated sub-types MO and M1 compared to other FAB sub-groups. Detailed long term studies will be required to realize their biological and clinical significance.

Adolescent↗
PubMed1993

Multiple CCAAT binding proteins regulate the expression of the angiotensinogen gene.

Angiotensinogen is a serum glycoprotein which is primarily synthesized in the liver and converted into the octapeptide hormone angiotensin-II in circulation. Transient transfection studies have identified a cis-acting DNA element located between 115 and 145 bp upstream from the transcriptional initiation site in the promoter of the rat angiotensinogen gene which is involved in the regulation of its transcription. This region of the promoter has sequence homology with NF-1/CCAT, C/EBP, and CP1 binding sites. We show here by DNase-I footprint and gel shift assay in presence of recombinant transcription factors and their antibodies that NF-1/CAAT and C/EBP like transcription factors bind to this region of the promoter. Our DNase footprint assay with recombinant NF-1/CAAT has also identified another NF-1 binding site between -180 and -190. Since our previous studies have identified a NF-1 site in the proximal promoter region and two C/EBP binding sites in the distal promoter region of the angiotensinogen gene, our data suggests that multiple CAAT binding factors regulate the expression of the angiotensinogen gene in liver cells. In accordance with these results, we show that cotransfection of mammalian expression vectors containing NF-1/CAAT or C/EBP coding sequence increases the promoter activity of the angiotensinogen gene in human hepatoma cells.

Angiotensinogen↗
PubMed1993

Platelet serotonin kinetics in acute myocardial infarction before and after thrombolysis.

Platelet count, platelet serotonin uptake and platelet serotonin content were analysed in 21 subjects consisting of 11 patients of evolving acute myocardial infarction (AMI) and 10 matched healthy controls before and after administration of streptokinase. Platelet counts were significantly reduced in AMI with a subsequent rise following thrombolysis. Platelet 5-HT uptake was also significantly increased in AMI and following thrombolysis, it showed a trend towards normalization. Platelet 5-HT content was significantly increased in AMI with no further significant change following thrombolysis. The results suggest that platelet activation as revealed by reduced platelet count and altered platelet serotonin kinetics, occurs in AMI and this activation is inhibited following thrombolysis. Further, it is also apparent that it is not the reperfusion but the thrombolytic agent that is responsible for inhibition of platelet activation.

Blood Platelets↗
PubMed1993

Trichobezoar.

Explore the source record for details and available documents.

Bezoars↗
PubMed1993

Oxidative stress and antioxidant defence mechanism in Plasmodium vivax malaria before and after chloroquine treatment.

The protection of Plasmodium vivax-parasitized red blood cells (PRBCs) against activated forms of oxygen was examined in relation to the non-parasitized and chloroquine-treated red blood cells. Increased parasitaemia was found to be accompanied with a decrease in the activities of enzymes of the glutathione system, namely glutathione peroxidase (GPx), glutathione reductase (GRx) and glutathione S-transferase (GTr) in the red blood cells (RBC) lysates. In contrast, however, the total amount of reduced glutathione (GSH) and the content of water-soluble antioxidant vitamin C was increased 2-3 fold over those of control RBCs. Chloroquine-treated red cells contained enzyme activities and antioxidant contents (GSH, vitamin C) comparable to those of control and non-parasitized red cells. Our results therefore indicate the oxidative stress experienced by RBCs during P. vivax infection and that this infection is accompanied with changes in the antioxidant defence system of the host, which are restored to near normal levels after treatment with chloroquine.

Animals↗
PubMed1992

Cloning and expression of an NADP(+)-dependent alcohol dehydrogenase gene of Entamoeba histolytica.

Ethanol is the major metabolic product of glucose fermentation by the protozoan parasite Entamoeba histolytica under the anaerobic conditions found in the lumen of the colon. Here an internal peptide sequence determined from a major 39-kDa amoeba protein isolated by isoelectric focusing followed by SDS/PAGE was used to clone the gene for the E. histolytica NADP(+)-dependent alcohol dehydrogenase (EhADH1; EC 1.1.1.2). The EhADH1 clone had an open reading frame that was 360 amino acids long and encoded a protein of approximately 39 kDa (calculated size). EhADH1 showed a 62% amino acid identity with the tetrameric NADP(+)-dependent alcohol dehydrogenase of Thermoanaerobium brockii. In contrast, EhADH1 showed a 15% amino acid identity with the closest human alcohol dehydrogenase. EhADH1 contained 18 of the 22 amino acids conserved in other alcohol dehydrogenases, including glycines involved in binding NAD(P)+ as well as histidine and cysteine residues involved in binding the catalytic zinc ion. Like the T. brockii alcohol dehydrogenase, EhADH1 lacked a 23-amino acid stretch present in other alcohol dehydrogenases that includes four cysteines that bind a second noncatalytic zinc ion. An EhADH1-glutathione-S-transferase fusion protein showed the expected NADP(+)-dependent alcohol dehydrogenase and NADPH-dependent acetaldehyde reductase activities. The enzymatic activities of the EhADH1 fusion protein were inhibited by pyrazole and 4-methylpyrazole.

Alcohol Dehydrogenase↗
PubMed1992

Mammalian DNA polymerase beta: characterization of a 16-kDa transdomain fragment containing the nucleic acid-binding activities of the native enzyme.

The 39-kDa DNA polymerase beta (beta-Pol) molecule can be readily converted into two constituent domains by mild proteolysis; these domains are represented in an 8-kDa N-terminal fragment and a 31-kDa C-terminal fragment [Kumar et al. (1990a) J. Biol. Chem. 265, 2124-2131]. Intact beta-Pol is a sequence-nonspecific nucleic acid-interactive protein that binds both double-stranded (ds) and single-stranded (ss) polynucleotides. These two activities appear to be contributed by separate portions of the enzyme, since the 31-kDa domain binds ds DNA but not ss DNA, and conversely, the 8-kDa domain binds ss DNA but not ds DNA [Casas-Finet et al. (1991) J. Biol. Chem. 266, 19618-19625]. Truncation of the 31-kDa domain at the N-terminus with chymotrypsin, to produce a 27-kDa fragment (residues 140-334), eliminated all DNA-binding activity. This suggested that the ds DNA-binding capacity of the 31-kDa domain may be carried in the N-terminal segment of the 31-kDa domain. We used CNBr to prepare a 16-kDa fragment (residues 18-154) that spans the ss DNA-binding region of the 8-kDa domain along with the N-terminal portion of the 31-kDa domain. The purified 16-kDa fragment was found to have both ss and ds polynucleotide-binding capacity. Thermodynamic binding properties for these activities are similar to those of the intact enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

DNA polymerase beta and DNA synthesis in Xenopus oocytes and in a nuclear extract.

The identities of the DNA polymerases required for conversion of single-strand (ss) M13 DNA to double-strand (ds) M13 DNA were examined both in injected Xenopus laevis oocytes and in an oocyte nuclear extract. Inhibitors and antibodies specific to DNA polymerases alpha and beta were used. In nuclear extracts, inhibition by the antibody to polymerase beta could be reversed by purified polymerase beta. The polymerase beta inhibitors, dideoxythymidine triphosphate (ddTTP) and dideoxycytidine triphosphate (ddCTP), also blocked DNA synthesis and indicated that polymerase beta is involved in the conversion of ssDNA to dsDNA. These results also may have particular significance for emerging evidence of an ssDNA replication mode in eukaryotic cells.

Animals↗
PubMed1992

A molecular model of RGD ligands. Antibody D gene segments that direct specificity for the integrin alpha IIb beta 3.

Following an ill-defined activation event, the Arg-Gly-Asp (RGD) recognition site of the platelet integrin, glycoprotein IIb-IIIa (alpha IIb beta 3), can bind to fluid-phase, RGD-containing protein ligands, such as fibrinogen, or to the murine monoclonal IgM, PAC-1, which contains the sequence Arg-Tyr-Asp (RYD) within the third complementarity-determining region of its heavy chain (H3). PAC-1 has thus become a widely exploited marker of platelet alpha IIb beta 3 activation. In this report, we compare PAC-1 with two murine IgG, OP-G2 (IgG1 kappa) and LJ-CP3 (IgG1 kappa), that also contain the sequence RYD in H3 but bind to alpha IIb beta 3 without prior activation. Each antibody can inhibit the binding of the other two to intact platelets or to purified IIb-IIIa, the binding of each antibody is completely inhibited by peptides containing RGD, and H3 of each antibody uses the germline D-gene DSP 2.10 (CTATAGGTACGAC) which includes the sequence RYD. Two other murine IgG, HP20 and PCG1-1, cloned and sequenced by other laboratories, also utilize the DSP 2.10 sequence, but neither antibody binds to alpha IIb beta 3. From a comparison of the H3 sequences of these antibodies, we have developed a molecular model of the H3 loop region which can explain these differences in specificity. This model predicts that both the ability to bind to alpha IIb beta 3 and the activation dependence of that binding are a function of the orientation and, therefore, accessibility of the RYD sequence. This model and refinements thereof can be exploited to study the molecular basis for specificity and affinity of RGD-containing ligands for integrins.

Amino Acid Sequence↗
PubMed1992

Ty1-copia group retrotransposons are ubiquitous and heterogeneous in higher plants.

We have used the polymerase chain reaction to isolate fragments of Ty1-copia group retrotransposons from a wide variety of members of the higher plant kingdom. 56 out of 57 species tested generate an amplified fragment of the size expected for reverse transcriptase fragments of Ty1-copia group retrotransposons. Sequence analysis of subclones shows that the PCR fragments display varying degrees of sequence heterogeneity. Sequence heterogeneity therefore seems a general property of Ty1-copia group retrotransposons of higher plants, in contrast to the limited diversity seen in retrotransposons of Saccharomyces cerevisiae and Drosophila melanogaster. Phylogenetic analysis of all these sequences shows, with some significant exceptions, that the degree of sequence divergence in the retrotransposon populations between any pair of species is proportional to the evolutionary distance between those species. This implies that sequence divergence during vertical transmission of Ty1-copia group retrotransposons within plant lineages has been a major factor in the evolution of Ty1-copia group retrotransposons in higher plants. Additionally, we suggest that horizontal transmission of this transposon group between different species has also played a role in this process.

Amino Acid Sequence↗
PubMed1992

Identification of double-stranded RNA-binding domains in the interferon-induced double-stranded RNA-activated p68 kinase.

The double-stranded RNA (dsRNA)-binding domain of the human p68 kinase has been localized to the N-terminal half of the enzyme by using progressive deletion analysis and in vitro binding assays. To further define the domains responsible for binding to dsRNA, we cloned the mouse dsRNA-activated p65 kinase and used sequence alignment to identify conserved domains in the N-terminal region. Deletions in either of two 12-amino-acid-long and arginine- or lysine-rich regions abrogated binding to dsRNA. Moreover, in an in vivo growth inhibition assay in the yeast Saccharomyces cerevisiae, these mutants failed to exhibit a slow-growth phenotype.

Amino Acid Sequence↗