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R Krishnamoorthy

Publications and source records attributed to R Krishnamoorthy.

At least 91 records · Page 5Linked to original sources
PubMed1995

Linkage-disequilibrium of the senegal haplotype with the beta S gene in the republic of guinea.

We have determined the beta gene cluster haplotype in 40 chromosomes carrying the beta S mutation from individuals of the major ethnic groups living in the Republic of Guinea. Thirty-one of these were either the typical (n = 29) or the atypical (n = 2) Senegal haplotype demonstrating that in this region of Atlantic West Africa, the sickle mutation is in linkage disequilibrium with this particular beta-gene cluster haplotype. Two individuals carrying one chromosome bearing the Benin haplotype were of Malinke ethnic origin. This is in keeping with the hypothesis that the Senegal beta-gene cluster haplotype is linked to the beta S gene in Atlantic West Africa.

Adolescent↗
PubMed1995

An unequal cross-over event within the CYP2D gene cluster generates a chimeric CYP2D7/CYP2D6 gene which is associated with the poor metabolizer phenotype.

1. The study of the CYP2D genotype and phenotype of a Caucasian family revealed that a XbaI-9 kb allele was associated with the poor metabolizer phenotype. 2. A Polymerase Chain Reaction (PCR)-based assay showed that the previously described mutations D6A and D6B are not associated with the XbaI-9 kb allele. 3. To explore the molecular basis of the poor metabolizer phenotype associated with the XbaI-9 kb allele, complete sequencing of the nine exons and intron-exon boundaries of the CYP2D6 gene was undertaken after amplification by PCR. 4. All the exons were successfully amplified using CYP2D6 gene-specific primers except exon 1 which required a combination of CYP2D7 gene-specific 5' primer and a CYP2D6 gene-specific 3' primer. 5. Sequence data derived from this amplified product revealed that the XbaI-9 kb allele corresponds to a novel rearrangement of the locus. This involved a deletion of an approximately 20 kilobase (kb) DNA segment generating a hybrid 5' CYP2D7/CYP2D6 3' gene. 6. The chimeric gene is non-functional presumably due to an insertion in exon 1 (characteristic of the exon 1 of the CYP2D7 gene) which causes a shift in the reading frame with premature termination of translation.

Base Sequence↗
PubMed1995

Point mutation in the pribnow box, the molecular basis of beta-lactamase overproduction in Klebsiella oxytoca.

Klebsiella oxytoca mutants resistant to a variety of beta-lactams were obtained in vitro on aztreonam. Constitutive beta-lactamase production was much higher in the mutants than in the susceptible strains (75-fold). The only difference observed in these mutants compared with the susceptible strains were point mutations in the Pribnow box: a transversion (G-->T) in the first base for one mutant or a transition (G-->A) in the fifth base of the -10 consensus sequence for the other three mutants. The transcriptional output of the beta-lactamase gene (blaOXY) from the mutants was significantly higher than that of the blaOXY gene from the susceptible strains.

Anti-Bacterial Agents↗
PubMed1995

Lack of correlation between HLA class II alleles and immune responses to Pf155/ring-infected erythrocyte surface antigen (RESA) from Plasmodium falciparum in Madagascar.

To investigate the relationships between predominant HLA class II alleles and immune responses to the Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA), 50 individuals from the highlands of Madagascar were followed-up from 1988 to 1991. The T cell reactivity and antibody responses to synthetic peptides (EENV)4, (EENVEHDA)4, and (DDEHVEEPTVA)3, representing major T and B epitopes of Pf155/RESA antigen, were assessed with an average of five determinations per individual over the four-year follow-up period. The T cell reactivity was investigated by lymphocyte proliferation and assays for interferon-gamma and interleukin-2 release. Antipeptide antibodies were measured using the Falcon assay screening test-enzyme-linked immunosorbent assay. The cumulative prevalence rates of cellular (range for the three peptides = 64-68%) and antibody responders (range = 70-74%) were similar for each peptide. The HLA class II typing was performed using polymerase chain reaction-restriction fragment length polymorphisms. The prevalent alleles or groups of alleles (frequency > 20%) were similar in responders and nonresponders, both for cellular and antibody responses to each peptide. These were HLA-DR 5 group and HLA-DQA1 *0601, *0101-0102-0104, HLA-DQB1 *0301, and HLA-DPB1 *0101-2601 alleles. Allelic distribution was similar in individuals presenting with (74%) or without (26%) a malaria attack during a 20-week follow-up conducted when malaria was hyperendemic (P > 0.05, by Fisher's exact test). Despite repeated immunologic measures that better identify the responders, no relationship was found between HLA class II alleles and the cellular or antibody responses to Pf155/RESA epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Nucleotide sequences of the genes coding for the TEM-like beta-lactamases IRT-1 and IRT-2 (formerly called TRI-1 and TRI-2).

Two blaTEM-like genes were characterized that encoded IRT beta-lactamases (previously called TRI) in clinical isolates of Escherichia coli resistant to amoxycillin alone and to combinations of amoxycillin with beta-lactamase inhibitors. Plasmids carrying this resistance were isolated from E. coli K 12 transconjugants and the genes were sequenced after amplification of defined fragments, using TEM-1-specific primers. The gene for IRT-1 beta-lactamase resembled the blaTEM-1B gene, and that for IRT-2 resembled blaTEM-2. However, both IRT enzymes have a glutamine residue at position 37, which is characteristic of TEM-1. The unique nucleotide difference with parental genes corresponding to amino acid variation was observed at nucleotide position 929. The consequence of C to T transition in the blaIRT-1 gene and C to A transversion in the blaIRT-2 gene was the substitution of arginine 241 in the native protein by cysteine and serine, respectively, in the mutants. Thus, the nature of amino acid 241 is critical in conferring resistance or susceptibility to beta-lactamase inhibitors. Furthermore, these basic to neutral amino acid replacements explain the more acidic pI (pI = 5.2) of these IRT enzymes compared to that of TEM-1 (pI = 5.4). The presence of cysteine-241 in IRT-1 also explains the selective sensitivity of this beta-lactamase to inhibition by p-chloromercuribenzoate.

Amoxicillin↗
PubMed1994

Hemoglobinopathies in the Dogon Country: presence of beta S, beta C, and delta A' genes.

The population of the Dogon, located in Mali, is divided in an endogamic Noble class and two endogamic servant castes (Tanners and Blacksmiths). We find that the polymorphic frequencies of beta c, beta S, and, unexpectedly, a mutation of the delta-chain (delta A'), are geographically (valley vs. plateau) as well as social status dependent.

Base Sequence↗
PubMed1994

Genomic fingerprinting of Yersinia enterocolitica species by degenerate oligonucleotide-primed polymerase chain reaction.

A novel version of the polymerase chain reaction (PCR) termed degenerate oligonucleotide-primed PCR (DOP-PCR) was used to fingerprint the bacterial genome of Yersinia enterocolitica species. Eight well-characterized reference strains of Y. enterocolitica (ribotype, serotype, biotype and zymotype) were examined. Optimal experimental conditions for reproducibility, sensitivity and specificity were obtained using a single DOP-primer. All the strains gave distinct DOP-PCR profiles composed of 12 to 19 fragments with sizes from 200 to 1.500 bp. Thus, the DOP-PCR, which has so far been used to fingerprint human, mouse, fruitfly and plant DNA, is also well-suited to bacterial DNA.

Base Sequence↗
PubMed1994

A simple procedure to differentiate ailA and ailNA gene variants among human pathogenic Yersinia enterocolitica strains.

The identification and differentiation of the two variants of the ail gene, ailA from the more virulent American serotypes (08, 013a, 13b, 018, 020, 021) and ailNA from the less virulent non-American serotypes (03, 04, 05, 06, 09, 027 and 07, 8) was studied in a panel of 32 Yersinia enterocolitica human pathogenic isolates. A 444 bp fragment corresponding to the ail gene was amplified using a PCR procedure in all tested strains. Subsequent digestion of the PCR product by Rsal and by HaeIII endonucleases, provide electrophoretic patterns that clearly discriminate ailA and ailNA variants. This non-radioactive and reliable procedure allows large clinical and epidemiological studies, and could be proposed to survey the spread of virulent clones.

Base Sequence↗
PubMed1994

DNA haplotype-dependent differences in the amino acid sequence of debrisoquine 4-hydroxylase (CYP2D6): evidence for two major allozymes in extensive metabolisers.

The molecular basis for DNA haplotype-dependent debrisoquine 4-hydroxylase (CYP2D6) expression was explored by sequencing all of the nine exons of the CYP2D6 gene. Two distinct exon sequence frameworks of the CYP2D6 gene were found, each associated with specific BamHI-defined DNA haplotypes of the CYP2D cluster. They corresponded to Arg296/Cys296 and Ser486/Thr486 amino acid polymorphisms in the CYP2D6 enzyme, and occurred in almost equal frequency among the Caucasians examined. These two major allozymes with amino acid differences in the presumed substrate recognition region and in the vicinity of the heme binding site could be the source of the observed DNA haplotype-dependent variation in phenotypic expression.

Alleles↗
PubMed1994

A novel mosaic Bantu/Benin/Bantu beta s haplotype found in several African populations.

In a survey of the chromosomal backgrounds associated with the sickle cell gene in Portuguese-speaking populations from Europe and Africa, a discordance between the classical haplotype and the predicted allele at the RsaI polymorphism 5' to the beta globin gene was observed in four patients. Extensive typing of the corresponding beta s chromosomes at simple polymorphic repeat motifs revealed a novel "extended" haplotype that appeared to be a mosaic of (1) a Bantu-type DNase I hypersensitive site 2 within the beta globin gene cluster locus control region, (2) a Benin 5' subhaplotype, and (3) a Bantu 3' subhaplotype. We propose two alternative schedules for the generation of yet another chromosomal background of the sickle cell gene.

Africa↗
PubMed1994

The physicochemical properties, plasma enzymatic hydrolysis, and nasal absorption of acyclovir and its 2'-ester prodrugs.

A series of 2'-(O-acyl) derivatives of 9-(2-hydroxyethoxymethyl)guanine (acyclovir) was synthesized by acid anhydride esterification. Aqueous solubilities in isotonic phosphate buffer (pH 7.4), partition coefficients in 1-octanol/phosphate buffer, and hydrolysis kinetics in rat plasma were determined. The ester prodrugs showed consistent increases in lipophilicity with corresponding decreases in aqueous solubility as a function of side-chain length. The bioconversion kinetics of the prodrugs appear to depend on both the apolar and the steric nature of the acyl substituents. When perfused through the rat nasal cavity using the in situ perfusion technique, acyclovir showed no measurable loss from the perfusate. Nasal uptake of acyclovir prodrugs, on the other hand, were moderately improved. Furthermore, the extent of nasal absorption appears to depend on the lipophilicity of the prodrugs in the descending order hexanoate > valerate > pivalate > butyrate. Simultaneous prodrug cleavage by nasal carboxylesterase was also noted in the case of hexanoate.

Absorption↗
PubMed1994

An improved DNA-based identification of fetuses at risk for HPA-1a (PlA1) neonatal alloimmune thrombocytopenia.

A simple and reliable procedure, based on DNA amplification and HpaII mapping, is proposed for the identification of fetuses at risk for HPA-1a (PlA1) neonatal alloimmune thrombocytopenia which could cause life-threatening haemorrhage, even in early fetal life. This typing procedure for HPA-1 alleles should help in deciding, very early, the therapeutic management of the fetuses at risk.

Antigens, Human Platelet↗