Search PubMed⌕ Search

Biomedical subjects

R Krishnamoorthy

Publications and source records attributed to R Krishnamoorthy.

At least 19 recordsLinked to original sources
PubMed2006

Isolation of mercury resistant bacteria and influence of abiotic factors on bioavailability of mercury -- a case study in Pulicat Lake North of Chennai, South East India.

Pulicat Lake sediments are often severely polluted with mercury compounds and other toxic heavy metals. Several mercury-resistant bacteria were isolated and identified from the sediments and all the isolates exhibited broad spectrum resistance (both organic and inorganic mercuric compounds). Mercury volatilization showed that four of the isolated Bacillus cereus strains were able to reduce water soluble ionic form of mercury into volatile form via the well known enzymatic reduction. The effect of increasing concentration of mercuric chloride and phenyl mercuric acetate in the growth of this mercury reducing strain was also determined. To study the native physico-chemical parameters, which influence the bioavailability of mercury to bacteria in Pulicat Lake ecosystem, a total of 60 water and 30 sediment samples were collected and analyzed for pH, temperature, dissolved oxygen, salinity, nitrate, nitrite, silicate, phosphate, organic matter and organic carbon. Increased levels of phosphate, nitrite, nitrate, silicate, organic matter and organic carbon during the post monsoon reduce the bioavailability of mercury by forming complexes which may increase the concentration of mercury in the sediments during post monsoon.

Drug Resistance, Bacterial↗
PubMed2006

Effects of hydroxyurea on malaria, parasite growth and adhesion in experimental models.

We recently raised concern over using hydroxyurea (HU) in the treatment of sickle cell disease in areas endemic for malaria, becauseit up-regulates the endothelial surface expression of ICAM-1, a major receptor for Plasmodium falciparum-infected erythrocytes in the brain. Using human in vitro models of cerebral malaria, we evaluated the interaction of HU with parasites and demonstrated that HU pretreatment increased the number of infected red blood cells adhering to the endothelium, but did not increase endothelial apoptosis. Moreover, using an experimental cerebral malaria model, HU pretreatment was found to prevent significantly mice from developing neurological syndrome by inhibiting parasite growth, opening potential therapeutic avenues.

Anemia, Sickle Cell↗
PubMed2005

The effect of the CYP2C19 genotype on the hydroxylation index of omeprazole in South Indians.

To investigate the relationship between CYP2C19 genotypes and the hydroxylation index (HI) of omeprazole in the South Indian population. Healthy unrelated South Indian subjects (n=300) were separated into three groups based on their CYP2C19 genotypes. They were administered a single oral dose of 20 mg omeprazole, and venous blood was collected 3 h later. Plasma was assayed using reversed-phase high-performance liquid chromatography, and the omeprazole HI was calculated. The means of HIs in individuals with CYP2C19*1/*1 (n=124), *1/*2 (n=129) and *2/*2,*2/*3 (n=47) were 2.4, 5.3 and 22.5, respectively, and were found to be significantly different between any two groups (P<0.0001). A good correlation was established between CYP2C19 genotype and omeprazole HI (r=0.54, 95% CI 0.45-0.62; P<0.0001). Of the 300 subjects, 42 (14.0%; 95% CI 10.1-17.9) were phenotypic poor metabolizers (PMs), but only 33 of them had two mutant alleles and the remaining 9 PMs had at least one wild-type allele. Among the 258 extensive metabolizers, 14 had two mutant alleles. The prevalence of PMs in the South Indian population was 14.0%, which is similar to that in North Indians and Orientals but significantly higher than in Caucasians and Africans. A genotype-phenotype relationship was established between the CYP2C19 genotype and HI of omeprazole, but 7.7% of subjects deviated from expected genotype-phenotype associations. This could be due to an additional mutation, either in the exons/introns or in the 5'-regulatory region of the CYP2C19 gene.

Adult↗
PubMed2005

Randomized trial of two different conditioning regimens for bone marrow transplantation in thalassemia--the role of busulfan pharmacokinetics in determining outcome.

In total, 94 patients with homozygous beta thalassemia were randomized to two different conditioning regimens: busulfan 600 mg/m2 + cyclophosphamide 200 mg/kg or busulfan 16 mg/kg + cyclophosphamide 200 mg/kg and antilymphocyte globulin (47 in each group), for bone marrow transplantation, to see whether increased myeloablation or increased immunosuppression would reduce rejection. Busulfan pharmacokinetics in determining outcome was evaluated. There was no significant difference in engraftment, graft-versus-host disease, rejection, and overall and disease-free survival in the two groups. Systemic exposure to busulfan was significantly higher in the 600 mg/m2 group, but in both groups there was a wide interindividual variation in the busulfan kinetics. Six patients rejected the graft, two in the busulfan 600 mg group and four in busulfan 16 mg group (P = 0.677 CI -0.17, 0.07), but in five patients (pharmacokinetic data not available in one patient) who rejected the graft busulfan first dose trough level (C(min)-1) was below 150 ng/ml while it was above this level in the 66 of 68 patients with successful engraftment (P < or = 0.001). This randomized trial shows that rejection is influenced by busulfan levels and suggests that monitoring of busulfan levels and dose adjustment based on first-dose kinetics may reduce the risk of rejection.

Antilymphocyte Serum↗
PubMed2004

Glutathione S-transferase M1 and T1 null genotype distribution in South Indians.

OBJECTIVE: To investigate the distribution of the homozygous null genotypes of GSTM1 and GSTT1 in the South Indian population. METHODS: Five hundred and seventeen unrelated natives of the South Indian states of Tamilnadu and Pondicherry (n=170), Kerala (n=122), Karnataka (n=110) and Andhra Pradesh (n=115) were analyzed for homozygous deletions of GSTM1 and GSTT1. A multiplex polymerase chain reaction method simultaneously detected both GSTM1 and GSTT1 homozygous null genotypes. The observed frequencies from the four groups were compared statistically with each other and the combined frequencies were compared with frequencies of other major populations previously reported in the literature. RESULTS: In South India, 30.4% (95% CI 26.4-34.3) lacked the GSTM1 gene, 16.8% (13.6-20.1) lacked the GSTT1 gene and 4.6% (3.0-6.8) lacked both the GSTM1 and GSTT1 genes. The highest frequency of GSTM1 null was observed in Karnataka (36.4%, 27.4-45.4), while Andhra Pradesh had the lowest frequency of the GSTM1 and GSTT1 combined double-null genotypes (1.7%, 0.21-6.2). CONCLUSION: The prevalence of the GSTM1 null genotype differed within India. The frequency of GSTM1 null in South Indians was significantly lower than that in Caucasians. The frequencies of both GSTM1 and GSTT1 null genotypes in South Indians were significantly lower than in the Japanese.

Adult↗
PubMed2003

Allele and genotype frequency of CYP2C9 in Tamilnadu population.

OBJECTIVES: To identify the frequency of CYP2C9*1, *2 and *3 alleles and the genotype of CYP2C9 gene in the Tamilian population. METHODS: The study was conducted on 135 unrelated healthy human volunteers. DNA was extracted from the peripheral leukocytes samples and was analyzed using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) protocol. The PCR products were digested with AvaII, KpnI or NsiI restriction enzymes. The digested products were separated using 8% polyacrylamide gel and stained by ethidium bromide. Genotyping of the subjects was done based on DNA fragment size. RESULTS: The frequencies of CYP2C9*1, *2 and *3 alleles in the Tamilian population were 0.907, 0.026 and 0.067, respectively. The distribution of CYP2C9*1/*1, *1/*2, *1/*3 and *2/*3 genotypes were 0.823, 0.044, 0.126 and 0.007, respectively. CONCLUSION: CYP2C9*3 is the most frequent mutant allele found in the Tamilian population. The distribution of this mutant allele in the Tamilian population was found to be lesser than in Caucasians but higher than in Chinese.

Adult↗
PubMed2003

Genotype and allele frequency of CYP2D6 in Tamilian population.

OBJECTIVE: To assess the frequency of CYP2D6 *3, *4, *5 and *10 allelic variants in a South Indian population and compare the frequencies with other major populations. METHODS: Polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism (RFLP)-based methods were used to identify the CYP2D6 genotypes of 106 healthy unrelated male and female volunteers of Tamilian origin. The allele and genotype frequencies observed were compared with other major populations. RESULTS: The *10 allele was the most frequent mutant allele in Tamilians (20.3%). The *5 allele occurred at 0.9% and the *3 allele was not detected. The most frequent allele causing enzyme inactivation was *4 allele in Tamilians (6.6%), which is significantly higher than that reported in Japanese (0%). CONCLUSIONS: The *10 allele is the most common mutant allele in Tamilians. The CYP2D6*4 and CYP2D6*5 alleles are distributed in a significantly different way in the Tamil population relative to Oriental populations.

Adult↗
PubMed2003

Mannose-binding lectin alleles in sub-Saharan Africans and relation with susceptibility to infections.

Mannose-binding lectin (MBL) plays an important role in the early stages of primary infections and during the decay of maternal antibodies in infants. Various studies have looked at the relation between serum MBL concentrations, MBL gene alterations and susceptibility to infections. We investigated the distribution of variant MBL alleles in 626 unrelated adults from sub-Saharan African countries and looked for a potential relation between these alleles and the incidence, prevalence and death rate of tuberculosis for sub-Saharan Africa. We also evaluated the relation between MBL genotypes and susceptibility to HIV-1 infection in 188 Gabonese adults. We found that (i) the prevalence of the common variant MBL alleles is correlated with the incidence of tuberculosis in sub-Saharan Africa (r=0.565), (ii) the mutant MBL G57E allele, in either the homozygous or compound heterozygous state, is associated with susceptibility to HIV-1 infection in the Gabonese population (P=0.019).Our data plus those in the literature suggest that individuals who are homozygous for the mutant MBL alleles display increased susceptibility to infections. Interestingly, we found that individuals who are heterozygous for MBL mutations are much less susceptible to infections than those who are homozygous for the wild-type MBL allele.

Africa↗
PubMed2003

Hydroxyurea downregulates endothelin-1 gene expression and upregulates ICAM-1 gene expression in cultured human endothelial cells.

The clinical efficacy of oral hydroxyurea (HU) in adults and children with sickle cell anemia (SCA) cannot solely be explained by its ability to enhance fetal hemoglobin (HbF) expression. Since increased adherence of sickle red blood cells to vascular endothelium is a possible contributing factor to vaso-occlusive crisis (VOC), we explored the effect of HU on human endothelial cell (EC) lines (TrHBMEC and EA-hy 926). We demonstrated that HU, in a dose-dependent and reversible manner, significantly decreased (up to three-fold) the release of endothelin-1 (ET-1), a vasoconstrictor peptide through downregulation (up to three-fold) of ET-1 gene expression. This finding is of therapeutic relevance as SCA patients exhibit elevated serum levels of ET-1 during episodes of VOC and levels correlate with disease severity. Unexpectedly, HU upregulated (up to three-fold) the expression of membrane-bound intercellular cell adhesion molecule 1 (mbICAM-1) and its soluble form (sICAM-1) with a parallel increase in ICAM-1 mRNA expression. Although ICAM-1 does not appear to be involved in the sickle cell adhesion to vascular endothelium, it may exacerbate vaso-occlusion by promoting leukocyte adhesion. The HU-induced increase in mbICAM-1 may appear inconsistent with the clinical benefits confered by HU. However, both the increase in sICAM-1- and HU-induced leukocyte reduction in patients, may counteract the potentially detrimental effect of elevated mbICAM-1 expression. Also HU reduces the expression of vascular cell adhesion molecule (VCAM-1) on EC. Since HU reduces the very late antigen 4-positive reticulocytes in SCA patients, a ligand for VCAM-1, HU-induced downregulation of VCAM-1 on EC will very likely decrease the reticulocyte-endothelium adhesion. Thus, HU, apart from inducing HbF expression in the red cell, also affects the expression profile of EC compartment.

Anemia, Sickle Cell↗
PubMed2003

Allele and genotype frequency of CYP2C19 in a Tamilian population.

AIMS: To investigate the frequencies of CYP2C19*1, CYP2C19*2 and CYP2C19*3 alleles and CYP2C19 genotypes in a Tamilian population. METHODS: The study was conducted in 112 unrelated healthy human volunteers. DNA was extracted from leucocytes and analyzed by the PCR-RFLP protocol. The PCR product was digested with restriction enzymes (SmaI and BamH1) and then separated electrophoretically using polyacrylamide gel. RESULTS: The frequencies of the CYP2C19*1, *2 and *3 alleles were 0.598 [95% confidence interval (CI) 0.507, 0.689], 0.379 (95% CI, 0.350,0.407) and 0.022 (95% CI -0.005, 0.049), respectively. The distribution of CYP2C19*1/*1,*1/*2, *1/*3, *2/*2 and *2/*3 genotypes were 0.295 (95% CI, 0.210, 0.379), 0.580 (95% CI, 0.488, 0.671), 0.027 (95% CI -0.003, 0.057), 0.080 (95% CI 0.030, 0.130) and 0.018 (95% CI -0.006, 0.042), respectively. CONCLUSIONS: The distribution of CYP2C19*1/*1 in the Tamilian population is lower than that in Caucasians, Africans and the North Indian population. The CYP2C19*1/*2 is significantly higher in Tamilians when compared with other populations. The CYP2C19*1/*3 allele, which was not reported in the North Indian and Caucasian populations has been identified in 2.7% of the Tamilian population.

Adult↗
PubMed2002

Two novel CD1 E alleles identified in black African individuals.

CD1 gene (CD1A to CD1E) products are involved in non-peptide antigen presentation, such as lipids and glycolipids, to T cells. With a similar function to MHC, namely antigen presentation, these genes nevertheless displayed a much lower level of polymorphism as compared to MHC. We report here two additional CD1E variants identified in black African individuals, designated herein CD1E*05 and CD1E*06. While the former differs from the common (wild type) allele sequence by two substitutions at nucleotide positions 217 and 229 of exon 2, the latter only by a single base change at position 91 of exon 3. These substitutions lead to amino acid changes at position 73 and 77 of the alpha1 domain in the former and at position 30 of the alpha2 domain in the latter. Identification of these additional variants suggests that the CD1 locus, especially the CD1E gene, is much more polymorphic than previously assumed.

Africa↗
PubMed2001

A novel delta beta fusion gene expresses hemoglobin A (HbA) not Hb Lepore: Senegalese delta(0)beta(+) thalassemia.

This study identified and characterized a novel delta beta fusion gene in which the delta-globin gene promoter is linked to intact beta-globin coding sequences in a Senegalese family. It results from a 7.4-kb deletion that removes the delta-globin coding sequences, the delta beta intergenic region as well as the beta-globin gene promoter and causes delta(0)beta(+) thalassemia with hemoglobin A expressed at the 11% to 15% range. The phenotype of this naturally occurring delta beta hybrid gene not only clarifies, in an in vivo context, the respective strength of delta- and beta-globin gene promoters, but also emphasizes the importance of beta-globin intragenic sequences in the expression of beta-globin chains. (Blood. 2001;98:1261-1263)

Adolescent↗
PubMed2001

High cholesterol diet down regulates the activity of activator protein-1 but not nuclear factor-kappa B in rabbit brain.

Cardiovascular risk factors and alterations in cholesterol metabolism are implicated in the pathogenesis of Alzheimer's dementia (AD). The hypercholesterolemic rabbit model of atheroslerosis and AD was utilized in this study to examine oxidative stress related changes in the brain. The high cholesterol diet induced dramatic increases in plasma and liver cholesterol concentrations, but brain cholesterol levels remained constant. Similar effects have been found regarding lipid oxidation products. The amounts of conjugated dienes, trienes and thiobarbituric acid reactive substances (TBARS) significantly increased in the plasma of cholesterol treated animals while the brain cortex showed no signs of increased lipid peroxidation. The oxidative damage sensitive nuclear transcription factor kappa B (NF-kappaB) and activator protein-1 (AP-1) diverged in their responses. Accordingly, the AP-1 DNA binding activity decreased by more than 50% in brain nuclear protein extracts while the NF-kappaB binding activity remained unaltered by the hypercholesterol diet. These results indicate that despite the relative resistance of the central nervous system to dietary manipulation of its lipid composition and lipid peroxidation products, chronic dietary intake of cholesterol can alter the function of certain proteins involved in regulation of gene expression in the brain.

Animals↗
PubMed2001

Molecular pathogenesis and clinical variability of beta-thalassemia syndromes among Indians.

Sixty-four homozygous beta-thalassemia patients comprising 40 patients with beta-thalassemia major and 24 patients with beta-thalassemia intermedia were investigated for the nature of their beta-thalassemia mutations, associated alpha-thalassemia, and XmnI polymorphism in the gamma gene which are known to affect the clinical course of the disease. This study was undertaken to look for the contribution of these associated factors in reducing the clinical severity of homozygous beta-thalassemia from a severe disease to a beta-thalassemia intermedia phenotype. Clinical severity of these patients was assessed by the degree of transfusion dependency and the age at which the patient presented with symptoms. Globin chain synthetic ratio was taken as the biochemical pointer of severity of the disease. Eleven different beta-thalassemia mutations were encountered among 128 beta-thalassemia chromosomes. It was observed that the nature of the beta-thalassemia mutations was not very different between the beta-thalassemia major and beta-thalassemia intermedia groups in our patients, but co-inheritance of one or more alpha-globin gene deletions (-alpha(3.7)) and the presence of the XmnI polymorphism were associated with lesser severity of the disease in Indians.

Adolescent↗
PubMed2001

A new HLA-B*27 allele (B*2719) identified in a Lebanese patient affected with ankylosing spondylitis.

Eighteen different HLA-B*27 alleles (B*2701-B2718) have so far been recognized by the WHO Nomenclature Committee for Factors of the HLA System. Frequency and disease association of these alleles with spondyloarthropathies differ among ethnic groups. We describe here a novel HLA-B*27 subtype identified in a Lebanese patient suffering from ankylosing spondylitis (AS). This new variant differs from the common HLA-B*2705 DNA sequence at five different nucleotide positions. These nucleotide changes lead to three amino acid differences in the alpha2 domain; Thr to Ile at position 94, Leu to Ile at position 95 and Asn to Arg at position 97. Since this novel allele is encountered in an AS patient, the associated sequence changes are not expected to affect significantly neither the presentation of a putative arthritogenic peptide nor the conformation-dependent recognition by effector cells.

Amino Acid Sequence↗
PubMed2001

A new HLA-Cw allele (Cw*1510), identified in a French Caucasian individual.

A novel HLA-Cw*15 allele, Cw*1510, found in a French Caucasian bone marrow recipient is described. Nucleotide sequence of the new variant is identical to the common Cw*15021 DNA sequences except nucleotides at positions 32 and 61 of exon 2. While the first difference is silent, the second cause substitution of an Histidine by an Arginine at amino acid position 21 of the alpha1 heavy chain domain.

Alleles↗