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S Thakur

Publications and source records attributed to S Thakur.

At least 19 recordsLinked to original sources
PubMed2006

Use of MR spectroscopy and functional imaging in the treatment planning of gliomas.

Routine anatomical imaging with CT and MRI does not reliably indicate the true extent or the most malignant areas of gliomas and cannot identify the functionally critical parts of the brain. The aim of the study was to see if the use of MR spectroscopic imaging (MRSI) along with functional MRI (fMRI) can better define both the target and the critical structures to be avoided to improve radiation delivery in gliomas. 12 patients with gliomas underwent multivoxel MRS and functional imaging using GE processing software. The choline to creatine ratio (Cho:Cr), which represents the degree of abnormality for each individual voxel on MRSI, was derived, converted into a grayscale grading system, fused to the MRI images and then transferred to the planning CT images. An intensity-modulated radiation therapy (IMRT) plan was developed using the dose constraints based on both the anatomical and the functionally critical regions. Cho:Cr consistently identified the gross tumour volume (GTV) within the microscopic disease (clinical target volume, CTV) and allowed dose painting using IMRT. No correlation between MRSI based Cho:Cr > or =2 and MR defined CTV nor their location was noted. However, MRSI defined Cho:Cr > or =3 was smaller by 40% compared with post-contrast T1 weighted MRI defined GTV volumes. fMRI helped in optimizing the orientation of the beams. In conclusion, both MRSI and fMRI provide additional information to conventional imaging that may guide dose painting in treatment planning of gliomas. A Phase I IMRT dose intensification trial in gliomas using this information is planned.

Brain↗
PubMed2006

y+ LAT-1 mediates transport of the potent and selective iNOS inhibitor, GW274150, in control J774 macrophages.

This study has characterised the transport mechanism(s) for the novel and selective inhibitor of inducible nitric oxide synthase (iNOS), GW274150, in murine macrophage J774 cells. Transport of GW274150 was saturable (K(m) = 0.24 +/- 0.01 mM and V(max) of 8.5 +/- 0.12 pmol.microg protein(-1) min(-1)), pH-insensitive and largely Na(+)-independent. Transport was also susceptible to trans-stimulation and was significantly inhibited by a 10-fold excess of L-arginine, L-lysine, L-leucine, L-methionine, L-glutamine and 6-diazo-5-oxo-L-norleucine but not by other amino acids or by N-ethylmaleimide. More importantly, the inhibitions caused by the neutral amino acids were critically dependent on Na(+). These results strongly implicate system y(+)L in the transport of GW274150. Northern blot analysis confirmed this by revealing the presence of transcripts for y(+)LAT-1 but not y(+)LAT-2. Thus, taken together, our data show for the first time that J774 macrophages express y(+)LAT-1 transporters and that these carriers mediate transport of GW2741500 at least in these cells.

Amino Acid Transport System y+L↗
PubMed2006

Molecular epidemiology and diversity of Salmonella serovar Typhimurium in pigs using phenotypic and genotypic approaches.

For epidemiological investigations of the most common and non-host-adapted Salmonella serotypes, such as Typhimurium, highly discriminatory approaches are essential. In the present study, we evaluated three genotyping methods; amplified fragment length polymorphism (AFLP), pulsed-field gel electrophoresis (PFGE) and repetitive palindromic extragenic-PCR (Rep-PCR) using 40 isolates. AFLP showed the highest discriminatory index (0.939), resolution and throughput. To determine clonality of Salmonella Typhimurium isolates and epidemiological relatedness in different commercial pig production units, we employed AFLP in combination with antimicrobial resistance pattern and phage typing. Salmonella serovar Typhimurium isolates (n=196) obtained from a longitudinal study of 18 pig farms over a 3-year period were studied. Using this approach, 16 distinct clonal types were identified. We found two common multidrug- resistant patterns including AmCmStSuTe and AmKmStSuTe. Two commonly multidrug- resistant phage types that are of known public health importance, DT104 and DT193, were also common. AFLP differentiated distinct clones within DT104, a phage type previously reported to be clonal. Fourteen of the clonal types were unique to one of the two production systems, showing diversity between independent commercial pig production systems located in the same geographical area. Clonal types obtained from nursery farms and corresponding finishing units were, however, similar.

Animal Husbandry↗
PubMed2006

Genetics of antimicrobial resistance.

Antimicrobial resistant strains of bacteria are an increasing threat to animal and human health. Resistance mechanisms to circumvent the toxic action of antimicrobials have been identified and described for all known antimicrobials currently available for clinical use in human and veterinary medicine. Acquired bacterial antibiotic resistance can result from the mutation of normal cellular genes, the acquisition of foreign resistance genes, or a combination of these two mechanisms. The most common resistance mechanisms employed by bacteria include enzymatic degradation or alteration of the antimicrobial, mutation in the antimicrobial target site, decreased cell wall permeability to antimicrobials, and active efflux of the antimicrobial across the cell membrane. The spread of mobile genetic elements such as plasmids, transposons, and integrons has greatly contributed to the rapid dissemination of antimicrobial resistance among several bacterial genera of human and veterinary importance. Antimicrobial resistance genes have been shown to accumulate on mobile elements, leading to a situation where multidrug resistance phenotypes can be transferred to a susceptible recipient via a single genetic event. The increasing prevalence of antimicrobial resistant bacterial pathogens has severe implications for the future treatment and prevention of infectious diseases in both animals and humans. The versatility with which bacteria adapt to their environment and exchange DNA between different genera highlights the need to implement effective antimicrobial stewardship and infection control programs in both human and veterinary medicine.

Animals↗
PubMed2006

ARDS complicating scrub typhus in Sub-Himalayan region.

Scrub typhus is a febrile illness widely endemic in Asia caused by Rickettsiae tsutsugamushi in which humans are accidental hosts. If there is delay in the initiation of the appropriate antimicrobial therapy patient may present with serious complications. We report three cases that presented in emergency with acute respiratory distress syndrome and history of fever for more than one-week duration. On investigation all the three patients were positive for Weil Felix reaction and showed dramatic response to doxycycline.

Adult↗
PubMed2004

Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans.

There are well-replicated, independent lines of evidence supporting a role for corticotropin-releasing hormone (CRH) in the pathophysiology of depression. CRH receptor 1 (CRHR1), which we first mapped in the brain in 1994, has been implicated in the treatment of depression and anxiety. We studied the association of CRHR1 genotypes with the phenotype of antidepressant treatment response in 80 depressed Mexican-Americans in Los Angeles who completed a prospective randomized, placebo lead-in, double-blind treatment of fluoxetine or desipramine, with active treatment for 8 weeks. Subjects were included into the study if they had a diagnosis of depression without other confounding medical or psychiatric diagnoses or treatments. All patients were followed weekly and assessed for changes in the Hamilton rating scales for anxiety (HAM-A) and depression (HAM-D). Inclusion criteria in the study included a HAM-D of 18 or higher. Because CRHR1 affects both depression and anxiety. Patients were classified into a high-anxiety (HA) group if their HAM-A score was 18 or higher and in a low-anxiety (LA) group if their HAM-A score was less than 18. Utilizing the haplotype-tag single-nucleotide polymorphisms rs1876828, rs242939 and rs242941, we tested for haplotypic association between CRHR1 and 8-week response to daily antidepressant treatment. In the HA group (n=54), homozygosity for the GAG haplotype was associated with a relative 70% greater reduction in HAM-A scores compared to heterozygous (63.1+/-4.5 vs 37.1+/-6.9%, respectively, P=0.002). For HAM-D, GAG haplotype homozygosity was associated with a 31% greater reduction in scores after treatment compared to heterozygous (67.3+/-4.3 vs 51.2+/-6.0%, respectively, P=0.03). In those with lower-anxiety levels at screening, there were no associations between CRHR1 genotype and percent change in HAM-A or HAM-D. These findings of increased response to antidepressants in highly anxious patients homozygous for the GAG haplotype of CRHR1 need to be independently validated and replicated. Such work would support the hypotheses that response to antidepressant treatment is heterogeneous and that the CRHR1 gene and possibly other genes in stress-inflammatory pathways are involved in response to antidepressant treatment. These findings also suggest that variations in the CRHR1 gene may affect response to CRHR1 agonists or antagonists. All data are deposited in www.pharmgkb.org.

Adult↗
PubMed2003

Cutaneous sporotrichosis: an unusual clinico-pathologic and therapeutic presentation.

This report presents a number of unusual clinico-histopathologic and therapeutic features in a culture proven case of cutaneous sporotrichosis. These include lymphocutaneous sporotrichosis involving face; its dissemination in an otherwise healthy patient; its histology mimicking cutaneous cryptococcosis; two episodes of severe purulent inflammatory reaction bordering the lesion during therapy with saturated solution of potassium iodide; no therapeutic response to potassium iodide therapy and rapid healing of lesion with high-dose of fluconazole.

Adult↗
PubMed2003

Environmental pollution in rural areas of Orissa state due to industrial emissions--with special reference to fluoride.

Angul - Talcher belt in Central Orissa, having a number of industries contributing to a great extent to deteriorate the air quality of the surrounding villages. Previous reports showed higher SPM, SO2, NO, levels in air and prevalence of respiratory illness, skin and teeth disorders among village population. Higher ground water fluoride, urine and serum fluoride among the cattle were also reported in some villages. Present study reports SPM, SO2, NOx and Fluorides (gaseous and Particulate) in ambient air around aluminium smelter during February and August 1996. High volume sampling technique for SPM and the standard colorimetric methods (BIS) for analyses of SO2 and NOx were adopted. Fluoride in air and water were estimated by standard fluoride ion selective electrode method. Higher SPM, SO2 and NOx values than prescribed CPCB standard were obtained in February. Gaseous fluoride in village air were varied between, 1.66 - 7.64 mg/m3 in February and 1.11 - 22.75 mg/m3 in August, whereas particulate fluoride ranged between, 0.054 - 19.61 mg/m3. Water sources of the villages near the smelter showed fluoride values above permissible limit. The study indicated higher fluoride pollution in air and water of the surrounding villages.

Air Movements↗
PubMed2002

Plasma vascular endothelial growth factor, soluble VEGF receptor FLT-1, and von Willebrand factor in glaucoma.

AIM: To investigate plasma indices of vascular permeability (vascular endothelial growth factor, VEGF-also an index of angiogenesis, as well as the soluble receptor for VEGF, sFlt-1) and endothelial damage/dysfunction (von Willebrand factor, vWf) in glaucoma. METHODS: Citrated plasma was assayed for VEGF, sFlt-1, and vWf (all ELISA) in a cross sectional study of 50 patients (20 male; mean age 63.9 years, SD 10.5) with glaucoma: 26 had normal tension glaucoma (NTG) and 24 had primary open angle glaucoma (POAG), who were compared with 26 healthy controls (mean age 73.4 years, SD 9.2). RESULTS: Median (interquartile range, IQR) levels of VEGF were significantly elevated in patients with NTG and POAG compared to healthy controls (Kruskal-Wallis test, p<0.001). Similarly, mean (SD) vWF levels were abnormal in NTG and POAG compared to healthy controls (one way ANOVA, p<0.001). Median levels of sFlt-1 were significantly lower in patients with NTG and POAG, when compared to healthy controls (Kruskal-Wallis test, p<0.001; p<0.05 with Tukey's post hoc test for controls v POAG). There were no significant differences in VEGF, sFlt-1 or vWf levels between the NTG and POAG groups (Tukey's test, all p=NS). In both NTG and POAG groups, there was a significant correlation between VEGF and sFlt-1 (Spearman, NTG: r=0.6517, p=0.001; POAG: r=0.6017, p=0.008). There were no significant correlations between VEGF and sFlt-1, or with vWf among the controls. CONCLUSIONS: The pathogenesis of optic nerve damage in both NTG and POAG may be associated with abnormal vascular permeability and endothelial damage/dysfunction, as indicated by abnormal plasma VEGF and vWf levels in these patients.

Aged↗
PubMed2001

Isolation, purification and some structural features of the mucilaginous exudate from Musa paradisiaca.

The water-soluble polysaccharides isolated from the vascular gel of Musa paradisiaca, were fractionated via anion exchange chromatography into four fractions. Fractionated polymers contained arabinose, xylose and galacturonic acid as major sugars, together with traces of galactose, rhamnose, mannose and glucose residues. Methylation analysis revealed the presence of a highly branched arabinoxylan with a significant amount of terminal arabinopyranosyl units and an arabinogalactan type I pectin. Periodate oxidation studies supported the results of methylation analysis.

Humans↗
PubMed2000

Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes.

C-terminal truncations of the NFKB2 p100 gene product have been observed in a number of cases of human cutaneous T cell lymphomas, as well as human B-cell lymphomas and myelomas. The contribution of these alterations to lymphomagenesis is not understood; however, truncation at amino acid 666 to generate 80 - 85 kD proteins in the HUT78 cell line is associated with addition of a short (serine-alanine-serine) fusion at the 3' end of p80HT, as well as with increased expression of NFKB2 mRNA. We therefore examined the effects of p80HT on the regulation of NFKB2 expression, as well as the properties of a series of other tumor-associated, and site directed mutations of NFKB2. While p80HT had not itself acquired novel transcriptional activation properties with respect to the NFKB2 P1 or P2 promoters or the IL-6 kappaB promoter, p80HT had lost the potent inhibitory (IkappaB-like) activity associated with the wild-type, p100 gene product. Loss of the inhibitory property depended on the SAS residues in the fusion protein, direct truncation at aa666 was fully inhibitory, as was a substitution of three alanines for the SAS residues. The presence of as few as two C-terminal ankyrin motifs was sufficient for inhibition of NF-kappaB-mediated transcriptional activation. Assays of a series of additional lymphoma-associated NF-kappaB-2 truncation suggested that the C-terminal truncation associated with these proteins was also associated with a loss of the IkappaB-like activities of p100 NF-kappaB-2, for at least some NF-kappaB target promoters. Thus, the loss of IkappaB-like activity of lymphoma-associated NFKB2 mutations may play an important role in the genesis of a subset of human lymphomas.

Gene Expression Regulation, Neoplastic↗
PubMed2000

Cytogenetic damage in bidi smokers.

The genotoxic effects of bidi smoke were investigated in the somatic chromosomes of 45 men habituated to smoking bidi. Mitotic index (MI), chromosomal aberrations (CA), sister chromatid exchanges (SCE) and satellite associations (SA) were used as parameters. When compared with the results obtained in the blood samples from the comparable non-smoker group of men, a significant increase (p < 0.01) was noted in all the above mentioned parameters of the smoker subjects: MI (3.71-6.24), CA (0.84-3.23), SCE (3.68-7.65) and SA (5.26-11.28). A clear time-dose-effect relationship has been observed. Bidi smoke thus is both clastogenic and genotoxic for human beings.

Adolescent↗
PubMed2000

Genetic risk assessment in hookah smokers.

The genotoxic effect of hookah smoke was investigated on somatic chromosomes of 35 occupationally nonexposed male hookah smokers. These were compared with an equal number of nonsmokers matched with respect to age, sex, drug intake, if any, and socio-economic status. The mitotic index (MI), chromosomal aberrations (CA), sister chromatid exchanges (SCE) and satellite associations (SA) were analysed. All the parameters showed a significant increase (p < 0.01) in the smokers compared with control individuals, viz MI, 3.88-5.41; CA, 0.94-2.22; SCE, 3.59-5.66; and SA, 5.2-8.65. A distinct time and dose effect relationship was observed. Hookah smoke is thus, both clastogenic and genotoxic for human beings.

Adult↗