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S Raja

Publications and source records attributed to S Raja.

At least 19 recordsLinked to original sources
PubMed2006

Antioxidant effect of Cytisus scoparius against carbon tetrachloride treated liver injury in rats.

The study was aimed to investigate the antioxidant activity of Cytisus scoparius L. (Family: Leguminosae) on CCl(4) (carbon tetrachloride) treated oxidative stress in Wistar albino rats. CCl(4) injection induced oxidative stress by a significant rise in serum glutamate oxaloacetate transaminases (SGOT), serum glutamate pyruvate transaminases (SGPT), lactate dehydrogenase (LDH) and thiobarbituric acid reactive substances (TBARS) along with reduction of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-transferase (GST) and glutathione reductase (GRD). Pretreatment of rats with different doses of plant extract (250 and 500mg/kg) significantly lowered SGOT, SGPT, LDH and TBARS levels against CCl(4) treated rats. GSH and hepatic enzymes like SOD, CAT, GPx, GRD, and GST were significantly increased by treatment with the plant extract, against CCl(4) treated rats. The activity of extract at the dose of 500mg/kg was comparable to the standard drug, silymarin (25mg/kg). Based on these results, it was observed that Cytisus scoparius extract protects liver from oxidative stress induced by CCl(4) in rats and thus helps in evaluation of the traditional claim on this plant.

Alanine Transaminase↗
PubMed2006

Prevalence of rheumatic heart disease in school children in Bikaner: an echocardiographic study.

OBJECTIVE: To determine prevalence of rheumatic heart disease (RHD) using clinical and echocardiographic criteria and to study influence of socioeconomic status (SES) we studied school children in a north-western Indian town. METHODS: 3292 school children, age range 5-14 years, in two private schools, ten middle SES government schools and six low SES government schools were invited to participate in the study. 3002 (1837 boys, 1165 girls) were clinically examined (response 91%) of which 1042 were in private schools, 1002 in middle SES schools and 958 in low SES schools. Prevalence of cardiac murmurs and RHD based on clinical diagnosis was determined in school by a trained team of physicians. Those with a murmur were further evaluated by Doppler-echocardiography in the hospital. Group-specific and age-specific rates (prevalence/thousand) of murmurs and cardiac lesions were determined. RESULTS: A significant cardiac murmur was observed in 55 subjects (18.3/1000) with similar prevalence in boys (20.7) and girls (14.6). The prevalence of murmur was significantly greater in children belonging to low SES schools (29.2/1000) as compared to middle SES (18.9) and higher SES schools (7.6). RHD prevalence based on clinical diagnosis was observed in 50 children (16.7/1000) and was similar in boys (19.1) and girls (12.9). Clinical RHD was more in the low SES school children (28.2/1000) as compared to middle (17.0) and high SES schools (5.8). RHD was demonstrated on echocardiography in 2 children (0.67/1000). Other prevalent cardiac lesions were congenital heart disease in 5 (1.66/1000) and mitral valve prolapse in 37 (12.3/1000). CONCLUSIONS: There is a low prevalence of RHD in school children in this region compared to previous Indian studies. Cardiac murmurs are more prevalent among low SES children.

Adolescent↗
PubMed2005

Monitoring of fogwater chemistry in the gulf coast urban industrial corridor: Baton Rouge (louisiana).

Seventeen fog events were sampled in Baton Rouge, Louisiana during 2002-2004 as part of characterizing wet deposition by fogwater in the heavily industrialized corridor along the Louisiana Gulf Coast in the United States. These samples were analyzed for chemical characteristics such as pH, conductivity, total organic and inorganic carbon, total metals and the principal ion concentrations. The dominant ionic species in all samples were NH4+, NO3-, Cl- and SO4(2-). The pH of the fogwater sampled had a mean value of 6.7 with two cases of acidic pH of 4.7. Rainwater and fogwater pH were similar in this region. The acidity of fogwater was a result of NO3- but partly offset by high NH4+. The measured gaseous SO2 accounted for a small percentage of the observed sulfate concentration, indicating additional gas-to-particle conversion of SO2 to sulfate in fogwater. The gaseous NOx accounted for most of the dissolved nitrate and nitrite concentration in fogwater. The high chloride concentration was attributable to the degradation of chlorinated organics in the atmosphere. The metal composition was traced directly to soil-derived aerosol precursors in the air. The major metals observed in fogwater were Na, K, Ca, Fe, Al, Mg and Zn. Of these Na, K, Ca and Mg were predominant with mean concentrations > 100 microM. Al, Fe and Zn were present in the samples, at mean concentrations < 100 microM. Small concentrations of Mn (7.8 microM), Cu (2 microM), Pb (0.07 microM) and As (0.32 microM) were also observed in the fogwaters, and these were shown to result from particulates (PM2.5) in the atmosphere. The contribution to both ions and metals from the marine sources in the Louisiana Gulf Coast was minimal. The concentrations of all principal ionic species and metals in fogwater were 1-2 orders of magnitude larger than in rainwater. Several linear alkane organic compounds were observed in the fogwater, representing the contributions from petroleum products at concentrations far exceeding their aqueous solubility. A pesticide (atrazine) was also observed in fogwater, representing the contribution from the agricultural activities nearby.

Adsorption↗
PubMed2003

Identification of genetic alterations related to chemoresistance in epithelial ovarian cancer.

OBJECTIVE: After the completion of primary chemotherapy, the majority of advanced ovarian cancer patients have persistent, chemoresistant disease. Comparative genomic hybridization (CGH) has been used to study genetic alterations that may be responsible for chemoresistance in ovarian cancer. CGH is a useful, genomewide screen but resolution is limited to 5-10 Mb. Recently, quantitative microsatellite analysis (QuMA), a TaqMan-based quantitative PCR technology, has been used for higher resolution of DNA copy number abnormalities. Our goal is to identify specific chromosomal aberrations correlated with platinum resistance. METHODS: Snap-frozen ovarian tissue samples taken from 22 patients with ovarian cancer between 1994 and 1998 were analyzed. Patients whose ovarian cancer actually demonstrated growth during platinum-combination treatment or no objective evidence of regression following four to six cycles of therapy were considered to have clinically defined platinum-resistant disease. QuMA was carried out at the following loci using the ABI Prism 7700 (TaqMan) instrument with a microsatellite repeat probe: D3S1553, D3S1617, D5S464, D5S630, D6S1581, D6S446, D8S557, D19S208, D20S196, DXS1068. Fisher's exact test, exact logistic regression, and the Cochran-Armitage trend test were used. Because of multiple hypothesis testing, the P values were adjusted with the Bonferroni procedure to limit the familywise error rate to at most 5%. RESULTS: Of the 22 patients, 12 (54.5%) were platinum-sensitive and 10 (45.5%) were platinum-resistant. When comparing sensitive and resistant patients, no statistically significant difference was noted among stage, grade, histology, and age (P = 0.1292, P = 1.0000, P = 1.0000, P = 1.0000, respectively). In the QuMA analysis, 10 of the 14 (71.4%) patients who had a low copy number of D6S1581 were platinum-resistant, while none of the patients with a normal or high copy number of D6S1581 were platinum-resistant. This was statistically significant when the marker data were treated as either a continuous or a categorical variable (P = 0.0410 and P = 0.0170, respectively). No other loci correlated significantly with platinum resistance. CONCLUSIONS: D6S1581 was the only genetic marker, of those examined, significantly related to chemoresistance. Patients with a loss of D6S1581 are more likely to be platinum-resistant. Identification of genetic alterations associated with platinum resistance detected by QuMA may contribute to a better understanding of clinical behavior and chemotherapy treatment options for patients.

Adenocarcinoma↗
PubMed2002

Structural basis for the unusual properties of 2',5' nucleic acids and their complexes with RNA and DNA.

To provide insights into the unusual properties of 2',5' nucleic acids (iso nucleic acids), that includes their rejection by Nature as information molecules, modeling studies have been carried out to examine if they indeed possess the stereochemical ability to form helical duplexes and triplexes, just as their 3',5' linked constitutional isomers. The results show that the formation of helical duplexes with 2',5' linkages demands a mandatory displacement of the Watson and Crick base pairs from the helical axis, as a direct consequence of the lateral shift of the sugar-phosphate backbone from the periphery towards the interior of the helix. Thus, both duplexes and triplexes formed with a 2',5'-sugar-phosphate backbone possess this intrinsic trait, manifested normally only in A type duplexes of DNA and RNA. It was found that only a 10-fold symmetric parallel triplex with isomorphous T.AT triplets is stereochemically favorable for isoDNA with 'extended' nucleotide repeats, unlike the 12-fold symmetric triplex favored by DNA. The wider nature of a 12-fold triplex, concomitant with mandatory slide requirement for helix formation in isoDNA, demands even larger displacement, especially with 'extended' nucleotide structural repeats, thereby violating symmetry. However, a symmetric triplex possessing higher twist, can be naturally formed for isoDNA with a 'compact' nucleotide repeat. Two nanosecond molecular dynamics simulation of a 2',5'-B DNA duplex, formed with an intrinsic base pair displacement of -3.3 A, does not seem to favor a total transition to a typical A type duplex, although enhanced slide, X-displacement, decrease in helical rise and narrowing of the major groove during simulation seem to indicate a trend. Modeling of the interaction between the chimeric isoDNA.RNA duplex and E. coli RNase H has provided a structural basis for the inhibitory action of the enzyme. Interaction of residues Gln 80, Trp 81, Asn 16 and Lys 99, of E. coli RNase H with DNA of the DNA.RNA hybrid, are lost when the DNA backbone is replaced by isoDNA. Based on modeling and experimental observations, it is argued that 2',5' nucleic acids possess restricted conformational flexibility for helical polymorphism. The inability of isoDNA to favor the biologically relevant B form duplex and the associated topological inadequacies related to nucleic acid compaction and interactions with regulatory proteins may be some of the factors that might have led to the rejection of 2',5' links.

Base Pairing↗
PubMed2002

The role of tumor suppressor genes in esophageal cancer.

Esophageal cancer remains one of the 10 most common cancers worldwide. Although patients with early lesions have a reasonable prognosis, most patients present with advanced disease resulting in an overall 5-year survival of 5-10%. Therefore, the current challenges in the management of esophageal cancer are to obtain a better understanding of the underlying molecular biological alterations to provide new treatment options. During the development of esophageal cancer, there is progression from a premalignant epithelium to a neoplasm that frequently demonstrates a heterogeneous mix of genetic alterations. The vast majority of esophageal cancers have inactivation of the p53 and p16 genes at an early stage followed by defects in genes such as APC, Rb and cyclin D1 at later stages of progression. There is also mounting evidence that numerous, specific regions throughout the genome are frequently lost in these cancers. As a result, we will in the next decade, likely see the discovery and characterizations of novel tumor suppressor genes that may be important in the development of esophageal cancer. The accumulating knowledge about the inactivation of the tumor suppressor genes could ultimately provide us with objective diagnostic tools, more accurate markers for prediction of malignant transformation from premalignant epithelium and facilitate the introduction of novel therapeutic options for the management of esophageal cancer.

Esophageal Neoplasms↗
PubMed2001

Lysine 114 of antithrombin is of crucial importance for the affinity and kinetics of heparin pentasaccharide binding.

Lys(114) of the plasma coagulation proteinase inhibitor, antithrombin, has been implicated in binding of the glycosaminoglycan activator, heparin, by previous mutagenesis studies and by the crystal structure of antithrombin in complex with the active pentasaccharide unit of heparin. In the present work, substitution of Lys(114) by Ala or Met was shown to decrease the affinity of antithrombin for heparin and the pentasaccharide by approximately 10(5)-fold at I 0.15, corresponding to a reduction in binding energy of approximately 50%. The decrease in affinity was due to the loss of two to three ionic interactions, consistent with Lys(114) and at least one other basic residue of the inhibitor binding cooperatively to heparin, as well as to substantial nonionic interactions. The mutation minimally affected the initial, weak binding of the two-step mechanism of pentasaccharide binding to antithrombin but appreciably (>40-fold) decreased the forward rate constant of the conformational change in the second step and greatly (>1000-fold) increased the reverse rate constant of this step. Lys(114) is thus of greater importance for the affinity of heparin binding than any of the other antithrombin residues investigated so far, viz. Arg(47), Lys(125), and Arg(129). It contributes more than Arg(47) and Arg(129) to increasing the rate of induction of the activating conformational change, a role presumably exerted by interactions with the nonreducing end trisaccharide unit of the heparin pentasaccharide. However, its major effect, also larger than that of these two residues, is in maintaining antithrombin in the activated state by interactions that most likely involve the reducing end disaccharide unit.

Antithrombins↗
PubMed2001

The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery.

Radiation necrosis and recurrent brain tumor have similar symptoms and are indistinguishable on both magnetic resonance imaging (MRI) and computed tomograph scans. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been proposed as a diagnostic alternative, particularly when co-registered with MRI. We studied 47 patients with brain tumors treated with stereotactic radiosurgery and followed with FDG PET. For all tumor types, the sensitivity of FDG PET for diagnosing tumor was 75% and the specificity was 81%. For brain metastasis without MRI co-registration, FDG PET had a sensitivity of 65% and a specificity of 80%. For brain metastasis with MRI co-registration, FDG PET had a sensitivity of 86% and specificity of 80%. MRI co-registration appears to improve the sensitivity of FDG PET, making it a useful modality to distinguish between radiation necrosis and recurrent brain metastasis.

Adolescent↗
PubMed2001

Cellular and molecular responses of the uterus to embryo implantation can be elicited by locally applied growth factors.

The implantation of a blastocyst into a receptive uterus is associated with a series of events, namely the attachment reaction followed by decidualization of the stroma. Previous studies established that the gene encoding heparin-binding EGF-like growth factor (HB-EGF) is expressed in the luminal epithelium solely at the site of blastocyst apposition preceding the attachment reaction. We report here the expression during implantation of 21 genes encoding other signaling proteins, including those belonging to the Bone morphogenetic protein (BMP), fibroblast growth factor (FGF), WNT, and Hedgehog (HH) pathways. We find that the attachment reaction is associated with a localized stromal induction of genes encoding BMP-2, FGF-2, and WNT-4. Despite efforts by many investigators, a simple in vitro model of implantation is not yet available to study either the hierarchy of the events triggered in the uterus by the embryo or the function of individual signaling proteins. We have therefore approached these questions by introducing beads loaded with purified factors into the receptive uterus. We show that beads soaked in HB-EGF or insulin-like growth factor-1 (IGF-1), but not other proteins, induce many of the same discrete local responses elicited by the blastocyst, including increased localized vascular permeability, decidualization, and expression of Bmp2 at the sites of the beads. By contrast, the expression domains of Indian hedgehog (Ihh), patched, and noggin become restricted as decidualization proceeds. Significantly, beads containing BMP-2 do not themselves elicit an implantation response but affect the spacing of implantation sites induced by blastocysts cotransferred with the beads.

Animals↗
PubMed2001

Correlation of expression of cyclooxygenase-2, vascular endothelial growth factor, and peroxisome proliferator-activated receptor delta with head and neck squamous cell carcinoma.

Cyclooxygenase (COX) is the rate-limiting enzyme in the formation of prostaglandins from arachidonic acid. COX exists in 2 isoforms, COX-1 and COX-2. These isoforms are encoded by separate genes and demonstrate cell-specific expression and regulation. Peroxisome proliferator-activated receptor delta (PPARdelta) is a nuclear transcription factor that is activated by prostacyclin. Vascular endothelial growth factor (VEGF) is a proangiogenic factor that is up-regulated in various tumors. Vascular endothelial growth factor has been shown to interact with COX-derived prostaglandins in angiogenesis. To better understand the roles of these genes in head and neck squamous cell carcinoma (HNSCCA), we examined the differential expression of the COX1, COX2, VEGF, and PPARdelta genes in these tumors. Tissue samples from patients with HNSCCA were analyzed for COX-1, COX-2, VEGF, and PPARdelta messenger RNAs (mRNAs) by in situ hybridization. COX-1 and COX-2 mRNAs were also evaluated with Northern blot hybridization. Immunohistochemistry was used to analyze for COX-2 and PPARdelta proteins. Results showed focal areas of accumulation for COX-2, VEGF, and PPARdelta but not COX-1 in human HNSCCA. Northern blot hybridization showed higher levels of COX-2 mRNA in HNSCCA than in normal tissue. This suggests a supportive role of COX-2 in development and/or progression of HNSCCA. In addition, PPARdelta may be a receptor for COX-2-produced prostaglandins in HNSCCA. There is a potential role for selective COX-2 inhibitors in the treatment of these lesions.

Blotting, Northern↗
PubMed2001

Multiple genetic alterations involved in the tumorigenesis of human cholangiocarcinoma: a molecular genetic and clinicopathological study.

PURPOSE: Cholangiocarcinoma (CC) is the second most common malignant tumor in the liver and the molecular genetic alterations involved in the tumorigenesis of CC have not been well studied. PATIENTS AND METHODS: The authors analyzed the loss of heterozygosity (LOH) in four tumor suppressor genes, including the adenomatous polyposis coli (APC) gene, the deleted in colon cancer (DCC) gene, the 8-hydroguanine-specific DNA glycosylase (OGG1) gene, and the p53 gene in 22 surgically resected primary CCs by using microdissection-based PCR amplification and direct DNA sequencing. RESULTS: A total of 19 (86.4%) out of 22 CCs exhibited genetic alterations, of which 11 (57.9%) and eight (42.1%) cases showed one and more than one gene alterations, respectively. The frequency of genetic alterations of the four genes studied ranged in order from high to low as APC (68.8%) > DCC (46.2%) > OGG1 (41.7%) > p53 (37.5%). Based on the pattern of altered genes and their correlation with clinical and pathological parameters, the genetic alterations were classified into three groups: group I: no detectable genetic alterations (n = 3, 13.6%); group II: LOH in APC and/or DCC (n = 9, 40.9%); and group III: LOH in OGG1 and/or p53 occurred separately or combined with LOH in APC and/or DCC (n = 10, 45.5%). The > or = 3-year survival rates between group II and group III are 88.9% and 30%, respectively (P < 0.05). No significant differences were found between genetic alterations and tumor size, tumor type, tumor invasion, TNM staging, and tumor differentiation (P > 0.05). CONCLUSION: Accumulation of multiple genetic alterations are involved in the tumorigenesis of CC, of which genetic alterations of APC and DCC occur at a relatively early stage, and of OGG1 and p53 occur at a relatively late stage during development of CC.

Aged↗
PubMed2001

Correlation between dysplasia and mutations of six tumor suppressor genes in Barrett's esophagus.

BACKGROUND: Barrett's esophagus (BE) may progress to adenocarcinoma through dysplastic progression. Classification of dysplasia in BE has significant interobserver variability. Our objective was to determine whether genetic alterations in BE correlate with degrees of histologic dysplasia. METHODS: Fixed tissue from 37 patients with BE and adenocarcinoma was studied for six tumor suppressor genes. Tissues were microdissected and analyzed for loss of heterozygosity. Microdissection of individual crypts showing metaplasia and dysplasia were performed and analyzed for 23 of the 37 patients whose tumors were heterozygous for at least four of the six genes studied. RESULTS: Frequency of alterations for MXI1, hOGG1, p53, MTS1, DCC, and APC were 7 of 32 (22%), 12 of 35 (34%), 12 of 26 (46%), 17 of 30 (57%), 17 of 27 (63%), and 23 of 36 (64%), respectively. Analysis of BE demonstrated that crypts with metaplasia, low-grade dysplasia, and high-grade dysplasia strongly correlated with alterations in tumor suppressor genes (p < 0.0001). CONCLUSIONS: This pilot study demonstrates that genetic analysis can be performed on individual crypts in patients with BE, and that alterations may facilitate objective classification of the severity of dysplasia.

Adenocarcinoma↗
PubMed2001

Prognostic value of quantitative reverse transcription-polymerase chain reaction in lymph node-negative esophageal cancer patients.

PURPOSE: In esophageal cancer, lymph node metastases are the strongest predictor of recurrence and poor outcome. However, many node-negative patients still recur despite a potentially curative resection. This is probably the result of microscopically occult metastases missed by histological examination. In this study, we used both standard, gel-based reverse transcription-PCR (RT-PCR) and Taqman quantitative RT-PCR (QRT-PCR) for carcinoembryonic antigen (CEA) mRNA to detect occult micrometastases in 387 lymph nodes from 30 histologically node-negative esophageal cancer patients. EXPERIMENTAL DESIGN: CEA expression was compared with clinical outcomes to determine correlation with disease recurrence. For quantitative data, an optimum CEA expression level cutoff value was defined as the value that most accurately classified patients on the basis of disease recurrence. Kaplan-Meier survival curves were generated, and multivariate analyses were performed to evaluate the prognostic value of QRT-PCR. RESULTS: CEA expression levels were above the optimum cutoff level in 12 tissue blocks, resulting in the identification of 11 CEA-positive patients. Of these patients, 9 suffered disease recurrence and 2 remain disease free. Of the 19 CEA-negative patients, there was 1 disease recurrence. The sensitivity and specificity for predicting disease recurrence were 90 and 90%, respectively. Kaplan-Meier analysis showed that CEA positivity resulted in significantly lower disease-free and overall survival (P <0.0001 and 0.0006 respectively). In multivariate analyses, CEA positivity measured by QRT-PCR was the strongest independent predictor of disease recurrence among other clinical and pathological factors examined. CONCLUSIONS: QRT-PCR offers significant benefits over standard RT-PCR and identifies node-negative patients at high risk for recurrence.

Aged↗
PubMed2000

Estrogen targets genes involved in protein processing, calcium homeostasis, and Wnt signaling in the mouse uterus independent of estrogen receptor-alpha and -beta.

Estrogen actions in target organs are normally mediated via activation of nuclear estrogen receptors (ERs). By using mRNA differential display technique, we show, herein, that estradiol-17beta (E(2)) and its catechol metabolite 4-hydroxy-E(2) (4OHE(2)) can modulate uterine gene expression in ERalpha(-/-) mice. Whereas administration of E(2) or 4OHE(2) rapidly up-regulated (4-8-fold) the expression of immunoglobulin heavy chain binding protein (Bip), calpactin I (CalP), calmodulin (CalM), and Sik similar protein (Sik-SP) genes in ovariectomized wild-type or ERalpha(-/-) mice, the expression of secreted frizzled related protein-2 (SFRP-2) gene was down-regulated (4-fold). Bip, CalP, and CalM are calcium-binding proteins and implicated in calcium homeostasis, whereas SFRP-2 is a negative regulator of Wnt signaling. Bip and Sik-SP also possess chaperone-like functions. Administration of ICI-182,780 or cycloheximide failed to influence these estrogenic responses, demonstrating that these effects occur independent of ERalpha, ERbeta, or protein synthesis. In situ hybridization showed differential cell-specific expression of these genes in wild-type and ERalpha(-/-) uteri. Although progesterone can antagonize or synergize estrogen actions, it had minimal effects on these estrogenic responses. Collectively, the results demonstrate that estrogens have a unique ability to influence specific genes in the uterus not involving classical nuclear ERs.

Animals↗
PubMed2000

Minimally invasive esophagectomy.

BACKGROUND: Open esophagectomy can be associated with significant morbidity and delay return to routine activities. Minimally invasive surgery may lower the morbidity of esophagectomy but only a few small series have been published. METHODS: From August 1996 to September 1999, 77 patients underwent minimally invasive esophagectomy. Initially, esophagectomy was approached totally laparoscopically or with mini-thoracotomy; thoracoscopy subsequently replaced thoracotomy. RESULTS: Indications included esophageal carcinoma (n = 54), Barrett's high-grade dysplasia or carcinoma in situ (n = 17), and benign miscellaneous (n = 6). There were 50 men and 27 women with an average age of 66 years (range 30 to 94 years). Median operative time was 7.5 hours (4.5 hours with > 20 case experience). Median intensive care unit stay was 1 day (range 0 to 60 days); median length of stay was 7 days (range 4 to 73 days) with no operative or hospital mortalities. There were four nonemergent conversions to open esophagectomy; major and minor complication rates were 27% and 55%, respectively. CONCLUSIONS: Minimally invasive esophagectomy is technically feasible and safe in our center, which has extensive minimally invasive and open esophageal experience. Open surgery should remain the standard until future studies conclusively demonstrate advantages of minimally invasive approaches.

Adult↗