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Biomedical subjects

S Singh

Publications and source records attributed to S Singh.

At least 37 records · Page 2Linked to original sources
PubMed2006

Comparison of some trace elements concentration in blood, tumor free breast and tumor tissues of women with benign and malignant breast lesions: an Indian study.

Fifty women residing in and around New Delhi, India and identified to have benign (25 nos.) and malignant (25 nos.) breast lesions were studied for the first time to access the association between environmental exposure to lead and risk of breast cancer and to determine the potential of changes in trace elements concentration as a diagnostic marker and/or its etiological involvement in the disease. Blood, tumor tissue and breast adipose tissue from tumor free area from each patient of the two groups, collected at the time of lumpectomy or mastectomy (only blood sample was collected from disease free control group), were analyzed to determine the concentration of Pb, Zn, Cu, Fe and Ca using Atomic Absorption Spectrometry. Blood lead was significantly higher in malignant cases than in those of benign and control (p<0.05 each). Lead level was also higher in tumor tissue when compared with their respective normal tumor free breast tissue, though non-significant, in both benign and malignant cases. Interestingly, Zn, Fe, and Ca levels were higher in blood of malignant cases than in those of their benign counterparts. Furthermore, these metals were also higher in tumor of malignant and benign cases as compared to normal tumor free breast tissue, many of them statistically significant (p<0.05/0.01/0.001). However, Cu level was insignificantly lower in the blood and tumor tissue of malignant cases when compared with their benign counterparts while it was significantly higher (p<0.05) in tumor of benign cases when compared with those of their respective normal tumor free breast tissue. There were statistically significant correlations between lead and trace element levels only in normal tumor free breast tissue of benign and malignant cases (r=0.41-0.73; p<0.05-0.001) but neither in blood nor tumor tissue of the two groups. These results suggest that in the backdrop of existing experimental and epidemiological evidences exposure to lead may be one of the risk factors for breast lesions; though it warrants further investigation. Further, modulation of trace elements level in both benign and malignant breast diseases patients may be of potential to be used as diagnostic marker of the disease process and its possible relationship etiologically.

Adult↗
PubMed2006

Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation.

H2S is highly toxic and selectively inhibits butyrate oxidation in colonocytes. Ineffective detoxification may result in mucosal insult, inflammation, and ultimately in colorectal cancer (CRC). Rhodanese can detoxify H2S and is comprised of two isoenzymes: thiosulfate sulfurtransferase (TST) and mercaptopyruvate sulfurtransferase (MST). Using specific antisera to discriminate TST from MST, we found that only TST could detoxify H2S. In sections of normal colon, both enzymes were located on the luminal mucosal surface, and they were expressed in the colonocytes but not in the mucin-secreting goblet cells. Expression of both enzymes was focally lost in ulcerative colitis and markedly reduced in advanced colon cancer, the disease progression correlating with the decreased expression of MST and TST. In HT-29 cells, a human colon cancer cell line, TST activity and expression were significantly increased by butyrate and by histone deacetylase inhibition, agents that promote HT-29 cell differentiation. Sulfide (0.1 mM) also increased TST activity, but higher sulfide concentrations (0.3-3 mM) were toxic. Preincubation in butyrate to increase TST expression, decreased sensitivity of the cells to sulfide toxicity. We conclude that decreased expression of TST (or MST) is a tumor marker for CRC. TST expression is increased in colonocyte differentiation. Dysregulation of TST expression and activity resulting in inability to effectively detoxify could be a factor in the cell loss and inflammation that accompany ulcerative colitis and ultimately then in CRC.

Cell Differentiation↗
PubMed2006

Limited IL-6 production following infection with murine gammaherpesvirus 68.

Murine gammaherpesvirus 68 (gammaHV-68) was found to induce IL-6 secretion following in vitro infection of macrophages, but not cultured dendritic or epithelial cells. A detectable, but very limited IL-6 response was observed in the lungs and mediastinal lymph nodes following intranasal infection. Surprisingly, no detectable in vivo IL-6 production was observed in the spleen or sera of infected mice despite observable systemic leukocytosis. These studies demonstrate that endogenous IL-6 production contributes little to the host response, or to the viral-induced mononucleosis-like disease, due to the fact that limiting amounts of this cytokine are produced in vivo during gammaHV-68 infection.

Animals↗
PubMed2006

Validated chiral high-performance liquid chromatography method for a novel anti-methicillin-resistant Staphylococcus aureus fluoroquinolone WCK 771.

A sensitive, simple, specific, precise, accurate and rugged method for the assay and determination of enantiomeric purity of S-(-)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid L-arginine salt tetrahydrate (WCK 771) in bulk drug has been developed. The method is RP-HPLC using endcapped C-18 stationary phase and chiral mobile phase. Chirality to the mobile phase was imparted with addition of beta-cyclodextrin. The UV-vis detector was operated at 290 nm. The flow rate of mobile phase was 2 ml/min. The method offers excellent separation of two enantiomers with resolution more than 2 and tailing factor less than 1.5. The method was validated for the assay of WCK 771 and quantification of R-(+)-enantiomer impurity in bulk drug. The calibration curves showed excellent linearity over the concentration range of 0.05-0.15 mg/ml for WCK 771 and 0.5-7.5 microg/ml for R-(+)-enantiomer. The precision (RSD) of the assay was 0.23%. The limit of detection and limit of quantitation of the method for WCK 771 were 0.015 and 0.06 microg/ml, respectively. The limit of detection and limit of quantitation for R-(+)-enantiomer were 0.025 and 0.09 microg/ml, respectively. The average recovery of the R-(+)-enantiomer was 100.5%. Same method was applied for the assay and determination of enantiomeric purity of WCK 771 in the intravenous formulation.

Chromatography, High Pressure Liquid↗
PubMed2006

Epidermal growth factor receptor dimerization status determines skin toxicity to HER-kinase targeted therapies.

Skin toxicity, a common drug-related adverse event observed in cancer patients treated with epidermal growth factor receptor (EGFR)-directed therapies is rarely seen with therapies targeting HER2. This study reports the significance of the EGFR and HER2 dimerization status in skin with regard to these dermatologic side effects. We demonstrate the differential effect of HER-directed therapies on the ligand driven activation status of EGFR, HER2 and MAPK in normal human epidermal keratinocytes. EGFR-directed therapies, such as gefitinib and cetuximab, inhibited ligand-induced activation of EGFR and MAPK in human keratinocytes. Pertuzumab, an antibody interfering with functional HER2 heterodimerization, failed to block ligand-induced HER signaling in primary keratinocytes. Using a novel proximity-based dimerization assay (eTagtrade mark) we show that EGFR homodimers are the predominant HER dimer pair in normal primary kertinocytes and in normal skin tissue from 16 patients with solid malignancies. The presence of [p]EGFR and [p]MAPK, but the absence of [p]HER2, demonstrates productive signaling via EGFR but not HER2 in human skin. These data illustrate the importance of the EGFR dimerization partner in human skin and suggests that inhibition of EGFR homodimer signaling rather than EGFR/HER2 heterodimer signaling maybe the key molecular event determining dermatologic toxicity discrepancies observed between EGFR-targeted versus HER2-targeted therapies.

Antibodies, Monoclonal↗
PubMed2006

Inhibition of early and late phase allergic reactions by Euphorbia hirta L.

A 95% ethanol extract from whole aerial parts of Euphorbia hirta (EH A001) showed antihistaminic, antiinflammatory and immunosuppressive properties in various animal models. EH A001 inhibited rat peritoneal mast cell degranulation triggered by compound 48/80. It significantly inhibited dextran-induced rat paw edema. EH A001 prevented eosinophil accumulation and eosinophil peroxidase activity and reduced the protein content in bronchoalveolar lavage fluid (BALF) in a 'mild' model of asthma. Moreover, the CD4/CD8 ratio in peripheral blood was suppressed. EH A001 attenuated the release of interleukin-4 (IL-4) and augmented interferon-gamma (IFN-gamma) in ovalbumin-sensitized mouse splenocytes. The results were compared with the effects of known compounds, ketotifen, cetirizine and cyclophosphamide. These findings demonstrated that Euphorbia hirta possessed significant activity to prevent early and late phase allergic reactions.

Animals↗
PubMed2006

Activation of NFkappaB and Ub-proteasome pathway during apoptosis induced by a serum factor is mediated through the upregulation of the 26S proteasome subunits.

We have been investigating differential gene expression associated with apoptosis in AK-5 cells (a spontaneously regressing rat histiocytoma) and have observed catalytic subunits beta 7 and alpha 5 of the 26S proteasome and ubiquitin to be upregulated during apoptosis induced by a variety of agents. The observed elevation in gene expression was parallel to a comparable increase in the cytosolic protein expression of the proteasome and ubiquitin and a markedly amplified increase in the proteasome activity. Inhibition of the increase in gene expression resulted in the inhibition of the rise in the proteasome activity subsequently leading to an inhibition of apoptosis. Similarly, pretreatment with proteasome inhibitors, MG132 and lactacystin, resulted in a significant inhibition of apoptosis pointing to the requirement of a highly active protein degradation machinery during apoptosis. The apoptosis inhibitory effect of the proteasome inhibitors involved an inhibition of the activation of various initiator and effector caspases but was independent of any changes in the mitochondrial membrane depolarization and cytochrome c release associated with apoptosis. Inhibition of proteasome activity or its upstream PI3 kinase activity inhibited NFkappaB translocation thereby suppressing apoptosis, which highlights the requirement of NFkappaB activation for completion of apoptosis in AK-5 cells. Hence, the apoptosis associated induction of the Ub-proteasome pathway components and the proteasome activity suggests that the proteasome, in its capacity as an efficient protein degradation complex, plays an important role in the successful execution of apoptosis.

Animals↗
PubMed2006

A comparative study of epiretinal membranes associated with Eales' disease: a clinicopathologic evaluation.

AIM: To study the histopathologic features and clinical correlation of epiretinal membranes (ERM) obtained from patients of Eales' disease and compare with other vasoproliferative disorders. METHODS: Retrospective analysis of epiretinal membranes submitted for histological evaluation between January 1995 and June 2001, from the patients of diabetic retinopathy and vascular occlusions (Group 1; vaso-occlusive disorders) and of Eales' disease (Group 2; vasoinflammatory disorders). Demographics, pre and postoperative visual acuity, and anatomic and histologic characteristics of membranes were studied. Histopathologic features and clinical outcomes were correlated between the groups. The results were analysed statistically by Student's t-test, Fisher's exact test and Kruskal-Wallis test. RESULTS: This study consisted of 42 patients, 24 in Group 1 and 18 in Group 2. Patients in Group 2 (33.0+/-9.2 years) were significantly younger than the patients in Group 1 (49.9+/-7.6 years) (P< or =0.0001). Final visual acuity of >20/400 was attained in 79.2% (19/24) patients in Group 1 and 83.3% (15/18) in Group 2 (P=1.0). Inflammatory membranes were significantly associated with presumed Eales' disease (94.4 vs 0%) (P< or =0.0001) and fibrovascular membranes with Group 1 (70.8% vs 33.3%) (P=0.028). Mast cells and eosinophils were observed as special features in epiretinal membranes of patients with Eales' disease. CONCLUSIONS: Histological features of ERM in Eales' disease are comparable to other vasoproliferative disorders except for features of inflammation. Presence of mast cells and eosinophils in epiretinal membranes of Eales' disease needs further investigation.

Adult↗
PubMed2006

Peptide alkaloids from Zizyphus sativa bark.

Two new cyclopeptide alkaloids, sativanine-N and sativanine-O were isolated from the stem bark of Zizyphussativa and their structures were established by spectral analysis.

Alkaloids↗
PubMed2006

Endocrine regulation in asymmetric intrauterine fetal growth retardation.

OBJECTIVE: The ponderal index (PI) is a widely accepted measure of disproportionate growth or asymmetrical growth retardation by pediatricians worldwide. Identification of disproportionately grown small for gestational age (SGA) neonates by using the ponderal index as a measure of the nutritional status at birth, is important because they constitute a high-risk group among SGA neonates. Poor nutritional status of the mother could have a direct effect on the organs of the developing fetus and/or affect the endocrine milieu in the maternal feto-placental unit resulting in an increased incidence of intrauterine growth-retarded (IUGR)/SGA births. IUGR is a significant risk factor for adult disease. In this study, we have investigated the endocrine adaptation by the fetus to overcome the growth disadvantage caused due to poor nutritional status of the mother. MATERIALS AND METHODS: We examined the quantitative variations in hormonal and growth factor profiles in paired maternal and cord blood samples obtained from mothers and their neonates who were classified based on their growth status into SGA and appropriate for gestational age (AGA). RESULTS: (1) A total of 24.7% neonates had a PI < 2, indicating a high incidence of asymmetric IUGR in the population studied. (2) Anthropometric parameters measured in the mothers indicate that the mothers giving birth to neonates with a PI < 2 had poor nutritional status, both prior to and during pregnancy. (3) We observed increased levels of placental lactogen and prolactin and decreased levels of insulin in the cord blood of neonates with PI < 2, while lower levels of insulin-like growth factor 1 (IGF-1) and higher levels of epidermal growth factor (EGF) were observed in their mothers. CONCLUSION: Poor maternal nutritional status results in fetal adaptation to a growth restricted environment via the modulation of the pituitary-thyroid axis thereby altering the endocrine milieu, thus affecting fetal growth.

Adult↗
PubMed2006

Radioprotection by Rhodiola imbricata in mice against whole-body lethal irradiation.

Rhodiola imbricata, an Indian medicinal plant, was investigated for protection against whole-body lethal gamma irradiation (10 Gy)-induced mortality in Swiss albino strain "A" mice. The maximum tolerance dose values for aqueous (RD-I) and aqua-alcoholic (RD-II) extracts were 1,100 and 1,300 mg/kg of body weight, respectively. Pre-irradiation administration of RD-I produced >90% survival, while RD-II produced >83% survival beyond the 30-day observation period. The optimal radioprotective dose for RD-I as well as RD-II was 350 mg/kg of body weight; the aqua-alcoholic extract, however, had an advantage over the aqueous extract at lower as well as at higher doses. The optimal time interval between administration of extract and irradiation was 30 minutes for both RD-I and RD-II. The number of colony-forming units per spleen in irradiated mice was 1.91 +/- 0.15, while in mice given RD-I or RD-II, 30 minutes before irradiation (10 Gy), it increased to 17.3 +/- 0.67 and 15.6 +/- 0.61, respectively. These findings have important implications in the development of a suitable radioprotector of herbal origin.

Animals↗
PubMed2006

Interdigital lesions and frequency of acute dermatolymphangioadenitis in lymphoedema in a filariasis-endemic area.

BACKGROUND: Lymphatic filariasis (LF) is a mosquito-borne nematode infection that causes permanent lymphatic dysfunction in virtually all infected individuals and clinical disease in a subset of these. One major sequel of infection is lymphoedema of the limbs. Lymphoedema of the leg affects an estimated 15 million persons in LF-endemic areas worldwide. Acute dermatolymphangioadenitis (ADLA) in people with filarial lymphoedema causes acute morbidity and increasingly severe lymphoedema. Episodes of ADLA are believed to be caused by bacteria, and it has been shown that entry lesions in the skin play a causative role. Clinical observations suggest that interdigital skin lesions of the feet, often assumed to be fungal, may be of particular importance. OBJECTIVES: To investigate the epidemiology and aetiology of interdigital lesions (IDL) of the feet in filarial lymphoedema. METHODS: The frequency and mycological aetiology of IDL in 73 patients with filarial lymphoedema were compared with 74 individuals without lymphoedema in a region of Guyana highly endemic for Wuchereria bancrofti. RESULTS: More than 50% of patients with lymphoedema had one or more IDL (odds ratio 2.69; 95% confidence interval 1.31-5.66; P<0.005 compared with controls). The number of lesions was the strongest predictor of frequency of ADLA. Only 18% of the lesions had positive microscopy or culture for fungi (dermatophytes and Scytalidium). CONCLUSIONS: These findings highlight the importance of interdigital entry lesions as risk factors for episodes of ADLA and have implications for the control of morbidity from filarial lymphoedema.

Acute Disease↗
PubMed2006

Immunogenetic association and thyroid autoantibodies in juvenile autoimmune thyroiditis in North India.

OBJECTIVES: Autoimmune thyroid diseases (AITD) encompass a number of conditions that have in common cellular and humoral responses targeting the thyroid gland. Interactions between susceptibility genes and environmental triggers are thought to initiate an autoimmune response to thyroid antigens leading to disease manifestation. Commencement of the disease in childhood leads to the presumption that genetics may have an important role in the causation of the disease. DESIGN: The present study was aimed at evaluating the human leucocyte antigen (HLA) encoded susceptibility to develop juvenile autoimmune thyroiditis (JAT) in patients from North India. PATIENTS: We studied 48 consecutive patients of JAT along with 176 first-degree relatives for their thyroid function (FT4, TSH) and anti-thyroid peroxidase antibody status (AbTPO). MEASUREMENTS: HLA studies were carried out using serology for HLA-class I antigens and DNA analysis of HLA-class II alleles. The data were compared with a cohort of 308 ethnically matched healthy individuals. RESULTS: We observed overt hypothyroidism in 50% and AbTPO positivity in 70.8% of the index cases. Among the first-degree relatives, goitre was observed in 51.7%, thyroid dysfunction in 28.4% and AbTPO in 29.5% of individuals. Of the 37 relatives who underwent fine-needle aspiration cytology (FNAC), 60% had evidence of chronic lymphocytic thyroiditis (CLT). A strong positive association of HLA-DRB1*1404 was observed with the JAT (35.4%vs. 10.4%, chi2 = 19.8, Pc = 0.0001). We also observed a higher (72%, P = 0.03) paternal transmission of HLA-DRB1*1404 to affected offspring in comparison to unaffected offspring. HLA-DRB1*03 was also increased among JAT patients but did not reach statistical significance. CONCLUSION: These studies point towards an important role of immune modifying genes, such as HLA, in influencing susceptibility to juvenile-onset AITD.

Adolescent↗
PubMed2006

Molecular fingerprinting of BMP2- and BMP4-treated embryonic maxillary mesenchymal cells.

OBJECTIVE: To determine the differences in gene expression between control-, bone morphogenetic protein (BMP)2- and BMP4-treated murine embryonic maxillary mesenchymal (MEMM) cells. DESIGN: Transcript profiles of BMP2-, BMP4- and vehicle-treated MEMM cells were compared utilizing the murine high-density GeneChip arrays from Affymetrix. The raw chip data (probe intensities) were pre-processed using robust multichip averaging with GC-content background correction and further normalized with GeneSpring v7.2 software. Cluster analysis of the microarray data was performed with the GeneSpring software. Changes in the gene expression were verified by TaqMan quantitative real-time PCR. RESULTS: Expression of approximately 50% of the 45 101 genes and expressed sequence tags examined in this study were detected in BMP2-, BMP4- and vehicle-treated MEMM cells and that of several hundred genes was significantly altered (up or downregulated) in these cells in response to BMP2 and BMP4. Expression profiles of each of the 26 mRNAs tested by TaqMan quantitative real-time PCR were found to be consistent with the microarray data. Genes whose expression was modulated following BMP2 or BMP4 treatment, could be broadly classified based on the functions of the encoded proteins such as the growth factors and signaling molecules, transcription factors, and proteins involved in epithelial-mesenchymal interactions, extracellular matrix synthesis, cell adhesion, proliferation, differentiation, and apoptosis. CONCLUSION: Utilization of the Affymetrix GeneChip microarray technology has enabled us to delineate a detailed transcriptional map of BMP2 and BMP4 responsiveness in embryonic maxillary mesenchymal cells and offers revealing insights into crucial molecular regulatory mechanisms employed by these two growth factors in orchestrating embryonic orofacial cellular responses.

Animals↗
PubMed2006

Novel NHLRC1 mutations and genotype-phenotype correlations in patients with Lafora's progressive myoclonic epilepsy.

BACKGROUND: Lafora's progressive myoclonic epilepsy (Lafora's disease) is an autosomal recessive neurodegenerative disorder characterised by the presence of polyglucosan intracellular inclusions called Lafora bodies. Mutations in two genes, EPM2A and NHLRC1, have been shown to cause the disease. A previous study showed mutations in the EPM2A gene in 14 Lafora's disease families and excluded the involvement of this gene in five other families who were biopsy proven to have the disease. OBJECTIVE: To relate the genetic findings to the clinical course of the disease. METHODS: As part of an ongoing mutational study of the Lafora's disease genes, five new families with the disease were recruited and the genetic analysis was extended to screen the entire coding region of the NHLRC1 gene. Genotype-phenotype correlations were carried out. RESULTS: Seven NHLRC1 mutations were identified, including five novel mutations (E91K, D195N, P218S, F216_D233del, and V359fs32), in eight families with Lafora's disease. On relating the genetic findings to the clinical course of the disease it was shown that patients with NHLRC1 mutations had a slower rate of disease progression (p<0.0001) and thus appeared to live longer than those with EPM2A mutations. A simple DNA based test is described to detect the missense mutation C26S (c.76T-->A) in the NHLRC1 gene, which is prevalent among French Canadians. CONCLUSIONS: Patients with NHLRC1 mutations have a slower rate of disease progression than those with EPM2A mutations.

Adolescent↗
PubMed2006

Dysphagia in stroke patients.

Swallowing musculature is asymmetrically represented in both motor cortices. Stroke affecting the hemisphere with the dominant swallowing projection results in dysphagia and clinical recovery has been correlated with compensatory changes in the previously non-dominant, unaffected hemisphere. This asymmetric bilaterality may explain why up to half of stroke patients are dysphagic and why many will regain a safe swallow over a comparatively short period. Despite this propensity for recovery, dysphagia carries a sevenfold increased risk of aspiration pneumonia and is an independent predictor of mortality. The identification, clinical course, pathophysiology, and treatment of dysphagia after stroke are discussed in this review.

Central Nervous System Diseases↗