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S Sharma

Publications and source records attributed to S Sharma.

At least 181 records · Page 10Linked to original sources
PubMed2002

Transient pluripotent cell populations during primitive ectoderm formation: correlation of in vivo and in vitro pluripotent cell development.

Formation and differentiation of a pluripotent cell population is central to mammalian development, and the isolation, identification and manipulation of human pluripotent cells is predicted to be of therapeutic use. Within the early mammalian embryo, two distinct populations of pluripotent cells have been described: the inner cell mass (ICM), which differentiates to form a second pluripotent cell populations, the primitive ectoderm. Indirect evidence suggests the existence of temporally distinct intermediate pluripotent cell populations as primitive ectoderm is formed. We coupled an in vitro model of primitive ectoderm formation (the transition of embryonic stem cells to early primitive ectoderm-like (EPL) cells) with ddPCR-based techniques to identify three novel genes, Psc1, CRTR-1 and PRCE, that were expressed differently during pluripotent cell progression. Detailed mapping of these genes with Oct4, Rex1 and Fgf5 on pregastrulation embryos provided the first molecular evidence for the existence of successive, temporally distinct pluripotent cell populations in the embryo between the ICM and primitive ectoderm. No evidence was found for spatial heterogeneity within the Oct4(+) pool. The transition between populations correlated with morphological or developmental alterations in pluripotent cells in vivo. Genes that are temporally expressed during pluripotent cell progression may provide an opportunity for molecular discrimination of pluripotent cells at different stages of maturation in vivo and an understanding of the cellular origins and properties of pluripotent cell lines isolated from diverse sources. Furthermore, the strong correlation of gene expression demonstrated between EPL cell formation in vitro and primitive ectoderm formation in vivo validates EPL cells as a model for primitive ectoderm, thereby providing a model system for the investigation of pluripotent differentiation and an opportunity for directed differentiation of pluripotent cells to therapeutically useful cell populations.

Amino Acid Sequence↗
PubMed2002

Pregnancy in patients with spina bifida and urinary diversion.

With better medical care the mortality and morbidity associated with spina bifida are improving and more such patients are reaching reproductive age. Significant problems may be encountered in the management of pregnancy in spina bifida, especially in patients with previous abdominal operations for the management of neuropathic bladder dysfunction. We report successful pregnancy outcomes in 2 such patients, both with urinary diversions, with combined obstetric and urological care. We also review the existing literature on the subject.

Adult↗
PubMed2002

Maternal and perinatal outcome in varying degrees of anemia.

OBJECTIVES: To analyze the maternal and perinatal outcome in varying degrees of anemia. METHODS: A total of 447 pregnant women were divided into group I (Hb>11 g%, n=123 women), group II (Hb 9-10.9 g%, n=214 women), group III (Hb 7-8.9 g%, n=79 women) group IV (Hb<7 g%, n=31 women). Their maternal and perinatal outcome, mode of delivery, duration of labor and postpartum complications were noted and analyzed using multiple logistic regression to calculate odds ratios (95% CI) for duration of labor, mode of delivery and low birth babies. Chi square or Fisher's exact test was employed for difference in proportions and Student's t-test for testing difference between means. RESULTS: Mean age (27+/-4.25 years) and number of women with parity >3 were highest in group IV. The patients with Hb<8.9 g% had a 4-6-fold higher risk of prolonged labor compared to Hb>11 g%. The odds ratios for abnormal delivery (cesarean and operative vaginal deliveries) showed a 4.8-fold higher risk (95% CI 1.82, 12.7) in patients with Hb </=7.5 g%. The mean birth weight was maximum in the 9.6-10.5 g% category that fell with both increasing and decreasing hemoglobin values, being lowest in Group IV. Women in Group II had lowest number of low birth weight and IUGR babies, no stillbirths and neonatal deaths, lowest induction and operative delivery rates. CONCLUSIONS: Mild anemia fared best in maternal and perinatal outcome. Severe anemia was associated with increased low birth weight babies, induction rates, operative deliveries and prolonged labor.

Adult↗
PubMed2002

Expression, purification, and characterization of equine lactoferrin in Pichia pastoris.

Lactoferrin is an 80kDa iron-binding glycoprotein. It is secreted by exocrine glands. Many functions such as iron sequestering, anti-bacterial activity, regulation of gene expression, and immunomodulation are attributed to it. In the present study, we report the production of recombinant equine lactoferrin (ELF) in the methylotropic yeast Pichia pastoris using pPIC9K vector. The recombinant protein was purified by one-step affinity chromatography using heparin-Sepharose column. The purified protein has a molecular weight of 80kDa and reacted with antibody raised against the native equine lactoferrin. Its N-terminal sequence was identical to that of the native ELF. The iron-binding behavior and circular dichroism studies of the purified protein indicate that it has folded properly. The recombinant protein appears to be hyperglycosylated by the host strain, GS115. This is the first heterologous expression of equine lactoferrin and also the first report of intact lactoferrin expression using P. pastoris system. An yield of 40mg/l obtained in shake-flask cultures with this system, which is higher than the reported values for other systems.

Amino Acid Sequence↗
PubMed2002

Neuromuscular fatigue of elbow flexor muscles of dominant and non-dominant arms in healthy humans.

The purpose of this study was to assess differences in fatigue-related changes in variables related to structures within the neuromuscular system, between the dominant and non-dominant elbow flexor muscles of right-handed individuals. Two experimental sessions were performed on the right arm and one on the left arm. For each session, maximum voluntary torque, level of voluntary activation, M-wave amplitude, twitch/train or twitch/doublet torque ratio and EMG median frequency were obtained before and up to 20 min after a sustained maximum isometric fatigue task. Our main results were: 1) reproducible fatigue-induced changes in all variables of interest between the two sessions performed with the right arm, 2) significantly greater failure in voluntary activation and neuromuscular propagation with sustained activity for the non-dominant compared with dominant side, and 3) no effect of dominance on MVC torque, endurance time, and fatigue-induced changes in EMG median frequency and elicited torques. These results suggest that the preferential use of elbow flexor muscles with the dominant arm leads to more fatigue resistance in certain structures/mechanisms of the neuromuscular system, but not in others.

Adult↗
PubMed2002

Spontaneous secretion of interleukin-4, interleukin-10 and interferon-gamma by first trimester decidual mononuclear cells.

PROBLEM: A T-helper cell type 2 (Th2) cytokine dominated microenvironment has been predicted to be crucial for successful pregnancy. However, little information is available about local cytokine secretion in the human decidua. We determined the spontaneous secretion of interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and IL-10 by decidual mononuclear cells at the single cell level and compared it with their secretion by peripheral blood mononuclear cells (PBMC) in the first trimester of pregnancy. METHODS OF STUDY: The cytokine secretion from decidual and blood cells was detected by a sensitive enzyme-linked immunosorbent spot-forming cell (ELISPOT)-assay. RESULTS: Cells secreting IL-4 (median 153, range 8-530), IL-10 (median 188, range 32-1600) and IFN-gamma (median 123, range 15-1140) were detected in all decidual and blood samples. The cytokine secretion showed a co-linear pattern in both the blood and decidua, i.e. when one cytokine was secreted at high levels, the others followed the trend. No correlation was found between the number of cytokine secreting cells in blood and decidua for any of the cytokines. CONCLUSIONS: Interleukin-4 and IL-10 are locally secreted in the decidua early during normal pregnancy, probably counteracting the fetal rejecting effects of co-expressed IFN-gamma. The cytokine secretion by blood cells does not generally reflect the local secretion pattern during first trimester pregnancy.

Adolescent↗
PubMed2002

Septal myotomy-myectomy and transcoronary septal alcohol ablation in hypertrophic obstructive cardiomyopathy. A comparison of clinical, haemodynamic and exercise outcomes.

AIMS: Surgical myectomy has been successfully used to treat patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). More recently, alcohol septal ablation has been advocated as a less invasive, but equally effective alternative therapy. The aim of this non-randomized cohort study was to compare subjective and objective outcomes in patients undergoing these therapies. METHODS: Forty-four patients (25 male; age 41+/-15 years) with symptomatic drug-refractory obstructive HCM were studied. Twenty-four patients underwent surgical myectomy and 20 alcohol septal ablation. All patients underwent clinical evaluation, echocardiography and upright maximal cardiopulmonary exercise testing using a cycle ergometer before and following their intervention. RESULTS: Peak gradient was reduced to a similar extent by both modalities (myectomy: 83+/-23 to 15+/-10 mmHg (P<0.000001); ablation: 91+/-18 to 22+/-14 mmHg (P<0.000002);P =0.48 for myectomy vs ablation) and led to similar improvements in NYHA class (myectomy: 2.4+/-0.6 to 1.5+/-0.7 (P<0.00001); ablation: 2.3+/-0.5 to 1.7+/-0.8 (P<0.0001);P=0.3 for myectomy vs ablation). Myectomy resulted in a greater improvement in peak oxygen consumption (myectomy: 16.4+/-5.8 to 23.1+/-7.1 ml.kg(-1) min(-1) (P<0.00002); ablation: 16.2+/-5.2 to 19.3+/-6.1 ml.kg(-1) min(-1) (P<0.05);P <0.05 for myectomy vs ablation) and work rate achieved (myectomy: 130+/-57 to 161+/-60 watts (P<0.04); ablation: 121+/-53 to 137+/-51 watts (P=0.11);P <0.05 for myectomy vs ablation). CONCLUSION: Surgical myectomy and alcohol septal ablation are equally effective at reducing obstruction and subjective exercise limitation in appropriately selected patients. However, the superior effect of surgical myectomy on exercise test parameters suggests that surgery remains the gold standard against which new treatment modalities should be compared.

Adult↗
PubMed2002

Intrapituitary regulatory system of mammotrophs in the mouse.

Estrogen stimulates the proliferation of pituitary cells, in particular mammotrophs. The present study was designed to clarify involvement of transforming growth factor alpha (TGF-alpha) in the estrogen-induced growth of mouse pituitary cells in vitro. Anterior pituitary cells obtained from ICR male mice were cultured in a primary, serum-free culture system. Proliferation of pituitary cells was detected by monitoring the cellular uptake of a thymidine analogue, bromodeoxyuridine. Secretory cell types were immunocytochemically determined. Treatment with TGF-alpha (0.1 and 1 ng/ml) for 5 days stimulated cell proliferation. Since TGF-alpha binds to the epidermal growth factor (EGF)-receptor, this action may be exerted through this receptor. Estradiol-17beta (E2, 10(-9) M) stimulated proliferation of mammotrophs. RG-13022, an EGF receptor inhibitor, reduced the cell proliferation induced by EGF or E2, showing that the EGF receptor was involved in this induction of mammotroph growth. Treatment with TGF-alpha antisense oligodeoxynucleotide (ODN) inhibited the cell proliferation induced by E2, but treatment with EGF antisense ODN did not. Dual detection of TGF-alpha mRNA and growth hormone by in situ hybridization and fluorescence-immunocytochemistry demonstrated that TGF-alpha mRNA was detected in most somatotrophs. Our recent RT-PCR analysis revealed that E2 stimulated TGF-alpha-mRNA and EGF-receptor mRNA expression. These results indicate that TGF-alpha produced in somatotrophs mediates the stimulatory effect of estrogen on pituitary cell proliferation in a paracrine manner, and that EGF-receptor expression is stimulated by estrogen. These findings indicate that intrapituitary cell-to-cell interaction plays an important role in the control of pituitary secretory cells.

Animals↗
PubMed2002

Gynaecological malignancies in a rural institute in India.

A rural institutional study was carried out with the object of recording the number and type of gynaecological malignancies in relation to socio-economic status, age, parity, contraceptive use and mode of presentation in current gynaecological practice. Between 1985 and 1999 gynaecological malignancies comprised 42.52% of all malignancies in women. Cancer of the cervix (33.3%) and breast (27.3%), constituted 60.6% of all cancers in women. Cervical cancer (80%) and ovarian cancer (15%) were the main gynaecological tumours. Endometrial cancer was found only in 2.0% of all female genital malignancies; 76.5% women were from villages. Seventy-two per cent of women with gynaecological malignancies were from a lower socio-economic class. Nearly half (44.6%) of the overall cases occurred between ages of 35 and 49 years. Most women, irrespective of the site of cancer, were multiparous. Sterilisation had been the main birth control method used. Other methods of contraception had hardly been used and hence had no relevance to the incidence of cancers. Over the years the number of gynaecological cancers is increasing, irrespective of social class, with more cases at younger age.

Adult↗
PubMed2002

Persistent organochlorine pesticide residues in milk and dairy products in India.

Monitoring of milk and dairy product samples of various brands from different cities in Maharashtra, India, was carried out to determine if there is any contamination due to organochlorine pesticide residues. The measurements were made using a gas chromatograph-electron capture detector system. Trace levels of DDT and HCH were detected in the samples. Total HCH levels in milk and milk product samples were lower than total DDT levels, which could be attributed to earlier extensive antimalaria sanitary activities. Butter had higher levels of DDT than cheese and milk powder. All levels of organochlorine pesticide residues in milk and milk products were well below the maximum permissible limits given by the FAO/ WHO. More importantly, as compared with an earlier report, present levels of the contaminants are substantially lower, which indicate the gradual phase out of these compounds.

Animals↗
PubMed2002

Assessing the diet of the British African-Caribbean population: frequency of consumption of foods and food portion sizes.

There is a very high prevalence of diet related disorders in the British African-Caribbean population but very few studies have determined associations between diet and disease within this community. There are virtually no published data on the frequency of foods consumed by this population or on the usual portion sizes which are necessary not only for nutritional epidemiological studies but also for treating diet related conditions such as diabetes. Here we present the frequency of foods consumed, assessed by a quantitative FFQ specifically developed for this sample, and the usual portion size reported by 210 randomly selected adult men and women. Frequency of consumption of foods and food portion sizes reported differed greatly from those consumed by the majority White population. This paper highlights the need to collect valid food consumption data for specific ethnic groups rather than using data available from another population, which is inappropriate. Such data will enable more precise dietary assessment and will further our understanding of the role of diet in the aetiology and prevention of diet-related diseases.

Black or African American↗
PubMed2002

A phase II trial of farnesyl protein transferase inhibitor SCH 66336, given by twice-daily oral administration, in patients with metastatic colorectal cancer refractory to 5-fluorouracil and irinotecan.

BACKGROUND: ras genes encode Ras proteins that are important for signal transduction in cancer cells. Farnesyl protein transferase (FPTase) is an enzyme that is responsible for a critical post-translational modification of Ras. PATIENTS AND METHODS: We report the results of a phase II trial of SCH 66336, an FPTase inhibitor, in patients with metastatic colorectal cancer. This is the first reported experience of an FPTase inhibitor in this disease. All patients were considered refractory to first- and second-line therapy. A total of 21 evaluable patients were treated with a starting dose of 200 mg b.i.d. given continuously. RESULTS: The major side-effects were fatigue (grade 1 in 42%, grade 2 in 42% and grade 3 in 14%), diarrhea (grade 1 in 23% and grade 3 in 42%) and nausea (grade 2 in 16%). Elevations in serum creatinine (grade 2 or 3) were observed in 19% of patients and appeared to be related to dehydration induced by diarrhea. Significant hematological toxicity was not observed (only grade 1 thrombocytopenia in 19% and grade 2 or 3 anemia in 28%). Pharmacological studies revealed adequate mean pre-dose plasma concentrations in this group of patients on day 15 of therapy. No objective responses were observed, although stable disease was seen in three patients for several months. Administration of SCH 66336 was accompanied by gastrointestinal toxicity. CONCLUSIONS: Future development of this compound cannot be recommended as monotherapy in this disease.

Administration, Oral↗
PubMed2002

Phase I study of weekly oxaliplatin plus irinotecan in previously treated patients with metastatic colorectal cancer.

BACKGROUND: In vitro synergy between Oxal (oxaliplatin) and CPT-11 (irinotecan) has been reported. Oxaliplatin exerts its antineoplastic activity through the formation of platinum-DNA adducts. Resistance to oxaliplatin is through repair of these adducts, which is inhibited by irinotecan. PATIENTS AND METHODS: Oxaliplatin and irinotecan were administered weekly for 4 weeks followed by a 2-week rest period. The dose of oxaliplatin was escalated first, starting at 30 mg/m(2). Once a dose of 60 mg/m(2) was attained, the weekly dose of irinotecan was escalated, from 40 mg/m(2) to 85 mg/m(2). A total of 49 previously treated patients with metastatic colorectal cancer were entered in order to establish the maximum tolerated dose. Pharmacokinetics of oxaliplatin and irinotecan were analyzed. RESULTS: Forty-nine patients were evaluable for toxicity. The recommended phase II doses for this combination are oxaliplatin 60 mg/m(2) and irinotecan 50 mg/m(2), weekly x 4 q 6 weeks. Diarrhea was the most common dose-limiting toxicity. No pharmacological interactions were noted between oxaliplatin and irinotecan. Twelve of the 47 evaluable patients (26%) achieved a partial response. CONCLUSION: Weekly combination of oxaliplatin and irinotecan appears to be a well tolerated and active regimen in patients previously treated for metastatic colorectal cancer. Further investigations of this regimen are warranted.

Adult↗
PubMed2002

Detection of root mucilage using an anti-fucose antibody.

Plant root mucilage is known to enhance soil quality by contributing towards the soil carbon pool, soil aggregation, detoxification of heavy metal ions and interactions with rhizospheric microflora. Mucilage consists of many monosaccharide units, including fucose which can be used as an indicator for plant root based polysaccharides. This is the first report of an immunological technique developed to use anti-fucose antibodies as markers for probing and localizing fucosyl residues in mucilage polysaccharide and, in turn, for localization of plant root mucilage. Fucose was complexed with bovine serum albumin to raise antibodies against fucose. A fucose-directed antibody was shown to cross-react with root cap mucilages from grasses. This antibody was used to localize root mucilage polysaccharide in maize and wheat root caps using immunogold electron microscopy. Abundant labelling could be localized on the cell wall, and in the intercellular matrix and vesicles of the peripheral root cap cells. Labelling was less intense in cells towards the centre of the root cap tissue. Control experiments confirmed that immunogold localization of fucose was specific and reliable.

Animals↗