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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 55 records · Page 3Linked to original sources

Efficacy of a hospital based cytology screening program.

From 1976 to 1986, a total of 117,471 women attending gynecologic outpatient departments of six hospitals in Delhi, India, were screened cytologically. The cytodiagnosis revealed 30,399 (25.9%) normal finding, 84,889 (72.3%) inflammatory changes, 1910 (1.6%) dysplasia of various grades and 213 (0.2%) malignant lesions. Of the 213 cases detected as malignant, clinical suspicion of cervical cancer was not present in 125 women (58.7%). Histologically malignancy was confirmed in 192 women (90.1%) of the 213 cytologically diagnosed malignant cases. The diagnosis revealed 94 (49.0%) as carcinoma in situ and the rest of the cases were invasive lesions. This was in contrast to only 5.2% (10/194) of cases with carcinoma in situ seen at the cancer clinic during 1983-1986 in one of the major collaborating hospitals of Delhi. The analysis of data according to age revealed that median age at detection of mild/moderate, severe dysplasia, carcinoma in situ (CIS) and invasive cancers was 34.0, 37.9, 38.6, and 47.8 years, respectively, indicating a latency period of one and a half decade from the onset of precursor lesions to invasive disease. Mass population screening in our country is not feasible in the near future and this may be true also for other developing countries. In its absence cytological screening of patients attending hospitals and maternity homes can give a large yield of early cervical cancers, which are curable.

Adult

Antifilarial activity of Centratherum anthelminticum seed extracts on Setaria cervi.

Effect of aqueous and alcoholic extract of C. anthelminticum was studied on the spontaneous movements of the whole worm and nerve-muscle preparation of S. cervi. Ethylacetate, acetone and methanol extract showed similar effect, of causing inhibition of spontaneous motility of the nerve-muscle preparation of S. cervi characterized by decreased amplitude and frequency of contractions. The inhibitory effect on the motility was reversible. Further, the extracts did not involve the blockade of cholinergic receptors as evidenced by the presence of unaltered stimulant response of acetylcholine in the presence of drug in bathing fluid.

Animals

The prognostic significance of ploidy analysis in operable breast cancer.

The nuclear DNA content of 98 operable breast cancers was determined by flow cytometric analysis using paraffin-embedded tissue. All patients were on follow-up and failure of treatment or recurrences were identified. DNA ploidy data in the form of ploidy status and DNA index (DI) has been correlated with various clinical and histopathologic factors. The only significant correlation using univariate analysis exists between the histologic grade and DI (P less than 0.025), recurrence of the disease and ploidy status (P less than 0.005), and recurrence of the disease and DI (P less than 0.005). The absence of correlation of ploidy status with other tumor derived factors indicates the independent nature of ploidy as a prognostic factor. Multivariate analysis showed that in the whole-group ploidy (P less than 0.01), tumor margin (P less than 0.01), and menopausal status (P less than 0.01) were significant factors in the order mentioned. DI with a cut of at 1.29 is not found to be a significant factor in the multivariate analysis. The maximum prognostic value of ploidy status was observed in the postmenopausal group (P less than 0.0005). In the node-negative group ploidy status (P less than 0.05) is the only independent significant factor predicting for early relapse. It is concluded that ploidy status is an independent prognostic factor predicting for recurrence of the disease. In the node-negative subgroup this could be used to identify the subset of patients who may benefit from adjuvant treatment.

Breast Neoplasms

Loss of transforming growth factor beta 1 receptors and its effects on the growth of EBV-transformed human B cells.

Transforming growth factor-beta (TGF-beta) is a potent negative regulator of normal human B cell growth mediated by exogenous signals, including IL-2 and low m.w. B cell growth factor 12 kDa (BCGF-12 kDa). In the present study, we investigated the regulatory linkage between viral or nonviral transformation of human B cells and the growth inhibitory effects of TGF-beta 1. A panel of EBV+ and EBV- B cell lines, derived either by in vitro EBV B cell transformation, or from cases of lymphoma was used to quantitate the negative growth effects of TGF-beta 1. The proliferative response of three EBV- B cell lines to rBCGF-12 kDa or serum was inhibited by low concentrations of TGF-beta 1 (0.2-0.5 ng/ml for 50% maximal effect), as measured by tritiated thymidine uptake and viable cellular recovery. In contrast, rBCGF-12 kDa or serum mediated proliferation of three EBV+ B cell lines was refractory to the growth inhibitory effects of TGF-beta 1. In an attempt to understand the mechanism(s) for this differential growth control in EBV+ and EBV- B cells, we studied the expression of TGF-beta 1, c-myc, and TGF-beta 1 receptors. No correlation was observed between the expression of TGF-beta 1 or c-myc gene and growth inhibition by TGF-beta 1 in the cell lines studied. Our results indicate that sensitivity or resistance to TGF-beta 1 correlated with the presence or absence (loss) of high affinity receptors for TGF-beta 1. EBV- B cell lines expressed levels of high affinity receptors similar to those found on activated normal B or T cells. In contrast, EBV+ B cell lines showed no detectable high affinity receptors. Chemical cross-linking studies with a bifunctional reagent, dissuccinimidyl suberate revealed a normal expression of type I (65-70 kDa), type II (85-90 kDa), and type III (280-300 kDa) TGF-beta 1 high affinity receptors on EBV- B cell lines. In contrast, EBV+ B cell lines did not express type I and type II receptors, whereas type III receptors were expressed but could not be inhibited by unlabeled TGF-beta 1.(ABSTRACT TRUNCATED AT 400 WORDS)

B-Lymphocytes

Epitope mapping by mutagenesis distinguishes between the two tertiary structures of the histidine-containing protein HPr.

Thirty-four of the 85 residues of the histidine-containing protein HPr of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system have been changed by site-directed mutagenesis. Many of the mutations have wild-type activity suggesting an unaltered tertiary structure but have altered binding to three monoclonal antibodies: Jel42, Jel44, and Jel323. This altered binding defines the residues that are involved in the epitopes of HPr. At present, two different three-dimensional structures have been determined for HPr, one from two-dimensional nuclear magnetic resonance spectra and the other from x-ray diffraction of HPr crystals. The epitope mapping for Jel42 does not distinguish between the tertiary structures. However, only the HPr structure derived from two-dimensional nuclear magnetic resonance spectra is consistent with a contiguous surface binding site that can be defined as the epitope for Jel44. Thus the x-ray structure may represent a partially unfolded HPr.

Amino Acid Sequence

Physical characterization of isozymes of endo-beta-1,4-glucanase and beta-1,4-glucosidase from Aspergillus species.

Electrophoretic data revealed the presence of various isozymes of endoglucanase and beta-glucosidase, the number of which varied from one to three in various species of the genus Aspergillus. pH 5.0 was optimum for all the isozymes whereas metal ion treatment showed complete inhibition of almost all the isozymes by Hg2+ and partial inhibition by Ca2+ and Co2+ of isozymes of both the enzymes. An alteration in the electrophoretic mobility of isozymes of beta-glucosidase was also noticed in some species with Hg2+ treatment.

Aspergillus

Concurrent double balloon valvotomy for combined rheumatic mitral and tricuspid stenosis.

We expanded the application of percutaneous balloon valvotomy (PBV) to 4 adults (age 14 to 30 years, average 22.2 years) with combined rheumatic mitral and tricuspid stenosis. Double balloon dilatation reduced the transmitral gradient from 17.36 +/- 3.54 to 5.52 +/- 0.89 (P less than 0.025) and transtricuspid gradient from 12.65 +/- 2.67 to 3.67 +/- 0.95 (P less than 0.025). Mitral and tricuspid valve area increased from 0.73 +/- 0.20 to 2.57 +/- 0.67 (P less than 0.005) and from 0.77 +/- 0.24 to 2.67 +/- 0.24 cm2 (P less than 0.005), respectively. The procedures were well tolerated, with no significant increase in valvular regurgitation or left to right shunt across the atrial septum. The excellent symptomatic and haemodynamic benefits are sustained at 3-24 months follow-up. It is concluded that combined dilatation of stenotic valves by double balloon technique can emerge as an alternative to surgery in selected patients with polyvalvar rheumatic heart disease.

Adolescent

Differential inhibition of interleukin 2- and interleukin 4-mediated human B cell proliferation by ionomycin: a possible regulatory role for apoptosis.

Surface immunoglobulin (Ig) cross-linking by anti-IgM (mu) antibodies leads to B cell activation resulting in numerous early biochemical events including an increase in intracellular [Ca2+]. Furthermore, anti-mu-activated B cells become able to proliferate in response to interleukin (IL)2 and IL4. These studies examined the effect of the calcium ionophore ionomycin, an enhancer of cytoplasmic [Ca2+] levels, on IL2 and IL4-mediated proliferation of anti-mu-stimulated normal human B cells. Ionomycin inhibited the proliferative response of anti-mu-activated B cells to IL4. In contrast, IL2 and phorbol 12,13 dibutyrate (PBu2)-mediated B cell proliferation was refractory to the growth inhibitory effects of ionomycin. In an attempt to delineate a possible mechanism(s) for this differential growth effect of ionomycin, we first studied direct effects of ionomycin on activated B cells. Our data suggested that ionomycin induced DNA fragmentation in anti-mu-costimulated B cells. Interestingly, in contrast to PBu2, IL4 did not prevent ionomycin-dependent DNA fragmentation. Importantly, H7, an inhibitor of protein kinase C activation, down-regulated only the IL2 and PBu2-driven B cell proliferation but not B cell proliferative response to IL4. These results suggest that putative protein kinase C activation, either by direct treatment with phorbol ester or during IL2 signaling, counteracts the inhibitory effects of ionomycin. In contrast, IL4 signaling does not exhibit the same protective properties.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Thoracoscopy in the diagnosis of pleural effusion of ambiguous etiology.

Between 1985 and 1989, 27 patients underwent thoracoscopy for an undiagnosed pleural effusion. Prior thoracocentesis (in all patients) and a needle pleural biopsy (in 15 patients) had been nondiagnostic. The rigid thoracoscope was used in 21 patients, the cystoscope in 4 patients, and the flexible bronchoscope in 2 patients. We had one mortality, and there was no operative morbidity. Thoracoscopy was diagnostic in 24 of the 27 patients (4 benign, 20 malignant). The average duration of stay in the hospital was 48 hr. We conclude that thoracoscopy is an important diagnostic aid in the management of a pleural effusion of ambiguous origin and that it is a relatively safe procedure that can be performed with an acceptable morbidity and mortality.

Aged

Guinea pig proacrosin is synthesized principally by round spermatids and contains O-linked as well as N-linked oligosaccharide side chains.

Proacrosin is the zymogen precursor of acrosin, a sperm protease believed to play an essential role in fertilization. In this study, we used primary cultures of guinea pig spermatogenic cells to examine the temporal appearance and mechanisms of synthesis and processing of proacrosin during acrosome development. Following [35S]methionine incorporation and immunoprecipitation, cultured spermatogenic cells were found to synthesize two forms of proacrosin (Mr 54,000 and 57,000). Proacrosin was synthesized mainly by round spermatids. By immunoblotting, proacrosin became very prominent in round spermatids and persisted throughout spermiogenesis. Pulse-chase experiments demonstrated that the Mr 54,000 form of proacrosin was converted to the Mr 57,000 form, presumably reflecting posttranslational processing of carbohydrate side chains. When spermatogenic cells were cultured in the presence of tunicamycin, the synthesized proacrosin had an Mr of 54,000. However, in vitro translation of mRNA extracted from guinea pig testis followed by immunoprecipitation indicated that the core polypeptide of proacrosin has an Mr of 44,000. Guinea pig spermatogenic cells incorporated glucosamine and fucose into the oligosaccharides of proacrosin. Treatment of guinea pig testis proacrosin with N-glycosidase or O-glycosidase reduced the Mr by 3-7%. These results indicate that proacrosin is synthesized by postmeiotic cells and the enzyme contains N- and O-linked oligosaccharides.

Acrosin

Maturation of guinea pig sperm in the epididymis involves the modification of proacrosin oligosaccharide side chains.

Proacrosin from guinea pig cauda epididymal sperm has a lower molecular weight compared with the testicular zymogen. In this study, we have examined the structural basis of this change and where the conversion in proacrosin molecular weight occurs during sperm maturation. Immunoblotting of trifluoromethanesulfonic acid-deglycosylated testicular and cauda epididymal sperm extracts with antibody to guinea pig testicular proacrosin demonstrated that the polypeptide backbones of proacrosins from the testis and cauda epididymal sperm had the same molecular weights (approximately 44,000). Keratanase, an endo-beta-galactosidase specific for lactosaminoglycans, partially digested testicular proacrosin but had no effect on proacrosin from cauda epididymal sperm. In extracts of testis, caput epididymis, and corpus epididymis analyzed by immunoblotting, anti-proacrosin recognized a major antigen with an apparent molecular weight (Mr) of 55,000, although a 50,000-Mr minor antigen began to appear in the corpus epididymis. By contrast, extracts of cauda epididymis, vas deferens, and cauda epididymal sperm had the 50,000 Mr protein as the only immunoreactive antigen. By enzymography following electrophoresis, the major bands of proteolytic activity in extracts of testis, caput epididymis, and corpus epididymis had 55,000 Mr. A band of protease activity with 55,000 Mr also appeared in extracts of the corpus epididymis. However, the most prominent bands of proteolytic activity in cauda epididymis, vas deferens, and cauda epididymal sperm had 50,000 Mr. In addition, two other major protease activities were detected with 32,000 and 34,000 Mr; the relationships of these proteases to proacrosin are unclear. From these results, we conclude that the oligosaccharides of proacrosin are altered during epididymal transit and that this modification occurs in the corpus epididymis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosin

Serum soluble interleukin-2 (IL-2) receptor levels in women with breast carcinoma and its correlation with IL-2 receptor expression on blood lymphocytes and lymphocytic infiltration within the tumour.

This study describes serum levels of soluble interleukin-2 receptor (sIL-2R) in 13 healthy women, 10 women with breast dysplasia and 37 patients with breast carcinoma. A difference was found between sIL-2R levels in normal women and cancer patients. sIL-2R increased with the advance in stage of cancer but the extent of increase fell from stage III to stage IV as compared to the change from stage II to stage III. Of the 15 patients who were followed after surgery and/or therapy, 10 (67%) showed a fall in the serum sIL-2R levels. A negative correlation was found between sIL-2R levels and lymphocytic infiltration only within the malignant tissue. These findings probably indicate that sIL-2R exerts an immunomodulatory effect on blood lymphocytes by preventing their infiltration into the tumour tissue. To our knowledge, this is the first report of its kind in immunology of breast carcinoma.

Adolescent

Altered hemolysin production in urine-grown uroisolates of Escherichia coli.

Fifteen uroisolates of E. coli were studied for both cell-free and cell-bound hemolysin production. Estimations were done in Trypticase soy broth (TSB, providing iron-replete medium) TSB + 2,2'-bipyridine (providing experimentally created iron-depleted conditions) and pooled normal human urine (providing natural iron-depleted growth medium). In TSB 40% of strains showed no detectable cell-free hemolysin, they were able to produce it in the presence of 2,2'-bipyridine and more so when grown in urine. The cell-bound hemolysin was produced by all the strains in TSB, but in the presence of 2,2'-bipyridine and urine an insignificant increase was observed. All the strains when given 2nd and 3rd passage in urine, were found to elaborate significantly more cell-free as well as cell-bound hemolysin.

Bacterial Proteins