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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 19 recordsLinked to original sources

Effect of 2,2'-dicarbomethoxylamino-5,5'-dibenzimidazolyl ketone on antioxidant defenses of Acanthocheilonema viteae and its laboratory host Mastomys natalensis.

The effect of the macrofilaricidal agent of 2,2'-dicarbomethoxylamino-5,5'-dibenzimidazolyl ketone (C.D.R.I. compound 82/437), on the metabolism of reactive oxygen species (ROs) in Acanthocheilonema viteae and Mastomys natalensis was measured following intraperitoneal administration at therapeutic doses. The recovered worms possessed substantially reduced levels of catalase and glutathione peroxidase (GPx), and thus were less able to detoxify H2O2. Nonetheless, the subcutaneous and adjoining muscle tissues, in which the parasites were lodged, exhibited elevated levels of antioxidant enzymes and reduced glutathione. It is concluded that compound 82/437 kills the filariid by paralysing its H2O2 detoxifying capacity without altering ROs metabolism in the tissue in which the parasite resides. Furthermore, since catalase and GPx of the liver and lungs do not show sign of inhibition, a difference appears to exist in the enzymes of the parasite and the host.

Animals

Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor beta 1.

In previous studies hepatocytes undergoing cell death by apoptosis but not normal hepatocytes in rat liver showed immunostaining for transforming growth factor beta 1 (TGF-beta 1). Staining was much stronger with antibodies recognizing the pro-region of TGF-beta 1 than the mature peptide itself. Therefore we investigated the ability of both forms of TGF-beta 1 to induce apoptosis in primary cultures of rat hepatocytes. Mature TGF-beta 1 induced rounding up of the cells and fragmentation into multiple vesicles. As revealed by the DNA-specific stain H33258, the chromatin of these cells condensed and segregated into masses at the nuclear membrane; this was obviously followed by fragmentation of the nucleus. Ultrastructurally the cytoplasm was well preserved, as demonstrated by the presence of intact cell organelles. These features strongly suggest the occurrence of apoptosis. Quantification of nuclei with condensed chromatin revealed that mature TGF-beta 1 was 30-fold more effective than the TGF-beta 1 latency-associated protein complex. Finally, we administered TGF-beta 1 in vivo using an experimental model in which regression of rat liver was initiated by a short preceding treatment with the hepatomitogen cyproterone acetate. Two doses of TGF-beta 1, each 1 nM/kg, augmented the incidence of apoptotic hepatocytes 5-fold. Equimolar doses of TGF-beta 1 latency-associated protein complex were ineffective. These studies suggest that TGF-beta 1 is involved in the initiation of apoptosis in the liver and that the mature form of TGF-beta 1 is the active principle.

Animals

L1 immunoreactivity in the developing fish visual system.

Previous studies have suggested that L1, the cell adhesion molecule, is present in the regenerating fish optic nerve. The present study was undertaken in order to determine whether L1 is expressed by fish neurons and specifically by non-myelinated axons, using fish retinal explants in vitro and the developing fish visual system in vivo. In vitro, the nonmyelinated axons emerging from retinal explants showed L1 immunoreactivity and in vivo, L1 immunoreactive sites were found to be associated with areas rich in non-myelinated axons. At embryonic stage 23, as the eye developed and optic nerve axons began to elongate towards the tectum, L1-like immunoreactivity was seen both in optic nerve and in plexiform layers of the retina. At this stage and until hatching, the cellular layers within the retina showed little or no staining relative to the layers containing axons or dendrites. After hatching, L1 immunoreactivity was also observed in the ganglion cell layer, but upon maturation both the retina and the optic nerve lost most of their L1 immunoreactivity. We therefore suggest that non-myelinated axons of the fish visual system express L1 during development, which is lost after myelination and presumably reappears during regeneration.

Animals

Balloon angioplasty for complete obstruction of inferior vena cava: needle puncture followed by balloon dilatation.

We report herein 2 cases with complete obstruction of the suprahepatic portion of the inferior vena cava successfully treated by balloon angioplasty after crossing the obstructing segment with the stiff end of the guidewire in 1 case and the Brockenbrough's trans-septal needle in the other. The gradients across the obstruction fell from 13 and 20 mm Hg to 3 and 4 mm Hg, respectively. Angioplasty resulted in dramatic clinical hemodynamic and angiographic improvement.

Adult

The usefulness of echocardiography in the surgical management of infants with congenital heart disease.

Between January 1988 and August 1991, at The Children's Heart Center, Atlanta, 83 infants with congenital heart defects were diagnosed by echocardiography and underwent surgery without cardiac catheterization. The diagnostic categories included 46 infants with left heart obstructive lesions, 19 infants with cyanotic heart lesions, and 18 infants with miscellaneous lesions. Forty-five infants (55%) underwent surgery under cardiopulmonary bypass. There were three errors in diagnosis, yielding a diagnostic accuracy of 95%. Many infants with congenital heart disease can be accurately and completely diagnosed by echocardiography and can safely undergo surgery without cardiac catheterization.

Aortic Coarctation

Low-molecular weight B cell growth factor (BCGF-12KD) as an autocrine growth factor in B cell chronic lymphocytic leukemia.

The role of cytokines in the growth and spreading of human hematologic malignancies has been underlined in recent years. Here we report evidence that a human 12-kDa B cell growth factor (BCGF-12KD) may function as a growth stimulatory factor in B cell chronic lymphocytic leukemia (B-CLL). First, recombinant BCGF-12KD induced dose-dependent DNA synthesis in neoplastic B cells of four B-CLL patients tested. Second, seven different B-CLL clones secreted a BCGF-12KD-like product that accounted for their proliferation. A neutralizing monoclonal antibody (mAb; Ac8) directed against a BCGF-12KD synthetic peptide inhibited the spontaneous growth of the leukemic B cells. The same mAb blocked DNA synthesis in normal tonsillar B lymphocytes induced by the culture supernatant of spontaneously proliferating B-CLL cells. Finally, BCGF-12KD mRNA was expressed in freshly isolated (two of three patients) as well as in vitro proliferating B-CLL cells (three of three patients). These findings strongly suggest that BCGF-12KD can modulate the growth of B-CLL cells in vivo as well as in vitro. They may offer significant insights into the biology of this frequent B lymphoproliferative disorder.

Adult

Ethanol enhances ADP-ribosylation of protein in rat hepatocytes.

Decreases in hepatocyte NAD+ produced by ethanol are only partially explained by the increased conversion of NAD+ to NADH and NADP+. The purpose of this study was to determine whether a mechanism for the ethanol-induced decrease in NAD+ is its increased use in ADP-ribosylation. Exposure of hepatocytes in culture for 2 hr to 100 mmol/L ethanol increased the incorporation of 14C-ribose from prelabeled NAD+ into 14C-ribosylated proteins. Poly (ADP-ribose) polymerase activity was increased by exposure of isolated hepatocytes to 100 mmol/L ethanol for 10 min. In hepatocyte culture, increases in poly (ADP-ribose) polymerase were not detected after exposure to 100 mmol/L ethanol for 10 min or 2 hr but rather occurred at 24 hr. Ethanol exposure of hepatocytes in culture for 2 hr, however, decreased the Km for NAD+ of poly (ADP-ribose) polymerase. Both nicotinamide and 5-aminobenzamide, which are inhibitors of poly (ADP-ribose) polymerase, prevented the decrease in NAD+ produced by 2-hr exposure of hepatocytes in culture to 100 mmol/L ethanol. The effect of ethanol in decreasing DNA synthesis on days 3 and 4 of culture was not reversed by the inhibitors of poly (ADP-ribose) polymerase. These results indicate that increased ADP-ribosylation of hepatocyte proteins is a mechanism for the effect of ethanol in decreasing NAD+.

Adenosine Diphosphate Ribose

Postoperative adjuvant chemotherapy for operable esophageal cancer: a pilot clinical study.

Thirty-eight patients with node positive squamous cell carcinoma of the esophagus were entered into a pilot clinical study using postoperative adjuvant chemotherapy (cisplatinum 100 mg/m2 and methotrexate 150 mg/m2 x 4 cycles) with an intent of improving cure rates and overall survival. Patient compliance was excellent and toxicity minimal. At 24 months of follow-up 22 patients (58%) were disease free, while 14 patients (37%) have relapsed and 2 were lost to follow-up. A highly significant correlation was noted between the number of nodes involved, the grade of the tumour, and the response to chemotherapy. Patients with poorly differentiated tumours and those with more than 4 nodes involved were more likely to develop recurrent disease (P less than 0.01 and P less than 0.005). We conclude that postoperative chemotherapy following resection for carcinoma of the esophagus is well tolerated with minimal side effects. It may also have an impact on improving disease free and overall survival.

Adult

Endobronchial brachytherapy: a preliminary experience.

Fourteen patients with malignant airway obstruction were treated with a placement of a flexible nylon catheter for low dose rate manual afterloading Iridium 192 endobronchial brachytherapy using a flexible fibreoptic bronchoscope. Eight patients had obstructive pneumonitis at initial presentation, while 6 cases were recurrences after previous external irradiation. Six evaluable patients of the former group had complete or partial reinflation of lung and were followed by external radiotherapy. Of the latter group, 3 were evaluable and had moderate to good palliation of their symptoms. No complication was observed. The technique is simple and safe with good patient compliance. Further evaluation is indicated to assess its role in the locoregional management of lung cancer.

Airway Obstruction

Functional results following esophagogastrectomy for carcinoma of the esophagus.

Fifty patients underwent esophagogastrectomy for histologically proven carcinoma of the esophagus from January to December 1989. The Ivor Lewis procedure was performed in 29 patients and 21 resections were performed by a left thoracoabdominal approach. There was one anastomotic leak which could not be salvaged and was responsible for the sole mortality within 30 days of surgery. The hospital stay averaged 12 days, ranging from 8-26 days. Swallowing was resumed by the 6th postoperative day for liquids and 8th day for soft solids. Following surgery, 5 patients developed dysphagia, 4 of whom responded to dilatation. The anastomosis was hand sutured in all cases except one. The suture material used had no relation to the incidence of leak or stricture formation. Eight patients complained of reflux that settled with medical management. Most patients were eating without dysphagia at the last follow-up or death. Esophagogastrectomy can be performed with a low morbidity and mortality and provides adequate palliation of the patient's most distressing symptom, dysphagia.

Adolescent

Sex differences in gastric alcohol dehydrogenase activity in Sprague-Dawley rats.

The effects of sex differences and of fasting on gastric alcohol dehydrogenase activity were determined in Sprague-Dawley rats. Gastric alcohol dehydrogenase activity and enzyme protein levels were higher in female than in male rats. Ovariectomy and orchiectomy had no effect on alcohol dehydrogenase and did not alter the sex difference in enzyme activity. Fasting decreased the enzyme activity more in female than in male rats, abolishing the sex difference. Serum gastrin levels measured in female rats decreased on fasting and returned to normal levels within 24 hours of refeeding. Short- and long-term administration of pentagastrin to fasted and fed female rats did not affect the enzyme activity or enzyme protein level, except for a transient increase in enzyme activity but not in enzyme protein level 12 hours after administration to fasted fats. Omeprazole, which increased serum gastrin levels and decreased enzyme activity but not enzyme protein levels, was found to be a competitive inhibitor of the enzyme with a Ki of 0.40 mmol/L. The mechanisms for the sex differences and changes with fasting in rat gastric alcohol dehydrogenase activity remain unknown.

Alcohol Dehydrogenase

Role of thioridazine in unexplained infertility.

A total of 452 women with unexplained infertility were selected for the present study. From them 310 women were put on thioridazine tablet (5 mg), 1 h after dinner from the 8th day of the menstrual cycle to the 18th day in each cycle. Coitus was advised about 1-2 h after the drug intake and proper posture was advised to the patients. The other 142 patients were given placebo therapy. Patients were followed up for pregnancy for 1 year which was confirmed by ultrasonographic examination. Ninety-four patients (30.2%) in the study group conceived in contrast to 22 (15.42%) in the control group (P less than 0.001). Incidence of abortions, congenital malformations and perinatal mortality and mode of delivery were not significantly different in the two groups. Thioridazine due to anxiolytic effect in low dosage appears to be promising in the treatment of unexplained infertility.

Adult

Effect of respiratory syncytial virus on adherence, colonization and immunity of non-typable Haemophilus influenzae: implications for otitis media.

Adherence of non-typable Haemophilus influenzae to respiratory epithelium was evaluated in a cotton rat model of respiratory syncytial virus (RSV) infection. Colonization with non-typable H. influenzae increased to a maximum within 4 days of RSV infection compared to RSV negative controls (4.58 +/- 0.17 vs 3.82 +/- 0.23 log colony forming units (CFU) per ml, P less than 0.05) and then declined over the subsequent 10 days (2.0 +/- 0 vs 3.78 +/- 0.39 CFU per ml, P less than 0.0001). In a second series of experiments, attachment of non-typable H. influenzae to epithelial cells collected from RSV infected cotton rats at the time of maximum virus replication was not different from controls (57.4 +/- 18.3 vs 52.0 +/- 24.3 bacteria per 50 cells). Systemic immunity to non-typable H. influenzae as measured by IgG-specific antibody to the outer membrane complex and bactericidal antibody did not influence colonization. These data suggest that colonization with non-typable H. influenzae is significantly affected by a concurrent infection with RSV; however, the site of bacterial attachment is not known.

Animals

Infective endocarditis following balloon dilatation of mitral valve.

Three cases of infective endocarditis were encountered following balloon dilatation of the mitral valve. The diagnosis was difficult due to negative blood cultures and nondiagnostic transthoracic echocardiogram, the latter the consequence of the preexisting severe rheumatic valvar disease. Transoesophageal echocardiography proved superior in diagnosis. The possible causes and means of preventing this potentially lethal complication are discussed.

Adolescent