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Biomedical subjects

A Mishra

Publications and source records attributed to A Mishra.

At least 91 records · Page 5Linked to original sources

Evidence for the involvement of a species-specific embryonic protease in zona escape of hamster blastocysts.

The source and nature of zona lytic factors during zona escape of hamster blastocyts were investigated. When cultured in hamster embryo culture medium (HECM)-2h, all 8-cell embryos (n = 135) developed to zona escaped-blastocysts with complete zona lysis. In addition, 2-cell embryos, when co-cultured with zona escaping-blastocysts (at a ratio of 1:10), exhibited zona lysis. Various other embryos at the 1-8-cell stages also showed zona lysis when cultured with zona-escaping blastocysts. However, zonae from mice, rats, sheep and humans were resistant to lysis under these conditions. Pronase treatment resulted in rapid zona lysis in hamsters (7 +/- 1 s), whereas in other species zona lysis was much slower: mouse (662 +/- 27 s), rat (532 +/- 16 s), sheep (120 +/- 12 s) and human (104 +/- 8 s). When cysteine protease inhibitors (antipain, leupeptin, E-64 and p-hydromercuricbenzoate) were tested, they completely inhibited zona escape, while trypsin inhibitors (TLCK and SBTI) did not. Uterine zona lysin contribution in zona escape was discounted since: (i) uterine luminal flushing and endometrial extract from day 4 (the time of zona escape in vivo) pregnant females failed to lyse zonae and (ii) endogenous oocytes and transferred 2-cell embryos (to day 3 pseudopregnant recipients) were all zona-intact, while 71% of transferred blastocysts exhibited zona escape, following their recovery after 24 h. These observations suggest that a species-specific, embryonic proteolytic factor, with a cysteine protease-like activity, is involved in the zona escape of blastocysts in hamsters.

Animals↗

Bleomycin-mediated pulmonary toxicity: evidence for a p53-mediated response.

Bleomycin damages DNA and causes lung injury and fibrosis. To determine whether bleomycin is associated with the appearance of DNA damage-inducible proteins, C3H mice received either 0.4 mg bleomycin or normal saline intratracheally and were killed 1 to 14 d later. The lungs were examined for expression of p53, p21(WAF1/PiCl), and proliferating cell nuclear antigen (PCNA) using immunohistochemistry and Western blotting. p53-positive cells first appeared at 5 d after treatment and peaked at 7 d; PCNA-positive cells appeared at 1 d after treatment and peaked at 7 d; and p21-positive cells appeared at 5 d and peaked at 9 d. Western blot analysis confirmed that bleomycin upregulated the DNA damage-inducible proteins in a similar fashion. This is the first evidence that bleomycin causes a p53-dependent response associated with acute injury in the lung.

Animals↗

Oropharyngeal foreign body.

An unusual extremely benign course of an 8 cm long, rusting, metallic oropharyngeal foreign body that had entered post-aurally (penetration injury) four years previously to lie completely within the pharyngeal lumen has not yet been reported in the world literature. The need for additional investigations and special precautions to be taken during surgical extraction are highlighted.

Accidents↗

Plasma levels of orally and subcutaneously administered pentoxifylline in rabbits.

In addition to its ability to improve microcirculation, pentoxifylline also has anti-tumor necrosis factor-alpha (TNF) actions which have prompted investigations into its potential efficacy in disease states involving elevated TNF levels. One such disease entity is AIDS where aberrant TNF seems to mediate axonal degeneration within thecentral nervous system. To this end, we have previously established a rabbit model of TNF-mediated axonal degeneration, and demonstrated that pentoxifylline attenuates this effect. Unfortunately, there has been to date only one limited report on the pharmacokinetics of pentoxifylline in rabbits. Therefore, the present report evaluates plasma levels of pentoxifylline and two of its primary metabolites through high-performance liquid chromatography after both the oral and subcutaneous administration of pentoxifylline. Our results indicate that in rabbits there is a very rapid absorption and metabolism of pentoxifylline after either oral or subcutaneous administration. In comparison with the mouse, the rabbit seems to absorb and metabolize pentoxifylline slower. In contrast to man, the rabbit had lower metabolite plasma levels than the parent drug itself.

Administration, Oral↗

Biotransformation of banana waste into protein by pleurotus sajor-caju.

Pseudostems and leaves from banana waste were used for biotransformation into protein by using P. sajor-caju, an oyster mushroom. Treatment of formalin (500 ppm) + carbendazim (12.5 ppm) of these substrates was found to favour relatively high percentage biological efficiency (BE) of P. sajor-caju.. Steam sterilization also exhibited comparable yield performance by P. sajor-caju. Fruiting bodies harvested from all the treatments had relatively higher protein contents. The spent substrate (steam sterilized) was found to be suitable as an ideal animal feed because of its rich nutritive composition.

Biodegradation, Environmental↗

Glutathione reduces the toxicity associated with antitumor therapy of ascites fluid adsorbed over Staphylococcus aureus Cowan I in tumor bearing mice.

It has been well documented in the literature that the removal of circulatory immune complexes (CICs) from the host circulation leads to the immunopotentiation as well as generation of antitumor responses in a variety of tumors in rats, cats, dogs and human patients. CICs are the major immunosuppressive factors in tumor bearing host. Protein A (PA) has been extensively used for the removal of these CICs from the sera/plasma of tumor bearers, because PA has the ability to bind with the Fc portion of mammalian immunoglobulins. Previously, we reported for the first time a potent antitumor response by the inoculation of cell free Ehrlich's ascites fluid adsorbed in vitro over PA containing Staphylococcus aureus Cowan I (SAC) in Ehrlich's ascites tumor model. However, there was toxicity associated with this form of therapy in terms of early death of treated animals and the depletion of hepatic glutathione pool as well as phase I biotransformation enzyme and increase in glutathione-S-transferase (GST) activities. In the present investigation, tumor bearing animals were treated intraperitoneally (i.p.) on alternate days for 15 days with adsorbed ascites fluid (ad-ASF) (0.1 ml) and glutathione (GSH) (250 mg/kg body weight) separately. We found that GSH supplementation increases mean survival time of GSH and ad-ASF treated mice up to 37.2 days in comparison with 19.9 days for only ad-ASF treated animals, while percent increase in body weight was found to be not affected by the GSH substitution, which remains significantly lower (P < 0.01) in comparison to the tumor control animals. GSH supplementation causes a significant decrease (P < 0.05) of glutathione-S-transferase and restoration of aniline hydroxylase activity (P < 0.05) and aminopyrine-N-demethylase activity. We have also observed that GSH supplementation does not alter the tumor cell viability and tumor cell counts in ad-ASF treated animals in comparison to only ad-ASF treated animals, which indicates that GSH supplementation does not alter the antitumor effect of the therapy. Treatment of Ehrlich's ascites tumor bearing mice with ad-ASF and glutathione increased their survival, but did not reduce the mortality of animals because of tumor.

Adsorption↗

Safety and efficacy of total thyroidectomy in hands of endocrine surgery trainees.

BACKGROUND: Fear of a high complication rate of total thyroidectomy, especially in the hands of less experienced surgeons, limits its routine use. The results of total thyroidectomy in the hands of endocrine surgery trainees and consultants were compared to know whether this procedure can be performed effectively and safely by trainees. METHODS: Medical records of 232 patients who underwent total thyroidectomy from 1990 to 1997 were reviewed. Patients were put into groups A (operated by consultants) and B (trainees). Safety (postoperative hypoparathyroidism, recurrent laryngeal nerve palsy, and hemorrhage) and efficacy (postoperative radioactive iodine uptake) in the two groups were compared. RESULTS: There were 127 patients in group A and 105 in group B. Rates of occurrence of permanent hypoparathyroidism and recurrent laryngeal nerve palsy were comparable in the two groups. Postoperative radioactive iodine uptake in the two groups was not significantly different. CONCLUSIONS: Total thyroidectomy can be safely and effectively performed by endocrine surgical trainees.

Adult↗

Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function.

OBJECTIVES: To evaluate the erectile function (EF) domain of the International Index of Erectile Function (IIEF) as a diagnostic tool to discriminate between men with and without erectile dysfunction (ED) and to develop a clinically meaningful gradient of severity for ED. METHODS: One thousand one hundred fifty-one men (1035 with and 116 without ED) who reported attempting sexual activity were evaluated using data from four clinical trials of sildenafil citrate (Viagra) and two control samples. The statistical program Classification and Regression Trees was used to determine optimal cutoff scores on the EF domain (range 6 to 30) to distinguish between men with and without ED and to determine levels of ED severity on the EF domain using the IIEF item on sexual intercourse satisfaction. RESULTS: For a 0.5 prevalence rate of ED, the optimal cutoff score was 25, with men scoring less than or equal to 25 classified as having ED and those scoring above 25 as not having ED (sensitivity 0.97, specificity 0.88). Sensitivity analyses revealed a robust statistical solution that was well supported with different assumed prevalence rates and several cross-validations. The severity of ED was classified into five categories: no ED (EF score 26 to 30), mild (EF score 22 to 25), mild to moderate (EF score 17 to 21), moderate (EF score 11 to 16), and severe (EF score 6 to 10). Substantial agreement was shown between these predicted and "true" classes (weighted kappa 0.80). CONCLUSIONS: The EF domain possesses favorable statistical properties as a diagnostic tool, not only in distinguishing between men with and without ED, but also in classifying levels of ED severity. Clinical validation with self-rated assessments of ED severity is warranted.

Erectile Dysfunction↗

Chemokines and chemokine receptors: their role in allergic airway disease.

One of the hallmarks of allergic pulmonary disorders is the accumulation of an abnormally large number of leukocytes including eosinophils, neutrophils, lymphocytes, basophils, and macrophages in the lung. There is now substantial evidence that eosinophils, under the control of T lymphocytes, are major effector cells in the pathogenesis of asthma. Therefore, understanding the mechanisms by which eosinophils accumulate and are activated in tissues is a fundamental question very relevant to allergic diseases. Another characteristic of allergic inflammation is the activation of leukocytes resulting in the release of biologically active mediators, such as histamine from mast cells and basophils. It is now apparent that chemokines are potent leukocyte chemoattractants, cellular activating factors, histamine releasing factors, and regulators of homeostatic immunity, making them particularly important in the pathogenesis of airway inflammation in asthma. In this regard, chemokines are attractive new therapeutic targets for the treatment of allergic disease. This article focuses on recently emerging data on the importance of chemokines and their receptors in allergic airway inflammation.

Animals↗

Acute pancreatitis associated with viral hepatitis: a report of six cases with review of literature.

Association of hepatitis viruses with acute pancreatitis in the setting of nonfulminant viral hepatitis is rare. We report six cases of nonfulminant viral hepatitis complicated by acute pancreatitis, including the first documented case of hepatitis E virus (HEV) associated acute pancreatitis. The other five patients had acute viral hepatitis caused by hepatitis A infection. Besides features of viral hepatitis, the presence of typical abdominal pain, high serum amylase, and ultrasound or CT scan features suggested the diagnosis of acute pancreatitis. This complication generally developed in the initial phase of the hepatitic illness. All of the patients had mild to moderate pancreatitis that recovered uneventfully with conservative treatment.

Acute Disease↗

Fundamental signals that regulate eosinophil homing to the gastrointestinal tract.

The histological identification of increased eosinophils in the gastrointestinal tract occurs in numerous clinical disorders; however, there is a limited understanding of the mechanisms regulating eosinophil trafficking into this mucosal surface. The results presented in this study characterize the processes regulating eosinophil homing into the gastrointestinal tract at baseline. Eosinophils were found to be present in the lamina propria of 19-day-old embryos and germ-free adult mice at concentrations comparable to those present in non-germ-free adult mice. Furthermore, eosinophil gastrointestinal levels were not altered by increasing circulating eosinophils after pulmonary allergen challenge. Gastrointestinal eosinophil levels were partially reduced in mice deficient in recombinase activating gene-1 (RAG-1), IL-5, or the beta common chain (betac), but these reductions paralleled reductions in circulating eosinophils. In contrast, mice deficient in eotaxin had a marked reduction in gastrointestinal eosinophils but normal levels of eosinophils in the hematopoietic compartments. Furthermore, eotaxin was important for regulating eosinophil levels, even in the presence of high levels of IL-5. These investigations demonstrate eosinophil homing into the gastrointestinal tract during embryonic development occurring independently of viable intestinal flora. Furthermore, eotaxin is identified as the primary regulator of eosinophil gastrointestinal homing under homeostatic states, and may therefore have a fundamental role in innate immune responses.

Allergens↗

The effects of erythromycin on the electrocardiogram.

BACKGROUND: Various cardiac electrophysiologic effects have been attributed to erythromycin. During the course of treating a pneumonia patient with IV erythromycin, the conversion of atrial fibrillation to a sinus rhythm, and its subsequent reversal, appeared to be causally related to the introduction and cessation of this antibiotic. OBJECTIVE: This observation suggested the need for studying the changes in the ECG following the use of IV erythromycin in a typical clinical setting. DESIGN: A prospective comparative drug study. SETTING: A university-affiliated teaching hospital. PATIENTS: Nineteen patients being treated for uncomplicated community-acquired pneumonia. INTERVENTION: IV erythromycin, 500 mg, and/or IV cefuroxime, 750 mg, infused in 250 mL of saline over 20 min. In the 11 patients who were receiving both of the antibiotics, cefuroxime was administered immediately before erythromycin was infused. MEASUREMENTS: The 12-lead ECG measurements were obtained before infusion, at 5-min intervals during each infusion, and at 5 and 10 min after the infusions had been completed. All of the ECG complexes and intervals were measured using a software program (Interpretive Cardiograph; Hewlett Packard; Palo Alto, CA). RESULTS: The administration of IV erythromycin increased heart rate and prolonged the corrected QT (QTc) interval. These changes were significant at 15 min of the infusion, and were no longer evident 5 min after the infusion had been stopped. The administration of IV cefuroxime did not produce any ECG changes. CONCLUSIONS: A single, standard dose of IV erythromycin prolongs the QTc interval; therefore, the drug should always be administered as a slow infusion. ECG monitoring should accompany erythromycin therapy in critically ill patients, in patients with electrolyte disorders, or in patients taking other drugs with similar cardiac effects.

Adult↗

Protein-A activates membrane bound multicomponent enzyme complex, NADPH oxidase in human neutrophils.

Protein-A, 42KD cell wall glycoprotein of S. aureus Cowan I enhance mononuclear and polymorphonuclear cell counts in vivo and possesses antitoxic, antitumor, properties. In order to explain the mechanism of its function, the respiratory burst phenomenon in cell and cell free system was studied using lucigenin-dependent chemiluminescence technique. A dose dependent increase in protein A-mediated generation of superoxide radical was observed in resting and PMA stimulated neutrophils. Superoxide dismutase (SOD) was used to confirm the production of superoxide radicals (O2-). To understand the mechanism of protein-A induced O2- generation; NADPH oxidase activity was measured in cell free system using NADPH as a substrate. A significant increase in NADPH oxidase activity was observed in the membrane and post-nuclear supernatant fraction of activated human neutrophils. Cytosolic fraction showed slight enzyme activation. Protein A (SpA)-induced NADPH oxidase activation in the membrane fraction was observed even in the absence of the substrate NADPH. These data indicate that protein A attenuate the NADPH oxidase system to produce O2- radicals.

Acridines↗

Ehrlich's ascites fluid adsorbed over protein A containing Staphylococcus aureus Cowan I produces inhibition of tumor growth.

Our earlier studies have shown that removal of various blocking factors from the sera of tumor-bearing animals and humans by adsorption over heat-attenuated and formalin-fixed-Staphylococcus aureus Cowan I (SAC) containing Protein A (PA) causes antitumor immune response. It was also shown that this procedure caused regression of a wide variety of established animal and human tumors. In the present investigation, the therapeutic potential of inoculation of ascites fluid adsorbed in vitro over non-viable SAC containing PA has been demonstrated in Ehrlich' s ascites tumor (EAT) in mouse. The antitumor effect was evident by a significant decrease in body weight (p<0.001) as well as significant reduction in viability of ascites tumor cells (p<0.001) in peritoneal cavity. However, some of the responding animals died earlier than controls, this may be due to the toxicity associated with therapy. The toxic effects were evident in decreased contents of glutathione, and increased activity of glutathione-S-transferase, decreased activity of microsomal enzymes and also in an early death of some of tumor regressed animals. The probable causes of toxicity of the therapy and prospects of reversing these toxic effects are discussed.

Albinism↗

Successful development in vitro of hamster 8-cell embryos to 'zona-escaped' and attached blastocysts: assessment of quality and trophoblast outgrowth.

The peri-implantation development involves zona escape (hatching) of blastocysts and their attachment and proliferation. These events are difficult to study in vivo, so in this study hamster 8-cell embryos were cultured through the hatched and attached blastocyst stages using different formulations of hamster embryo culture medium (HECM)-2. Supplementation of succinate, amino acids, vitamins (inositol, pantothenate, choline chloride) and bovine serum albumin (BSA) to HECM-2 supported 100% development of 'zona-escaped' blastocysts. In this medium (designated as hatching, i.e. HECM-2h) all blastocysts invariably deflated and escaped from focally lysed zonae, which underwent complete dissolution. In their presence, pre-morula stage embryos also escaped from zonae. Omission of BSA from HECM-2h failed to support zona escape whereas that of vitamins reduced zona escape (34.0% +/- 7.0). Blastocysts with the potential to undergo zona escape in HECM-2h were of high quality as they had a higher mean cell number (MCN) than the MCN of those developing in BSA-free HECM-2h (35.2 +/- 1.6 v. 24.3 +/- 1.1). Cell allocation (i.e. trophectoderm to inner cell mass ratio) in blastocysts remained unaltered in both media (2.6 +/- 0.2 v. 2.7 +/- 0.2). Supplementation of 10% bovine fetal serum (BFS) to HECM-2h was detrimental to the development of blastocysts (22.3% +/- 7.4) and none of them underwent zona escape. Interestingly, BFS was required either as a supplement to the medium or as a coating on dishes for azonal blastocysts to attach (> or = 70%) and exhibit trophoblast (TB) outgrowth (30.3 x 10(3) +/- 2.9 x 10(3) micron 2 at 48 h). These results show that HECM-2h supports maximal development of zona-escaped blastocysts with the potential to attach and exhibit TB outgrowth, and there is a developmental stage-specific requirement for serum during peri-attachment in hamster development.

Animals↗

Polylysine-Gd-DTPAn and polylysine-Gd-DOTAn coupled to anti-CEA F(ab')2 fragments as potential immunocontrast agents. Relaxometry, biodistribution, and magnetic resonance imaging in nude mice grafted with human colorectal carcinoma.

RATIONALE AND OBJECTIVES: Immunocontrast agents used for magnetic resonance imaging require antibodies that preserve the immunoreactivity while containing a high number of chelated paramagnetic ions. METHODS: Anti-CEA F(ab')2 fragments were coupled to polylysine-Gd-DOTA and polylysine-Gd-DTPA. A paramagnetic load as high as n = 24 to 28 metal ions per antibody was reached. RESULTS: The immunoreactivity of the gadolinium (Gd)-labeled anti-CEA F(ab')2 immunoconjugates was 80% to 85%. Compared with that of commercial chelates, the relaxivity (R1) increase is as follows: Gd-DTPA < Gd-DOTA < Gd-H2O < PL-Gd-DTPA24-28 < PL-Gd-DTPA24-28 F(ab')2 < PL-Gd-DOTA24-28 < PL-Gd-DOTA24-28 F(ab')2. 1H nuclear magnetic relaxation dispersion data of immunoconjugates showed that the high relaxivity enhancement was the result of a reduction of the molecular tumbling rate. Twenty-four hours after intravenous injection of 50 micrograms (1 mumol Gd/kg) of Gd-labeled immunoconjugates to nude mice grafted with human colorectal carcinoma LS 174T, the tumor uptake was 10% to 15%, resulting in an increase of R1 of up to 15% to 20% versus noninjected mice. No difference was found between PL-Gd-DTPA24-28 F(ab')2 and PL-Gd-DOTA24-28 F(ab')2 immunoconjugates for tumor, liver, and kidney uptake. A high signal intensity of tumor was observed in 50% of the tested mice.

Adenocarcinoma↗