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Biomedical subjects

S Mohanty

Publications and source records attributed to S Mohanty.

At least 19 recordsLinked to original sources
PubMed2001

Regulated protein degradation controls PKA function and cell-type differentiation in Dictyostelium.

Cullins function as scaffolds that, along with F-box/WD40-repeat-containing proteins, mediate the ubiquitination of proteins to target them for degradation by the proteasome. We have identified a cullin CulA that is required at several stages during Dictyostelium development. culA null cells are defective in inducing cell-type-specific gene expression and exhibit defects during aggregation, including reduced chemotaxis. PKA is an important regulator of Dictyostelium development. The levels of intracellular cAMP and PKA activity are controlled by the rate of synthesis of cAMP and its degradation by the cAMP-specific phosphodiesterase RegA. We show that overexpression of the PKA catalytic subunit (PKAcat) rescues many of the culA null defects and those of cells lacking FbxA/ChtA, a previously described F-box/WD40-repeat-containing protein, suggesting CulA and FbxA proteins are involved in regulating PKA function. Whereas RegA protein levels drop as the multicellular organism forms in the wild-type strain, they remain high in culA null and fbxA null cells. Although PKA can suppress the culA and fbxA null developmental phenotypes, it does not suppress the altered RegA degradation, suggesting that PKA lies downstream of RegA, CulA, and FbxA. Finally, we show that CulA, FbxA, and RegA are found in a complex in vivo, and formation of this complex is dependent on the MAP kinase ERK2, which is also required for PKA function. We propose that CulA and FbxA regulate multicellular development by targeting RegA for degradation via a pathway that requires ERK2 function, leading to an increase in cAMP and PKA activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Differential sensitivity of breast cancer cells to tumor necrosis factor-alpha: involvement of protein kinase C.

We have compared several breast cancer cell lines that differ in their responsiveness to TNF to determine the involvement of PKC isozymes in regulating sensitivity of breast cancer cells to TNF. While MCF-7 and BT-20 cells were responsive to TNF without any metabolic inhibitors, CAMA-1 and SKBR-3 cells responded to TNF in the presence of cycloheximide; MDA-MB-231 and Hs578t cells were resistant to TNF even in the presence of cycloheximide. Bisindolylmaleimide (BIM), an inhibitor of PKC, either alone (MCF-7 and BT-20) or in combination with cycloheximide enhanced sensitivity of these cells to TNF. The PKC isozyme profile of MCF-7 cells was similar to BT-20 cells and that of CAMA-1 cells was similar to SKBR-3 cells. MCF-7, BT-20 and MDA-MB-231 cells that were most responsive to BIM-mediated sensitization to TNF contained relatively high level of PKC epsilon and proteolytic cleavage of PKC epsilon correlated with TNF-induced cell death. BIM did not inhibit NF-kappa B activation by TNF but caused activation of caspases and enhanced cleavage of PKC delta and -epsilon. These results suggest that proteolytic cleavage of PKC epsilon may be associated with PKC inhibitor mediated sensitization of breast cancer cells to TNF.

Antimetabolites↗
PubMed2001

High lane density slab-gel electrophoresis using micromachined instrumentation.

In this paper, micromachined pipette arrays (MPAs) and microcombs were studied as a means of enabling high lane density gel electrophoresis. The MPA provide a miniaturized format to interface sub-microliter volumes of samples between macroscale sample preparation formats and microscale biochemical analysis systems. The microcombs provide a means of creating sample loading wells in the gel material on the same center-to-center spacing as the MPAs. Together, the two micromachined instruments provide an alternative to current combs and pipetting technologies used for creating sample loading wells and sample delivery in gel electrophoresis systems. Using three designs for the microcomb-MPA pair, center-to-center spacings of 1.0 mm, 500 microm, and 250 microm are studied. The results demonstrate an approximate 10-fold increase in lane density and a 10-fold reduction in sample size from 5 microL to 500 pL. As a result, the number of theoretical plates has increased 2.5-fold, while system resolution has increased 1.5-fold over the conventional agarose gel systems. An examination of changes in resolution across the width of individual separation lanes in both systems revealed dependence in the case of the conventional gels and no dependence for the gels loaded with the micromachined instrumentation.

Bromphenol Blue↗
PubMed2001

Stereoselective halofantrine disposition and effect: concentration-related QTc prolongation.

AIMS: 1) To characterize the variability of multiple-dose halofantrine pharmacokinetics over time in healthy adults, 2) to correlate the pharmacodynamic measure electrocardiographic (ECG) QT interval with (+)- and (-)-halofantrine plasma concentration and 3) to evaluate the safety and tolerance of halofantrine hydrochloride given over time to healthy adults. METHODS: Twenty-one healthy subjects were enrolled and 13 completed the study (180 days). Subjects received either 500 mg of racemic halofantrine once daily in the fasted state for 42 days, or placebo, and then halofantrine washout was documented for the following 138 days. Pharmacokinetic and pharmacodynamic (ECG QTc) measurements were obtained. RESULTS: Mean accumulation half-times (days) for halofantrine were: 7.0 +/- 4.8 [(+)-halofantrine] and 7.3 +/- 4.8 [(-)-halofantrine]. Mean steady-state concentrations were: 97.6 +/- 52.0 ng ml(-1) [(+)-halofantrine] and 48.5 +/- 20.8 [(-)-halofantrine]. Steady-state oral clearance was: 139 +/- 73 l h(-1) [(+)-halofantrine] and 265 +/- 135 l h(-1) [(-)-halofantrine]. Peak plasma concentrations of both (+)- and (-)-halofantrine were attained at 6 h and maximal ECG QTc prolongation was at 4-8 h following drug administration. Fourteen of 16 subjects who received active drug had ECG QTc prolongation that was positively correlated with both (+)- and (-)-halofantrine concentration. The five subjects who received placebo had no demonstrable change in ECG QTc throughout the study. Conclusions Halofantrine accumulates extensively and shows high intersubject pharmacokinetic variability, is associated with concentration-related ECG QTc prolongation in healthy subjects, and is clinically well tolerated in this subject group.

Adult↗
PubMed2001

Clinico-myocological profile of tinea capitis in North India and response to griseofulvin.

There is a paucity of literature on tinea capitis from North India. The response to griseofulvin has not been studied as well. We studied 153 consecutive patients of tinea capitis for clinical patterns, causative dermatophytic species, clinico-etiological correlation, and response to griseofulvin. Culture and sensitivity were done on all patients. All patients were treated with griseofulvin for 6-8 weeks; non-responders were further treated with fluconazole. Ninety percent of the patients were less than 15 years of age, 75% belonged to poor socioeconomic groups and 19% had a family history of tinea capitis. The seborrheic variant was the commonest clinical pattern seen in 47.8% of patients, followed by grey patch, black dot, kerion, and alopecia-areata-like tinea capitis in 35.9%, 8.5%, 6.5% and 1.3% of patients, respectively. Only 66% of patients had a positive culture. T. violaceum was the commonest dermatophytic species isolated in 38% patients. M. audouinii, T. schoenleinii, T. tonsurans, M. gypseum, T. verrucosum and T. mentagrophytes were isolated in 34%, 10%, 9%, 3%, 3% and 3% of patients, respectively. Of the isolates 94% were susceptible to griseofulvin, and 100% were susceptible to fluconazole. By using griseofulvin for 6-8 weeks 97.4% of the patients were cured; nonresponders required therapy with fluconazole for cure. To conclude, tinea capitis is still a disease of younger people of poor socioeconomic status. T. violaceum and M. audouinii are the most common responsible dermatophytes. The response to griseofulvin was excellent, and it should be used as a first line therapy.

Adolescent↗
PubMed2001

Capnocytophaga cynodegmi cellulitis, bacteremia, and pneumonitis in a diabetic man.

Capnocytophaga cynodegmi (formerly "DF-2 like organism"), a commensal organism of the canine oral cavity, is a capnophilic, gram-negative, facultative bacillus. C. cynodegmi has rarely been encountered in human diseases. We report the first known case of cellulitis, bacteremia, and pneumonitis caused by C. cynodegmi in a diabetic man from central India following a dog bite.

Animals↗
PubMed2001

Rhinocerebral mucormycosis in a patient of acute renal failure.

Mucormycosis is the name for invasive fungal infection caused by mucorales. The disease is uncommon and produces serious and rapidly fatal infection in patients with serious pre-existing illness. The classical presentation of rhinocerebral mucormycosis is involvement of nasal mucosa with invasion of paranasal sinuses and orbit. We report a case of mucormycosis in an otherwise healthy female who had developed acute renal failure following gastroenteritis.

Acute Kidney Injury↗
PubMed2001

A multicentric study with arteether in patients of uncomplicated falciparum malaria.

Two hundred and sixty seven patients of uncomplicated P. falciparum malaria completed study in a multicentric phase III clinical trial of Arteether. Arteether was given intramuscularly in a dose of 150 mg daily for three consecutive days. Each patient was followed upto 28 days of alpha, beta arteether therapy. The cure rate was 97% with fever clearance time between 1-7 days (24-168 hours) and parasite clearance time between 1-3 days (24-72 hours). Parasite reappearance rate was found to be 3% and reported at only three of the centres. Following the treatment no adverse effect was observed on haematological, biochemical and vital clinical parameters.

Adolescent↗
PubMed2001

Multicentric clinical trials for safety and efficacy evaluation of alpha;beta arteether in complicated P. falciparum malaria.

OBJECTIVE: To evaluate efficacy of alpha;beta arteether in patients of P. falciparum malaria presenting with complications was undertaken in a multicentric clinical trial. METHOD: Each patient who consented to undergo clinical trial with parenteral Arteether was treated with a fixed dose schedule of Arteether given intramuscularly in a dose of 150 mg once a day on three consecutive days. Every patient was followed upto 28 days with clinical, haematological and parasitological monitoring every day upto one week and thereafter at 14, 21 and 28 days. The response was assessed in terms of fever clearance time, parasite clearance time, cure rate and parasite reappearance rate. RESULTS: A total of 211 patients of P. falciparum malaria were included in the study from four centres (Bhilai, Guwahati, Jamshedpur and Rourkela). Results of this study showed that fever clearance time ranged between 24-168 hours, parasite clearance time ranged between 24-120 hours and overall mortality ranged between 4-8.5%. Out of 211, only 14 patients expired during the study, of these, 10 patients expired within first two days i.e. before completing the three day schedule of arteether therapy. Tolerability to arteether injection was good in all these patients and no untoward effects were experienced or reported during the study. Overall cure rate observed in these studies was 93%. CONCLUSION: This study shows a rapid parasite and fever clearance in patients of complicated P. falciparum malaria.

Adolescent↗
PubMed2000

An F-Box/WD40 repeat-containing protein important for Dictyostelium cell-type proportioning, slug behaviour, and culmination.

FbxA is a novel member of a family of proteins that contain an F-box and WD40 repeats and that target specific proteins for degradation via proteasomes. In fruiting bodies formed from cells where the fbxA gene is disrupted (fbxA(-) cells), the spore mass fails to fully ascend the stalk. In addition, fbxA(-) slugs continue to migrate under environmental conditions where the parental strain immediately forms fruiting bodies. Consistent with this latter behaviour, the development of fbxA(-) cells is hypersensitive to ammonia, the signaling molecule that regulates the transition from the slug stage to terminal differentiation. The slug comprises an anterior prestalk region and a posterior prespore region and the fbxA mRNA is highly enriched in the prestalk cells. The prestalk zone of the slug is further subdivided into an anterior pstA region and a posterior pstO region. In fbxA(-) slugs the pstO region is reduced in size and the prespore region is proportionately expanded. Our results indicate that FbxA is part of a regulatory pathway that controls cell fate decisions and spatial patterning via regulated protein degradation.

Amino Acid Motifs↗
PubMed2000

Blockade of histamine H2 receptors attenuate blood-brain barrier permeability, cerebral blood flow disturbances, edema formation and cell reactions following hyperthermic brain injury in the rat.

Role of histamine H2 receptors in blood-brain barrier (BBB) disturbances, cerebral blood flow (CBF), brain edema formation, and cell injury caused by heat stress in a rat model was examined using the pharmacological approach. Blockade of histamine H2 receptors by cimetidine or ranitidine significantly attenuated the BBB permeability to Evans blue albumin and [131]I-sodium extravasation, brain edema formation and cell injury following 4 h heat stress in rats at 38 degrees C. These drug treatments also restored the CBF to near normal values. These beneficial effects in heat stress were most marked in rats treated with ranitidine compared to cimetidine given in identical dosage. Our observations suggest that blockade of histamine H2 receptor is beneficial in hyperthermic brain injury and indicates that histamine is involved in the pathophysiology of heat stress induced brain dysfunction. Our study strongly suggests further need to develop more specific and sensitive histaminergic H2 receptor blockers for the treatment of neurological ailments.

Animals↗
PubMed2000

p-Chlorophenylalanine, an inhibitor of serotonin synthesis reduces blood-brain barrier permeability, cerebral blood flow, edema formation and cell injury following trauma to the rat brain.

The role of serotonin in trauma induced alterations in blood-brain barrier (BBB) permeability, cerebral blood flow (CBF), brain edema and cell changes were examined in a new model of cortical injury in the rat using a pharmacological approach. A longitudinal incision into the right parietal cerebral cortex (about 3 mm deep and 5 mm long) was associated with a profound increase in the BBB permeability to Evans blue and [131]I-sodium, brain water content, and a reduction in the CBF in both the ipsilateral and contralateral hemispheres 5 h after trauma. Nissl staining showed a profound nerve cell reaction in the parietal cerebral cortex of both hemispheres. The intensity of these pathological changes was most pronounced in the traumatised hemisphere. Pretreatment with p-CPA, a serotonin synthesis inhibitor, significantly attenuated breakdown of the BBB permeability, brain edema and the CBF disturbances. Damaged and distorted nerve cells were markedly less frequent in p-CPA treated rats. This effect of the drug was most pronounced in the contralateral hemisphere. The observations strongly suggest that serotonin is one of the important neurochemical mediators of BBB permeability disturbances and brain edema formation in the trauma induced brain damage.

Animals↗
PubMed2000

Tactual recognition of cognitive stimuli: roles of hemisphere and lobe.

Four groups of focal brain-damaged patients, involving left and right hemisphere damage with or without the involvement of parietal lobe, and a control group of general medical patients, were required (a) dichaptically to perceive two cognitive stimuli (letter letter, figure figure, or letter figure), and (b) haptically match the target stimulus from a set of test stimuli. The number of trials taken to match the target stimulus correctly was the dependent measure. The significant main effect of lobe suggested that the parietal lobe is the primary locus for tactual recognition. All interaction effects involving lobe were nonsignificant. The main effect of hemisphere was nonsignificant, although the interaction of hemisphere x lobe was significant. Left and right hemisphere damaged patients required more trials to recognize "letter" and "figure", respectively.

Adult↗
PubMed2000

Therapy of acanthamoeba keratitis--an experimental study.

The study was conducted to determine the efficacy of various drugs/agents in the treatment of experimentally induced Acanthamoeba Keratitis (A. keratitis). Thirty rabbits were divided into 5 equal treatment groups and polyhexamethylene biguanide (PHMB) 0.02%, fluconazole 0.2%, povidone iodine 5%, aprotinin 40 IU/ml and normal saline were administered in a double blind manner, at a dose of one drop, 5 times/day. Neomycin 1700 U/ml was used as a common drug in all groups, with same frequency. Post therapy subsidence of lid oedema, mucopurulent discharge, conjunctival congestion, corneal epithelial defect and anterior chamber reactions were noted. Average healing time in days (Mean +/- S.D.) were 13.67 +/- 1.21, 22 +/- 1.41, 23.5 +/- 1.05, 17.0 +/- 1.41 and 28.0 +/- 1.90 for PHMB, fluconazole, povidone iodine, aprotinin and normal saline respectively. Lid oedema, mucopurulent discharge and conjunctival congestion improved faster in PHMB and aprotinin treated eyes. The results of this study suggest that PHMB is a better drug for A. keratitis, while aprotinin may be used as an adjuvant drug in the management of A. keratitis.

Acanthamoeba Keratitis↗