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Biomedical subjects

A Chakrabarti

Publications and source records attributed to A Chakrabarti.

At least 91 records · Page 5Linked to original sources

Decreased membrane permeability in a polymyxin B-resistant Escherichia coli mutant exhibiting multiple resistance to beta-lactams as well as aminoglycosides.

A laboratory mutant of Escherichia coli stably resistant to more than 36,000 U ml-1 of polymyxin B was isolated. The mutant exhibited moderate increases in minimum inhibitory concentration to fluoroquinolones and bacitracin but high levels of cross-resistance to beta-lactams and aminoglycosides. However, it remained susceptible to tetracycline, nalidixic acid and novobiocin. Changes were observed in the outer membrane proteins and lipopolysaccharide profile leading to a decrease in permeability as evident from reduction in the following: (i) minimum inhibitory concentration values in the presence of Tween 80, (ii) uptake of 1-N-phenyl naphthylamine and norfloxacin, (iii) hydrolysis of beta-lactams and (iv) diffusion of lactose and cefazolin into proteoliposomes reconstituted with outer membrane proteins. We therefore suggest that the novel pattern of cross-resistance of our isolate is due to the decrease in its permeability.

Anti-Bacterial Agents↗

Dose-finding study with nimodipine: a selective central nervous system calcium channel blocker on aminophylline induced seizure models in rats.

Nimodipine, a dihydropyridine derivative central nervous system (CNS) selective calcium channel blocker was studied at four different dosage schedules in five different models of seizures in rats. At a dose of 5 mg/kg, i.p. with pretreatment time of 15 min, nimodipine significantly antagonized aminophylline (175 and 200 mg/kg, i.p.), electroshock (150 mA for 0.2 s), pentylenetetrazole (60 and 75 mg/kg, i.p.), aminophylline (100 mg/kg i.p.) + electroshock (66mA for 0.2 s), and aminophylline (100 mg/kg, i.p.) + pentylenetetrazole (40 mg/kg, i.p.) induced seizures in rats. No hemodynamic alteration was observed with this dose of nimodipine. However, 2 mg/kg, i.p. (pretreatment time of 15 min and 30 min) and 5 mg/kg, i.p. (pretreatment time of 30 min) doses of nimodipine failed to demonstrate any significant anticonvulsant effect. The study highlighted the critical role of calcium ion flux into the neurons for the genesis of seizure activity to aminophylline, electroshock, and pentylenetetrazole in rats. Furthermore, the critical dose requirement for nimodipine could be explained on the basis of its short half-life and shorter duration of protection against seizures. Therefore, nimodipine may be tried clinically as an anticonvulsant in patients who are on aminophylline because of bronchial asthma or chronic obstructive pulmonary disease, when such patients have concomitant epilepsy or other seizure prone neurological deficits or are scheduled to undergo electroshock therapy.

Aminophylline↗

Multilamellar vesicular clusters of phosphatidylcholine and their sensitivity to spectrin: a study by fractal analysis.

The cluster patterns of multilamellar vesicles (MLV) of dimyristoylphosphatidylcholine (DMPC) were analyzed using a combination of fractal analysis and lattice simulation. Self-assembly of DMPC MLVs resulted in two types of microscopically observable clusters. The clusters were classified on the basis of their mass fractal dimension, two-dimensional porosity, and the light scattering properties. Spectrin, a cytoskeletal protein, well known for its role in determining the cellular morphology, was used to perturb such spontaneously formed clusters. The fragmentation of the clusters by hydrodynamic perturbation followed a power law, implying again a fractal behavior. A lattice-based simulation was performed generating different class of cluster patterns. The observed correspondence between the cluster patterns and their stability was discussed in the framework of the proposed lattice simulation.

Dimyristoylphosphatidylcholine↗

Chloral hydrate alters the organization of the ciliary basal apparatus and cell organelles in sea urchin embryos.

The mitotic inhibitor, chloral hydrate, induces ciliary loss in the early embryo phase of Lytechinus pictus. It causes a breakdown of cilia at the junction of the cilium and the basal body known as the basal plate. This leaves the plasma membrane temporarily unsealed. The basal apparatus accessory structures, consisting of the basal body, basal foot, basal foot cap, striated side arm, and striated rootlet, are either misaligned or disintegrated by treatment with chloral hydrate. Furthermore, microtubules which are associated with the basal apparatus are disassembled. Mitochondria accumulate at the base of cilia - underneath the plasma membrane - and show alterations in their structural organization. The accumulation of mitochondria is observed in 40% of all electron micrograph sections while 60% show the areas mostly devoid of mitochondria. The microvilli surrounding a cilium and striated rootlet remain intact in the presence of chloral hydrate. These results suggest that deciliation in early sea urchin embryos by chloral hydrate is caused by combined effects on the ciliary membrane and on microtubules in the cilia. Furthermore, it is suggested that chloral hydrate can serve as a tool to explore the cytoskeletal mechanisms that are involved in cilia motility in the developing sea urchin embryo.

Animals↗

The cytoskeleton of Drosophila-derived Schneider line-1 and Kc23 cells undergoes significant changes during long-term culture.

Insect cell cultures derived from Drosophila melanogaster are increasingly being used as an alternative system to mammalian cell cultures, as they are amenable to genetic manipulation. Although Drosophila cells are an excellent tool for the study of genes and expression of proteins, culture conditions have to be considered in the interpretation of biochemical results. Our studies indicate that significant differences occur in cytoskeletal structure during the long-term culture of the Drosophila-derived cell lines Schneider Line-1 (S1) and Kc23. Scanning, transmission-electron, and immunofluorescence microscopy studies reveal that microfilaments, microtubules, and centrosomes become increasingly different during the culture of these cells from 24 h to 7-14 days. Significant cytoskeletal changes are observed at the cell surface where actin polymerizes into microfilaments, during the elongation of long microvilli. Additionally, long protrusions develop from the cell surface; these protrusions are microtubule-based and establish contact with neighboring cells. In contrast, the microtubule network in the interior of the cells becomes disrupted after four days of culture, resulting in altered transport of mitochondria. Microtubules and centrosomes are also affected in a small percent of cells during cell division, indicating an instability of centrosomes. Thus, the cytoskeletal network of microfilaments, microtubules, and centrosomes is affected in Drosophila cells during long-term culture. This implies that gene regulation and post-translational modifications are probably different under different culture conditions.

Actin Cytoskeleton↗

Primary cutaneous aspergillosis: our experience in 10 years.

We describe nine patients with primary cutaneous aspergillosis who were diagnosed during the 10-year period between 1987 and 1996. All except one were adults. Seven of those nine cases had an immunocompromised state. Among the immunocompromised patients, six had burn wounds and one was a renal transplant recipient. Aspergillus flavus was isolated from seven patients and A. fumigatus from one, and in one other case the species could not be determined. Three patients who had total burn surface area of more than 70% died. The other patients responded well to extensive surgical debridement with or without institution of oral itraconazole.

Adult↗

Centrosome structure and function is altered by chloral hydrate and diazepam during the first reproductive cell cycles in sea urchin eggs.

This paper explores the mode of action of the tranquillizers chloral hydrate and diazepam during fertilization and mitosis of the first reproductive cell cycles in sea urchin eggs. Most striking effects of these drugs are the alteration of centrosomal material and the abnormal microtubule configurations during exposure and after recovery from the drugs. This finding is utilized to study the mechanisms of centrosome compaction and decompaction and the dynamic configurational changes of centrosomal material and its interactions with microtubules. When 0.1% chloral hydrate or 350-750 microM diazepam is applied at specific phases during the first cell cycle of sea urchin eggs, expanded centrosomal material compacts at distinct regions and super-compacts into dense spheres while microtubules disassemble. When eggs are treated before pronuclear fusion, centrosomal material aggregates around each of the two pronuclei while microtubules disappear. Upon recovery, atypical asters oftentimes with multiple foci are formed from centrosomal material surrounding the pronuclei which indicates that the drugs have affected centrosomal material and prevent it from functioning normally. Electron microscopy and immunofluorescence studies with antibodies that routinely stain centrosomes in sea urchin eggs (4D2; and Ah-6) depict centrosomal material that is altered when compared to control cells. This centrosomal material is not able to reform normal microtubule patterns upon recovery but will form multiple asters around the two pronuclei. When cells are treated with 0.1% chloral hydrate or 350-750 microM diazepam during mitosis, the bipolar centrosomal material becomes compacted and aggregates into multiple dense spheres while spindle and polar microtubules disassemble. With increased incubation time, the smaller dense centrosome particles aggregate into bigger and fewer spheres. Upon recovery, unusual irregular microtubule configurations are formed from centrosomes that have lost their ability to reform normal mitotic figures. These results indicate that chloral hydrate and diazepam affect centrosome structure which results in the inability to reform normal microtubule formations and causes abnormal fertilization and mitosis.

Animals↗

Neurobehavioral effects of anandamide and cannabinoid receptor gene expression in mice.

The objective of the present study was to determine the neurobehavioral effects of the putative endogenous cannabinoid ligand, anandamide, and its influence on cannabinoid (CB1) receptor gene expression. The effect of acute administration of anandamide to C57BL/6, DBA/2, and ICR mice were evaluated in motor function and emotionality tests. The C57BL/6 and ICR mouse strains were more sensitive than the DBA/2 strain to the depression of locomotor activity and stereotyped behavior caused by anandamide. Although anandamide produced catalepsy in all three strains, anandamide induced ataxia in the minus-maze test only in the C57BL/6 animals and only at the lowest dose used. In the plus-maze test system, anandamide produced a mild aversive response, and by the third day of treatment the mouse strains developed an intense aversion to the open arms of the plus-maze. Northern analysis data using the recently cloned mouse cannabinoid receptor cDNA as a probe indicated that there was abundant expression of CB1 gene in the whole brain of the ICR mouse than in the brains of the C57BL/6 and DBA/2 strains with or without pretreatment with anandamide. The anandamide induced neurobehavioral profile does not seem to correspond to the CB1 gene expression in the mouse strains. It is, therefore, unlikely that the CB1 receptor mediates all the cannabinomimetic effects of anandamide in the brain.

Animals↗

Azathioprine in the treatment of Parthenium dermatitis.

BACKGROUND: Parthenium dermatitis is a chronic disorder whose management is extremely difficult. Allergen avoidance is almost impossible, topical corticosteroid therapy provides only partial relief, and prolonged systemic corticosteroid therapy has unacceptable side-effects. METHODS: Twenty patients with chronic Parthenium dermatitis, with relative contraindications to systemic corticosteroids or their side-effects, were treated with oral azathioprine (100-150 mg daily). The severity of dermatitis was assessed at 0, 1, 3, 6, and 12 months using a modified PASI scoring system. RESULTS: The mean age of the patients was 54 years (range, 40-72 years) and the mean duration of dermatitis was 7.6 years (range, 3 months to 36 years). The mean initial score was 18.9 (range, 3.3-42), which decreased to 8.8 (range, 1.6-18.2) at 3 months, 4.8 (range, 0.6-14.6) at 6 months, and 0.7 (range, 0.2-1.4) at 12 months. Of the 15 patients evaluated at 6 months, all but one showed a response. Ten (66.6%) patients showed near-total clearance, i.e. reduction in score by more than 90%, and three patients (20%) showed more than 50% reduction in score. No significant side-effects were noted. CONCLUSIONS: Azathioprine is an effective and safe alternative to corticosteroid therapy in the treatment of chronic Parthenium dermatitis. It is especially useful in patients with side-effects or contraindications to corticosteroid therapy.

Administration, Oral↗

Activity profiles of two hyperforin-containing hypericum extracts in behavioral models.

The behavioral activity profile of a therapeutically used alcoholic hypericum extract containing hyperforin (4.5%) in rodent models was compared with that of an experimental CO2 extract devoid of hypericines but highly enriched in hyperforin (38.8%). The antidepressant activities of 50, 150 and 300 mg/ kg/day of the alcoholic extract were similar to those of 5, 15 and 30 mg/kg/day respectively of the CO2 extract. The ethanol extract in the same dose range potentiated dopaminergic behavioral responses, whereas these effects were either absent or less pronounced in the CO2 extract treated groups. By contrast, serotoninergic effects of the CO2 extract were more pronounced than those of the alcoholic extract. These and various other observations made during the study confirm that although the antidepressant action of hypericum extracts depends on their hyperforin contents, their spectrums of central activity are due to other component(s). Our working hypothesis that hyperforin and serotoninergic mechanisms are involved in the therapeutically observed antidepressant activities of hypericum extracts is in agreement with these observations.

Animals↗

Epidemiology of systemic candidiasis in a tertiary care neonatal unit.

143 neonates were diagnosed to have acquired systemic candidiasis out of a total 4530 admissions (3.2 per cent) to the neonatal intensive care unit (NICU) during a period of 6 1/2 years from January 1990 to June 1996. Mean age at onset was 10.4 days, mean birth weight 1454 g, and mean gestation was 31.7 weeks. Ninety-four per cent were premature, 95 per cent low birth weight (LBW), and all had undergone peripheral vein catheterization and had received broad spectrum antibiotics, except one, prior to the diagnosis. Fifty-eight per cent were ventilated and 15 per cent received parenteral nutrition. Persistent/recurrent pneumonia, apnoea, lethargy, high gastric aspirates, and abdominal distension were the common clinical manifestations. Candida tropicalis, C. albicans, and C. guillermondii were the most common isolates. Blood and urine were the predominant sites for isolation of Candida. Fluconazole was the most used antifungal agent, with 24 per cent resistance against it. Fifty per cent of babies died due to all causes. Of all the deaths, two-thirds were Candida related. Candida-attributable deaths occurred in 24 cases (17 per cent).

Age of Onset↗

Common contact sensitizers in Chandigarh, India. A study of 200 patients with the European standard series.

200 patients (122 male, 78 female) with suspected allergic contact dermatitis were patch tested with the European standard series (ESS) and the results compared with other Asian centres. 131 (65.5%) patients showed 1 or more patch test positives to the ESS. Patch tests were positive to all allergens except primin. Potassium dichromate was the most common allergen (20.5%) followed by nickel sulfate (16.5%), SQL mix (14%), PPD (11.5%), cobalt (8%), fragrance mix (7.5%), formaldehyde (6.5%), colophony (5.5%), neomycin sulfate and mercapto mix (5% each). In women, nickel sulfate was the commonest allergen (30.8%) followed by SQL mix (16.7%) and potassium dichromate (15.4%). In men, potassium dichromate was the commonest sensitizer (23.8%) followed by SQL mix and PPD (12.3% each). Our results are at variance with other centres in Asia. SQL mix was able to detect less than 1/2 (42.2%) of patients allergic to ethanolic dilutions of ether extracts of parthenium. We conclude that the European standard series, with exclusion of primin, is suitable for detection of allergic contact dermatitis in India. However, SQL mix is not a adequate screen for parthenium sensitivity and patch testing with extracts of the plant should be continued, wherever indicated.

Adolescent↗

Isolated bilateral renal aspergillosis: an unusual presentation in an immunocompetent host.

A 35 year old apparently immunocompetent farmer developed isolated bilateral renal aspergillosis. He presented with acute renal failure due to granulomatous interstitial nephritis and had bilateral renal abscesses on CT scan. Diagnosis came from renal histology and was confirmed on serology. The patient responded quite satisfactorily to single agent antifungal chemotherapy with IV amphotericin B.

Acute Kidney Injury↗

Stress and water balance: the roles of ANP, AVP and isatin.

Stress is often associated with water retention and its resolution with diuresis. The biological systems for the control of stress and water balance are very closely related. Corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) are co-localised in the hypothalamus and often act synergistically. Atrial natriuretic peptide (ANP) can exert a feedback control on the hypothalamic/pituitary/adrenal axis. ANP has been shown to be anxiolytic, whereas AVP may be anxiogenic. AVP and ANP levels have been found to be abnormal in a range of stress disorders and psychiatric illnesses. Isatin is an endogenous anxiogenic factor which is also a potent inhibitor of the ANP receptor. It may provide a link between the function of monoamines during stress, and the control of water balance by ANP.

Arginine Vasopressin↗

Dose-related proconvulsant and anticonvulsant activity of isatin, a putative biological factor, in rats.

Isatin (indole-2, 3-dione) is an endogenous compound with anxiogenic properties, which occur within a narrow dose range (15-20 mg/kg, i.p.). Dose increment beyond 50 mg/kg, i.p. leads to the loss of anxiogenesis. Since a link has been postulated between anxiogenic and convulsant activity, the effect of a range of doses of isatin (20-80 mg/kg, i.p.) was investigated on subconvulsant and convulsant doses of two seizure-inducing agents, namely, pentylenetetrazole (PTZ) and 3-mercapto-propionic acid (3MPA) in rats. Isatin was found to induce a dose-related effect on PTZ and 3MPA convulsions. The lower dose (20 mg/kg, i.p.) potentiated PTZ and 3MPA convulsions, a median dose (40 mg/kg, i.p.) had insignificant effect, whereas higher doses (60 and 80 mg/kg, i.p.) of isatin exhibited significant anticonvulsant effect against both PTZ and 3MPA induced clonic convulsions. The investigation, thus, supports the contention that anxiogenic agents increase the susceptibility to chemical seizures. The proconvulsant effect of isatin, may be due to its inhibitory effect on central atrial natriuretic peptide receptors and stimulation of 5-hydroxytryptamine3 (5-HT3) rather than its monoamine oxidase (MAO) B inhibitory action. The anticonvulsant effect on higher doses of isatin, on the contrary, may be induced by its metabolites, including 5-hydroxyisatin.

3-Mercaptopropionic Acid↗

Biochemical characterization of mammalian translation initiation factor 3 (eIF3). Molecular cloning reveals that p110 subunit is the mammalian homologue of Saccharomyces cerevisiae protein Prt1.

Eukaryotic translation initiation factor 3 (eIF3), which plays an essential role in initiation of protein synthesis, was purified from rabbit reticulocyte lysates using an assay that specifically measures its ability to stimulate the binding of Met-tRNAf (as a Met-tRNAf.eIF2.GTP ternary complex) to 40 S ribosomal subunits. Purified eIF3 consisted of six major polypeptides of molecular masses 110, 67, 42, 40, 36, and 35 kDa but lacked the 170-kDa polypeptide reported to be a constituent of other eIF3 preparations. Characterization of purified eIF3 lacking the 170-kDa polypeptide showed that the eIF3-mediated 40 S initiation complex formed in the presence of AUG codon efficiently joined 60 S ribosomal subunits in an eIF5-dependent reaction to form a functional 80 S initiation complex. eIF3, which was originally bound to the 40 S initiation complex, was released from the 40 S subunit during the subunit joining reaction. Additionally, chicken antibodies raised against rabbit reticulocyte eIF3 were used to immunochemically characterize eIF3 subunits and to isolate a 3.1-kilobase pair human cDNA that encodes the p110 subunit of mammalian eIF3. The derived amino acid sequence (calculated Mr 95,214) shows that the p110 subunit is the mammalian homologue of Saccharomyces cerevisiae protein Prt1p, a subunit of yeast eIF3.

Amino Acid Sequence↗