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N Kumar

Publications and source records attributed to N Kumar.

At least 127 records · Page 7Linked to original sources

Molecular characterization and ultrastructural localization of Plasmodium falciparum Hsp 60.

Heat shock proteins (Hsp) are a group of highly conserved proteins which are widely represented phylogenetically. Genes for members of the Hsp 70, 90 and 60 families have been cloned from the human malaria parasite Plasmodium falciparum. In this study, we have cloned and expressed the P. falciparum Hsp 60 (PfHsp60) in E. coli. The sequence analysis identified a previously unknown intron of 257 bp beginning after the nucleotide 142 in the coding sequence. Antisera raised against the recombinant PfHsp60 was employed in immunoprecipitation studies with biosynthetically labeled parasite extracts to investigate regulation of expression of PfHsp60 at various temperatures. In contrast to the three to four fold accumulation of PfHsp60 transcripts in heat shocked parasites (37-40 degrees C), the expression of PfHsp60 was not induced in the blood stages of P. falciparum. On the other hand, the effect of heat induction on PfHsp70 was seen both at the level of specific mRNA and protein. In these studies we also observed co-immunoprecipitation of a number of other cellular proteins suggesting possible interaction with PfHsp60. Immunofluorescence analysis indicated the presence of PfHsp60 in the cytoplasm of all the various stages of the parasite. In addition, immunoelectron microscopic analysis distinctly localized PfHsp60 in the mitochondrion of P. falciparum. This study suggests that different mechanisms are involved in the regulation of expression of various members of the heat shock proteins in the parasite.

Animals↗

Anti-invasive activity of alkaloids and polyphenolics in vitro.

Invasiveness, the ability of certain tumour cells to migrate beyond their natural tissue boundaries, often leads to metastasis, and usually determines the fatal outcome of cancer. The need for anti-invasive agents has led us to search for possibly active compounds among alkaloids and polyphenolics. One hundred compounds were screened in an assay based on the confrontation of invasive human MCF-7/6 mammary carcinoma cells with fragments of normal embryonic chick heart in vitro. Anti-invasive activity was frequently found among chalcones having a prenyl group. Six compounds were found to inhibit invasion when added to the culture medium at concentrations as low as 1 microM. For at least three of them the anti-invasive effect could be associated with a cytotoxic effect on the MCF-7/6 cells, but not on the heart tissue. This selective cytotoxicity was substantiated by different methods, such as histology and growth assays (volume measurements, cell counts, MTT and sulforhodamine B assays). The anti-invasive effects of the compounds could neither be ascribed to induction of apoptosis nor to the promotion of cell-cell adhesion. Our data indicate that among the alkaloids and polyphenolics a number of molecules can inhibit growth and invasion of human mammary cancer cells via selective cytotoxicity.

Alkaloids↗

Mutations that prevent associative learning in C. elegans.

The nematode Caenorhabditis elegans offers a promising system for the reductionist study of learning and memory. In this article, classical conditioning in C. elegans is demonstrated with a variety of associative learning assays. These assays allowed for the isolation and behavioral characterization of 2 mutant C. elegans lines impaired in associative learning. Both lines show no short-term or long-term associative conditioning; however, they appear relatively normal in tests of nonassociative learning and sensorimotor function. In combination with the well-described genetics and neuroanatomy of C. elegans, the isolation of mutants selectively, yet completely, blocked in associative learning provides the basis for an effective characterization of the cellular and molecular aspects of associative learning.

Animals↗

Amphotericin B is superior to sodium antimony gluconate in the treatment of Indian post-kala-azar dermal leishmaniasis.

Parasitologically confirmed cases of post-kala-azar dermal leishmaniasis (PKDL) were treated by infusion with amphotericin B deoxycholate (ABD; 1 mg/kg.day on days 1-20, 21-40 and 61-80) or by intramuscular injection with sodium antimony gluconate (SAG; 20-day courses at 20 mg/kg day, with 20-day, drug-free intervals). Of the 11 patients given ABD, all were cured with the three courses, none relapsed in 12 months of follow-up, all developed mild adverse effects (shivering and fever) because of the infusion, five lost their appetites, and three showed increases in their serum creatinine concentrations (although none exceeded 'normal' limits). In contrast, only seven (63%) of the 11 patients given SAG were considered treatment successes (improvement in lesions by the end of the third course) and these took six courses (two cases), nine courses (four cases) or 10 courses (one case) to cure completely. Two of the patients given SAG developed arthralgia and two others developed non-specific ST changes in their electrocardiograms (ECG), although their ECG were normal between courses. The better cure rate with ABD was not statistically significant, probably because of the small sample size. However, ABD appears to be a superior to SAG in terms of the speed of response and cure, although it is more expensive and has some nephrotoxicity. As the effectiveness of SAG against PKDL is apparently declining over time and the cost of ABD is prohibitive in poor countries such as India, a safe, cheap and more effective drug for the treatment of PKDL is needed.

Adolescent↗

Neuromuscular effects of rocuronium in patients receiving beta-adrenoreceptor blocking, calcium entry blocking and anticonvulsant drugs.

We have studied the onset and duration of action of rocuronium 0.6 mg kg-1 in patients receiving therapy for more than 1 month with beta-receptor blocking drugs (n = 16), calcium entry blocking drugs (n = 17) or anticonvulsant drugs (n = 14) and compared these data with those from a control group (n = 27). Anaesthesia comprised fentanyl, propofol infusion and nitrous oxide in oxygen. Neuromuscular block was monitored by measuring the force of contraction of the adductor pollicis muscle in response to train-of-four (TOF) stimulation. There were no significant differences in onset times between the four groups (mean 62-76 s). Mean times to 25% recovery of T1 (first response in the TOF) and of the TOF ratio of 0.7 were 38 (SD 15) and 58 (22) min, 36 (8) and 61 (19) min, 40 (11) and 68 (22) min, and 25 (6) and 35 (9) min in the control, beta-blocker, calcium entry blocker and anticonvulsant groups, respectively (P < 0.01 between the anticonvulsant and other groups). We conclude that chronic therapy with anticonvulsant drugs reduces the duration of action of rocuronium.

Adolescent↗

Pharmacokinetics and pharmacodynamics of 7alpha-methyl-19-nortestosterone after intramuscular administration in healthy men.

7alpha-Methyl-19-nortestosterone (MENT) is a potent synthetic androgen that is resistant to 5alpha-reductases and therefore less prone to over-stimulate the prostate. It is a good candidate for implant administration in long-term androgen replacement therapy for hypogonadal men or as part of a male contraceptive system. To investigate the pharmacokinetics of MENT after i.m. administration, single i.m. injections of 2, 4 or 8 mg of micronized MENT were given in aqueous suspension to 18 healthy men in two clinics. Blood was sampled frequently for 8 h and 1, 2, 3, 4 and 9 days after the injections. Serum MENT concentrations were determined by radioimmunoassay. Peak MENT concentrations were dose-dependent and were reached about 1-2 h after the injections. Doubling the dose of MENT resulted in an increase of 60% in peak serum MENT concentrations. The mean +/- SE clearance rate was 1790 +/- 140 l/day. The antigonadotrophic activity of MENT was investigated by giving six consecutive daily i.m. injections of 1, 2 or 4 mg of MENT to 24 healthy men in two clinics. Blood was sampled before each injection and up to 24 days after the last injection. Serum testosterone and gonadotrophin concentrations (determined by radioimmunoassay and fluoroimmunoassay respectively) decreased in a dose-dependent and statistically significant manner. The highest dose caused a 74% fall in testosterone, a 70% fall in luteinizing hormone, and a 57% fall in follicle stimulating hormone concentrations. MENT injections did not cause any side-effects. The results show that MENT is a potent antigonadotrophic agent in men.

Adult↗

Postoperative intravenous drip infusion is not required after minilaparotomy cholecystectomy.

OBJECTIVE: To determine if drip infusion should be discontinued after full recovery of the patient from anaesthesia after minilaparotomy cholecystectomy in uncomplicated cases. DESIGN: A randomised controlled clinical trial on 60 patients, from the waiting list, of cholelithiasis/cholecystitis operated by minilaparotomy cholecystectomy between November 1995 to March 1996. 30 patients did not receive postoperative i.v. drip infusion and in 30 patients 12-24 hours of standard drip transfusion was continued according to the current practice. SETTING: Single Surgical Unit, SS Hospital, Banaras Hindu University, Varanasi, India. MAIN OUTCOME MEASURE: Recognition of clinical indication for continuation of i.v. drip infusion after full recovery from anaesthesia. RESULTS: In the cohorts of 30 patients each who were or were not given i.v. drip infusion after full recovery from anaesthesia following minilaparotomy cholecystectomy the observations on pulse rate, blood pressure, time to first voiding of urine and time to start first oral intake of fluids were identical. However postoperative urinary retention occurred in 6 (20%) patients in whom the IV drip infusion was given. CONCLUSION: There is no clinical indication to continue IV drip infusion after full recovery from anaesthesia in patients operated for minilaparotomy cholecystectomy.

Adult↗

Use of intermediate acting muscle relaxants by infusion: the future.

The usefulness of newer intermediate-acting muscle relaxants rocuronium and cisatracurium when used by infusion has been reviewed briefly and their main features pointed out. Comparative features of atracurium, vecuronium and mivacurium have also been described. Both new agents may have advantages for use by infusion particularly for longer procedures, due to the lack of detectable metabolites with rocuronium and production of comparatively smaller amounts of metabolites with cisatracurium.

Androstanols↗

Mycotic keratitis in children: epidemiologic and microbiologic evaluation.

PURPOSE: To evaluate the demographic features, clinical profile, and laboratory diagnosis in cases of mycotic keratitis in children. METHODS: We retrospectively analyzed 211 cases of mycotic keratitis in children younger than 16 years over a 5-year period in a tertiary eye center. Culture-proven cases of fungal keratitis were reviewed. RESULTS: Trauma was the most common predisposing factor (55.3%), followed by associated systemic illness (11.2%), previous ocular surgery (9.8%), and others. Corneal injury contaminated with vegetable matter was responsible for 60.5% of traumatic cases. Aspergillus species were the most frequent isolates (39.5%). Others included Fusarium (10.7%), Alternaria (10.2%), Curvularia (7.4%), and Penicillium (7%). A seasonal variation in the incidence of mycotic keratitis revealed a peak incidence in the months of September and October. One hundred sixty-two children (76.7%) cooperated for examination and scraping under topical anesthesia with or without sedation. General anesthesia for scraping was required in 49 (23%) of 211 children for corneal scraping. Gram stains of corneal scraping were positive for hyphal elements in 54.5% of cases, and potassium hydroxide wet-mount preparation was positive in 90.2% of cases. CONCLUSIONS: This study highlights important risk factors and organisms responsible for mycotic keratitis in children.

Adolescent↗

The changing face of long-term care insurance in 1994: profiles and innovations in a dynamic market.

This study examines buyers and nonbuyers of long-term care insurance. The findings show that consumers purchased more comprehensive products in 1994-95 than they did in 1990, and that they appeared to get better value for the premium dollar. While annual sales are increasing at a rate of 25%, the market for long-term care insurance remains small, and many of the market barriers that existed four to five years ago persist today. These include confusion about public coverage, concerns about the adequacy of products and how to choose them, policy cost, and inadequate information about potential risk for needing long-term care. As states target limited public funds toward the indigent, older middle-class people will have to deal with exposure to risk for long-term care, and insurance may be one way to minimize this exposure.

Age Factors↗

Further characterization of a 58 kDa Plasmodium berghei phosphoprotein as a cochaperone.

Molecular chaperones are important for proper protein folding during protein biogenesis. This report describes a protein from Plasmodium berghei which is 30% identical and 40% similar to a recently described mammalian cochaperone, or heat shock protein 70 interacting protein. The P. berghei cochaperone accumulates throughout the trophozoite stage and decreases during the schizont stage. The stage specific expression is consistent with its presumed role in protein folding or protein-protein interactions. The largest difference between the Plasmodium and mammalian sequences is a more extensive domain of imperfect glycine-glycine-methionine-proline (GGMP) tandem repeats in the parasite's cochaperone sequence. Immunofluorescence studies show that the protein is an abundant cytosolic protein of the parasite. However, antibodies raised against the GGMP repeat domain, which is also found in other parasite chaperones, react with both the parasite and host erythrocyte membrane. The reactivity with the host membrane suggests that the parasite exports molecular chaperones into the infected erythrocyte.

Amino Acid Sequence↗