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Biomedical subjects

J Kumar

Publications and source records attributed to J Kumar.

At least 37 records · Page 2Linked to original sources
PubMed2001

Granulysin: a novel antimicrobial.

Granulysin is a novel lytic molecule produced by human cytolytic T-lymphocytes (CTLs) and natural killer (NK) cells. It is active against a broad range of microbes, including Gram-positive and -negative bacteria, parasites and Mycobacterium tuberculosis. It is functionally related to other antibacterial peptides, like defensins and magainins, but is structurally distinct. It has structural similarity to porcine NK-lysin and to amoebapores made by Entamoeba histolytica. Synthetic peptides derived from granulysin have differential activity against eukaryotic cells and bacteria. Selective bactericidal peptides may have therapeutic roles as novel antibiotics.

Amino Acid Sequence↗
PubMed2001

Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y-27632.

PURPOSE: The goal of this study was to investigate the role of Rho kinase in the modulation of aqueous humor outflow facility. Rho kinase, a critical downstream effector of Rho GTPase is recognized to control the formation of actin stress fibers, focal adhesions, and cellular contraction. METHODS: Expression of Rho GTPase, Rho kinase, and other downstream targets of Rho GTPase were determined in human trabecular meshwork (HTM) and Schlemm's canal (SC) primary cell cultures by Western blot analysis. The Rho kinase-specific inhibitor (Y-27632)-induced changes in actin stress fibers, focal adhesions, and protein phosphotyrosine status were evaluated by staining with rhodamine-phalloidin, anti-paxillin, and anti-phosphotyrosine antibodies, respectively. Myosin light-chain phosphorylation was determined by Western blot analysis. Y-27632-induced changes in SC cell monolayer permeability were quantitated using a colorimetric assay to evaluate horseradish peroxidase diffusion through SC cell monolayers grown in transwell chambers. Aqueous humor outflow facility was measured using enucleated porcine eyes and a constant-pressure perfusion system. RESULTS: Treatment of HTM and SC cells with Y-27632 (10 microM) led to significant but reversible changes in cell shape and decreases in actin stress fibers, focal adhesions, and protein phosphotyrosine staining. SC cell monolayer permeability increased (by 80%) in response to Y-27632 (10 microM) treatment, whereas myosin light-chain phosphorylation was decreased in both HTM and SC cells. Aqueous humor outflow facility increased (40%-80%) in enucleated porcine eyes perfused with Y-27632 (10-100 microM), and this effect was associated with widening of the extracellular spaces, particularly the optically empty area of the juxtacanalicular tissue (JCT). The integrity of inner wall of aqueous plexi, however, was observed to be intact. CONCLUSIONS: Based on the Rho kinase inhibitor-induced changes in myosin light-chain phosphorylation and actomyosin organization, it is reasonable to conclude that cellular relaxation and loss of cell-substratum adhesions in HTM and SC cells could result in either increased paracellular fluid flow across Schlemm's canal or altered flow pathway through the JCT, thereby lowering resistance to outflow. This study also suggests Rho kinase as a potential therapeutic target for the development of drugs to modulate intraocular pressure in glaucoma patients.

Actins↗
PubMed2001

A prospective study of 413 cases of lens-induced glaucoma in Nepal.

PURPOSE: To determine the frequency and types of lens-induced glaucoma (LIG), reasons for late presentation and outcome of current management. METHODS: Prospective case series of 413 patients/eyes with LIG over a 12-month period in 1998; 311 of these patients underwent cataract surgery. Visual acuity and intraocular pressure (IOP) were pre- and postoperatively assessed. RESULTS: Four hundred and thirteen (1.5%) of 27,073 senile cataracts seen in the outpatient department of Sagarmatha Choudhary Eye Hospital, Lahan, Nepal presented with LIG. There were 298 (72%) phacomorphic cases and 115 (28%) phacolytic glaucoma. Pain for more than 10 days was reported by 293 (71%) patients. The majority, 258 (62.4%), travelled a distance of more than 100 kms to the hospital. The major reasons for late presentation were "no escort" in 143 (34.6%) and "lack of money" in 128 (31.0%) cases. At presentation the IOP was more than 30 mm Hg in 327 (79%) eyes. Following cataract surgery, 251 (80.7%) had 21 mm Hg or less at discharge. The visual acuity was hand-movement or less before surgery in all eyes; at discharge 120 of 311 operated eyes (38.6%) achieved 6/60 or better, 97 (31.2%) less than 6/60, and 94 (30.2%) less than 3/60. The main causes for poor outcome in 94 cases were optic atrophy in 32 (34%) eyes, uveitis in 25 (26.6%)eyes and corneal oedema in 24 (25.5%) eyes. CONCLUSION: The results highlight the importance of early diagnosis and treatment of visually disabling cataract. There is a need to educate both the patient and the cataract surgeon of the dangers of lens-induced glaucoma and of the poor outcome if treatment is delayed.

Adult↗
PubMed2000

Hepatitis B and C viral infections in Indian kala-azar patients receiving injectable anti-leishmanial drugs: a community-based study.

BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis B and hepatitis C viruses have emerged as major blood-borne infections. Several cases of infections through the use of unsterile injection needles also are on record. Kala-azar, or visceral leishmaniasis, is a hemoparasitic disease caused by Leishmania donovani. All the anti-kala-azar medications require multiple intramuscular injections of the anti-leishmanial drugs. To find whether these patients were at higher risk of contracting blood-borne infection, than those who were not on medication, a community-based study was conducted in the kala-azar-endemic state of Bihar, India. METHODS: Five villages (4050 families) of three highly endemic districts of Bihar were included in this study. The sociodemographic data of the affected families and their annual income were determined as per Government of India guidelines. The diagnosis of kala-azar and its sequelae, post-kala-azar dermal leishmaniasis (PKDL), was made, and their therapeutic details were noted. All the leishmania-infected patients, their spouses, family members, and villagemates were tested for hepatitis B surface antigen, hepatitis C virus antibodies, and anti-HIV (1 + 2) antibodies, using commercially available kits. RESULTS: Of the 4050 families, 61 (1.5%) were found affected with kala-azar or PKDL. These 61 families had 77 cases of leishmaniasis, of which 64 (83%) had kala-azar and 13 (17%) PKDL. The most affected (4.5%) age group was 11 to 40 years. Of the 61 families, 57 (93.4%) families belonged to so-called untouchable castes, and 9 of them could not afford to have any anti-kala-azar treatment. Only 64 patients received treatment in the form of injectables. The number of injections received by these patients ranged from 3 to 120. Hepatitis B and C viral infections were found to be significantly more prevalent in those who received multiple injections. Compared to their male counterparts infected with L. donovani, females who received injectable medicines were at higher risk of contracting hepatitis B infections (20% vs. 11.3%) and hepatitis C virus infection (26.7% vs. 18.9%). Overall, hepatitis C virus infections were more common (20.6%) than hepatitis B virus infection (13.2%) in this group of patients. Villagemates with a history of injections for other ailments also were found to have a high rate of infection with hepatitis viruses. One patient with kala-azar was found to be co-infected with HIV, although probably not related to injections. CONCLUSIONS: The treatment of Indian kala-azar and post-kala-azar dermal leishmaniasis consists of multiple intramuscular injections of sodium stibogluconate, pentamidine, or amphotericin B. Though the original disease gets cured, all these therapeutic regimens were found to carry a significantly high risk of transmitting yet more dangerous blood-borne infections, such as HIV and hepatitis B and C viruses, through the shared use of unsterile injection needles. All needles should be appropriately sterilized, if they are to be re-used.

Adolescent↗
PubMed2000

Intra-oral distribution of dental fluorosis in Newburgh and Kingston, New York.

Previous studies of intra-oral distribution of dental fluorosis in low-fluoride areas reported that teeth that formed later in life were more frequently affected compared with the early-forming teeth. The steady increase of plasma fluoride with age, even under constant fluoride exposure, has been suggested as a possible mechanism for this clinical manifestation. To determine the intra-oral distribution of Dean's Index scores and the effect of fluoride exposure on early- and late-forming teeth, we analyzed data collected on 2193 seven- to 14-year-old lifelong residents of fluoridated or non-fluoridated areas. Logistic regression procedures were used to determine the effects of fluoridation, early brushing, daily supplements, and other socio-demographic variables on early- and late-forming teeth. The results show that the occurrence of very mild or greater levels of fluorosis in the upper anterior teeth was 7 to 10% in the fluoridated area and 5 to 9% in the nonfluoridated area. In the fluoridated area, the occurrence of fluorosis increased from anterior to posterior teeth. Both early- and late-forming teeth were affected by exposure to fluoridation, daily fluoride supplement use, or brushing before the age of two years. This analysis showed that the esthetic consequence of exposure to multiple sources of fluoride was less dramatic, as evidenced by the lower frequency in upper anterior teeth compared with posterior teeth. The longer maturation process of the posterior teeth and the thicker enamel appear to be the likely explanation for the higher occurrence of dental fluorosis in posterior teeth.

Adolescent↗
PubMed2000

Trend of antimicrobial resistance in Neisseria gonorrhoeae at New Delhi, India.

We aim to monitor the trends of antimicrobial resistance in Neisseria gonorrhoeae and to compare the results of antimicrobial sensitivity by disc diffusion and minimum inhibitory concentration (MIC). Two hundred and eleven confirmed strains of N. gonorrhoeae were subjected to antimicrobial sensitivity testing by disc diffusion using penicillin, tetracycline, ciprofloxacin and ceftriaxone from 1995 to June 1999. Penicillinase-producing Neisseria gonorrhoeae (PPNG) were detected by lodometric method. Minimum inhibitory concentration was determined by E test. A low level of penicillin resistance and PPNG detected in 1996 was maintained over the years. Significant increasing trend of tetracycline and ciprofloxacin resistance with high MIC i.e. 2-96 microg/ml and 1-32 microg/ml respectively were found. Ceftriaxone was found to be the drug of choice, being 100% sensitive. Comparison of resistance pattern by the 2 tests showed satisfactory agreement. Emergence of penicillin, quinolone and tetracyline resistance in N. gonorrhoeae isolates from a major STD centre at New Delhi indicates the need for increased awareness, prudent use of antimicrobials, and evaluation of new antimicrobials for the treatment of gonorrhoea.

Ceftriaxone↗
PubMed1999

Ovarian response after laparoscopic ovarian cystectomy for endometriotic cysts in 132 monitored cycles.

OBJECTIVE: To investigate the follicular response of ovaries after laparoscopic ovarian cystectomy for endometriotic cysts. DESIGN: A retrospective, controlled study. SETTING: Obstetrics and Gynaecology Department of a university hospital. PATIENT(S): Patients with history of infertility who had laparoscopic ovarian cystectomy for endometriotic cysts. INTERVENTION(S): Laparoscopic ovarian cystectomy, transvaginal ultrasound monitoring of follicles in natural cycles, stimulated cycles using clomiphene citrate (CC), chronic low-dose FSH, and "flare down" regimen. MAIN OUTCOME MEASURE(S): Follicular response of postcystectomy and normal ovaries. RESULT(S): For women < 35 years of age, the mean follicular response of postcystectomy ovaries was reduced significantly when compared with normal ovaries in natural cycles (0.30 versus 1.00 follicle per cycle) and in CC-stimulated cycles (0.87 versus 1.27 follicles per cycle). The mean follicular response was not statistically significantly different when the ovaries were stimulated with chronic low-dose FSH or with the flare down regimen. For women > or = 35 years, postcystectomy ovaries responded with a comparable number of follicles as the normal ovaries in natural cycles and the three different ovarian stimulation regimens. CONCLUSION(S): Postcystectomy ovaries showed reduced follicular response in natural and CC-stimulated cycles for women < 35 years of age. Postcystectomy ovaries produced a comparable number of follicles as normal ovaries when stimulated with gonadotropins.

Adult↗
PubMed1999

Stabilization of azadirachtin A in neem formulations: effect of some solid carriers, neem oil, and stabilizers.

Formulation of azadirachtin A on attapulgite, kaolinite, fuller's earth, hydrated calcium silicate, and fly ash revealed that it degraded to the tune of 70-95% on different solid carriers as compared to 56% in neem oil, during the 14 day heat storage studies at 54 +/- 1 degrees C in the laboratory. The degradation was reduced by 26-60% on different carriers by employing either anthraquinone or epichlorohydrin as stabilizer. Pyrogallol and hydroquinone enhanced the degradation. The cation exchange capacity and surface area of the carriers revealed a significant negative correlation with t(1/2) of azadirachtin A.

Chemistry, Pharmaceutical↗
PubMed1999

Population structure and dynamics of Magnaporthe grisea in the Indian Himalayas.

The population genetics of Magnaporthe grisea, the rice blast pathogen, were analyzed in a center of rice diversity (the Uttar Pradesh hills of the Indian Himalayas) using multilocus and single-, or low-copy, DNA markers. Based on DNA fingerprinting with the multilocus probe MGR586 and single-locus probes, 157 haplotypes clustered into 56 lineages (at >/=70% MGR586 band similarity, each with unique single-locus profiles) and high diversity indices were detected among 458 isolates collected from 29 sites during 1992-1995. Most valleys sampled had distinct populations (73% of the lineages were site specific) with some containing one or a few lineages, confirming the importance of clonal propagation, and others were very diverse. Widely distributed lineages suggested that migration occurs across the region and into the Indo-Gangetic plains. Repeated sampling at one site, Matli, (170 isolates, 1992-1995) yielded 19 lineages and diversity significantly greater than that reported from similar samples from Colombia and the Philippines. Analysis of allelic associations using pairwise comparisons and multilocus variance analysis failed to reject the hypothesis of gametic phase equilibrium. The Matli population shifted from highly diverse in 1992 to almost complete dominance by one lineage in 1995. Such population dynamics are consistent with recombination followed by differential survival of clonal descendants of recombinant progeny. At another site, Ranichauri, population (n = 84) composition changed from 2 to 11 lineages over 2 yr and yielded additional evidence for equilibrium. Sexually fertile and hermaphrodite isolates of both mating types were recovered from rice in both Matli and Ranichauri. We demonstrate that Himalayan M. grisea populations are diverse and dynamic and conclude that the structure of some populations may be affected to some extent by sexual recombination.

Crosses, Genetic↗
PubMed1999

Evidence for a protein mutator in yeast: role of the Hsp70-related chaperone ssb in formation, stability, and toxicity of the [PSI] prion.

Propagation of the yeast protein-based non-Mendelian element [PSI], a prion-like form of the release factor Sup35, was shown to be regulated by the interplay between chaperone proteins Hsp104 and Hsp70. While overproduction of Hsp104 protein cures cells of [PSI], overproduction of the Ssa1 protein of the Hsp70 family protects [PSI] from the curing effect of Hsp104. Here we demonstrate that another protein of the Hsp70 family, Ssb, previously implicated in nascent polypeptide folding and protein turnover, exhibits effects on [PSI] which are opposite those of Ssa. Ssb overproduction increases, while Ssb depletion decreases, [PSI] curing by the overproduced Hsp104. Both spontaneous [PSI] formation and [PSI] induction by overproduction of the homologous or heterologous Sup35 protein are increased significantly in the strain lacking Ssb. This is the first example when inactivation of an unrelated cellular protein facilitates prion formation. Ssb is therefore playing a role in protein-based inheritance, which is analogous to the role played by the products of mutator genes in nucleic acid-based inheritance. Ssb depletion also decreases toxicity of the overproduced Sup35 and causes extreme sensitivity to the [PSI]-curing chemical agent guanidine hydrochloride. Our data demonstrate that various members of the yeast Hsp70 family have diverged from each other in regard to their roles in prion propagation and suggest that Ssb could serve as a proofreading component of the enzymatic system, which prevents formation of prion aggregates.

Adenosine Triphosphatases↗
PubMed1999

The clinical management of male infertility.

Male infertility is a common cause of subfertility for which sperm disorders are the single most common cause. Genetic abnormalities, for example, microdeletions associated with the Y chromosome, defects in the androgen receptor gene and cystic fibrosis have gained recent prominence and it is envisaged that many of the 60% of men for which no cause is found may have a genetic basis for their subfertility. Although an abnormal semen analysis is commonly the first indicator of a male factor problem, further tests are usually required. Empirical treatment with hormones, varicocelectomy and immunological treatment have been proven to be disappointing whilst the treatment of infection and obstruction do not always translate into significantly higher fertility rates. Ejaculatory disorders and impotence can be effectively treated today whilst donor insemination can be offered to men with untreatable infertility. The advent of assisted reproduction and micromanipulation has greatly improved prospects for fertility of men with very poor semen quality. However, the genetic implications of these procedures have to be quickly addressed so that fertility is maximised without risk to the progeny.

Diagnosis, Differential↗
PubMed1999

Assisted reproductive techniques--promises and problems.

Assisted reproductive techniques (ART) are procedures in which the oocyte is handled before replacement, either as an oocyte or embryo. The current success rates and pregnancy outcomes of in-vitro fertilisation (IVF), gamete intra-fallopian transfer (GIFT), zygote intra-fallopian transfer (ZIFT), intra-cytoplasmic sperm injection (ICSI), donor oocyte and frozen embryo programmes are reviewed. Some problems associated with assisted reproductive procedures are also discussed.

Female↗
PubMed1998

Ultrastructural and biochemical properties of the 120-kDa form of chick kinectin.

Kinectin, an integral membrane protein (160 kDa), was identified as a kinesin-binding protein. Analysis of the predicted amino acid sequence of kinectin cDNA indicated an alpha-helical coiled-coil structure from amino acid 320 to 1310. A 120-kDa kinectin has been observed consistently, and N-terminal sequencing showed that 232 amino acids were missing from the N terminus of full-length kinectin. 120-kDa kinectin was distributed in the supernatant and a low density fraction of vesicles, whereas both forms were in the high density fraction of vesicles. In the electron microscope, the 120-kDa form appeared as a linear molecule of 133 nm in length. In hydrodynamic studies, the cytosolic 120-kDa kinectin was a dimer. Monoclonal antibody molecules (anti-kinectin KR160.9) bound asymmetrically to kinectin often with two antibodies/kinectin, indicative of a parallel coiled-coil. Metabolic labeling with [3H]myristic acid showed that both the 120- and 160-kDa kinectin are myristoylated in chick embryo fibroblasts. The myristoylation of 120-kDa kinectin may provide a mechanism for linking it to a low density fraction of vesicles. Immunoprecipitation with a 160-kDa kinectin-specific antibody brought down the 120-kDa kinectin. Thus, we suggest that kinectin is an extended parallel coiled-coil dimer, often a heterodimer.

Amino Acid Sequence↗
PubMed1998

Blastocyst transfer after enzymatic treatment of the zona pellucida: improving in-vitro fertilization and understanding implantation.

It has been shown recently that delayed transfers improve implantation rates in assisted reproductive technology programmes. In a prospective study, the pregnancy rates and safety of outcome were evaluated in a group of patients after the transfer of day 5 blastocysts with enzymatic treatment of the zona pellucida. Nineteen women with a mean age of 32.6+/-5.2 years and mean 2.1+/-2.2 repeated attempts had blastocyst transfers with a mean number of 2.5+/-0.7 embryos replaced per patient. The clinical pregnancy rates per cycle/transfer and implantation rate were 53% and 33%, respectively. The multiple pregnancy rate was 40% (two pregnancies were triplets). The pregnancy and implantation rates were very much higher than observed for most assisted reproduction technology centres. The 'in-vitro implantation' rates of zona-free blastocysts on a variety of feeder monolayers was 92%, offering some thoughts as to the role of the zona and interaction of the inner cell mass and trophoectoderm with the endometrium in implantation. Based on the in-vitro studies and the high multiple pregnancy rates, it appears that zona-manipulated blastocysts implant relatively well and there would be a need to reduce the number of transferred embryos to one or two, thus reducing multiple pregnancies and having spare blastocysts available for cryopreservation. The results also suggest that using the embryo culture protocol and method of transfer in the present study offers encouraging improvements to assisted reproduction technology, and enzymatic treatment of the zona may allow better anchorage and dialogue of the embryo with the endometrium, helping us to improve and understand implantation.

Adult↗
PubMed1998

The first 2 case reports of frozen embryo donation twin pregnancies in Singapore: hormonal profiles and obstetrical outcome.

A 35 year old women with premature ovarian failure and another 30 year old women with gonadal dysgenesis were the recipients of donated supernumerous frozen embryos after successfully prepared with cyclic steroid replacement therapy as described previously. One patient received 4 and the second 2 frozen embryos, transferred transcervically on the 3rd day of progesterone administration. Both patients had viable twin pregnancies. The plasma beta hCG levels for both patients at 2 weeks post replacement (4 weeks gestation) were lower than the median values in our normal, uncomplicated singleton pregnancy for the same gestation. The level after 4 weeks post-replacement (6 weeks gestation) became comparable. Plasma progesterone profiles suggested a level of above 70 ng/ml would be enough to support the twin pregnancies. The first patient developed antepartum haemorrhage of unknown origin at 34 weeks of gestation preceding preterm premature rupture of membranes and subsequently had preterm labour. The second patient developed proteinuric hypertension at 33 weeks of gestation. Both ended in a lower segment cesarean section. Both sets of twins and their mothers were discharged well.

Adult↗
PubMed1997

Responses of polycystic ovarian syndrome and related variants to low-dose follicle stimulating hormone.

OBJECTIVE: To determine whether patients with classical polycystic ovarian syndrome (PCOS) respond differently to low-dose FSH therapy in comparison with anovulatory patients (PCOS-like) where only some features of PCOS are present. METHODS: Two groups of patients were studied. The PCOS group (25 patients, 51 cycles) and the PCOS-like group (38 patients, 57 cycles) were treated with the same protocol of purified FSH, commencing with an initial dosage of 75 IU/day and increasing by 37.5 IU/day after 14 days, where necessary. Estradiol levels and ultrasonographic evidence of follicular development were used for monitoring. RESULTS: PCOS patients required more ampules of FSH, needed more days of gonadotropin stimulation, secreted higher levels of E2 and had increased numbers of intermediate follicles compared to the PCOS-like group. CONCLUSIONS: This study demonstrated significant differences between PCOS and other PCOS-like conditions when treated with low-dose FSH. Classification of the subvariants of PCOS may have therapeutic implications.

Adult↗