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V Ramesh

Publications and source records attributed to V Ramesh.

At least 37 records · Page 2Linked to original sources
PubMed2004

Reversible immunocontraception in male monkeys immunized with eppin.

Various forms of birth control have been developed for women; however, there are currently few options for men. The development of male contraceptives that are effective, safe, and reversible is desired for family planning throughout the world. We now report contraception of male nonhuman primates (Macaca radiata) immunized with Eppin, a testis/epididymis-specific protein. Seven out of nine males (78%) developed high titers to Eppin, and all of these high-titer monkeys were infertile. Five out of seven (71%) high-anti-Eppin titer males recovered fertility when immunization was stopped. This study demonstrates that effective and reversible male immunocontraception is an attainable goal. This method of immunocontraception may be extended to humans.

Animals↗
PubMed2004

Infantile hereditary spastic paraparesis due to codominant mutations in the spastin gene.

The authors describe an infant with a severe spastic paraparesis caused by two codominant mutations of the spastin gene. This highlights the multiple molecular mechanisms that are likely to be involved in the molecular pathology of SPG4 and illustrates the importance of complete screening of the spastin gene in affected individuals, particularly if the index case has an unusual phenotype.

Adenosine Triphosphatases↗
PubMed2004

Mycobacterium tuberculosis Rv2118c codes for a single-component homotetrameric m1A58 tRNA methyltransferase.

Modified nucleosides in tRNAs play important roles in tRNA structure, biosynthesis and function, and serve as crucial determinants of bacterial growth and virulence. In the yeast Saccharomyces cerevisiae, mutants defective in N1-methylation of a highly conserved adenosine (A58) in the TPsiC loop of initiator tRNA are non-viable. The yeast m1A58 methyltransferase is a heterotetramer consisting of two different polypeptide chains, Gcd14p and Gcd10p. Interestingly, while m1A58 is not found in most eubacteria, the mycobacterial tRNAs have m1A58. Here, we report on the cloning, overexpression, purification and biochemical characterization of the Rv2118c gene-encoded protein (Rv2118p) from Mycobacterium tuberculosis, which is homologous to yeast Gcd14p. We show that Rv2118c codes for a protein of approximately 31 kDa. Activity assays, modified base analysis and primer extension experiments using reverse transcriptase reveal that Rv2118p is an S-adenosyl-l-methionine-dependent methyltransferase which carries out m1A58 modification in tRNAs, both in vivo and in vitro. Remarkably, when expressed in Escherichia coli, the enzyme methylates the endogenous E.coli initiator tRNA essentially quantitatively. Furthermore, unlike its eukaryotic counterpart, which is a heterotetramer, the mycobacterial enzyme is a homotetramer. Also, the presence of rT modification at position 54, which was found to inhibit the Tetrahymena pyriformis enzyme, does not affect the activity of Rv2118p. Thus, the mycobacterial m1A58 tRNA methyltransferase possesses distinct biochemical properties. We discuss aspects of the biological relevance of Rv2118p in M.tuberculosis, and its potential use as a drug target to control the growth of mycobacteria.

Amino Acid Sequence↗
PubMed2004

Cerebral edema associated with betaine treatment in classical homocystinuria.

A child with cystathionine beta-synthase deficiency developed cerebral edema 4 to 6 weeks after starting betaine therapy. There was no evidence of intracranial thrombosis, but there was widespread edema of the white matter. He recovered fully after emergency decompressive craniotomy and withdrawal of betaine.

Betaine↗
PubMed2004

Induction of infertility in adult male bonnet monkeys by immunization with phage-expressed peptides of the extracellular domain of FSH receptor.

Active immunization of proven fertile adult male bonnet monkeys (Macaca radiata) with phage-expressed follicle-stimulating hormone receptor (FSHR)-specific peptides from the extracellular domain resulted in a progressive drop in sperm count with all animals becoming azoospermic by day 100. However, serum testosterone concentrations were unaltered during the entire course of study and animals exhibited normal mating behaviour. Breeding studies with proven fertile female monkeys revealed that all the immunized males were infertile. Following interruption of immunization on day 225, sperm counts returned to normal with restoration of fertility. These results indicate that infertility can be induced in adult male monkeys by interfering with the action of FSH using specific peptides of the extracellular domain of FSHR as antigens, without the risk of producing cross-reacting antibodies to the other glycoprotein hormones.

Animals↗
PubMed2004

T1 and M1 polymorphism in glutathione S-transferase gene and coronary artery disease in North Indian population.

BACKGROUND: DNA damage has been found to play an important role in atherosclerosis and coronary artery disease. Genetic polymorphisms of the genes coding for enzymes involved in the metabolism of genotoxins result in different phenotypes with respect to their ability to detoxify these agents. In the present study the contribution of the polymorphism in the glutathione S-transferase gene to the development of coronary artery disease has been investigated. METHODS: One hundred and ninety seven angiographically proven patients with coronary artery disease and one hundred and ninety eight age-matched controls were genotyped for glutathione S- transferase polymorphism by polymerase chain reaction. Genotype frequencies were compared in patients and controls by Chi-square test. Binary logistic regression was used to examine the relationship between genotype and disease, incorporating other variables into the model. RESULTS: GSTT1 null genotype was significantly decreased in patients with coronary artery disease. No significant association was found with GSTM1 genotypes. No such association was seen with smokers. CONCLUSION: Null genotype of GSTT1 is protective against coronary artery disease in our population.

Adult↗
PubMed2003

Serial MRI in a case of familial hemiplegic migraine.

We report MRI findings in a patient with familial hemiplegic migraine (FHM) with repeated episodes of hemiparesis. FHM is caused by a penetrant autosomal dominant genetic mutation; several mutations have been genotyped, involving brain-expressed ion channels. We found cerebral oedema, dilatation of intracerebral vessels and decreased water diffusion contralateral to the hemiparesis, not respecting vascular territories, with subsequent complete resolution of both clinical and imaging abnormalities. These results are thought to be consistent with an underlying primary neuronal pathology with secondary vascular effects, as opposed to the traditional, primarily vascular, model of migraine aetiology.

Adolescent↗
PubMed2003

Identification of parasite antigen, correlation of parasite density and inflammation in skin lesions of post kala-azar dermal leishmaniasis.

BACKGROUND: Post kala-azar dermal leishmaniasis (PKDL) is an unusual dermatosis following kala-azar (KA). Demonstration of the amastigotes in lesions plays an important role in the diagnosis of PKDL. It was aimed to evaluate the utility of an antibody G2D10 in detecting leishmania parasite antigen, to correlate the parasite number/percentage of parasites with the inflammation, and to assess the epidemiological significance associated with the location of the parasites. MATERIAL AND METHODS: The study was conducted on 50 cases. Hematoxylin and eosin (H & E) stains and immunohistochemical (IHC) stains, using G2D10 antibody, was performed on the skin biopsies. The number of parasites and density of inflammation were semiquantitatively assessed. RESULTS: Leishmania donovan bodies (LDBs) were identified in 50% of cases with the H & E compared to 80% positivity with the IHC. All 50 cases showed inflammation in the superficial dermis (SD). About 44% showed dense inflammation compared to 16% sparse and 40% moderate inflammation. Parasite percentage was maximum in the SD (100%) compared to 75 and 42% in the mid and deep dermis, respectively. CONCLUSIONS: The IHC showed a higher percentage of LDB localization (80 vs. 50%). Density of inflammation was maximum in the SD. The parasite percentage was correlated with the inflammation. Location of parasites could have an epidemiological significance.

Adolescent↗
PubMed2003

Aspects of tuberous sclerosis complex (TSC) protein function in the brain.

Tuberous sclerosis complex (TSC), an autosomal dominant disease caused by mutations in either TSC1 or TSC2, is characterized by the development of hamartomas in a variety of organs. Concordant with the tumour-suppressor model, loss of heterozygosity (LOH) is known to occur in these hamartomas at both TSC1 and TSC2 loci. LOH has been documented in renal angiomyolipomas, but loss of the wild-type allele in cortical tubers appears very uncommon. We analysed 24 hamartomas from 10 patients for second-hit mutations by several methods, and found no evidence for the inactivation of the second allele in many of the central nervous system (CNS) lesions, including tumours that appear to be clonally derived. We believe that somatic mutations in TSC1 and TSC2 resulting in the loss of wild-type alleles may not be necessary in some tumour types, and other mechanisms may contribute to tumorigenesis in this setting. We have shown that hamartin interacts with neurofilament light chain (NF-L) and could integrate the neuronal cytoskeleton through its direct interaction with NF-L and ERM (ezrin/radixin/moeisin) proteins. Our unpublished work further documents the binding of tuberin with Pam, a protein associated with c-Myc, which is enriched in brain. All these observations suggest that the tuberin-hamartin complex is likely to have distinct functions in the CNS.

Cytoskeleton↗
PubMed2003

Parasite detection in patients with post kala-azar dermal leishmaniasis in India: a comparison between molecular and immunological methods.

AIMS: To evaluate the sensitivity and specificity of serological, immunohistochemical, and molecular methods in the diagnosis of post kala-azar dermal leishmaniasis (PKDL). METHODS: Twenty five patients with confirmed PKDL and 25 controls were included in the study. G2D10, a monoclonal antibody against Leishmania, was used for the immunohistochemical (IHC) staining of lesion sections to visualise anti-Leishmania donovani antibodies. The diagnostic usefulness of IHC was compared with enzyme linked immunosorbent assay (ELISA) with a recombinant (rk39) antigen, and a species specific polymerase chain reaction (PCR) assay, amplifying a kinetoplast minicircle DNA sequence. RESULTS: IHC detected 22 of 25 PKDL cases, giving a sensitivity of 88%. The diagnostic sensitivity of both the ELISA and PCR tests was higher (96%). All of the 25 controls examined were negative in PCR, indicating 100% specificity of the test, whereas ELISA showed 96% specificity. CONCLUSIONS: IHC with G2D10 significantly enhances the sensitivity of detection of PKDL over routine haematoxylin and eosin staining. ELISA with a recombinant antigen is an economical and practical assay. PCR is the most sensitive and specific diagnostic method for PKDL. The tests described would facilitate the recognition of patients with PKDL, enabling timely treatment, which would contribute greatly to the control of kala-azar.

Adolescent↗
PubMed2003

Kindler syndrome: two additional features.

Kindler syndrome is a hereditary condition that combines the features of blistering and photosensitivity in infancy and early childhood with progressive poikiloderma. We report additional features observed in one affected individual.

Adult↗
PubMed2003

Absence of factor V Leiden (G1691A) mutation, FII G20210A allele in coronary artery disease in North India.

BACKGROUND: Interaction between various genetic and environmental factors is associated with coronary artery diseases (CADs). Factor V Leiden mutation (FVL) and FII G20210A polymorphism are two recently described genetic factors with a propensity towards venous thrombosis, however, with a doubtful role in coronary artery disease and myocardial infarction. AIM: Present study was conducted to assess the relationship of both these factors in coronary artery disease in population from North India. SETTING AND DESIGN: Case control study. MATERIAL AND METHODS: Two hundred angiographically proven coronary artery disease patients were studied to examine the association of Factor V Leiden mutation and FII G20210A mutation with coronary artery disease and myocardial infarction. Out of 200 patients, 51 had myocardial infarction. Two hundred controls were selected who were from north India and were also age and sex matched. RESULTS AND CONCLUSIONS: Our results indicate that both these polymorphisms were totally absent in our population, therefore, these variants cannot be considered as independent risk factors or as a predictor for CAD. However, there is a need to confirm the above findings on patients from different populations from different parts of the country as there are reports which show that the incidence of Factor V Leiden varies from 1.3 % to 10%.

Adult↗
PubMed2003

Fixed drug eruption to ibuprofen in daughter and father.

Fixed drug eruption (FDE) is a common cutaneous reaction which may be seen in reaction to several medications. The usual etiologic agents associated with FDE are phenazones, sulfonamides, and tetracyclines. Often the causative agent is made out from the patients history; in some cases, oral challenge or topical testing may be required. The pathophysiology of FDE is unclear. Cell-mediated, rather than humoral immunity is thought to be involved. Herein we report a case of FDE in a daughter and father.

Adolescent↗
PubMed2002

Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep-wakefulness and prolonged wakefulness: an in vivo microdialysis study.

Increased activity of the histaminergic neurons of the posterior hypothalamus has been implicated in the facilitation of behavioral wakefulness. Recent evidence of reciprocal projections between the sleep-active neurons of the preoptic/anterior hypothalamus and the histaminergic neurons of the tuberomammillary nucleus suggests that histaminergic innervation of the preoptic/anterior hypothalamic area may be of particular importance in the wakefulness-promoting properties of histamine. To test this possibility, we used microdialysis sample collection in the preoptic/anterior hypothalamic area of cats during natural sleep-wakefulness cycles, 6 h of sleep deprivation induced by gentle handling/playing, and recovery sleep. Samples were analyzed by a sensitive radioenzymatic assay. Mean basal levels of histamine in microdialysate during periods of wakefulness (1.155+/-0.225 pg/microl) did not vary during the 6 h of sleep deprivation. However, during the different sleep states, dramatic changes were observed in the extracellular histamine levels of preoptic/anterior hypothalamic area: wakefulness>non-rapid eye movement sleep>rapid eye movement sleep. Levels of histamine during rapid eye movement sleep were lowest (0.245+/-0.032 pg/microl), being significantly lower than levels during non-rapid eye movement sleep (0.395+/-0.081 pg/microl) and being only 21% of wakefulness levels. This pattern of preoptic/anterior hypothalamic area extracellular histamine levels across the sleep-wakefulness cycle closely resembles the reported single unit activity of histaminergic neurons. However, the invariance of histamine levels during sleep deprivation suggests that changes in histamine level do not relay information about sleep drive to the sleep-promoting neurons of the preoptic/anterior hypothalamic area.

Animals↗