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Biomedical subjects

N Singh

Publications and source records attributed to N Singh.

At least 361 records · Page 20Linked to original sources
PubMed1996

Replication error phenotype and p53 gene mutation in lymphomas of mucosa-associated lymphoid tissue.

Low grade mucosa-associated lymphoid tissue (MALT) lymphomas commonly arise from a background of chronic inflammatory lesions and can transform into high grade tumors at a late stage. Because chronic inflammation is closely associated with genetic instability, which is one of the mechanisms leading to activation of oncogenes and inactivation of tumor suppressor genes, it is possible that genetic instability plays an important role in MALT lymphomagenesis. In this study, we have examined the frequency of replication error (RER+) phenotype, a newly defined manifestation of genetic instability, and its relationship to p53 mutations in 40 MALT lymphomas (16 high grade and 24 low grade). RER+ phenotype was detected in 21/40 (52.5%) MALT lymphomas (12/24, 50% in low grade; 9/16, 56.2% in high grade). Five of seven reactive lymphoid infiltrates adjacent to tumors also showed one microsatellite alteration, four of which were identified in the corresponding lymphoma lesions in the same patient. In five RER+ high grade lymphomas with low grade lesions, homogeneous and heterogeneous microsatellite alterations were observed between the two components. The same 40 cases were investigated for p53 gene mutations at exons 5 to 8 by PCR-SSCP and direct sequencing. p53 point mutations were found in 11 (27.5%) of the 40 cases. These mutations were statistically related to RER+ phenotype (P < 0.05). Our results demonstrate that the RER+ phenotype is a common genetic feature of MALT lymphomas. Genetic instability occurs throughout the spectrum of the lymphoma development and may be related to the accumulation of genetic aberrations such as p53 mutations. The observation of identical microsatellite alterations between the adjacent lymphoid infiltrates and their corresponding lymphomas provides genetic evidence for evolutionary link of the two lesions. The homogeneous and heterogeneous microsatellite alterations observed between low and high grade components indicate their clonal lineage and genetic diversity.

Base Sequence↗
PubMed1996

Malaria parasite density in pregnant women of district Jabalpur, Madhya Pradesh.

Twenty-two cases (nineteen Plasmodium falciparum and three P. vivax) of severe malaria among 200 pregnant women from District Jabalpur, M.P. were studied for malaria parasite density. Almost all of them were found anaemic. The patients were treated with quinine/chloroquine intravenously but seventeen Pf cases died within 96 h of admission in hospital. Out of twenty-two, thirteen were primigravidae.

Adolescent↗
PubMed1996

Parvovirus B19 infection in a liver transplant recipient: case report and review in organ transplant recipients.

We report an adult liver transplant recipient with parvovirus B19 infection, presenting as chronic transfusion-dependent anemia ensuing 1 month post-transplantation. Both serum and bone marrow cells were positive for parvovirus B19 DNA detected by polymerase chain reaction. The bone marrow biopsy revealed erythroid hypoplasia with a selective decrease of nucleated red cell precursors, and giant pronormoblasts with prominent intranuclear inclusions, characteristic of parvovirus B19 infection. Anemia and viremia resolved shortly after administration of immunoglobulin, suggesting a therapeutic role. This case and several similar ones in the literature provide justification for a controlled clinical trial of immunoglobulin for parvovirus-induced anemia in transplant recipients.

Adult↗
PubMed1996

Dynamics of malaria transmission in forested and deforested regions of Mandla District, central India (Madhya Pradesh).

A longitudinal malaria study was undertaken in 1990-91 in 2 adjacent ecological zones in central India: villages in forest and villages away from the forest. The prevalence of Anopheles species varied widely between the 2 ecological settings. In the villages in forest, Anopheles culicifacies and An. fluviatilis were mainly exophilic, whereas in the villages away from forest, An. culicifacies was predominantly endophilic and An. fluviatilis was equally prevalent both indoors and outdoors. The seasonal patterns of malaria transmission were also different between the 2 zones. Plasmodium falciparum was the dominant parasite species in the villages in forest, whereas malaria infection was mainly due to Plasmodium vivax in the villages away from forest. The annual parasite incidence was high in the villages in forest. The failure to control malaria in forested areas is rooted in the terrain and a variety of poorly understood sociological factors.

Animals↗
PubMed1996

Interferon-alpha therapy for hepatitis C virus recurrence after liver transplantation: long-term response with maintenance therapy.

Interferon-alpha is currently the only available treatment for HCV hepatitis. We assessed the safety and efficacy of 6 month course of interferon therapy in 18 consecutive liver transplant recipients with recurrent HCV hepatitis and report the long-term response with maintenance interferon. Median follow-up after the institution of interferon was 24 months. Complete response was defined as normalization of both aspartate and alanine aminotransferase. Complete response after 6 months of interferon was observed in 28% (5/18); an additional 33% (6/18) of the patients were late responders. Overall, 61% (11/18) of the patients had long-term sustained normal response at a median follow-up of 24 months. Long-term sustained response was observed in 73% (8/11) of the patients who continued interferon beyond 6 months vs. 43% (3/7) in those who received 6 months of interferon. Fatigue, headache and cytopenia were the most commonly observed side-effects occurring in 39%, 22% and 28% of the patients, respectively. Discontinuation of interferon, however, was not required in any of the patients. Rejection was documented in 6% (1/18) patients receiving interferon; this incidence was not higher than rejection episodes occurring > 6 months post-transplant in other recipients transplanted during the same period and who did not receive interferon. Responders had a trend towards later recurrence of HCV hepatitis after transplantation. In conclusion; maintenance interferon was well tolerated and appeared to improve the long-term outcome in our patients; however, future studies should evaluate this in a controlled trial.

Adult↗
PubMed1996

The role of telomeres and telomerase in human cancer.

Human cancers/malignant transformation of normal cells occur from multiple independent genetic changes/mutations that can subvert the normal growth controls of cells, leading to distinct phenotypic changes and immortalization. Normal human somatic cells have limited proliferative capacity both in vitro and in vivo and undergo senescence. Recent studies have implicated telomeres and telomerase in the regulation of lifespan of cells. Telomeres are the stretches of DNA consisting of tandem repeats of nucleotide sequences that cap chromosomes and prevent its degradation and play a role, both in normal control of cell proliferation and abnormal growth of cancers. They are highly conserved during evolution. Telomerase, the novel reverse transcriptase enzyme that synthesizes telomeric DNA is repressed in most human somatic cells, it results in telomere shortening with each cell division, leading to a process thought to contribute to senescence. Recent research proposes that activation of telomerase is important for cells to proliferate indefinitely and that all human cancer cells require activation of this enzyme to maintain telomeric DNA, to overcome cellular senescence and to attain immortality. Thus telomeres and telomerase offer potential for diagnostics, cancer therapy as well as for understanding the process of aging.

Humans↗
PubMed1996

Benzoyl peroxide modulates gene expression by epigenetic mechanism in mouse epidermal JB6 cells.

The mechanism by which an oxidant tumor promoter benzoyl peroxide (BP) influences signal transduction, was studied in promotion insensitive (P-), promotion sensitive (P+) and transformed (Tx) mouse epidermal JB6 cells. The basal levels of antioxidant enzymes CuZn-superoxide dismutase and catalase were higher in P+ and Tx JB6 cells. BP decreased the activities of these enzymes transiently in P+ and Tx cells, but induced them in P- JB6 cells. BP increased poly ADPR polymerase activity accompanied by a drop in NAD+ levels more significantly in P- JB6 cells, but did not affect PKC activity. It induced c-jun and c-fos gene expression in JB6 variants but to different extents, suggesting that it mediates its effects via genetic- epigenetic mechanism(s).

Animals↗
PubMed1996

Application of peptide ELISA in tribal malaria of Madhya Pradesh.

A recently developed peptide ELISA method was used for monitoring the efficacy of malaria control programme in the tribal areas of Madhya Pradesh. Both crude Pf antigen and synthetic nonapeptide were used in ELISA for seroepidemiological studies. Both antigen responded equally well but the synthetic peptide had advantages of purity, defined characteristic and easy availability. Population of Mandla protected by vector control measures showed lower antibody titre and lower percentage positivity compared to the unprotected population of Jabalpur. A 0-5 yrs sentinel population from Haldwani almost seronegative has been taken as control.

Animals↗
PubMed1995

Variant B human herpesvirus-6 associated febrile dermatosis with thrombocytopenia and encephalopathy in a liver transplant recipient.

Human herpesvirus 6 (HHV-6) is a recently discovered virus the pathogenicity of which in solid organ transplant recipients has not been defined. We describe a unique febrile syndrome due to disseminated invasive variant B HHV-6 infection in a liver transplant recipient with evidence of direct tissue invasion by the virus. Acute febrile illness characterized by life-threatening thrombocytopenia, progressive encephalopathy and skin rash developed in association with invasive HHV-6 infection in a liver transplant recipient. HHV-6 was isolated from the patient's peripheral blood in cell culture; variant B HHV-6 DNA was detected in the patient's peripheral blood mononuclear cells (PBMC) at a concentration greater than 1000 virus genomes per 10(6) PBMC. A bone marrow biopsy was also positive for HHV-6, documenting direct tissue invasion. Intravenous ganciclovir for three weeks led to a prompt clinical response. Although larger studies are warranted, our case suggests that HHV-6 should be considered in the diagnostic evaluation of patients with fever, cytopenia, and encephalopathy, particularly since HHV-6 is susceptible to ganciclovir and foscarnet.

Adult↗
PubMed1995

The accumulation of p53 abnormalities is associated with progression of mucosa-associated lymphoid tissue lymphoma.

The genetic mechanisms underlying the genesis of low-grade mucosa-associated lymphoid tissue (MALT) lymphomas and their transformation into high-grade lymphoma are poorly understood. p53 inactivation, commonly caused by mutation and allele loss, has been shown to play an important role in the early development and/or the late disease progression of many human tumors including lymphoid malignancies and, thus, may also be important in MALT lymphomagenesis. We examined 75 cases (48 low grade and 27 high grade) of MALT lymphoma for p53 allele loss and mutation as well as protein accumulation. DNA samples prepared from microdissected cell populations were used for the detection of p53 gene abnormalities. Loss of heterozygosity (LOH) of the gene was detected by polymerase chain reaction-based analysis of p53 CA repeat polymorphism, whereas p53 mutation was studied by single-strand conformation polymorphism analysis and direct sequencing. p53 expression was assessed by immunostaining with CM1 polyclonal antibody. p53 allele loss and mutation, which resulted in the alteration in the amino acid sequence, were found in both low-grade (LOH, 3 of 44 [6.8%]; mutation, 9 of 48 [18.8%]) and high-grade (LOH, 6 of 21 [28.6%]; mutation, 9 of 27 [33.3%]) MALT lymphomas, particularly in the latter group. p53 staining was not observed in any low-grade tumors but in 6 high-grade cases that harbored missense mutations. There were also differences in the extent of p53 abnormalities, between low- and high-grade tumors. Of the 11 low-grade tumors showing p53 abnormalities, only 1 tumor showed the concomitance of p53 mutation and allele loss, whereas in high-grade tumors, 6 of 9 affected cases displayed both p53 mutation and allele loss. Our results suggest that p53 partial inactivation may play an important role in the development of low-grade MALT lymphomas, whereas complete inactivation may be associated with high-grade transformation.

Alleles↗
PubMed1995

sur-2, a novel gene, functions late in the let-60 ras-mediated signaling pathway during Caenorhabditis elegans vulval induction.

We describe here a new gene acting downstream of let-60 ras in the vulval signaling pathway of Caenorhabditis elegans. The sur-2 (suppressor of ras) gene is defined by eight mutations identified in a genetic screen for suppressors of the Multivulva phenotype of let-60(n1046), an activated let-60 ras mutation. sur-2 mutations result in pleiotropic, incompletely penetrant phenotypes that include a Vulvaless phenotype in hermaphrodites, defects in development of the male tail, gonadal abnormalities, and larval lethality, indicating a role for the sur-2 gene product in multiple developmental events. Genetic epistasis analyses suggest that sur-2 is required late in the vulval signaling pathway, downstream of let-60 Ras, and is likely to act downstream of the Raf/MAP Kinase cascade. We cloned the sur-2 gene by DNA-mediated transformation and have shown that it encodes a novel protein. We also show that a sur-2::lacZ transgene is expressed in the vulval precursor cells at the time of vulval determination.

Amino Acid Sequence↗
PubMed1995

The membrane of peroxisomes in Saccharomyces cerevisiae is impermeable to NAD(H) and acetyl-CoA under in vivo conditions.

We investigated how NADH generated during peroxisomal beta-oxidation is reoxidized to NAD+ and how the end product of beta-oxidation, acetyl-CoA, is transported from peroxisomes to mitochondria in Saccharomyces cerevisiae. Disruption of the peroxisomal malate dehydrogenase 3 gene (MDH3) resulted in impaired beta-oxidation capacity as measured in intact cells, whereas beta-oxidation was perfectly normal in cell lysates. In addition, mdh3-disrupted cells were unable to grow on oleate whereas growth on other non-fermentable carbon sources was normal, suggesting that MDH3 is involved in the reoxidation of NADH generated during fatty acid beta-oxidation rather than functioning as part of the glyoxylate cycle. To study the transport of acetyl units from peroxisomes, we disrupted the peroxisomal citrate synthase gene (CIT2). The lack of phenotype of the cit2 mutant indicated the presence of an alternative pathway for transport of acetyl units, formed by the carnitine acetyltransferase protein (YCAT). Disruption of both the CIT2 and YCAT gene blocked the beta-oxidation in intact cells, but not in lysates. Our data strongly suggest that the peroxisomal membrane is impermeable to NAD(H) and acetyl-CoA in vivo, and predict the existence of metabolite carriers in the peroxisomal membrane to shuttle metabolites from peroxisomes to cytoplasm and vice versa.

Acetyl Coenzyme A↗