Biomedical subjects

N Singh

Publications and source records attributed to N Singh.

At least 181 records · Page 10Linked to original sources

PubMed2000

Rational empiric antibiotic prescription in the ICU.

The prescribing of antibiotics in the ICU is usually empiric, given the critical nature of the conditions of patients hospitalized there. Appropriate antibiotic utilization in this setting is crucial not only in ensuring an optimal outcome, but in curtailing the emergence of resistance and containing costs. We propose that research in the ICUs is vitally important in guiding antibiotic prescription practices and, therefore, the achievement of above-stated goals. There is wide institutional diversity in the relative prevalence of predominant pathogens and their antimicrobial susceptibilities, and within individual ICUs there exist unique patient populations with varying risks for and susceptibilities to infections and specific pathogens. Appropriate antibiotic prescription practices should be formulated based on surveillance studies and research at individual ICUs; these goals can be accomplished utilizing existing resources.

Anti-Bacterial Agents↗

PubMed2000

Malakoplakia of the appendix. An unusual association with eggs of Taenia species.

Malakoplakia of the appendix is an unusual condition that has been reported to occur in association with tumors, infections, and immunocompromised states. We describe a case of appendicular malakoplakia associated with eggs of Taenia species. The diagnosis was made on histopathologic examination of surgically resected tissue from an appendicular mass. To the best of our knowledge, this is the first time that helminths have been documented to be associated with malakoplakia. We also discuss the implications of helminthic infestation in the pathogenesis of the lesion.

Animals↗

PubMed2000

Glandular abnormalities on cervical smear: a study to compare the accuracy of cytological diagnosis with underlying pathology.

The interpretation of glandular abnormalities detected by cervical smear provides a diagnostic dilemma. This study aims to compare the accuracy of cytological diagnosis with underlying pathology so that guidelines for the investigation and management of abnormal glandular smears may be formulated. A retrospective review of 150 women with glandular abnormalities reported on cervical smear collected over 12 months from 1996 in a University hospital was performed. Smears were graded by the initial report into 3 groups, dependent on the severity of abnormality. Investigation, treatment and subsequent 3-year follow-up were recorded. The accuracy of prediction for a significant neoplastic or preneoplastic glandular pathology only was 0% with mild, 9% (3/35) with moderate, and 24% (9/38) with severe abnormalities. When squamous lesions were included, the chance of finding any dysplastic squamous or glandular abnormality was 16% (12/77), 51% (18/35) and 82% (31/38), respectively, following a smear showing a suspected glandular abnormality only. Our results highlight the poor specificity of predicting glandular neoplasia or preneoplasia from cervical smears, with a final diagnosis of high grade CIN in 35% (17/49) of patients with dyskaryotic glandular cytological changes only and 83% (20/24) where concomitant squamous dyskaryosis was reported. The reporting of reactive or minor changes in endocervical cells was of no diagnostic value. Management protocols for moderate and severe glandular abnormalities should include visualisation and biopsy of the uterine cavity to exclude endometrial neoplasia.

Carcinoma, Squamous Cell↗

PubMed2000

A left atrial paraganglioma patient presenting with compressive dysphagia.

Paragangliomas are rare neoplasms of neural crest origin arising in the chromaffin (pheochromocytoma) and chemoreceptor (chemodectoma) tissues. Only a few cases of paragangliomas have been reported in the heart. Most of the cardiac paragangliomas are located in, or adjacent to, the left atrium. The biological activity indicative of catecholamine production has rarely been shown in cardiac paragangliomas. Patients with cardiac paragangliomas may present with hypertension, or with various obstructive or compressive symptoms, depending on the location of the tumour. A left atrial paraganglioma compressing the esophagus causing dysphagia is presented. A 37-year-old female patient underwent work-up for dysphagia to solids. Transesophageal echocardiography showed the presence of a large mass in the dilated left atrium. The tumour was removed completely intact and was a benign noncatecholamine-secreting paraganglioma. The patient's dysphagia was relieved. The clinical perspectives of cardiac paraganglioma and cardiac dysphagia are discussed.

Adult↗

PubMed2000

The cell cycle.

The cell cycle and the cell cycle control system are the engines that drive life. They allow for the processes of cell renewal and the growth of organisms, under controlled conditions. The control system is essential for the monitoring of normal cell growth and replication of genetic material and to ensure that normal, functional daughter cells are produced at completion of each cell cycle. Although certain clinical applications exist which take advantage of the events of the cell cycle, our understanding of its mechanisms and how to manipulate them is infantile. The next decades will continue to see the effort of many researchers focused upon unlocking the mysteries of the cell cycle and the cell cycle control system.

Animals↗

PubMed2000

Histological assessment of dermal nerve damage occurring during multidrug therapy for leprosy.

This is a prospective histomorphological assessment of dermal innervation in biopsies taken before and after multidrug therapy (MDT) from 41 leprosy patients: 35 borderline tuberculoid (BT), 3 borderline lepromatous (BL), 3 lepromatous (LL). Biopsies of the same lesions taken before commencement (diagnostic therapy) and at the end of therapy (check biopsy) were compared. Hematoxylin and eosin, immunoperoxidase stain for S-100 protein, and the Holmes' silver impregnation method for nerve cells and fibers were used. Skin biopsies were classified as having detectable or undetectable nerves. Of 35 patients with BT leprosy, 17 had no detectable nerves in their diagnostic biopsies; in the check biopsies of 13 of these 17, dermal nerves remained undetectable, in 2 they were S-100 positive but were Holmes negative. Identifiable dermal nerves were present in diagnostic biopsies from 18 patients; in the check biopsies 5 of these 18 had no detectable nerves while in the remaining 13 nerve branches could be detected. The study provides histological documentation of complete damage to dermal innervation in 62.85% (22/35) of patients with BT leprosy, of which 14.28% (5/35) occurred during MDT. Of the patients with detectable dermal innervation at the onset of MDT, 27.7% (5/18) suffered continuing damage during MDT.

Biopsy↗

PubMed2000

Anopheline ecology and malaria transmission at a new irrigation project area (Bargi Dam) in Jabalpur (Central India).

Anopheline ecology and malaria transmission were studied in a newly irrigated area of the Bargi Project, District Jabalpur, Madhya Pradesh, Central India. Observations were made for 2 years (1993-95) in 10 villages along the Bargi irrigation canal, which are situated between 44 km (head end of canal) and 78 km (tail end of canal) from the dam site. Anopheles annularis was the predominant species in the head-end villages and its abundance was directly related to the opening of the canal, whereas Anopheles culicifacies was the most abundant species in tail-end villages, where irrigation is limited. Anopheles culicifacies showed 2 typical peaks not related to canal irrigation. Site-related differences in species prevalence were significant in both immatures and adults. Malaria infection was due to Plasmodium vivax and Plasmodium falciparum. The annual parasite incidence in children and adults was significantly higher in head-end villages (>4-fold) as compared to that in tail-end villages. However, seasonal trends in the prevalence of P. falciparum and P. vivax were the same in each group, with some fluctuations. In this study, preliminary results of the investigation are presented, demonstrating the trends in anopheline ecology and parasite prevalence in relation to the dynamics of irrigation development.

Adolescent↗

PubMed1999

Characterization of kinetoplast DNA minicircles of an Indian isolate of Leishmania donovani.

Characterization of the kinetoplast DNA minicircles in a human pathogenic Indian isolate of Leishmania donovani has not been reported previously. Using inverse PCR, we constructed a library of PCR-amplified minicircle variable region from the kinetoplast DNA of this isolate. A combination of restriction enzyme digestion and nucleotide sequence analysis revealed five minicircle DNA sequence classes within the library, one of which was predominant, representing 75% of the kDNA network. Another distinct sequence class represented 15% of the minicircle network. Other minor sequence classes collectively constituted the remaining 10% of the network. Apart from generating basic information on the organisation and distribution of the different sequence classes within the minicircles, the DNA sequence analysis also revealed unique attributes to our minicircles. One was the surprising homology of our isolate (an Old World sp.) with distantly related New World Leishmania species. Secondly, open reading frames were also identified, indicating the possibility that these minicircles may have more than a structural role to play within the kinetoplast network.

Amino Acid Sequence↗

PubMed1999

Unexpected reactivities of T cells selected by a single MHC-peptide ligand.

In H2-DM mutant mice, most MHC class II molecules are bound by a single peptide, CLIP, derived from the class II-associated invariant chain. Previous studies showed that H2-DM- cells are defective in presenting synthetic peptides to class II-restricted T cells. In sharp contrast, however, the same peptides elicited strong CD4+ T cell responses in H2-DM- animals. We now provide an explanation for this apparent discrepancy. Peptide-specific CD4+ T cells from wild-type mice were efficiently stimulated by H2-DM+, but not by H2-DM- cells pulsed with the cognate peptide. In sharp contrast, CD4+ T cells from mutant animals specific for the same MHC-peptide combination recognized peptide-pulsed H2-DM+ and H2-DM- cells equally well. In addition, unlike Ag-specific T cells from wild-type animals, the reactivities of peptide-specific T cells from mutant animals could not be efficiently blocked by Abs specific for the cognate MHC class II-peptide combination. We further demonstrated that the distinct reactivities of CD4+ T cells from H2-DM+ and H2-DM- mice are due to differences in thymic selection. Collectively, these findings indicate that the CD4+ T cell repertoires of H2-DM+ and H2-DM- mice are remarkably different.

Amino Acid Sequence↗

PubMed1999

Cutting edge: activation of NK T cells by CD1d and alpha-galactosylceramide directs conventional T cells to the acquisition of a Th2 phenotype.

NK T cells recognize glycolipid Ags such as alpha-galactosylceramide (alpha-GalCer) presented by the MHC class I-like molecule CD1d. In this paper we have studied the in vivo effects of alpha-GalCer on the generation of adaptive immune responses. Treatment of mice with alpha-GalCer resulted in rapid activation of NK T cells and production of the cytokines IL-4 and IFN-gamma. However, after this initial stimulation, NK T cells became polarized for the production of IL-4. Further, as soon as 6 days after alpha-GalCer injection, a marked increase in serum IgE levels was observed. Administration of alpha-GalCer at the time of priming of mice with protein Ag resulted in the generation of Ag-specific Th2 cells and a profound increase in the production of IgE. Collectively, these findings indicate that alpha-GalCer may be useful for modulating immune responses toward a Th2 phenotype during prophylaxis and therapy.

Adjuvants, Immunologic↗

PubMed1999

Proteasomal degradation and N-terminal protease resistance of the codon 145 mutant prion protein.

An amber mutation at codon 145 (Y145stop) of the prion protein gene results in a variant of an inherited human prion disease named Gerstmann-Sträussler-Scheinker syndrome. The characteristic features of this disorder include amyloid deposits of prion protein in cerebral parenchyma and vessels. We have studied the biosynthesis and processing of the prion protein containing the Y145stop mutation (PrP(145)) in transfected human neuroblastoma cells in an attempt to clarify the effect of the mutation on the metabolism of PrP(145) and to gain insight into the underlying pathogenetic mechanism. Our results demonstrate that 1) a significant proportion of PrP(145) is not processed post-translationally and retains the N-terminal signal peptide, 2) most PrP(145) is degraded very rapidly by the proteasome-mediated pathway, 3) blockage of proteasomal degradation results in intracellular accumulation of PrP(145), 4) most of the accumulated PrP(145) is detergent-insoluble, and both the detergent-soluble and -insoluble fractions are resistant to mild proteinase K (PK) treatment, suggesting that PK resistance is not simply because of aggregation. The present study demonstrates for the first time that a mutant prion protein is degraded through the proteasomal pathway and acquires PK-resistance if degradation is impaired.

Cell Compartmentation↗

PubMed1999

Role of AKT1 in 17beta-estradiol- and insulin-like growth factor I (IGF-I)-dependent proliferation and prevention of apoptosis in MCF-7 breast carcinoma cells.

AKT1 (c-AKT, PKBalpha) is the cellular homolog of the protein-serine/threonine kinase oncogene, v-akt. AKT1 is activated through the insulin and platelet-derived growth factor signaling pathways in transfected fibroblasts, but little is known about the regulation of endogenous AKT1 in tumor cells. AKT1 levels were higher in a panel of human breast carcinoma cell lines than in breast epithelial cells, particularly those with higher HER2 expression. AKT1 activity was increased by either estradiol or IGF-I in estrogen-dependent MCF-7 cells, and both factors acted synergistically to increase AKT1 activity and promote cell proliferation. Stimulation of AKT1 activity by estradiol and IGF-I was blocked by the antiestrogen ICI 182780 and by the phosphatidylinositol-3-kinase inhibitor wortmannin. MCF-7 cells transfected with AKT1 exhibited partial estrogen- and IGF-I-independent growth and were more responsive to the combination of IGF-I and estradiol. AKT1-overexpressing MCF-7 cells were less sensitive to apoptosis induced by wortmannin. These findings suggest that AKT1 is a downstream effector of estrogen- and IGF-I-dependent proliferation and survival in hormone-responsive MCF-7 breast carcinoma cells.

Apoptosis↗

PubMed1999

Endogenous presenilin 1 redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix.

Most familial early-onset Alzheimer's disease cases are caused by mutations in the presenilin 1 (PS1) gene. Subcellular localization of the endogenous PS1 is essential for understanding its function, interactions with proteins, and role in Alzheimer's disease. Although numerous studies revealed predominant localization of PS1 to endoplasmic reticulum and Golgi, there are conflicting reports on the localization of PS1 to the cell surface. We found that endogenous PS1 is highly expressed in T lymphocytes (Jurkat cells). Using a variety of methods, we present evidence that endogenous PS1 is localized to the cell surface in addition to intracellular membrane compartments. Moreover, PS1 appeared in high levels on the surface of lamellipodia upon adhesion of the cells to a collagen matrix. The redistribution of PS1 in adhered cells was strikingly similar to that of the well characterized adhesion protein CD44. Cell surface PS1 formed complexes in vivo with actin-binding protein filamin (ABP-280), which is known to form bridges between cell surface receptors and cytoskeleton and mediate cell adhesion and cell motility. Taken together, our results suggest a role of PS1 in cell adhesion and/or cell-matrix interaction.

Algorithms↗

PubMed1999

Microcephaly with simplified gyral pattern in six related children.

We describe clinical and neurophysiological findings in six related children with congenital microcephaly, seizures that began within the first 2-4 months of life, and severe mental retardation (MR). These affected children (five girls and one boy), born to two women who are half-sisters, inherited the disease as an autosomal recessive trait. Physical examination of these children did not show any of the anomalies in the known cortical malformation syndromes such as lissencephaly types I and II. Neuroradiological studies in these children documented microcephaly and a simplified gyral pattern with no pachygyria. Chromosomal analysis showed neither karyotypic abnormalities nor a microdeletion at 17p13.3, site of the lissencephaly type I gene locus (LIS1). Genetic studies failed to show linkage of this family to LIS1, LIS2 (a region on chromosome 2p homologous to LIS1), or MCPH1 (a locus for primary autosomal recessive microcephaly). The unique clinical and genetic findings in this family suggest that these children may be affected by an as-of-yet unmapped neuronal proliferation disorder.

Adolescent↗

PubMed1999

Boronate affinity adsorption of RNA: possible role of conformational changes.

Batch equilibrium adsorption isotherm determination is used to characterize the adsorption of mixed yeast RNA on agarose-immobilized m-aminophenylboronic acid. It is shown that the affinity-enhancing influence of divalent cations depends strongly on the precise nature of the cation used, with barium being far more effective than the conventionally-used magnesium. This adsorption-promoting influence of barium is suggested to arise primarily from ionic influences on the structure and rigidity of the RNA molecule, as the adsorption of ribose-based small molecules is not similarly affected. The substitution of barium for the standard magnesium counterion does not greatly promote the adsorption of DNA, implying that the effect is specific to RNA and may be useful in boronate-based RNA separations. RNA adsorption isotherms exhibit sharp transitions as functions of temperature, and these transitions occur at different temperatures with Mg2+ and with Ba2+. Adsorption affinity and capacity were found to increase markedly at lower temperatures, suggestive of an enthalpically favored interaction process. The stoichiometric displacement parameter, Z, in Ba2+ buffer is three times the value in Mg2+ buffer, and is close to unity.

Adsorption↗

PubMed1999

Pulmonary infiltrates in liver transplant recipients in the intensive care unit.

BACKGROUND: A frequent dilemma is discerning the likelihood of pneumonia and the need for empiric antibiotic therapy in liver transplant recipients with pulmonary infiltrates in the intensive care unit (ICU). METHODS: We performed a prospective, observational study of consecutive liver transplant recipients developing pulmonary infiltrates in the ICU. RESULTS: Of 90 consecutive liver transplant patients in the ICU over a 3-year period, 44% (40) developed pulmonary infiltrates. The etiologies were pneumonia (38%, 15 of 40), pulmonary edema (40%, 16 of 40), atelectasis (10%, 4 of 40), adult respiratory distress syndrome (8%, 3 of 40), contusion (3%, 1 of 40), and unknown (3%, 1 of 40). Pneumonia was due to methicillin-resistant Staphylococcus aureus in 27% (4 of 15), Pseudomonas aeruginosa (27%, 4 of 15), invasive aspergillosis (20%, 3 of 15), and Enterobacter cloacae, Serratia marcescens, Pneumocystis carinii pneumonia, and unknown (7%, 1 of 15) in one each. None of the patients had cytomegalovirus or herpes simplex virus pneumonia. Seventy-five percent of methicillin-resistant Staphylococcus aureus and all Aspergillus pneumonias, but only 14% of the Gram-negative pneumonias, occurred within 30 days of transplantation. Twenty-seven percent of the pneumonias occurred >365 days after transplantation; all of these were in patients with recurrent viral hepatitis C virus or hepatitis B virus, disseminated posttransplant lymphoproliferative disorder, or late rejection. Of patients with pneumonia, 87% were ventilated and 40% had bacteremia. Clinical pulmonary infection score (Pugin score) >6 (73% vs. 6%, P = 0.0001), abnormal temperature (73% versus 28%, P = 0.005), and creatinine level >1.5 mg/dl (80% versus 50%, P = 0.05) were predictors of pneumonia versus other etiologies of pulmonary infiltrates. Overall mortality in patients with pulmonary infiltrates was 28% (11 of 40); pneumonia as etiology (P = 0.06), creatinine level >1.5 mg/dl (P = 0.028), higher blood urea nitrogen (P = 0.017), and worse APACHE neurological score (P = 0.04) were predictors of poor outcome. CONCLUSIONS: Our data have implications not only for identifying pneumonia as a potential cause of pulmonary infiltrates, but for the likely etiology of the pneumonia and thus the selection of empiric antibiotic therapy in critically ill liver transplant recipients. Pugin score >6 in patients with pulmonary infiltrates warrants antimicrobial therapy. Early onset within 30 days after transplantation raises the spectra of aspergillosis.

Adult↗

PubMed1999

Intraoperative hypothermia is an independent risk factor for early cytomegalovirus infection in liver transplant recipients.

BACKGROUND: Early cytomegalovirus (CMV) reactivation infections have been found to be associated with a number of stress responses such as severe bacterial infection. Intraoperative hypothermia is known to be a significant physiological stressor. Hence, we sought to evaluate a relationship between intraoperative hypothermia during liver transplantation and early CMV infection. METHODS: Relationships between intraoperative hypothermia and early CMV infection were assessed using univariate and multivariate analysis. RESULTS: There were 11 of 100 patients who had CMV infection detected within the first 30 days after the transplant and 16 of 100 in the next 3 months after the transplant. The median intraoperative temperature (34.4 degrees C) of those who subsequently developed early CMV infection was significantly lower than that in patients who did not develop early CMV infection (35.3 degrees C; P = 0.032). Multivariate analysis showed that only hypothermia was an independent predictor of early CMV infection (odds ratio 2.8, 95% confidence intervals 1.2-6.4; P = 0.047). CONCLUSIONS: Intraoperative hypothermia during liver transplantation increases the risk of CMV infection in the 1st month postoperatively and active warming seems to reduce this risk.

Body Temperature↗

PubMed1999

Kinetoplast DNA minicircles of Leishmania donovani express a protein product.

We describe an unprecedented finding of an open reading frame present in the variable region in one of the minicircle sequence classes of a human pathogenic strain of Leishmania donovani (MHOM/IN/90/RMRI 68) which is transcribed and translated. The encoded protein showed homologies to known transport proteins.

Amino Acid Sequence↗