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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 379 records · Page 21Linked to original sources

Dengue/DHF: an emerging disease in India.

Dengue/DHF is an emergent disease in India and some parts of country are endemic and periodically contributing annual outbreaks of dengue/DHF. Dengue infection manifests as undifferentiated fever, dengue haemorrhagic fever (DHF) which leads to hospitalization large number of people in a localized area. There is high mortality and morbidity associated with the onset of each dengue outbreak leading to great socio-economic impact. The prevention and control of dengue outbreak depends upon the proper monitoring of the disease case through disease surveillance so as to ensure timely management of cases. Vector surveillance helps in the proper and timely implementation of emergency control measures against dengue vector i.e. Aedes aegypti. There is an urgent need for an effective diagnostic strategy for early diagnosis to shorten the illness duration, hospitalization time and the associated complications.

Aedes↗

Prevalence of enterotoxigenic motile aeromonads in children, fish, milk and ice-cream and their public health significance.

Motile aeromonads, which have been implicated as causative agents of human gastroenteritis, meningitis. endocarditis and osteomyelitis, were isolated from fish, pasteurized and flavored milk and ice creams. Forty-five isolates of Aeromonas from diarrheic children (100) and 285 food samples comprising of fish (100), milk (85) and ice creams (100) were identified as A. hydrophila (21), A. sobria (16) and A. caviae (8). Five of these 45 isolates of Aeromonoas (3 A. sobria, 2 A. hydrophila) were from fecal samples of diarrheic children under five years of age. Twenty-six of these 45 isolates were found to be enterotoxin producing by ligated rabbit ileum loop technique. Isolation of enterotoxigenic motile aeromonads from food as well as diarrheic children have great public health significance which will be further discussed.

Aeromonas hydrophila↗

Human anthrax in India: urgent need for effective prevention.

Anthrax is a zoonotic illness caused by Bacillus anthracis. Sporadic cases continue to be reported from many parts of the world. From India, both sporadic cases and outbreaks are being reported regularly. The Union Territory of Pondicherry (a former French colony) lies on the coast of Bay of Bengal, where the incidence of anthrax is on the rise with 28 cases being detected in the year 1999 and 2000 alone. So far, about 34 human cases have been encountered in this region. Recently, an increase in the number of anthrax cases has been noted in veterinary and human practice in this area. Most cases have occurred in agricultural labourers who gave history of handling animal meat or skin of infected animals. The meningitic form of the disease has a very bad prognosis. Patients with this form of disease died despite treatment with high dose penicillin. The typical bacilli were seen in the CSF in all cases of anthrax meningitis and was diagnostic of the condition. The cutaneous form of illness had a benign course and responded favourably to penicillin treatment. Awareness among clinicians and mandatory reporting of cases to public health departments along with public education will help control morbidity and mortality due to anthrax. Effective immunization of animals is the other important control measure for anthrax.

Animals↗

Primary PNET of kidney: report of two cases and review of literature.

PNET of the kidney is a rare tumor with only a few published reports. In view of poorer prognosis and different therapeutic approach, renal PNET should therefore be differentiated from other primary renal neoplasma such as Wilms tumor, renal neuroblastoma and malignant rhabdoid tumor which on histology resemble renal PNET. Two cases of renal PNET have been described in this report. Cut surface of the tumor in both cases was greyish white lobulated, with multiple tiny cystic areas. Histologically, tumor consisted of loosely cohesive sheets of small to medium sized monomorphic cells with round nuclei and little cytoplasm. Tumor cells showed diffuse strong membrane positivity for MIC2 and focal weak to moderate positivity for NSE and vimentin. Renal PNET should therefore be included in differential diagnosis of rapidly enlarging renal lumps presenting with local infiltration and aggressive behaviour, particularly in children and young adults. Diffuse strong membrane positivity for MIC2 in PNET is helpful in differentiating it from other primary renal neoplasms.

12E7 Antigen↗

Transcriptional regulation of Fas gene expression by GA-binding protein and AP-1 in T cell antigen receptor.CD3 complex-stimulated T cells.

Fas (CD95 or APO-1), a transmembrane cell surface receptor of the tumor necrosis factor receptor family, is up-regulated in activated T lymphocytes. Our present study identified an upstream enhancer element (between nucleotide positions -862 and -682) containing a GA-binding protein (GABP) site and a low affinity activating protein-1 (AP-1)-binding site. T cell activation increased the DNA binding of GABP and AP-1 to this enhancer site. The specificity of GABP and AP-1 binding was demonstrated by competition electrophoretic mobility shift assay and supershift electrophoretic mobility shift assay with antibodies against GABP and AP-1, respectively. Mutational analysis of Fas promoter revealed that both GABP- and AP-1-binding sites were required for initiating Fas gene transcription. We further show that anti-CD3 mAb, phorbol 12-myristate 13-acetate, and phorbol 12-myristate 13-acetate/ionomycin strongly activated promoters carrying multiple copies of the Fas enhancer, and mutation of either the GABP or AP-1 binding site severely reduced transcriptional activity. Taken together, these results suggest that the transcription factors GABP and AP-1 play a critical role in the induction of Fas gene expression in T cell antigen receptor.CD3-stimulated Jurkat cells.

Base Sequence↗

Effect of whole-body vibration on the low back. A study of tractor-driving farmers in north India.

STUDY DESIGN: A retrospective cohort study of tractor-driving farmers (study group) and non-tractor-driving farmers (control group) matched for age, gender, generic/ethnic group, land-holding, and work routines. OBJECTIVES: To determine, using magnetic resonance imaging and clinical investigations, the effect of whole-body vibrations on the back in tractor-driving farmers. SUMMARY OF BACKGROUND DATA: Low back pain and pathologic changes in the lower backs of tractor drivers have been reported. However, no study with a control group matched for work-related risk factors has been reported. METHODS: Fifty tractor-driving farmers were compared with 50 non-tractor-driving farmers matched for age, gender, ethnic group, land-holding, and work routine. Both groups were interviewed for details of work routine, assets held, family profile, and vibration exposure to assess the influence of these parameters on signs and symptoms of backache. Magnetic resonance imaging was done to assess the effect of exposure on whole-body vibration and degenerative changes in the back. Vibration measurements also were done on tractors to observe the actual severity of the vibrations. RESULTS: Regular work-related backache was more common among tractor-driving farmers (40%) than among non-tractor-driving farmers (18%, P = 0.015). Anthropometric evaluation showed abdominal girth and weight to be significantly higher in tractor-driving farmers (P = 0.006 and 0.046, respectively), whereas while height and arm span were similar between the two groups. Clinical examination for evidence of disc or facet degeneration showed no difference between the two groups. Evaluation of magnetic resonance images of tractor-driving farmers and non-tractor-driving farmers by an orthopedic surgeon, radiologist, and neurosurgeon showed degenerative changes to be similar between the two groups (P > 0.050). CONCLUSIONS: Tractor-driving farmers report backache more often than non-tractor-driving farmers, but no significant objective differences on clinical or magnetic resonance imaging evaluation were found between the two groups.

Adult↗

Functional and structural properties of lipid-associated apolipoprotein J (clusterin).

Apolipoprotein J (apoJ, clusterin) is a multifunctional protein normally associated with lipids in plasma and cerebrospinal fluid, and secreted as lipoparticles by hepatocytes and astrocytes. To investigate whether the structural and functional properties of apoJ are modulated upon binding to lipids, we prepared apoJ high-density lipoprotein (HDL)-like particles employing either synthetic or plasma HDL-derived lipids. The majority of the resulting lipoparticles contained one molecule of apoJ per particle and exhibited the same alpha2 electrophoretic mobility characteristic of apoJ-containing plasma HDL. Particle size seemed to be dependent on the presence of cholesterol in the lipid mixture and ranged from diameters of 10 nm in the presence of cholesterol to 20 nm in the absence of cholesterol. CD analysis and Fourier-transform infrared spectroscopy revealed similar changes in the apoJ secondary structure induced by its incorporation into lipoparticles, namely a decrease in alpha-helix content and an increase in beta-turn structures. Two functional assays, the binding interaction with Alzheimer's amyloid beta peptides and the inhibitory activity of the complement membrane-attack complex, did not detect any changes in apoJ activity following its lipidation (P>0.05). On the contrary, the binding affinity to the cellular receptor megalin was enhanced significantly (P<0.01) after the association with lipids; the K(d) value decreased from 78.8+/-10.7 nM for the delipidated form to 37. 0+/-7.3 nM for apoJ-HDL. Although it is not known whether the structural changes observed are directly responsible for the higher receptor-binding affinity, the data suggest that the complement inhibition and amyloid beta-binding motifs are located in areas of the molecule different from those involved in the apoJ-megalin interaction.

Amyloid beta-Peptides↗

Human immunodeficiency virus-1-tat induces matrix metalloproteinase-9 in monocytes through protein tyrosine phosphatase-mediated activation of nuclear transcription factor NF-kappaB.

We have previously shown that human immunodeficiency virus (HIV)-1-tat induces the production of matrix metalloproteinase-9 (MMP-9) in human monocytes by a mechanism that is not understood. In the present report, we demonstrate that HIV-tat-induced expression of MMP-9 is blocked by inhibitors of protein tyrosine phosphatases (PTPases). PTPase inhibitors also blocked HIV-tat-induced nuclear transcription factor NF-kappaB activation and IkappaBalpha degradation required for MMP-9 induction. These results suggest that HIV-tat induces MMP-9 in human monocytes through activation of PTPase and NF-kappaB.

DNA-Binding Proteins↗

Large-scale analysis of the yeast genome by transposon tagging and gene disruption.

Economical methods by which gene function may be analysed on a genomic scale are relatively scarce. To fill this need, we have developed a transposon-tagging strategy for the genome-wide analysis of disruption phenotypes, gene expression and protein localization, and have applied this method to the large-scale analysis of gene function in the budding yeast Saccharomyces cerevisiae. Here we present the largest collection of defined yeast mutants ever generated within a single genetic background--a collection of over 11,000 strains, each carrying a transposon inserted within a region of the genome expressed during vegetative growth and/or sporulation. These insertions affect nearly 2,000 annotated genes, representing about one-third of the 6,200 predicted genes in the yeast genome. We have used this collection to determine disruption phenotypes for nearly 8,000 strains using 20 different growth conditions; the resulting data sets were clustered to identify groups of functionally related genes. We have also identified over 300 previously non-annotated open reading frames and analysed by indirect immunofluorescence over 1,300 transposon-tagged proteins. In total, our study encompasses over 260,000 data points, constituting the largest functional analysis of the yeast genome ever undertaken.

Algorithms↗

Use of herpesvirus saimiri-immortalized macaque CD4(+) T cell clones as stimulators and targets for assessment of CTL responses in macaque/AIDS models.

Herpesvirus saimiri (HVS), a nonhuman primate gamma herpes virus, was used to immortalize pig-tailed macaque CD4(+) T lymphocytes. The HVS-immortalized T cell lines were used to develop CD4(+) T cell clones from two animals. Three CD4(+) T cell clones were further characterized for the expression of cell surface markers. All expressed CD2, CD4, CD58, CD69 and CD80 and therefore resembled activated T cells. These clones required exogenous IL-2 for efficient growth and were found to be highly susceptible to infection by the challenge virus, Chimeric simian/human immunodeficiency virus (SHIV(KU-1)). They could also be productively infected not only by the quasispecies of the challenge virus (SHIV(KU-1/PDJ) and SHIV(KU-1/PNA), isolated from macaque PDj and PNa, respectively) but also by a different chimeric simian/human immunodeficiency virus (SHIV(89.6P)) and simian immunodeficiency virus (SIV(MAC239)). The virus-infected CD4(+) T cell clones were also used as stimulators for generation of CTL effectors. These effectors exhibited excellent virus-specific lysis in chromium-release assays when syngenic SHIV(KU-1) infected autologous CD4(+) T cell clones were used as targets. The target cell lysis was virus specific, as uninfected control cells showed no or minimal lysis.

Acquired Immunodeficiency Syndrome↗

Functional dichotomy within the vomeronasal system: distinct zones of neuronal activity in the accessory olfactory bulb correlate with sex-specific behaviors.

Chemosensory neurons in the vomeronasal organ (VNO) detect pheromones that elicit social and reproductive behaviors in most terrestrial vertebrates. Vomeronasal receptor neurons are chemoarchitecturally divided into two populations based on their position in the VNO, the type of G-protein subunit expressed, the family of putative pheromone receptor expressed, and termination site of their axons in the accessory olfactory bulb (AOB). To investigate the functional implications of these two segregated VNO-AOB pathways, we stimulated mice with pheromonal cues associated with different behavioral contexts and examined cellular activation patterns in the AOB. Exposure of ICR male mice to BALB/c males resulted in aggressive behavior, accompanied by a VNO-dependent increase in c-fos immunoreactivity in a cluster of cells located almost exclusively in the caudal AOB in both strains. This caudal cluster of activated cells did not appear to require the overt display of aggressive behavior because it was present in both the dominant and submissive males and could be evoked when the stimulus animal was anesthetized. In contrast, exposure of an ICR male to an ICR female in diestrus resulted in activation of cells located predominantly in the rostral AOB. Our findings indicate that male-to-male interactions involving interstrain recognition activate a separate population of vomeronasal receptor neurons than chemosensory cues detected in a sexual context. The results suggest that the dichotomy in the peripheral vomeronasal system serves to separate pheromones based on the behaviors they drive. As such, the results provide a bioassay for identifying pheromone molecules.

Aggression↗

Alignment of the B" subunit of RNA polymerase III transcription factor IIIB in its promoter complex.

TFIIIB, the central transcription initiation factor of the eukaryotic nuclear RNA polymerase (pol) III is composed of three subunits: the TATA-binding protein; Brf, the TFIIB-related subunit; and B", the Saccharomyces cerevisiae, TFC5 gene product. The orientation of the B" subunit within the TFIIIB-DNA complex has been analyzed at two promoters by two approaches that involve site-specific photochemical protein-DNA cross-linking: a collection of B" internal and external deletion proteins has been surveyed for those deletions that alter the interaction of B" with DNA or change the orientation of B" relative to DNA; a method for regionally mapping cross-links between specific DNA sites and (32)P-end-labeled protein has also been applied. The results map an N-proximal segment of B" to the upstream end of the TFIIIB-DNA complex and amino acids 299-315 to the principal DNA-contact site, approximately 8 base pairs upstream of the TATA box. The analysis also indicates that a segment comprising amino acids 316-434 loops away from DNA, and locates the C-proximal 170 amino acids of B" downstream of the TATA box. Examination of two-cross-link products formed by DNA with adjacent and nearby photoactive nucleotides supports the conclusion that Brf and B" share an extended interface along the length of the TFIIIB-DNA complex.

Base Sequence↗

Tubulointerstitial nephritis antigen: an extracellular matrix protein that selectively regulates tubulogenesis vs. glomerulogenesis during mammalian renal development.

Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix protein and is expressed in the renal tubular basement membranes. Its role in metanephric development was investigated. TIN-ag cDNA, isolated from the newborn mouse library, had an ORF of 1,425 nucleotides, a putative signal sequence, and an ATP/GTP-binding site. The translated sequence had approximately 80% identity with rabbit TIN-ag. Among various tissues, TIN-ag mRNA was primarily expressed in the newborn kidney. In the embryonic metanephros, TIN-ag expression was confined to the distal convolution or pole of the S-shaped body, the segment of the nascent nephron that is the progenitor of renal tubules. Treatment with TIN-ag antisense oligodeoxynucleotide induced dysmorphogenesis of the embryonic metanephroi, malformation of the S-shaped body, and a decrease in the tubular population, whereas the glomeruli were unaffected. Treatment also led to a decrease of TIN-Ag mRNA, de novo synthesis of TIN-ag protein, and its antibody reactivity. The mRNA expression of glomerular epithelial protein 1 (a marker for renal podocytes), anti-heparan-sulfate-proteoglycan antibody reactivity, and wheat germ agglutinin lectin staining of the metanephros were unaffected. The anti-TIN-ag antibody treatment also caused deformation of the S-shaped body and a reduction in the tubular population, whereas the glomeruli were unchanged. The data suggest that the TIN-ag, unlike other basement membrane proteins, selectively regulates tubulogenesis, whereas glomerulogenesis is largely unaffected.

Amino Acid Sequence↗

Molecular cytogenetics of a de novo interstitial deletion of chromosome arm 6q in a developmentally normal girl.

Using fluorescence in situ hybridization and microsatellite analysis, we have characterized a de novo interstitial deletion on the long arm of chromosome 6 [46,XX,del(6) (q23.3q24.2)] in a developmentally normal girl with very mild phenotypic abnormalities. The deletion was paternal in origin and was between markers WI-5023 and D6S1042. The size of the deletion was estimated to be approximately 4-5 Mb. The normal phenotype in this patient might be the result of imprinting of paternal copies of genes located in the segment 6q23. 3-q24.2. Alternatively, the genes located in the segment 6q23.3-q24. 2 might not be subject to dosage effects and therefore the haploinsufficiency of genes in this segment might not have phenotypic consequences.

Child, Preschool↗

Age of onset of depression and quantitative neuroanatomic measures: absence of specific correlates.

The purpose of our study was to examine the relationship between volumetric neuroanatomic measures and age of onset of illness in subjects with late-life major depression. Our sample was composed of 51 elderly subjects with Major Depressive Disorder who were scanned using a 1.5-tesla GE magnetic resonance imaging scanner with head coil. Absolute total and focal brain volumes were obtained together with quantified estimates of high intensity lesions. The relationship of these measures to onset age was examined using a regression while adjusting for subjects' current age and total intracranial volume. There was no significant linear relationship between age of onset of the first episode and any of the neuroanatomic measures examined. These data do not support the notion that neuroanatomical contributions to depression increase with a later age of onset of illness.

Brain↗

Sustained suppression of plasma HIV RNA is associated with an increase in the production of mitogen-induced MIP-1alpha and MIP-1beta.

The chemokine receptor CCR5 has been shown to be a major coreceptor for HIV-1. The chemokines that bind to this receptor (MIP-1alpha, MIP-1beta, and RANTES) are potent inhibitors of HIV replication and may play an important role in the pathophysiology of HIV disease. We investigated the effect of potent antiretroviral therapy (ritonavir and saquinavir) on the production of MIP-1alpha, MIP-1beta, and RANTES in 19 HIV-infected patients who had sustained decreases in plasma HIV RNA levels (<200 copies/ml). Chemokine concentrations were measured in serum, plasma, and PHA-stimulated PBMCs at baseline and 24 and 48 weeks after initiating therapy. MIP-1alpha, MIP-1beta, and RANTES levels in serum and plasma did not significantly change in the 48-week period. In contrast, MIP-1alpha and MIP-1beta secreted by PHA-stimulated PBMCs increased at 24 weeks, with this increase sustained at 48 weeks, whereas no significant change was observed in PHA-induced RANTES production. A significant positive correlation was found between the changes in PHA-induced chemokine production and baseline CD4+ T cell counts. These data demonstrate that sustained suppression of viral replication by potent antiretroviral therapy has a potentially beneficial effect on chemokine production and early initiation of this therapy appears to confer a more favorable chemokine profile.

Anti-HIV Agents↗

Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung.

Fibrillin-2 is an extracellular matrix protein. It is associated with elastic fibers in several tissues and is believed to serve as a ligand for alphavbeta3 integrin, the latter being a known morphogen. In this study, the role of fibrillin-2 in lung development was investigated. Also, rat fibrillin-2 cDNA was isolated and sequenced and its spatiotemporal expression determined. It had approximately 88% homology with human fibrillin-2 and had Ca(2+) binding epidermal growth factor-like domains, transforming growth factor-beta binding protein motifs, and two RGD binding sites. Northern blot analysis revealed an approximately 10-kb transcript, and fibrillin-2 expression was developmentally regulated, and it paralleled that of tropoelastin. At day 13 of gestation, fibrillin-2 was expressed in the mesenchyme and at the epithelial:mesenchymal interface. From day 13 to 19 of gestation, its expression intensified and was confined around the tracheobronchial airways, while it lessened during the postnatal period. Immunoprecipitation revealed an approximately 350-kDa band by SDS-PAGE. Treatment with fibrillin-2 antisense oligodeoxynucleotide induced dysmorphogenesis of the lung explants. They were smaller and had rudimentary lung bud branches, collapsed conducting airways, and loose expanded mesenchyme. Concomitantly, fibrillin-2 mRNA, antibody reactivity in the explants, and fibrillin-2-specific radioincorporation were reduced. Anti-alphav and -laminin antibody reactivity and their respective incorporated specific radioactivities were unaltered. These data indicate that fibrillin-2 modulates organogenesis of the lung in the context of epithelial:mesenchymal interactions. Conceivably, the collapse of the conducting airways may also be related to the perturbed biology of the fibrillin-2 interacting protein, i.e., elastin, the latter being critical for the normal biophysiology of the lungs.

Actins↗