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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 343 records · Page 19Linked to original sources

The therapeutic potential of interleukin 10 in infection and inflammation.

Interleukin 10 (IL-10), a cytokine with inhibitory activity on inflammation and cell-mediated immune responses, holds enormous potential for the treatment of inflammatory and autoimmune disorders. In addition, IL-10 has also been implicated in the immunopathogenesis of a number of infectious diseases through the use of IL-10 knock-out or IL-10 transgenic mouse models. In this review, we delineate infectious and inflammatory conditions in which IL-10 has shown potential for therapeutic manipulation. Specifically, we review the role of IL-10 in human endotoxemia/sepsis and in HIV infection, conditions for which preliminary phase I trials have recently been undertaken. It is suggested that the therapeutic potential of IL-10 to selectively ameliorate human infectious and inflammatory processes can be realized through a careful selection of the clinical conditions in which patients are undergoing concomitant treatment with anti-microbial regimens.

Animals↗

Patient-reported complications after cryoablation therapy for prostate cancer.

To define the patient-reported complications after cryoablation therapy for prostate cancer and to compare these results to previously published patient-reported complications for radical prostatectomy and external beam irradiation. A questionnaire similar to previously published patient-reported complication studies was sent to the first 290 patients treated by cryoablation therapy at our Institution. The questionnaire was returned by 267 patients. Forty-four patients were excluded from analysis because of prior irradiation, transurethral prostatectomy, or cryoablation, resulting in a study group of 223 patients. Of the 208 patients with good urinary control preoperatively, 9 (4.3%) patients used incontinence pads after cryoablation. Seven of the 8 patients who used one pad daily reported leakage of only a few drops. Impotency, defined as an inability to obtain erections adequate for vaginal penetration, occurred in 85% of men who were potent preoperatively. Urethrorectal fistula occurred in 1 patient (0.4%). Bladder outlet obstruction caused by stricture of sloughed necrotic prostatic tissue required dilation or transurethral resection in 10% of patients. Scrotal swelling, penile tingling, and pelvic pain occurred in 18, 15, and 12% of patients, respectively; typically, these resolved spontaneously within 3 months. Patient-reported complications for cryoblation compared favorably to those reported for radical prostatectomy and external beam irradiation. Patient satisfaction was high; 96% of patients reported that they would choose cryosurgery as a treatment option again.

Aged↗

Analgesic and anti-inflammatory effects of phosphodiesterase inhibitors.

The aim of the present study was to investigate the role of phosphodiesterase (PDE) enzyme inhibitors namely rolipram and theophylline in pain and inflammation in experimental animals. Rolipram, a selective PDE IV inhibitor and theophylline a nonspecific PDE inhibitor exerted dose dependent analgesic and anti-inflammatory effect against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. Nimesulide (1, 2 mg/kg) produced significant anti-inflammatory effect. Further, nimesulide (0.5 mg/kg) potentiated analgesic effect of rolipram but it failed to modulate the anti-inflammatory effect of PDE inhibitors. Present study suggests that PDE enzymes might be playing a role in nociceptive and inflammatory responses in animals.

Abdominal Pain↗

Modulation of antigenicity of mycelial antigens during developmental cycle of Karnal bunt (Tilletia indica) of wheat.

Indirect enzyme linked immunosorbent assays (ELISA) were developed using polyclonal antibodies against soluble cytoplasmic (SCA) and insoluble cell wall antigens (ICWA) for monitoring modulation of mycelial antigens during growth cycle of T. indica. With SCA, continuous decrease in ELISA reactivity was observed in maturing fungus cultures, suggesting that SCA were expressed predominantly during early vegetative phase and their decreasing role was apparent as the fungus matures possibly towards sporogenous mycelium. In case of ICWA, the reaction profile showed an increase up to exponential phase of growth probably due to increase in the cell division and branching of mycelium. But later, ICWA antibody reactivity was decreased which may be due to conversion of mycelial phase to sporogenous phase, a quiescent stage of growth. Characterization of changes in antigenic configuration during developmental cycle of Tilletia indica by these antibodies could prove to be useful in identification of developmentally related and virulence marker(s).

Antigens, Fungal↗

Occurrence of enterotoxigenic Aeromonas species in foods.

Out of a total of 246 food samples of animal origin screened for isolation of Aeromonas spp., 33 (13.41%) were positive for these organisms. Maximum positivity was shown by the samples from fish (28.57%), followed by poultry meat (16.67%), poultry eggs (12.50%), goat meat (12%), buffalo meat (7.69%) and cow milk (5.56%). A. hydrophila was the predominant species (51.52%) followed by A. sobria (39.39%) and A. caviae. Of these, 70.59% A. hydrophila, 69.23% A. sobria and 33.33% A. caviae showed enterotoxigenic reaction in mouse paw oedema test.

Aeromonas↗

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↗