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Biomedical subjects

Sanjay Kumar

Publications and source records attributed to Sanjay Kumar.

At least 55 records · Page 3Linked to original sources
PubMed2003

Quantitative evaluation of AgNORs in bone tumours.

AIMS: Primary tumours of bone present a significant diagnostic and therapeutic challenge at times. Silver stained nucleolar organiser regions (AgNORs) have been widely used in a variety of tissues but with a limited study on bone tumours. Our study was aimed at the evaluation of AgNOR count in various neoplastic lesions of bone. METHODS: : One hundred biopsies of bone lesions were included in this study. Five samples of foetal lumbar vertebrae obtained from foetal autopsies were taken as control. The study included 58 males and 42 females with age ranging from 5 to 70 years. Fifty-two cases were malignant while 48 were benign in nature. Silver staining for nuclear organiser regions was performed according to one-step silver staining technique in these cases. NORs seen as black dots were counted in the nuclei of 100 cells. RESULTS: Our study revealed that the mean count was highest in malignant lesions (4.00+/-0.69) compared with benign lesions (2.16+/-0.43) and normal bone (1.32+/-0.14). Statistically, the AgNOR count showed a significant difference (P<0.001) in all these lesions. CONCLUSIONS: The results of the current study revealed that malignant lesions had a greater mean AgNOR count than benign tumours and the normal bone. Thus, quantification of AgNORs strongly correlates with the type as well as aggressiveness of the bone tumour and is diagnostically useful in tumour differentiation.

Adolescent↗
PubMed2002

A complex of the IL-1 homologue IL-1F7b and IL-18-binding protein reduces IL-18 activity.

IL-1F7 was discovered in expressed sequence tag databases as a member of the increasing family of proteins sharing sequence homology to IL-1alpha/beta, IL-1Ra, and IL-18. In the present study using immunohistochemical staining, IL-1F7 was localized in human peripheral monocytic cells, suggesting its role in immune regulation. Recombinant human IL-1F7b was shown to bind to the IL-18Ralpha but without IL-18 agonistic or antagonistic function. Using chemical cross-linking, we observed that, unlike IL-18, IL-1F7b fails to recruit the IL-18Rbeta chain to form a functionally active, ternary complex with the IL-18Ralpha chain. IL-1F7b shares two conserved amino acids with IL-18 (Glu-35 and Lys-124), which participate in the interaction of IL-18 with the IL-18Ralpha chain as well as the IL-18-binding protein (IL-18BP), a secreted protein that neutralizes IL-18 activity. In testing whether IL-1F7b interacts with IL-18BP, we unexpectedly observed that IL-1F7b enhanced the ability of IL-18BP to inhibit IL-18-induced IFNgamma by 25-30% in a human natural killer cell line. This effect was observed primarily at limiting concentrations of IL-18BP (3.12-12.5 ng/ml) and at a 50- to 100-fold molar excess of IL-1F7b. Similar results were obtained by using isolated human peripheral blood mononuclear cells. To study the molecular basis of this effect we performed binding studies of IL-1F7b and IL-18BP. After cross-linking, a high molecular weight complex consisting of IL-1F7b and IL-18BP was observed on SDS/PAGE. We propose that after binding to IL-18BP, IL-1F7b forms a complex with IL-18Rbeta, depriving the beta-chain of forming a functional receptor complex with IL-18Ralpha and thus inhibiting IL-18 activity.

Amino Acid Sequence↗
PubMed2002

Role of long-range repulsive forces in organizing axonal neurofilament distributions: evidence from mice deficient in myelin-associated glycoprotein.

When the axon of a motor neuron is sectioned and visualized by electron microscopy, a two-dimensional distribution of neurofilaments (NFs) with nonrandom spacing is revealed; this ordered arrangement implies the presence of physical interactions between the NFs. To gain insight into the molecular basis of this organization, we characterized NF distributions from mouse sciatic nerve cross sections using two statistical mechanical measures: radial distribution functions and occupancy probability distributions. Our analysis shows that NF organization may be described in terms of effective pairwise interactions. In addition, we show that these statistical mechanical measures can detect differences in NF architecture between wild-type and myelin-associated glycoprotein null mutant mice. These differences are age dependent, with marked contrast between the NF distributions by 9 months of age. Finally, using Monte Carlo simulations, we compare the experimental results with predictions for models in which adjacent NFs interact through rigid cross bridges, deformable cross bridges, and long-range repulsive forces. Among the models tested, a model in which the filaments interact through a long-range repulsive force is most consistent with the results of our analysis.

Aging↗
PubMed2002

Vaccination of donkeys against Babesia equi using killed merozoite immunogen.

Protective efficacy of a killed Babesia equi immunogen was assessed in donkeys. The immunogen was prepared from B. equi infected blood so as to contain lysate of 2 x 10(10) parasitised erythrocytes per dose. The immunogen was mixed with an adjuvant Quil A (3mg) and inoculated into four susceptible donkeys (group I). A booster inoculation was given after 21 days of first inoculation followed by challenge with fresh infected blood containing 1x10(11) parasitised erythrocytes 14 days later. Two groups of two donkey each were included as adjuvant only control (group II) and uninoculated control (group III), respectively. After challenge, donkeys were observed for a period of 4 weeks. The immunised donkeys (group I) showed significantly high (P<0.05%) enzyme linked immunosorbant assay (ELISA) antibody titres and significantly high (P<0.05%) stimulation indices (SI) in lymphocyte proliferation assay (LPA) than that of groups II and III donkeys from day 14 PI and day 7 PI onwards, respectively. All the immunised donkeys withstood lethal challenge, whereas, control donkeys died within 10 days post-challenge (PC). Parasitaemia rose to mean maximum 8.0+/-6.0% for 5-7 days in group I donkeys after challenge, whereas, it rose to 55.5% in control groups. The percent rise in rectal temperature, total leucocyte count (TLC), fall in haemoglobin (Hb) was less severe in immunised group as compared to the control groups. Two immunised-challenged donkeys were splenectomised recovery. No parasites appeared in the blood during the observation period following splenectomy 4-week. Three times increase in skin-fold thickness at 24h of intradermal inoculation prior to challenge in group I donkeys was observed, thus, indicating a good in vivo cell mediated immunity. It can be concluded that the B. equi immunogen along with adjuvant Quil A, used in the present study, was optimum to elicit a strong immune response against B. equi in experimental donkeys.

Adjuvants, Immunologic↗
PubMed2002

A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway.

The eukaryotic intra-S-phase checkpoint, which slows DNA synthesis in response to DNA damage, is poorly understood. Is DNA damage recognized directly, or indirectly through its effects on replication forks? Is the slowing of S phase in part because of competition between DNA synthesis and recombination/repair processes? The results of our genetic analyses of the intra-S-phase checkpoint in the fission yeast, Schizosaccharomyces pombe, suggest that the slowing of S phase depends weakly on the helicases Rqh1 and Srs2 but not on other recombination/repair pathways. The slowing of S phase depends strongly on the six checkpoint-Rad proteins, on Cds1, and on Rad4/Cut5 (similar to budding yeast Dpb11, which interacts with DNA polymerase epsilon) but not on Rhp9 (similar to budding yeast Rad9, necessary for direct damage recognition). These results suggest that, in fission yeast, the signal activating the intra-S-phase checkpoint is generated only when replication forks encounter DNA damage.

Cell Cycle Proteins↗
PubMed2002

Adsorption and collapse transitions in a linear polymer chain near an attractive wall.

We deduce the qualitative phase diagram of a long flexible neutral polymer chain immersed in a poor solvent near an attracting surface using phenomenological arguments. The actual positions of the phase boundaries are estimated numerically from series expansion up to 19 sites of a self-attracting self-avoiding walk in three dimensions. In two dimensions, we calculate phase boundaries analytically in some cases for a partially directed model. Both the numerical and analytical results corroborate the proposed qualitative phase diagram.

Journal Article↗
PubMed2002

Interleukin-1F7B (IL-1H4/IL-1F7) is processed by caspase-1 and mature IL-1F7B binds to the IL-18 receptor but does not induce IFN-gamma production.

We have recently reported the identification of four novel members of the interleukin-1 (IL-1) family which we designated as IL-1 homologue 1-4 (IL-1H1-4). These proteins exhibit significant sequence homology to other members of the IL-1 family. Of these homologues, only IL-1H4 (renamed IL-1F7b) was predicted to contain a propeptide domain and a caspase cleavage site. We now report that caspase-1 cleaves IL-1F7b at the predicted site to generate mature IL-1F7b. Caspase-4 was also able to process IL-1F7b, albeit inefficiently. Other caspases and Granzyme-B did not cleave IL-1F7b. Furthermore, adenovirus-mediated expression of IL-1F7b in HEK 293 cells led to in situ processing and secretion of mature IL-1F7b. In a screen to identify a potential receptor, both pro and mature IL-1F7b bound to the soluble IL-18 receptor alpha-Fc (IL-18Ralpha-Fc) but not to the soluble IL-1R-Fc or ST2R-Fc fusion proteins. Mature IL-1F7b bound to the IL-18Ralpha-Fc protein with higher affinity than the pro form, although the affinities for both proteins were significantly lower than that observed for IL-18. Consistent with this observation, only IL-18 and not IL-1F7b induced IFN-gamma production by KG1a cells. We also report that pro and mature IL-1F7b form homodimers with association constants of 4 microM and 5 nM, respectively, suggesting biological relevance to IL-1F7b processing. Finally, we have localized the expression of IL-1F7b protein in discrete cell populations including plasma cells and tumor cells. These data suggest that IL-1F7b may be involved in immune response, inflammatory diseases and/or cancer.

Amino Acid Sequence↗