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Biomedical subjects

J Chandra

Publications and source records attributed to J Chandra.

At least 55 records · Page 3Linked to original sources
PubMed1997

Immune clearance of phosphatidylserine-expressing cells by phagocytes. The role of beta2-glycoprotein I in macrophage recognition.

The function of beta2-glycoprotein I (beta2GPI), a 50-kDa serum glycoprotein, is not completely understood but has been suggested to be involved in the regulation of thrombosis (Brighton, T. A., Hogg, P. J., Dai, Y.-P., Murray, B. H., Choing, B. H., and Chesterman, C. N. (1996) Br. J. Haematol. 93, 185-194) and the clearance of phosphatidylserine (PS)-expressing cells (Chonn, A., Semple S. C., and Cullis P. R. (1995) J. Biol. Chem. 270, 25845-25849). To further understand the role of this protein, we characterized the ability of beta2GPI to interact with PS vesicles and influence their uptake by macrophages in vitro. beta2GPI bound to and precipitated vesicles containing anionic but not zwitterionic phospholipids in a gel diffusion assay. beta2GPI also inhibited the procoagulant activity of PS liposomes. In vitro phagocytosis studies showed 20-fold greater uptake of PS liposomes over phosphatidylcholine liposomes. This enhanced uptake was maintained even after PS was "shielded" with beta2GPI and further increased upon the addition of beta2GPI antibodies. Similar to liposomes, PS-expressing apoptotic thymocytes and lipid symmetric red blood cell ghosts bound beta2GPI. Macrophage uptake of these cells was also maintained or enhanced in the presence of beta2GPI and further increased upon the addition of beta2GPI antibodies. It is concluded that beta2GPI can play a critical role in hemostasis by influencing both thrombosis and the clearance of PS-expressing cells.

Apolipoproteins↗
PubMed1997

Protease activation is required for glucocorticoid-induced apoptosis in chronic lymphocytic leukemic lymphocytes.

Recent work has demonstrated that glucocorticoids, nucleoside analogues, and other cancer chemotherapeutics induce apoptosis in chronic lymphocytic leukemia (CLL) cells. In this study, we investigated the involvement of protease activation in these responses using selective peptide inhibitors of the interleukin-1beta converting enzyme (ICE)/caspase family and a Ca2+-activated protease we recently implicated in thymocyte apoptosis. Apoptosis was associated with proteolytic cleavage of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) and increased caspase protease activity, and cell-permeant caspase antagonists [zVAD(OMe)fmk and Boc-D(OBzl)cmk] blocked apoptosis in response to the glucocorticoid methylprednisolone or the nucleoside analogue fludarabine, indicating that caspase activation was required for these responses. However, a peptide-based inhibitor of the Ca2+-dependent lamin protease (zAPFcmk) also completely suppressed DNA fragmentation and the cleavage of lamin B1 . Strikingly, treatment of cells with zAPFcmk alone led to characteristic PARP cleavage, depletion of the precursor forms of two ICE family proteases (CPP32 and ICH-1), and phosphatidylserine exposure, suggesting that blockade of the lamin protease led to activation of the ICE family. Our results implicate the lamin protease as a target for Ca2+ during chemotherapy-induced apoptosis in CLL lymphocytes, and they identify a novel functional interaction between the protease and members of the ICE family.

Apoptosis↗
PubMed1996

Apoptosis sensitivity in chronic lymphocytic leukemia is determined by endogenous endonuclease content and relative expression of BCL-2 and BAX.

Therapeutic agents used in the treatment of chronic lymphocytic leukemia (CLL) are capable of inducing apoptosis in some (but not all) patient isolates. It is not yet clear whether cells that are resistant to one agent will also be resistant to others, and the mechanisms contributing to differential apoptosis sensitivity are not known. Here we report that glucocorticoid hormone and a clinically relevant chemotherapy combination (fludarabine plus mitoxantrone) fail to induce apoptosis in four of 24 CLL patient isolates. Apoptosis resistance was associated with elevated BCL-2 and BAX expression. Interestingly, incubation in vitro led to down-regulation of BCL-2 expression in both apoptosis-sensitive and apoptosis-resistant cells, whereas parallel down-regulation of BAX occurred only in the resistant samples. Evaluation of nuclear endonuclease content indicated that all of the apoptosis-sensitive samples contained appreciable levels of activity, whereas the endonuclease was not detected in the four populations of resistant cells. Our results indicate that nuclear endonuclease activity represents an excellent prognostic indicator of CLL apoptosis sensitivity that may be controlled by differential BCL-2 family polypeptide expression and signals from the in vivo microenvironment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Kala-azar: experience from a non-endemic area in India.

Resurgence of Kala-Azar in India has posed many problems. Apart from patients from endemic areas, cases are being reported from non-endemic areas also. In the present series, four out of 26 patients were from non-endemic areas. Other than diagnostic difficulties, resistance to stibogluconate and relapse are common problems which were seen in eight patients. The clinical profile of cases, their management, and how the problem of resistance was tackled are described.

Antimony Sodium Gluconate↗
PubMed1995

Status of membrane lipids and amino acid transport in morphological mutants of Candida albicans.

The phospholipid composition of various morphological mutants of Candida albicans revealed a complete absence of phosphatidylinositol (PI) from plasma membranes of those cells which completely lacked mycelial growth. No other phospholipid was found to be specific to morphogenesis. The plasma membrane fractions isolated from mutants were more rigid than its wild type as was evident from their unsaturation index and fluorescence polarization measurements. The enhanced membrane rigidity of mutant cells was noted regardless whether the cells could grow only as mycelia or in their budding forms. Although some amino acids are considered to affect the morphological transition of C. albicans, this was not reflected in the transport activities of L-proline, L-alanine, L-lysine and L-glutamic acid.

Amino Acids↗
PubMed1995

Neuromuscular manifestations of diarrhea related hypokalemia.

Twenty-three children from 8-60 months (mean age 21.13 months) admitted with neuromuscular manifestations of diarrhea related hypokalemia were studied. Forty four per cent cases were suffering from diarrhea at the time of admission but in majority of cases (56%), the diarrheal episode had already terminated. Mild hypokalemia was seen in 17.4%, moderate in 43.5% and severe in 39.1%. Neck flop was the commonest (100%) neuromuscular manifestations followed by diminished bowel sounds (82.6%), truncal weakness (52.2%), weakness of limbs (52.2%), lethargy (43. 5%), abdominal distension (43.5%), respiratory involvement (4.3%) and phantom hernia (4.3%). Two cases (8.7%) had flaccid paralysis of both the lower limbs. Severe hypokalemia was more frequently observed in children below 24 months of age and those who had received i.v. fluids or salt sugar solution before reporting in the hospital. A significant correlation was noticed between severity of hypokalemia and frequency of stools (p < 0.05), degree of dehydration (p < 0.01), severity of nutrition (p < 0.01) and extent of neuromuscular involvement (p < 0.01). Our results highlights the importance of diarrhea related hypokalemia particularly in young malnourished children who are rehydrated with solutions inadequate in potassium. Early diagnosis and appropriate treatment can promptly reverse these manifestations within 48-72 hours.

Child, Preschool↗
PubMed1993

Effect of toxaphene toxicity on enzyme activity & residue levels in vital organs of guineapig.

Guineapigs exposed to acute and subacute levels of toxaphene revealed a marginal reduction in the body weight. There was a significant inhibition of acetylcholinesterase and ATPases in the brain, liver and kidney. The effect of subacute toxicity of toxaphene resulted in an enhancement of cytochrome P450 and induction of aniline hydroxylase in liver and kidney. Biochemical investigations on the backbone revealed that toxaphene toxicity caused an increase in the calcium content and a decrease in the collagen content significantly. Toxaphene was accumulated more in the liver than in the kidney as reflected by residue studies.

Animals↗
PubMed1992

Myelofibrosis.

Explore the source record for details and available documents.

Biopsy↗
PubMed1992

Multidrug resistant typhoid fever: therapeutic considerations.

Forty six blood culture positive cases were studied during the current outbreak of multidrug resistant typhoid fever (MRTF). The present outbreak was caused by E1 phage type and organisms were resistant to all commonly used drugs for the treatment of typhoid fever, viz., chloramphenicol (78%), co-trimoxazole (76%) and ampicillin (68%). Treatment failures with chloramphenicol (45.5%) corroborated well with in vitro resistance. No treatment failure was seen with chloramphenicol and ceftriaxone, when these drugs were used in cases infected with sensitive strains. Among the alternative drugs used in cases with in vitro sensitivity, successful clinical response was seen with ceftriaxone (4/4) and cefotaxime (8/9) as compared to cephalexin (3/5) or a combination of cephalexin and furazolidone (9/12).

Ampicillin Resistance↗