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Biomedical subjects

R K Puri

Publications and source records attributed to R K Puri.

At least 109 records · Page 6Linked to original sources
PubMed1993

Tumor necrosis factor upregulates interleukin-4 receptors on murine sarcoma cells.

We have previously shown that murine solid tumor cells express high affinity IL-4 receptors (IL-4R) which are internalized after binding to ligand. In the present study, we have examined the regulation of IL-4R by TNF. We demonstrate that TNF upregulated the expression of IL-4R on murine MCA-106 sarcoma cells. Maximum upregulation of IL-4R surface expression occurred after 24 h, whereas, maximum elevation in IL-4R mRNA levels was observed after only 4 hours of TNF treatment. This increase in mRNA levels for IL-4R occurred in a dose dependent manner. As little as 0.83 ng/ml of TNF significantly upregulated mRNA levels, whereas maximum effect was obtained with 83 ng/ml TNF. IL-4 receptor density was increased in response to TNF, no effect on IL-4R affinity was observed. Cycloheximide and Actinomycin D treatment decreased the surface expression of IL-4R by 50% in about 2 h and 7 h, respectively, in both TNF treated and untreated cells indicating the half life for the IL-4R protein expression. These studies may help understand the mechanism of cytokine interaction on tumor cells.

Animals↗
PubMed1993

Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor.

The interleukin-2 (IL-2) receptor gamma chain (IL-2R gamma) is an essential component of high- and intermediate-affinity IL-2 receptors. IL-2R gamma was demonstrated to be a component of the IL-4 receptor on the basis of chemical cross-linking data, the ability of IL-2R gamma to augment IL-4 binding affinity, and the requirement for IL-2R gamma in IL-4-mediated phosphorylation of insulin receptor substrate-1. The observation that IL-2R gamma is a functional component of the IL-4 receptor, together with the finding that IL-2R gamma associates with the IL-7 receptor, begins to elucidate why deficiency of this common gamma chain (gamma c) has a profound effect on lymphoid function and development, as seen in X-linked severe combined immunodeficiency.

Animals↗
PubMed1993

A wide range of human cancers express interleukin 4 (IL4) receptors that can be targeted with chimeric toxin composed of IL4 and Pseudomonas exotoxin.

A chimeric toxin has been constructed by fusion of a gene encoding human interleukin 4 (hIL4) to a gene encoding a mutant form of Pseudomonas exotoxin A (PE) which cannot bind to its receptors (PE4E). The chimeric gene was expressed in Escherichia coli where large amounts of the chimeric toxin, hIL4-PE4E, was produced. Purified hIL4-PE4E was very cytotoxic to cancer cell lines of both hematopoietic and solid tumor origin. In the HUT 102 T cell leukemia and Daudi B cell lymphoma cell lines, protein synthesis was inhibited by 50% (ID50) at a hIL4-PE4E concentration of 2 and 7 ng/ml (25 and 86 pM, respectively). hIL4-PE4E was also very cytotoxic to cell lines derived from carcinomas of the colon, breast, stomach, liver, adrenals, and prostate, as well as melanoma and epidermoid carcinoma, indicating that hIL4 receptors are widely expressed on human malignancies. We also found that human phytohemagglutinin-activated peripheral blood lymphocytes were extremely sensitive to hIL4-PE4E with an ID50 of 0.2 ng/ml (2.5 pM). The cytotoxic action of hIL4-PE4E was specific because it was blocked by an excess of hIL4 and not of human interleukin 2. In addition, hIL4-PE4ED553, an enzymatically inactive form of the chimeric toxin, was not cytotoxic. These results suggest that the hIL4 receptor may be a target for therapy in malignant and immunologic disorders using hIL4 chimeric toxin.

ADP Ribose Transferases↗
PubMed1993

Local anesthetic-phospholipid interactions. Effects of ionic strength, temperature, and phospholipid mixtures on the binding of dibucaine to phospholipids.

The nature of the interaction of amphipathic drugs, such as dibucaine, with phospholipid bilayer membranes was investigated using equilibrium dialysis. Profiles for the binding of cationic dibucaine to unilamellar vesicles were obtained at different temperature and ionic strengths, and for mixtures of neutral phospholipid dimyristylphosphatidylcholine (DMPC) with negatively charged dimyristylphosphatidylglycerol (DMPG). The degree of binding of the cationic drug at pH 5 was found to be higher at temperatures above the Tm of DMPC (24 degrees C) than below Tm. Also enhanced drug binding was found to occur as the concentration of monovalent salt was increased (0.01-0.85 M) and as the percentage of DMPG was increased. Using the Stern and Guoy-Chapman model, which takes into consideration electrostatic effects, we were able to simultaneously fit all our binding data with a minimum of fitting parameters. These parameters (for data at 45 degrees C) are an association constant, K, of 330 M-1, a maximum possible number of drug molecules absorbed per unit surface of vesicle, sigma m+, of 1.70 x 10(-2) A2, and a surface area per bound drug, gamma D, of 48 A2. The data were fitted equally well by an alternate model in which binding of the drug is described as a partitioning equilibrium, with factors included for electrostatic effects and surface expansion caused by drug intercalation between the fatty acid chains.

Data Interpretation, Statistical↗
PubMed1993

Rectal histopathology in endemic Shigella and Salmonella diarrhea.

Rectal histopathology was evaluated in 34 cases (2 months-12 yrs old) of endemic "invasive diarrhea" [> 20 WBCs per high-power field on stool microscopy with (RBC positive) or without (RBC negative) associated RBCs] where S. dysenteriae (n = 9), S. flexneri (n = 11), and nontyphoidal Salmonella were isolated as the sole identifiable enteropathogens. Persistent diarrhea (> 14 days duration) was more common with Salmonella infection whereas RBC-positive "invasive diarrhea" was more frequent with Shigella, particularly S. dysenteriae (all cases) infection. The histopathological profile was comparable to the earlier descriptions of infective colitis to a large extent and the nature of the infecting organism could not be determined on the basis of rectal histology alone. The other noteworthy features were as follows: (i) mild crypt distortion (26%) and branching (21%) in both Shigella and Salmonella infection; in Salmonella infection, dilation of the glands was significantly greater with persistent diarrhea; (ii) presence of chronic inflammatory cells either alone or in combination with neutrophils in 62%; a predominant neutrophilic response was significantly higher with S. dysenteriae infection and an acute presentation; (iii) pseudomembrane formation (six subjects; 18%) especially in S. dysenteriae (four cases); and (iv) a significant association of neutrophilic response, edema, and neutrophils within the vessels in the lamina propria and mucin depletion in the glands with RBC-positive "invasive diarrhea."

Ampicillin↗
PubMed1993

Exchange transfusion in neutropenic septicemic neonates: effect on granulocyte functions.

Depletion neutropenia caused by overwhelming bacterial infection is associated with fatal outcome and is an objective indicator of the severity of sepsis. Studies on controlled evaluation of exchange transfusion in the management of severe neonatal sepsis have not considered neutropenia as an inclusion criterion, and randomized, controlled trials on evaluation of neutrophil functions after exchange transfusion are scarce. This prompted us to carry out the present study. Septicemic neonates were enrolled if they had neutropenia and were randomized to undergo exchange transfusion (study group, n = 20) or not (controls, n = 10). Granulocyte functions were assessed using the nitro blue tetrazolium (NBT) reduction test and the staphylococcidal index. Blood was drawn for granulocyte function tests once from controls and donors, and before, immediately after and 6 h after exchange transfusion in the study group. Mortality was 35% in the study group and 70% in controls. Gram-negative organisms accounted for 80% in the study group and 90% in controls. Mean total leukocyte count and neutrophil count increased significantly immediately after exchange transfusion and 6 h later. Absolute band count decreased significantly immediately after exchange transfusion and increased 6 h later. NBT reduction in septicemic neonates in the study group, as well as in controls, was significantly decreased as compared to donor cells. NBT reduction improved significantly immediately after exchange transfusion and 6 h later. The values of the percentage of viable staphylococci recovered from neutrophils also improved significantly immediately after exchange transfusion and 6 h later.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteremia↗
PubMed1993

Expression of high affinity interleukin-4 receptors on human renal cell carcinoma cells and inhibition of tumor cell growth in vitro by interleukin-4.

Previously, Puri et al. (Puri, R. K., M. Ogata, P. Leland, G. M. Feldman, D. Fitzgerald, and I. Pastan. 1991. Cancer Res. 51:3011-3017) have demonstrated that murine sarcoma and colon adenocarcinoma cells express high affinity interleukin-4 receptors (IL-4R) which are internalized after binding to a chimeric ligand consisting of IL-4 and Pseudomonas exotoxin. In the present study, we have tested primary cultures of human renal cell carcinoma (RCC) cells, generated from tumor specimens obtained after nephrectomy, for the expression of IL-4R and their modulation by IL-4. By using iodinated IL-4 in a receptor binding assay, we observed that renal cell carcinoma cells expressed a single class of high affinity IL-4R ranging from 1,425 +/- 207 (mean +/- SEM) to 3,831 +/- 299 (mean +/- SEM) IL-4R molecules/cell with a Kd ranging from 112 +/- 11 pM to 283 +/- 71 pM. Northern blot analysis for IL-4R gene expression, performed with a cDNA probe to IL-4R, revealed that all RCC cells exhibited a single mRNA species of 4 kb. IL-4 downregulated the surface expression of IL-4R on one RCC tumor cell line. The function of IL-4R expression on RCC tumor cells was further determined by investigating the effect of IL-4 on tumor cell growth in vitro and comparing it with IL-4 effect on growth of normal fibroblast and endothelial cell lines. Tumor cell growth, as measured by [3H]thymidine incorporation, was inhibited by IL-4 from 20 to 68% in a dose-dependent manner. A neutralizing antibody to human IL-4 was able to reverse the growth inhibitory effect of IL-4. Normal human fibroblast and endothelial cell lines also expressed high affinity IL-4R, however, IL-4 did not inhibit their growth in vitro. In fact, IL-4 caused modest stimulation of their growth. Taken together, our findings can help develop strategies for the treatment of RCC in which IL-4R may be used as a target for IL-4 itself, for IL-4 toxin therapy or, alternatively, in gene therapy.

Carcinoma, Renal Cell↗
PubMed1993

Immunostaining of interleukin-4 receptor on human renal cell carcinoma.

Immunocytochemistry on three primary cultures of RCC tumor cells and immunohistochemistry on five frozen sections of RCC were performed by utilizing a monoclonal antibody (M-57) to human IL-4R. We found that all three RCC tumor cell cytospin preparations stained with anti-IL-4R monoclonal antibody. Tumor cells stained with IgG control did not show any staining. Similarly, five histologically proven RCC frozen sections prepared from nephrectomy specimens had moderate to intense immunoreactivity to IL-4 receptor antibody. RCC sections stained with normal mouse IgG2b showed only background type staining. Frozen section prepared from uninvolved kidney showed only nonspecific staining. A flow cytometric analysis of primary cultures of RCC tumor cells confirmed the immunohistochemical data and showed that almost all of the cells were positive for IL-4 receptor expression. These results demonstrate that human RCC express immunoreactive IL-4 receptors, which may be a target for diagnosis and therapy by an anti-IL-4 receptor antibody fused to toxins or radionuclides or alternatively by IL-4 toxins.

Animals↗
PubMed1993

Desferrioxamine induced urinary iron excretion in thalassemia.

Twenty one children of beta thalassemia major aged between 2 and 14 years of age on regular blood transfusion were given subcutaneous desferrioxamine. Their serum ferritin, 24 hours baseline urinary iron excretion and subcutaneous desferrioxamine induced urinary iron excretion were measured. The result showed a close correlation between serum ferritin and amount of blood transfusions received by the patient. There was good correlation between serum ferritin and desferrioxamine induced urinary iron excretion. A negative iron balance could be achieved in 15 out of 21 children with one dose of desferrioxamine therapy.

Adolescent↗
PubMed1993

Why breast feed?

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Bottle Feeding↗
PubMed1993

Serum enzyme abnormalities in protein energy malnutrition.

Six serum enzymes, alkaline phosphatase, cholinesterase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase were studied in 30 cases of protein energy malnutrition (PEM). The mean serum values of alkaline phosphatase, cholinesterase and lactate dehydrogenase in cases of PEM were significantly lower than the controls, lowering being maximum in PEM Grade IV. The mean serum values of aspartate aminotransferase and alanine aminotransferase in patients with PEM were significantly higher than the controls. The mean serum values of gamma-glutamyl transpeptidase showed similar significant rise in all but PEM Grade IV. The degree of increase in the serum values of these three enzymes were maximum in cases with PEM Grade I. These findings suggest that abnormalities in blood levels of these enzymes occur in any form of PEM and these are related to the severity of the disease.

Adolescent↗