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Biomedical subjects

R K Puri

Publications and source records attributed to R K Puri.

At least 19 recordsLinked to original sources
PubMed1992

Human immunodeficiency virus type 1 tat gene up-regulates interleukin 4 receptors on a human B-lymphoblastoid cell line.

The human immunodeficiency virus type I (HIV-1) regulatory gene, tat III, is a powerful trans-activator of gene expression from the viral long terminal repeat and is essential for HIV replication. In addition, tat III protein has been shown to be immunosuppressive as indicated by the inhibition of antigen mediated T-cell proliferation. To further test whether tat III might play a direct role in the immunosuppressive effects of HIV-1 in addition to its role in virus replication, we examined the regulation of interleukin 4 (IL-4) receptors on a human B-lymphoblastoid cell line (Raji) transfected with HIV-1 tat gene (Raji-tat III). We used radioligand receptor binding analysis for cell surface expression and Northern blot analysis for the expression of human IL-4 receptor gene in Raji-tat III cells. Control Raji cells expressed 1383 +/- 361 (SE; n = 3) IL-4 binding sites/cell with a dissociation constant (Kd) of 144 +/- 27 pM (n = 3). However, Raji-tat III cells expressed about three times higher IL-4 receptors (4000 +/- 633 IL-4 binding sites/cell; P less than 0.03 compared to Raji cells) with a similar Kd of 273 +/- 90 pM (n = 3; P greater than 0.05 compared to Raji cells). Whereas both Raji and Raji-tat III cells exhibited a single mRNA species (approximately 4 kilobases) of IL-4 receptors by Northern blot analysis, the mRNA level was about 3-fold higher in Raji-tat III cells compared to Raji cells. Cycloheximide inhibited the expression of IL-4 receptors by 50% in about 2 h in both cell types indicating both the half-life of IL-4 receptors and the requirement for protein synthesis for the tat III up-regulation of IL-4 receptors. Since IL-4 under certain circumstances has been shown to be immunosuppressant, our observation that the HIV-1 tat gene up-regulates IL-4 receptors suggests the possibility that the immunosuppressive effects of HIV-1 are mediated at least in part through IL-4 receptors.

Cell Line↗
PubMed1992

The effects of interleukin 2 and alpha-interferon administration on hepatic drug metabolism in mice.

We have administered the cytokines interleukin 2 (IL-2), alpha-interferon (IFN-alpha), and gamma-interferon (IFN-gamma) to mice and measured the alterations in hepatic drug-metabolizing enzyme activities. For comparative purposes and to understand the mechanism of diphtheria and tetanus toxoids and pertussis (DTP) vaccine-induced inhibition of drug metabolism, we also studied the effects of vaccine administration in mice. The administration of IL-2 alone or in combination with IFN-alpha or IFN-gamma causes dose-dependent increases in hexobarbital-induced sleep times. These increases correlate well with the inhibition of specific microsomal mixed-function oxidase activities. Sublethally irradiated mice and athymic nude mice receiving injections of IL-2 or IL-2 plus IFN-alpha do not show the inhibition of drug metabolism seen in normal mice. However, the inhibition of drug metabolism in DTP vaccine-treated mice was similar in all three groups. These observations indicate a possible role for immune cells (probably T-lymphocytes) in the inhibition of drug metabolism caused by administration of these cytokines, which is different from the inhibition of drug metabolism caused by DTP vaccine.

Animals↗
PubMed1992

Human herpesvirus-6: tumorigenicity and tumor infiltrating lymphocytes.

We previously reported that human herpes-virus-6 (HHV-6) genome (strain GS) and a cloned subfragment (pZVH14) transfected NIH 3T3 cells, induced foci of transformation with a frequency significantly above the background level. The transformed cells produced tumors in nude mice and immunocompetent (Swiss) mice. In the current study, nude mice tumors were passed into Swiss mice and more aggressive tumors (G-2TS and 14-2TS derived from HHV-6 genome and pZVH14 DNA, respectively) were produced. 14-2TS tumors caused lung metastasis upon intravenous injection. In the case of subcutaneously growing aggressive tumors, tumor infiltrating lymphocytes (TIL) were isolated and characterized as T cells but lacked tumor specific killing as monitored by 51Cr-release assays. TIL lost activity at day 52 in a 4 h assay (but not in a 19 h assay) against the autologous tumor, but not a Maloney virus induced tumor (Yac-1). These studies indicate that an established nontumorigenic fibroblast cell line, when transfected with pZVH14 DNA of HHV-6, acquires both tumorigenic and metastatic potential and tumor bearing hosts mount immune response against such tumors.

Animals↗
PubMed1992

In vitro and in vivo suppression of interleukin-2-activated killer cell activity by chimeric proteins between interleukin-2 and Pseudomonas exotoxin.

The biological effects of IL-2 are mediated through high (complex of alpha and beta chain) or intermediate (beta chain) affinity IL-2 receptors. Previously, chimeric proteins composed of IL-2 and Pseudomonas exotoxin (IL-2-PE) were shown to be specifically cytotoxic to cells bearing IL-2 receptors. It has also been shown that IL-2-PE chimeric proteins can abrogate T cell-mediated immune response in vitro. In the current study, we have investigated the effects of IL-2-PE on LAK activity both in vivo and in vitro. We administered either IL-2-PE40 (comprised of IL-2 and 40-kDa portion of PE) or IL-2-PE66 (comprised of IL-2 and 66-kDa molecule of PE) to normal C57BL/6 mice for 3 or 8 days and LAK activity was assessed in various organs of mice. We found that IL-2-PE40 generated LAK activity in various compartments of mice and the level of activity was slightly lower than that observed with an equivalent amount of recombinant (r) IL-2 alone. However, IL-2-PE66 failed to generate LAK activity which would have been induced due to an equivalent concentration of rIL-2. IL-2-PE66 also did not induce LAK activity from the splenocytes during in vitro culture while IL-2-PE40 generated good LAK activity. An equivalent amount of IL-2 also generated potent LAK activity. The suppression of LAK activity by IL-2-PE66 was also evident in cells preactivated with IL-2; however, this inhibition was partial. The suppressive activity of IL-2-PE66 was shown to be mediated through IL-2 receptor interactions as excess amounts of rIL-2 were able to abrogate its effect. Both IL-2 toxins were equivalently cytotoxic to IL-2 receptor-bearing HUT 102 cells and both were able to compete from high and intermediate affinity IL-2 receptors. Taken together, our data indicate that IL-2-PE66 is highly cytotoxic to LAK cells while IL-2-PE40 is less cytotoxic. Thus, data from our study and from other published reports indicate that IL-2-PE66 is more potent immunosuppressive agent than IL-2-PE40.

ADP Ribose Transferases↗
PubMed1992

Classification of nutritional status as 'Z score' or per cent of reference median--does it alter mortality prediction in malnourished children?

The objective of the study was to evaluate, using a prospective cohort study, whether classification of nutritional status by 'Z score' or per cent of reference median alters the prediction of death in malnourished children. The subjects were children with diarrhoea requiring hospitalization due to moderate or severe dehydration and/or associated complications. There were 382 participants under 5 years of age, of whom 37 died (cases), 320 were discharged in a satisfactory condition (controls) and 25 left before diarrhoea was completely cured (lost to follow-up--excluded). Rehydrated weight and recumbent length (under 2 years) or standing height were recorded and the three indices (weight for age, height for age and weight for height) derived as both 'Z scores' and per cents of reference National Centre for Health Statistics (NCHS) medians. Logistic regression, sensitivity specificity curves and Zda test for normalized distances were used to compare the relative utility of these two classification methods in identifying children with a high risk of dying. The per cent of reference median and 'Z scores' were highly correlated (r = 0.9540, 0.9787 and 0.9667, respectively). Both methods yielded virtually identical results in predicting death of malnourished children for all the three indices. It was concluded that 'Z score' and per cent classification of nutrition are equally efficient in predicting death of malnourished children.

Child, Preschool↗
PubMed1992

Commercial oral rehydration solutions--pitfalls, knowledge, attitude and practices.

Locally available commercial preparations of oral rehydration solutions (ORS) were analyzed for their composition, package instructions and availability. A survey from 50 chemist stores, revealed that ORS packets available belonged to 28 different pharmaceutical companies. None of the shops stored more than five different brands and alternate preparations were handed over the counter freely. Only 48% of the available ORS formulations had the WHO recommended composition. In about one-fourth preparations, the sodium concentration was 30 mEq or less per litre. Forty-one per cent solutions had glucose concentrations more than 2%. The glucose and sodium ration of 1:1 was maintained in only 48% of the formulae. Bicarbonate and citrate both were used with almost equal frequency in these preparations. Cost, flavor, additional ingredients and package instructions varied widely in different packets. ORS formulations most commonly found in the drug stores had low sodium and high glucose concentration. The attitude of doctors and nurses of Pediatric Department and Chemists towards commercial ORS was also studied. While 92% doctors were aware about WHO-ORS, none of the chemists and only 4% nurses had this awareness. All the respondents could remember only up to 3 or 4 brand names and except 30% doctors, none were aware about the composition of those brands of ORS. Regarding importance of composition, preparations and precautions, practically nobody was up to the mark, but doctors were definitely better as compared to nurses and chemists.

Drug Compounding↗
PubMed1992

Systemic administration of recombinant interleukin-6 in mice induces proliferation of lymphoid cells in vivo.

Interleukin-6 (IL-6) is a pleiotropic cytokine and has been shown to support the growth of T and B lymphocytes in the presence of mitogens in vitro. IL-6 can induce human natural killer (NK) and interleukin-2 (IL-2)-induced lymphokine-activated killer cell (LAK) activity in vitro. It can also mediate antitumor effects in various murine models. In order to understand the mechanism of in vivo action, we have investigated the proliferation of lymphoid cells in vivo and the effects on NK, and LAK cell activities in response to IL-6 administration in mice. In vivo proliferation was measured by labeling the DNA of dividing cells with [125I]iodo-2'-deoxyuridine. C57BL/6 mice were injected ip with either IL-6 or HBSS control two times a day for 3 days and in vivo proliferation was measured. For comparative purpose IL-2 was administered and in vivo effects were analyzed. IL-6 caused significant proliferation of cells mainly in the spleen, while, IL-2 caused proliferation in the lungs, liver, spleen, and kidneys. Pretreatment irradiation (500 rad) of mice abrogated the IL-6-induced proliferation indicating radiosensitive cells are involved. Furthermore, in vivo proliferation was not observed in young nude mice treated with IL-6. To investigate whether the proliferating cells were cytotoxic, we tested for LAK (vs. fresh MCA-102 tumor targets) and NK (vs. Yac-1 tumor targets) activities in the organs of mice treated with IL-6 or IL-2 by 4 h 51Cr-release assay. IL-2 administration induced the generation of LAK activity and increased NK cytotoxicity in various organs, but IL-6 had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Loose stools in the early neonatal period.

During a two-year period, the various factors associated with loose stools in the early neonatal period were studied among hospital born babies. Low birth weight babies had a lower incidence of non-infective loose stools when compared to neonates with a birth weight of more than 2500 g (p < 0.001). Newborns delivered by Cesarean section (p < 0.001) and those born to women with more than two children (p < 0.02) had a greater frequency of loose stools. Initiation of supplementary feeding and administration of antibiotics were important factors in causing loose stools. Bacterial etiology could be found only in 9.3% of newborns having loose stools. A later onset of loose stools was noted in those, whose stool culture grew bacterial organisms. Only nine newborns with loose stools required antibiotic therapy. Although loose stools were less common among low birth weight babies, they often required treatment with antimicrobials. None of them developed any complications. Since majority of them are non-bacterial and non-infective, great caution must be exercised before administering antibiotics to newborns with loose stools.

Anti-Bacterial Agents↗
PubMed1992

Clinical and etiological profile of acute viral hepatitis.

There is a paucity of data on the incidence of sporadic viral hepatitis in Indian children. Clinical, biochemical and etiological profile of 54 patients with acute viral hepatitis was evaluated. Of these, 32 (59.25%) patients had Hepatitis A, 18 (33.33%) had NANB, 2 (3.7%) had Hepatitis B and 2 (3.7%) concurrent Hepatitis A and B infection. It was not possible to distinguish the etiological agents on the basis of the clinical and biochemical profile. Fulminant hepatitis was documented in 8 (14.8%) cases. Children with NANB infection were at a greater risk (p less than 0.05) of developing fulminant hepatitis as compared to Hepatitis A infection.

Acute Disease↗
PubMed1992

Health effects of consanguinity in Pondicherry.

Of 1000 pregnant women studied, consanguinity was observed in 30.8%, with a higher frequency among women from rural areas, and among Hindus. In the consanguineous group, first cousin marriages were present in 47.4%, and uncle niece marriages in 23.4% of women. Coefficient of inbreeding was highest in Harijans (0.0258), followed by non-Brahmins (0.0220) and Brahmins (0.0204). Fertility was not influenced by consanguinity. There was a significantly higher rate of still births and infant mortality in consanguineous matings as compared with non-consanguineous. Total morbidity was higher in the consanguineous group as compared with the non-consanguineous (p less than 0.01), especially that due to neonatal infections and jaundice. There was no significant difference in the prevalence of congenital malformations, chromosomal and genetic disorders between the two groups, although the number of abnormal births in this group was small.

Consanguinity↗
PubMed1992

Impact of national immunization schedule on vaccine preventable diseases: a hospital based study.

An analysis of vaccine preventable diseases (VPD) in two block years, i.e., 1972-1975 and 1986-1989 showed an overall decline in morbidity and mortality. Improvement in morbidity was most noticeable in typhoid fever followed by polio and tetanus. However, in tuberculosis and measles with compilations, there was a significant increase in admission rates 3.8 vs 4.4% and 1.8 vs 2.2%, respectively. Mortality in vaccine preventable diseases except polio has declined significantly.

Child↗
PubMed1992

Aminoglycosides.

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Aminoglycosides↗
PubMed1991

An ultrastructural study of in vivo interactions between lymphocytes and endothelial cells in the pathogenesis of the vascular leak syndrome induced by interleukin-2.

Lymphokine-activated killer (LAK) cells play a major role in the induction of the vascular leak syndrome (VLS). To understand the mechanism of this syndrome, the authors examined light and electron microscopic alterations in the lung, liver, spleen, kidney, and heart of mice in which VLS was produced by the administration of interleukin-2 (IL-2) (seven injections of 600,000 IU each for a period of 4 days). The results of these studies disclosed that considerable damage had been done to the endothelial cells that consisted of cytoplasmic edema, vacuoles, and myelin figures; in addition, there were frequent sites of transendothelial passage of lymphoid cells, probably IL-2-activated cells, that penetrated through their cytoplasm by means of "temporary migration pores" and accumulated in the perivascular spaces. The results of this study indicate that a direct in vivo interaction between IL-2-activated cells (probably LAK cells) and endothelium results in cytotoxicity to endothelial cells.

Animals↗