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Biomedical subjects

A Puri

Publications and source records attributed to A Puri.

At least 55 records · Page 3Linked to original sources
PubMed1998

The neutral glycosphingolipid globotriaosylceramide promotes fusion mediated by a CD4-dependent CXCR4-utilizing HIV type 1 envelope glycoprotein.

Previously, we showed that the addition of human erythrocyte glycosphingolipids (GSLs) to nonhuman CD4(+) or GSL-depleted human CD4(+) cells rendered those cells susceptible to HIV-1 envelope glycoprotein-mediated cell fusion. Individual components in the GSL mixture were isolated by fractionation on a silica-gel column and incorporated into the membranes of CD4(+) cells. GSL-supplemented target cells were then examined for their ability to fuse with TF228 cells expressing HIV-1LAI envelope glycoprotein. We found that one GSL fraction, fraction 3, exhibited the highest recovery of fusion after incorporation into CD4(+) nonhuman and GSL-depleted HeLa-CD4 cells and that fraction 3 contained a single GSL fraction. Fraction 3 was characterized by MS, NMR spectroscopy, enzymatic analysis, and immunostaining with an antiglobotriaosylceramide (Gb3) antibody and was found to be Gal(alpha1-->4)Gal(beta1-->4)Glc-Cer (Gb3). The addition of fraction 3 or Gb3 to GSL-depleted HeLa-CD4 cells recovered fusion, but the addition of galactosylceramide, glucosylceramide, the monosialoganglioside, GM3, lactosylceramide, globoside, the disialoganglioside, GD3, or alpha-galactosidase A-digested fraction 3 had no effect. Our findings show that the neutral GSL, Gb3, is required for CD4/CXCR4-dependent HIV-1 fusion.

Acetylation↗
PubMed1998

Immunosuppressant activity in human beta-casein fragment analogs.

Human beta-casein fragment (54-59) having the amino acid sequence Val-Glu-Pro-Ile-Pro-Tyr, has been shown potent immunostimulant activity. Several analogs of this hexapeptide have been synthesized with modification in the N-terminal region and tested for their immunomodulatory activity. Interestingly, two hexapeptides have shown significant immunosuppressant activity.

Amino Acid Sequence↗
PubMed1998

Human erythrocyte glycolipids promote HIV-1 envelope glycoprotein-mediated fusion of CD4+ cells.

We examined the role of target membrane glycolipids in CD4-mediated HIV-1 fusion by altering the glycolipid levels in CD4+ cells. CD4+ human cells exhibited 50% reduction in extent of fusion with gp120-gp41 expressing cells (TF228) when grown in the presence of a glycolipid synthesis inhibitor PPMP. We added erythrocyte glycolipids (GL) to fusion-incompetent CD4+ non-human cells by influenza-hemagglutinin-mediated fusion between GL-containing liposomes and target cells. Human erythrocyte GL (HuGL)-modified CD4+ non-human cells became susceptible to fusion with TF228 cells. Transfer of bovine erythrocyte glycolipids (BoGL) to CD4+ non-human cells under similar conditions did not complement HIV-1 fusion. Furthermore, addition of HuGL, but not BoGL, to PPMP-inhibited cells rescued fusion to the original levels. Our observations demonstrate that human erythrocyte glycolipids promote CD4-mediated HIV-1 fusion and certain glycolipid(s) from human erythrocytes may serve as alternative and/or additional cofactors in HIV-1 entry.

Animals↗
PubMed1998

The metabotropic glutamate receptors of the vestibular organs.

This research sought to test the presence and function of metabotropic excitatory amino acid receptors (mGluR) in the frog semicircular canal (SCC). The mGluR agonist +/- 1-aminocyclopentane-trans-1,3-dicarboxylate (ACPD) produced an increase in afferent firing rates of the ampullar nerve of the intact posterior canal. This increase was not due to a stimulation of cholinergic efferent terminals or the acetylcholine (ACh) receptor, since atropine, in concentrations which blocked the response to exogenous acetylcholine, did not affect the response to ACPD. Likewise, ACPD effects were not due to stimulation of postsynaptic NMDA receptors, since the NMDA antagonist D(-)-2-amino-5-phosphonopentanoate (AP-5) did not affect the response to ACPD, reinforcing the reported selectivity of ACPD for mGluRs. When the SCC was superfused with artificial perilymph known to inhibit hair cell transmitter release (i.e. low Ca-high Mg), ACPD failed to increase afferent firing. This suggests that the receptor activated by ACPD is located on the hair cell. Pharmacological evidence suggested that the mGluRs involved in afferent facilitation belong to Group I (i.e. subtypes 1 and 5). In fact, the Group III agonist AP-4 had no effect, and the ACPD facilitatory effect was blocked by the Group I mGluR antagonists (S)-4-carboxyphenylglycine (CPG) and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA). Additional pharmacological evidence supported the presence of Group I mGluRs. Interestingly, the mGluR antagonists, AIDA and 4CPG, by themselves did not affect the resting firing rates of ampullar afferents. This may suggest that the mGluRs are not involved in resting activity but perhaps only in evoked activity (as suggested in Guth et al. (1991) Hear. Res. 56, 69-78). In addition, the mRNA for the mGluR1 has been detected in hair cells of both SCC, utricle, and saccule. In summary, the evidence points to an mGluR localized to the hair cell (i.e. an autoreceptor) which may be activated to produce a positive feedback augmentation of evoked but not resting transmitter release and thus affect afferent activity.

Afferent Pathways↗
PubMed1998

Epilepsies among twins born in families of Indian probands with epilepsy.

Twins have a high frequency of adverse perinatal events and have been reported to have an increased risk of seizures. Contrary to popular belief, a recent study reported that twins do not have an increased risk of seizures. We studied the relationship of twinning and epilepsy in India. The frequency of twinning in families of probands with epilepsy was compared with the frequency of twinning among hospital births in the same region of India. We also compared consecutively ascertained probands with epilepsy for their twin status and the occurrence of epilepsies in their twin and non-twin relatives. The frequency of twin births in families of 524 probands with epilepsy was comparable to the twin births among consecutive deliveries over a 3-year period in another government hospital in the same catchment area (1:99 vs. 1:75). Every 1 in 58 of probands with epilepsy was a twin while a twin was born in these families every 1 in 71 live births. The frequency of epilepsy in non-proband twin relatives was 1.5% compared with 2% among non-proband, non-twin relatives. This data suggests that twin birth is not a major risk factor for seizures even in families of Indian probands with epilepsy. Family data such as ours can be used to study the contribution by genetic factors in the pathogenesis of complex genetic diseases such as human epilepsies.

Adult↗
PubMed1998

Juvenile myoclonic epilepsy: disease expression among Indian families.

OBJECTIVES: Juvenile myoclonic epilepsy (JME) is a common, age related, idiopathic generalized epileptic syndrome. We aimed to define the expression of JME in Indian probands and study the occurrence of seizures/epileptic syndromes in their family members. METHODS: We studied 225 JME probands with a uniform protocol. recording the type and frequency of seizures, precipitating factors, EEG data, and family history. Detailed family pedigrees were drawn to include all the 1st- and 2nd-degree relatives of probands. The seizures/epileptic syndromes in relatives examined were classified in a uniform way. RESULTS: The clinical and EEG characteristics of 225 JME probands from India were similar to those reported in probands from different ethnic backgrounds. The incidence of febrile convulsions in probands with JME was similar to that of the general population but was much lower (0.2%) among their relatives. A positive family history of seizures among 1st- or 2nd-degree relatives was noted in 79 of 225 (35%) probands. The risk of relatives being affected as well as their risk of expressing a type of idiopathic generalized epilepsy (IGE) varied as a function of the degree of relation with the probands. CONCLUSIONS: The clinical expression of JME among probands from India is fairly similar to that reported in probands of different ethnic backgrounds. The risk of relatives being affected as well as their risk of expressing a type of IGE (including JME) varies as a function of the degree of relation with the probands. The reduced occurrence of febrile convulsions among the relatives of JME probands probably represents an ascertainment bias. A much larger database of this type should be helpful in understanding the interactions of different genes that are believed to be responsible for some of the inherited human epileptic syndromes like JME and other IGEs.

Adolescent↗
PubMed1997

Conformational changes and fusion activity of vesicular stomatitis virus glycoprotein: [125I]iodonaphthyl azide photolabeling studies in biological membranes.

The interaction of VSV glycoprotein (VSV G) with biological membranes was studied by photosensitized labeling. The method is based on photosensitized activation by the fluorescent lipid analog 3,3'-dioctadecyloxacarbocyanine (DiO) of a hydrophobic probe, [125I]iodonaphthyl azide (125INA), that rapidly partitions into the membrane bilayer of virus and cells. 125INA labeling of proteins and lipids can be confined to the site of chromophore localization by photosensitized labeling. Photoactivation using visible light of target membrane labeled with DiO and 125INA, to which unlabeled virions are bound, results in exclusive labeling of envelope glycoproteins inserted into the target membrane [Pak et al. (1994) J. Biol. Chem. 269, 14614]. In this study, we labeled lipid symmetric erythrocyte ghosts with 125INA and DiO. Photosensitized activation of VSV prebound to labeled ghosts with visible light resulted in VSV G labeling under fusogenic conditions. Photoactivation of 125INA by UV light, which is nonspecific, produced labeled VSV G at both acidic and neutral pH. Photosensitized labeling of VSV G by DiO-125INA-ghosts was also observed at pH 5.5, 4 degrees C, in the absence of mixing between viral and cellular lipids, suggesting insertion of the ectodomain of VSV G. Soluble VSV G lacking the transmembrane domain inserted into DiO-125INA-ghosts under the same conditions as intact VSV G. DiO inserted into intact VSV appeared to be a suitable fluorophore for continuous kinetic measurements of membrane fusion by fluorescence dequenching. Our photosensitized labeling results establish biochemical correlates for the three states of VSV G, which we had proposed based on kinetic data [Clague et al., Biochemistry 29, 1303]. In addition, we found that VSV G insertion into the target membrane is reversible, suggesting a "velcro"-like attachment of the fusogenic domain with the target membrane.

Affinity Labels↗
PubMed1997

Management of giardiasis by a herbal drug 'Pippali Rasayana': a clinical study.

Pippali Rasayana (PR), an Indian ayurvedic drug prepared from Palash (Butea monosperma (Lamk) Kuntze; Leguminaceae) and Pippali (Piper longum L.; Piperaceae), was administered at a dose of 1 g p.o. three times daily for a period of 15 days to patients (25 treated, 25 placebo controls) suffering from giardiasis with clinical signs and symptoms, and stools positive for trophozoites/cysts of Giardia lamblia. After 15 days of drug treatment there was a complete disappearance of G. lamblia (trophozoites/cysts) from the stools of 23 out of 25 patients. General signs and symptoms of ill health and abdominal discomfort, presence of mucus, pus cells and RBCs were significantly reduced. There was a marked improvement in the clinical and haematological profile of the patients. Spontaneous recovery in 20% cases was recorded in placebo controls.

Adjuvants, Immunologic↗
PubMed1997

Occurrence of epilepsies in family members of Indian probands with different epileptic syndromes.

PURPOSE: Large numbers of families with many members having seizures have been used to understand the role of hereditary factors in the pathogenesis of human epileptic syndromes. We aimed to establish a genetic database to form a hypothesis on the possible genetic contributions in different epileptic syndromes. METHODS: The occurrence and patterns of different epilepsies and epileptic syndromes in 1,219 Indian probands and their relatives were studied. The concordance of epilepsies between probands and relatives was also analyzed. RESULTS: Of probands, 231 (19% of 1219) had first- or second-degree relatives affected with seizures. Incidence of family history in probands with generalized epilepsies (GES) and syndrome of single, small, enhancing lesions (SSEL) was comparable and significantly higher than that in probands with localization-related epilepsies (LRES). The ratio of affected first- to second-degree relatives was close to 4:1. Generalized epilepsies were the commonest type of epileptic syndromes seen among all relatives. The proportion of sibs and second-degree relatives with epileptic syndromes similar to probands was significantly greater in the GES group as compared with the concordant relatives of probands with LRES and SSEL. CONCLUSIONS: A significant percentage of first- and second-degree relatives of probands with all types of epileptic syndromes have seizures. The risk of relatives being affected varied as a function of the relation with the proband. Concordance of epileptic syndromes between probands and relatives was related to the epileptic syndromes in probands. The syndrome of SSEL is probably a benign epileptic syndrome seen in Indians genetically predisposed to seizures. Hereditary factors may play an almost equal role in the predisposition of relatives to epilepsy in families of probands with different epileptic syndromes.

Brain↗
PubMed1996

Heat-resistant factors in human erythrocyte membranes mediate CD4-dependent fusion with cells expressing HIV-1 envelope glycoproteins.

It has been shown that human CD4 expressed in nonhuman cells does not support HIV-1 entry into those cells and that components from human cells in addition to CD4 are required to overcome the block. We have used human red blood cells (huRBC) as a source for the accessory components since their membrane composition is less complex than that of nucleated cells and they are well characterized. Components were transferred by fusion of huRBC to nonhuman CD4(+) cells mediated by influenza hemagglutinin or polyethylene glycol. The RBC-modified nonhuman CD4(+) cells were labeled with fluorescent markers and incubated with gp 120-gp41-expressing cells labeled with a different fluorescent probe. Fusion between RBC- modified nonhuman CD4(+) cells and gp 120--gp41-expressing cells was quantified by fluorescence video microscopy. Human erythrocyte components transferred to nonhuman CD4+ cells conferred HIV-1 envelope glycoprotein-mediated fusion susceptibility to those cells. The fusion was enhanced by pretreatment of the erythrocytes for 10 min at 56 degrees. No gp 120--gp41-mediated fusion was observed when components from nonhuman RBC were transferred to nonhuman CD4+ cells. Human cell lines with pre-RBC characteristics (K562-CD4) also supported HIV-1 envelope glycoprotein-mediated fusion.

Animals↗
PubMed1996

Synthesis and immunostimulant activity of novel analogs of human casein fragment (54-59).

Structural analogs of the hexapeptide sequence 54-59 (A) human casein, reported to stimulate immune response, were synthesized and evaluated for immunostimulant activity. Hexapeptide 91/409 (C), 90/649 (D) and 91/361 (E) stimulated higher antibody titre and delayed type of hyper-sensitivity (DTH) response than the natural casein hexapeptide in BALB/c mice-sheep red blood cells (SRBC) and guinea pig-ovalbumin models. These peptides also induced higher stimulation of non-specific immune response as evidenced by increase in macrophage migration index (MMI), phagocytosis of (14C) lecuine labelled Escherchia coli, incorporation of (14C)-glucosamine in peritoneal macrophages and proliferative response of mouse thymocytes. Significant suppression on the course of Plasmodium berghei infection was also observed on day 4, in the animals treated with hexapeptidse C and D.

Adjuvants, Immunologic↗
PubMed1995

Double-blind, randomized trial of one versus three prophylactic doses of synthetic surfactant in 826 neonates weighing 700 to 1100 grams: effects on mortality rate. American Exosurf Neonatal Study Groups I and IIa.

At 33 hospitals in the United States, a double-blind, randomized clinical trial was performed to compare one versus three prophylactic doses of synthetic surfactant in 700 to 1100 gm inborn infants. All 826 infants received an initial prophylactic dose of surfactant within 30 minutes of birth. Subsequently 410 infants received two doses of placebo (air) 12 and 24 hours later, and 416 infants received two additional doses of surfactant. By the age of 28 days, 70 infants who received one dose of surfactant and 40 infants who received three doses were dead, a 43% relative reduction in the mortality rate (30 fewer deaths; p = 0.002). By the age of 1 year after term, 87 infants who received one dose and 62 infants who received three doses were dead: a 29% relative reduction in the mortality rate (25 fewer deaths; p = 0.027). Infants who received three doses of surfactant required significantly less oxygen and less mean airway pressure for the first week of life. Necrotizing enterocolitis (9 vs 25 infants; p = 0.005), and use of high-frequency ventilation (13 vs 26 infants; p = 0.037); pancuronium (43 vs 62 infants; p = 0.045); and leukocyte transfusions (0 vs 4 infants; p = 0.042) were less frequent in the three-dose group, but air leak, bronchopulmonary dysplasia, intraventricular hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, and infections were not different. These results indicate that physiologic findings, mortality rates, and probably morbidity rates are improved by two additional prophylactic doses of synthetic surfactant.

Bronchopulmonary Dysplasia↗
PubMed1994

Management of giardiasis by an immuno-modulatory herbal drug Pippali rasayana.

Pippali rasayana (PR), an Ayurvedic herbal medicine, prepared from Piper longum (Pippali) and Butea monosperma (Palash), and prescribed for the treatment of chronic dysentery and worm infestations was tested for anti-giardial and immuno-stimulatory activity in mice, infected with Giardia lamblia trophozoites. It produced up to 98% recovery from the infection. The rasayana had no killing effect on the parasite in vitro. It induced significant activation of macrophages as evidenced by increased macrophage migration index (MMI) and phagocytic activity. Enhancement of host resistance could be one of the possible mechanisms contributing towards the recovery of animals from the giardial infection.

Adjuvants, Immunologic↗
PubMed1994

Immunostimulant activity of Nyctanthes arbor-tristis L.

Nyctanthes arbor-tristis L. (Oleaceae), a plant widely used in the traditional medicinal systems of India, has recently been reported to possess hepatoprotective, antileishmanial, antiviral and antifungal activities. In the present study strong stimulation of antigen specific and non-specific immunity, as evidenced by increases in humoral and delayed type hypersensitivity (DTH) response to sheep red blood cells (SRBC) and in the macrophage migration index (MMI), has been demonstrated in mice fed with 50% ethanolic extract of seeds, flowers and leaves of this plant. Maximum activity was found in the seeds in which the active principle(s) appear to be mainly associated with lipids. In flowers and leaves, however, the major activity was found in the aqueous fraction of the 50% ethanol extract. The immunostimulant substance(s) found in N. arbor-tristis L. are likely to play a role in its antiamoebic, antileishmanial, antiviral and certain other activities.

Adjuvants, Immunologic↗
PubMed1993

A new approach to measure fusion activity of cloned viral envelope proteins: fluorescence dequenching of octadecylrhodamine-labeled plasma membrane vesicles fusing with cells expressing vesicular stomatitis virus glycoprotein.

Fusion between fluorescently labeled plasma membrane vesicles (PMV) and cells expressing vesicular stomatitis virus (VSV) glycoprotein (G-protein) was investigated by utilizing a lipid mixing assay based on fluorescence dequenching of octadecyl rhodamine (R18). The PMVs were prepared from Vero cells by hypotonic lysis. The G-protein was expressed on the cell surface either following infection with intact VSV or with an adenovirus vector (AdG12) containing the gene for the G-protein. Fusion was temperature and pH dependent and was inhibited by VSV G-antiserum. The pH dependence of PMV fusion paralleled that observed for VSV-cell fusion and VSV-induced syncytia formation. The kinetics of fusion followed an exponential dependence on time without an observable time lag after lowering pH. These findings indicate that dequenching R18-labeled PMV reliably represents the basic features of fusion of VSV with cells and can be used as a new tool in the study of fusion activity of virus envelope proteins expressed in cells.

Animals↗