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Biomedical subjects

A Puri

Publications and source records attributed to A Puri.

At least 37 records · Page 2Linked to original sources

Entry of influenza virus into a glycosphingolipid-deficient mouse skin fibroblast cell line.

A glycosphingolipid (GSL)-deficient mouse skin fibroblast mutant cell line (GM95) was tested for its susceptibility to influenza virus infection and/or fusion. Octadecyl rhodamine labeled influenza virus fused at 37 degrees C and low pH with GM95 cells at similar rates and extents as with the parental cell lines which did bear glycosphingolipids. Influenza virus infected the GM95 cells at the same level as the parental cell lines. The infection and fusion was blocked when the cell lines were pre-treated with neuramindase. We conclude that influenza virus uses mainly sialoglycoproteins and that gangliosides are not essential for influenza virus fusion and infection.

Animals↗

Syntheses and immunomodulatory activity of 3-O-[2'-hydroxy-3'-N,N-disubstituted aminopropan-1'-yl]-alpha-D-glucofuranoses.

A number of 3-O-[2'-hydroxy-3'-N,N-aminopropan-1'-yl]-alpha-D-glucofuranoses were synthesised by regioselective oxirane ring opening in compound 2 with different secondary amines followed by selective deacetalisation. All the compounds were tested for their immunomodulatory potential in vitro; seven of them expressed significant immunostimulant activity.

Adjuvants, Immunologic↗

Immunomodulatory potential of hydrophobic analogs of Rigin and their role in providing protection against Plasmodium berghei infection in mice.

Here, we report the immunomodulating potential of N-palmitoyl-amino-ethyl-rigin amide (PR) and N-cholestanyl-amino-ethyl-rigin amide (CR), the two new structural analogs of rigin (an IgG-derived tetrapeptide). Their activity profiles are compared with native tuftsin (NT) and/or N-palmitoyl-amino-ethyl-tuftsin amide (PT) taken as positive control. To explore the possibility of their use as targeting molecules, they are incorporated into the liposome bilayer and, subsequently, interacted with macrophages in an in vitro study. The new analogs of rigin with the hydrophobicity introduced at the C-terminus are found to considerably improve both the cell-mediated and the humoral immune responses in mice. However, unlike tuftsin and its analog, which mainly activate polymorphonuclear leukocytes and macrophages, the rigin analogs appear to manifest their response more through lymphocytes. When administered prophylactically to a group of mice, at the dose of 100 micrograms/0.5 ml/mouse/day for 2 days (i.v.), followed by a challenge presented with 1 x 10(6) rbcs parasitised with Plasmodium berghei on day 0, substantial reduction in parasitaemia and rate of mortality is observed. This led to increase the median survival time (MST) of the treated group in comparison to the control group. The response is found to be more prominent in CR-treated mice possibly because of the presence of steroid moiety, which is likely to have more productive interaction with cell membranes. Incorporation of these peptides into the bilayer of liposomes does not alter the permeability behavior of vesicles and, in fact, enhances their uptake by the macrophages in an in vitro study. The effect, however, is dependent on both, the concentration of peptide liposomes and the time of incubation. Present study, thus, establishes the possible use of these analogs not only as adjuvant in chemotherapy, but also as a prophylactic supplement to boost the natural immune status. The activity response of rigin analogs is manifested through lymphocytes, they can also find use in the chemotherapy of diseases, like leishmaniasis, tuberculosis and leprosy, where macrophage activity is either tamed or impaired by pathogens.

Adjuvants, Immunologic↗

Core needle biopsy for bone tumours.

INTRODUCTION: Percutaneous core biopsy of bone lesions provides early and definitive diagnosis and guides decisions on management. It is an inexpensive examination technique and has negligible complication rates. METHODS: We performed a prospective study of 136 patients who underwent core biopsies for bone lesions over an 18-month period. A Jamshidi (J) needle was used to obtain a core of tissue and specimens were sent for histopathological examination. Biopsy results were analysed for adequacy, ability to yield diagnostic information and for accuracy of diagnosis. RESULTS: The mean age of patients was 27.5 years with a range of 3-72 years. There were 84 males and 52 females in the study. Histopathological diagnosis was obtained in 121 (89%) patients. The specimen was non-diagnostic in 15 patients. Fourteen patients required two attempts and two patients required three attempts at biopsy. Sixty-two of 64 patients (96.9%) who had a confirmed final diagnosis had an accurate J-needle histopathological diagnosis. None of the patients had any major complications. DISCUSSION: Core needle biopsy is an important tool in the evaluation of bone lesions. It is a safe, reliable and accurate procedure and yields diagnostic information in a high proportion of patients. It has several advantages over an open bone biopsy.

Adolescent↗

Pediatric extragonadal germ cell tumor of the scalp.

Extragonadal germ cell tumors are relatively rare tumors, accounting for 5% to 10% of all germ cell tumors in adults. In children, approximately two thirds of germ cell tumors are extragonadal. Extragonadal germ cell tumor of the scalp is exceedingly rare. The authors report the case of a 1(1/2)-year-old boy with extragonadal germ cell tumor over the occipital region. Examination of the chest, abdomen, and gonads was normal. Computed tomography scan of the head showed a large, well-defined, lobulated, heterogeneously enhancing soft tissue mass lesion in the occipital region. The underlying bone was normal with no evidence of intracranial extension. Biopsy results of the scalp mass showed features consistent with embroynal carcinoma. Serum alpha-fetoprotein (AFP) level was elevated. The child was started on chemotherapy and received 4 cycles of cisplatin, etoposide, and bleomycin (PEB). There was more than 90% reduction in the size of the mass at the end of the fourth cycle. The residual mass was excised and followed up with 2 cycles of postoperative PEB. Ten months after excision the patient is well, without recurrence, and the AFP level is normal.

Antineoplastic Combined Chemotherapy Protocols↗

Enhanced immunostimulant activity and protective effect of a synthetic lipopeptide after liposomization against Plasmodium berghei infection in mice.

The immunostimulant activity of non-pyrogenic, sugar-free immunomodulator lipopeptide, Ala-D-Glu(Gly-Lys-CO.C11H23)-NH2 (comp. no 84/201), and its liposomized formulation has been studied. Liposomization of this lipopeptide significantly enhanced its antigen specific as well as nonspecific immune responses, as compared to the free lipopeptide. The liposomized formulation of lipopeptide significantly stimulated both the antibody and delayed-type hypersensitivity responses in Balb/c mice, and also enhanced nonspecifically the macrophage migration index, phagocytic activity and incorporation of 14C glucosamine in peritoneal macrophages of the mice that received pretreatment with this preparation. Further, the mice that received pretreatment with the liposomized preparation strongly resisted lethal P. berghei infection and consequently survived for longer period of times. These results indicate that liposomization of the compound no 84/201 significantly improves its ability to enhance not only antigen-specific immune response but also the nonspecific host's resistance against infections.

Adjuvants, Immunologic↗

The structure of human beta-defensin-2 shows evidence of higher order oligomerization.

Defensins are small cationic peptides that are crucial components of innate immunity, serving as both antimicrobial agents and chemoattractant molecules. The specific mechanism of antimicrobial activity involves permeabilization of bacterial membranes. It has been postulated that individual monomers oligomerize to form a pore through anionic membranes, although the evidence is only indirect. Here, we report two high resolution x-ray structures of human beta-defensin-2 (hBD2). The phases were experimentally determined by the multiwavelength anomalous diffraction method, utilizing a novel, rapid method of derivatization with halide ions. Although the shape and charge distribution of the monomer are similar to those of other defensins, an additional alpha-helical region makes this protein topologically distinct from the mammalian alpha- and beta-defensin structures reported previously. hBD2 forms dimers topologically distinct from that of human neutrophil peptide-3. The quaternary octameric arrangement of hBD2 is conserved in two crystal forms. These structures provide the first detailed description of dimerization of beta-defensins, and we postulate that the mode of dimerization of hBD2 is representative of other beta-defensins. The structural and electrostatic properties of the hBD2 octamer support an electrostatic charge-based mechanism of membrane permeabilization by beta-defensins, rather than a mechanism based on formation of bilayer-spanning pores.

Amino Acid Sequence↗

Immunomodulatory activity of hexapeptides related to proline rich peptide from colostrum.

Twelve analogues of an immunomodulatory hexapeptide YVPGFP (I) derived from Proline rich peptide (from colostrum) have been synthesized with modifications at positions 2, 4 and 6. In MLR assay one of the analogues exhibited approx 50% inhibition at 0.1 microg/mL concentration in contrast to prednisolone and I which caused around 70 and 20% suppression respectively, at the same concentration.

Adjuvants, Immunologic↗

Varying effects of temperature, Ca(2+) and cytochalasin on fusion activity mediated by human immunodeficiency virus type 1 and type 2 glycoproteins.

We examined fusion mediated by the human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) envelope glycoproteins under various experimental conditions. Incubation of HeLa cells expressing HIV-2(ROD) and HIV-2(SBL/ISY) envelope glycoproteins with HeLa-CD4 target cells resulted in fusion at temperatures >/=25 degrees C whereas fusion with cells expressing HIV-1(Lai) occurred only at >/=31 degrees C. HIV-2 envelope glycoprotein-mediated fusion proceeded in the absence of Ca(2+) in the culture medium, whereas HIV-1 fusion required Ca(2+) ions for fusion. In contrast to HIV-2 envelope glycoprotein fusion, incubations in the presence of the 0.5 microM cytochalasin B completely inhibited HIV-1 envelope glycoprotein-mediated fusion. Our results suggest that in contrast to HIV-2, HIV-1 fusion is dependent on dynamic processes in the target membrane.

Actins↗

Influenza virus upregulates CXCR4 expression in CD4+ cells.

We examined the effect of prior influenza virus infection on the susceptibility of CD4+ cells to HIV-1 infection. Influenza virus infection of HeLa-CD4 cells resulted in a marked increase in susceptibility to infection by CXCR4-dependent but not CCR5-dependent HIV isolates. Influenza virus infection resulted in an increase in the steady state level of CXCR4 transcripts and an increase in cell surface CXCR4 expression. Our observations suggest that infectious agents such as influenza may contribute to HIV disease progression by modulating coreceptor availability.

CD4-Positive T-Lymphocytes↗

Dietary restraint and self-reported meal sizes: diary studies with differentially informed consent.

Psychometric methods were used to explore the reliability and criterion validity of self-reported food intake in studies of dietary restraint. In Study 1 the reliabilities over days of daily aggregate intakes and of intakes at meals at particular times of day were assessed in 7 day food diaries by 27 low-BMI females. The sizes of particular meals correlated poorly with each other and with the total of all other meals; daily aggregate intakes also had poor reliability (Cronbach's alpha). Individuals meal sizes were consistent from day to day, with high inter-correlations between meal sizes, high correlations between meals at particular times and the sum of the remainder and high reliabilities. Aggregate intake had moderate criterion validity. Of individual meals, only breakfast achieved criterion validity, but there was a significant cubic component in its relationship with restraint. In Study 2, young male and female participants with various BMIs, completed a food diary on a single day. Again, aggregate daily intake had low reliability. Total intake and breakfast both had criterion validity, dietary restraint correlating negatively with total intake and breakfast size in the whole sample and in females, but there were significant quadratic components in the relationships. In contrast, restraint correlated positively with lunch size in the whole sample and in males. The combination of low reliability of individual meals as estimates of total intake, and the low criterion validity of all meals except breakfast, suggests that it may be inappropriate to study dietary restraint using aggregate self-reported intake measures.

Adult↗

Immunostimulant activity of dry fruits and plant materials used in indian traditional medical system for mothers after child birth and invalids.

Products of certain plants given to mothers after child birth or to invalids were studied for immunostimulant activity using the macrophage migration index (MMI) as a parameter of macrophage activation and cell-mediated immunity and haemagglutinating antibody (HA) titres and plaque-forming cell (PFC) counts as parameters of humoral immunity. Feeding of Prunus amygdalus (Almond(1)) and Buchanania lanzan (Chirronji(1)) significantly stimulated both CMI and humoral immunity in BALB/c mice as evidenced by the enhancement of MMI, HA titres, and PFC counts. Euryale ferox (Tel makhana(1)), Phoenix dactylifera (Chhohara(1)) and Zingiber officinale (Sonth(1)), however, stimulated humoral immunity to a greater extent than CMI. The observation provides scientific basis for feeding the products of above plants to mothers after child birth and to invalids with a relatively poor immune status.

Adjuvants, Immunologic↗

P-glycoprotein-overexpressing multidrug-resistant cells are resistant to infection by enveloped viruses that enter via the plasma membrane.

The multidrug resistance gene product P-glycoprotein confers drug resistance to tumor cells by acting as a transporter that blocks the entry into the cell of a great variety of drugs and hydrophobic peptides. In this study we find that in drug-resistant cells, the insertion of the influenza virus fusion protein (hemagglutinin-2) into the plasma membrane is blocked and that the fusion of the viral envelope with the plasma membrane of these cells is impaired. Multidrug-resistant cells display significant resistance to infection by envelope viruses that invade cells by fusion with the plasma membrane, but not to infection by pH-dependent viruses that penetrate cells by fusion with endocytic vesicles. These observations suggest that multidrug resistance phenomena may protect cells from infection by a large group of disease-causing viruses that includes human immunodeficiency virus, herpes simplex virus, and some cancer-inducing retroviruses.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Causal implications of viscous damping in compressible fluid flows

Classically, a compressible, isothermal, viscous fluid is regarded as a mathematical continuum and its motion is governed by the linearized continuity, Navier-Stokes, and state equations. Unfortunately, solutions of this system are of a diffusive nature and hence do not satisfy causality. However, in the case of a half-space of fluid set to motion by a harmonically vibrating plate the classical equation of motion can, under suitable conditions, be approximated by the damped wave equation. Since this equation is hyperbolic, the resulting solutions satisfy causal requirements. In this work the Laplace transform and other analytical and numerical tools are used to investigate this apparent contradiction. To this end the exact solutions, as well as their special and limiting cases, are found and compared for the two models. The effects of the physical parameters on the solutions and associated quantities are also studied. It is shown that propagating wave fronts are only possible under the hyperbolic model and that the concept of phase speed has different meanings in the two formulations. In addition, discontinuities and shock waves are noted and a physical system is modeled under both formulations. Overall, it is shown that the hyperbolic form gives a more realistic description of the physical problem than does the classical theory. Lastly, a simple mechanical analog is given and connections to viscoelastic fluids are noted. In particular, the research presented here supports the notion that linear compressible, isothermal, viscous fluids can, at least in terms of causality, be better characterized as a type of viscoelastic fluid.

Journal Article↗

Glycosphingolipids promote entry of a broad range of human immunodeficiency virus type 1 isolates into cell lines expressing CD4, CXCR4, and/or CCR5.

Treatment of human osteosarcoma cells, expressing CD4 and various chemokine receptors, with the glucosylceramide synthase inhibitor 1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP), blocked target membrane glycosphingolipid (GSL) biosynthesis and reduced the susceptibility of cells to infection and fusion mediated by envelope glycoproteins from a variety of human immunodeficiency virus type 1 (HIV-1) isolates that utilize CXCR4 and/or CCR5. PPMP treatment of the cell lines did not significantly change the cell surface expression of CD4, CXCR4, and/or CCR5, nor did it alter the chemokine receptor association with CD4. PPMP-treated cells exhibited no changes in chemokine-induced Ca(2+) mobilization and chemotaxis. However, massive envelope glycoprotein conformational changes triggered by CD4 and the appropriate chemokine receptor on the target membrane were inhibited when the target cells were treated with PPMP. Addition of various purified GSLs to PPMP-treated target cells showed that for all isolates tested, globotriaosylceramide (Gb3) was the most potent GSL in restoring the fusion susceptibility of target cells with cells expressing HIV-1 envelope glycoproteins; addition of the monosialoganglioside GM3 yielded a slight enhancement of fusion susceptibility. Our data are consistent with the notion that a limited number of specific GSL species serve as crucial elements in organizing gp120-gp41, CD4, and an appropriate chemokine receptor into a membrane fusion complex.

3T3 Cells↗

Role of glycosphingolipids in HIV-1 entry: requirement of globotriosylceramide (Gb3) in CD4/CXCR4-dependent fusion.

We have recently shown that addition of human erythrocyte glycosphingolipids (GSL) to non-human CD4+ or GSL-depleted human CD4+ cells rendered those cells susceptible to gp120-gp41-mediated cell fusion (Puri et al., BBRC, 1998). One GSL fraction (Fraction 3) isolated from human erythrocyte GSL mixture exhibited the highest recovery of fusion following incorporation into CD4+ non-human and GSL-depleted HeLa-CD4 cells (HeLa-CD4/GSL-). Structural analysis of Fraction 3 showed that this GSL had identical head group as the known GSL, Gal(alpha1-->4)Gal(beta1-->4)Glc-Ceramide (Gb3) (Puri et al., PNAS, 1998). Here we report that presence of Gb3 in CD4+/CXCR4+ cells but not CD4+/CXCR4 cells allows fusion with HIV-1Lai-envelope glycoprotein expressing cells (TF228). Therefore, Gb3 functions in conjunction with HIV-1 co-receptor, CXCR4 to promote fusion. We propose that Gb3 functions by recruiting CD4 and/or CXCR4 at the fusion site through structurally specific interactions.

CD4 Antigens↗

Family studies and human leukocyte antigen class II typing in Indian probands with seizures in association with single small enhancing computed tomography lesions.

PURPOSE: To define the clinical features of the syndrome of seizures associated with single, small, enhancing computed tomography (CT) lesions (SSELs) in 235 Indian probands and seizure types among their family members. Human leukocyte antigen (HLA) class II genomic typing in randomly selected 41 probands was done to identify the role of hereditary factors in this syndrome. METHODS: The seizure types among 235 probands, their clinical outcome, and seizures in their family members were studied. Family data were collected on relatives of 212 additional probands with neurologic diseases other than epilepsy. HLA class II antigens were studied by using polymerase chain reaction (PCR) amplified DNA and sequence-specific oligonucleotide probe (PCR-SSOP) hybridization. RESULTS: The seizures in 86% were partial with or without generalization; 77% had fewer than five seizures before the first CT scan. Evanescent focal neurologic deficits after seizures were noted in 40%. Most patients (97%) were treated with a single antiepileptic drug (AED). Significant resolution of the CT scan lesion was noted within 6 months in 125 (53%) of 235 cases. Two thirds of patients had no seizures while taking a single AED, and an additional 18% had no seizures even after their AEDs were discontinued. Epilepsy among relatives of Indian probands having seizures in association with SSELs was more common as compared with relatives of probands with other neurologic diseases. A family history of seizures was noted in 21% probands, the ratio of affected first- to second-degree relatives was 4.3:1, and 60% of affected sibs had syndromic concordance with probands. There was a positive association of HLA-DRB1*13 (Pc = 0.036) with this syndrome. CONCLUSIONS: The syndrome of seizures in association with SSELs seems to be a benign localization-related epileptic syndrome. Our results of HLA studies point to an inherited susceptibility to an infective agent, which in most cases is of cysticercal etiology.

Adult↗