Search PubMed⌕ Search

Biomedical subjects

O Bagasra

Publications and source records attributed to O Bagasra.

At least 73 records · Page 4Linked to original sources
PubMed1992

Demonstration by in situ hybridization of the proopiomelanocortin gene in the rat heart.

A biotinylated oligonucleotide probe was used to demonstrate the presence in the heart of the portion of the proopiomelanocortin messenger RNA which contains the sequence for beta-endorphin. The probe indicated the presence of beta-endorphin messenger RNA in cardiac tissue and specifically in the cardiac muscle cell. The probe also confirmed the well-documented presence of messenger RNA for beta-endorphin in the anterior and neurointermediate lobes of the pituitary. These findings indicate that in addition to the pituitary, beta-endorphin is produced in situ in the heart.

Animals↗
PubMed1992

Cellular latency of human immunodeficiency virus type 1.

The infection of humans by human immunodeficiency virus type 1 is characterized by a prolonged stage of clinical quiescence. This clinically asymptomatic period may be based, in part, on the development of cell populations within the body that maintain human immunodeficiency virus type 1 in a state of latency. Recent advances in the understanding of the molecular mechanisms involved in various forms of cellular latency of human immunodeficiency virus type 1 have begun to shed light on the variable period of asymptomatic infection. The elucidation of cellular retroviral latency, in vivo, will also be critical to the design of novel therapeutic approaches with which to combat human immunodeficiency virus type 1 infections.

DNA Replication↗
PubMed1992

Adenosine-deaminase-associated immunodeficiency. I. Differential sensitivities of lymphocyte subpopulations exposed to 2-deoxycoformycin in vivo.

In order to obtain a better understanding of the degree of immune dysfunctions caused by the absence of adenosine deaminase, we gave a single i.p. injection of 2'-deoxycoformycin (2-dcf), a potent inhibitor of the enzyme ADA at various doses into adult Syrian hamsters. These animals were examined for their ability to mount primary in vivo antibody responses to helper T cell dependent (Th-d) and helper T cell independent (Th-ind) antigens. Hamsters treated with 0.5 mg/kg of 2-dcf mounted enhanced splenic plaque-forming cell (PFC) responses to sheep erythrocytes, a Th-d antigen, and to pneumococcal polysaccharide type III (SIII), a Th-ind antigen. Treatment of animals with 1.0 mg/kg of 2-dcf resulted in a significantly depressed (P less than 0.001) PFC response to Th-d antigen, but a further enhanced response to Th-ind antigen. One mechanism which may be responsible for such a dichotomous response to these two types of antigens was selective dysfunction of T cell subpopulations. At higher doses (1.5-4.0 mg/kg), PFC responses to both types of antigens were significantly suppressed. Immunoenhancement at low doses of 2-def was attributed to an increased susceptibility of T suppressor cells to 2-dcf. This hypothesis was confirmed by priming the 2-dcf-treated animals with low-dose Th-ind antigens. These animals failed to induce low-dose tolerance by stimulation of antigen-specific suppressor T cell subsets. At low doses, B cells and T helper cell functions were found to be intact, as further confirmed by priming the animals with the carrier keyhole limpet haemocyanin (KLH) and challenging with trinitrophenyl-KLH. This dose-dependent selective susceptibility of various T cell subpopulations and B cells may explain the heterogeneity of clinical, biochemical and immunological parameters observed in children with ADA deficiency severe combined immunodeficiency.

Adenosine Deaminase↗
PubMed1992

TAR-independent replication of human immunodeficiency virus type 1 in glial cells.

The molecular mechanisms involved in the replication of human immunodeficiency virus type 1 (HIV-1) may differ in various cell types and with various exogenous stimuli. Astrocytic glial cells, which can support HIV-1 replication in cell cultures and may be infected in vivo, are demonstrated to provide a cellular milieu in which TAR mutant HIV-1 viruses may replicate. Using transfections of various TAR mutant HIV-1 proviral constructs, we demonstrate TAR-independent replication in unstimulated astrocytic cells. We further demonstrate, using viral constructs with mutations in the tat gene and in the nuclear factor kappa B (NF-kappa B)-binding sites (enhancer) of the HIV-1 long terminal repeat, that TAR-independent HIV-1 replication in astrocytic cells requires both intact NF-kappa B moiety-binding motifs in the HIV-1 long terminal repeat and Tat expression. We measured HIV-1 p24 antigen production, syncytium formation, and levels and patterns of viral RNA expression by Northern (RNA) blotting to characterize TAR-independent HIV-1 expression in astrocytic glial cells. This alternative regulatory pathway of TAR-independent, Tat-responsive viral production may be important in certain cell types for therapies which seek to perturb Tat-TAR binding as a strategy to interrupt the viral lytic cycle.

Astrocytes↗
PubMed1991

Human immunodeficiency virus infection of fibroblasts of dental pulp in seropositive patients.

Presence of human immunodeficiency virus (HIV) within noninflamed human dental pulps was documented by polymerase chain reaction assays in 11 of 12 pulps from HIV-seropositive patients. The purpose of the present study was to determine the cellular location of HIV in vivo within these tissues by means of in situ hybridization. Results of the in situ hybridization indicated HIV within fibroblasts of the pulp. These results are especially relevant because fibroblasts lack the CD4 receptor thought necessary for in vivo infection with HIV. These results suggest the fibroblast as a possible reservoir for HIV in the body.

CD4-Positive T-Lymphocytes↗
PubMed1991

Anti-human immunodeficiency virus type 1 activity of sulfated monosaccharides: comparison with sulfated polysaccharides and other polyions.

Previously, the anti-human immunodeficiency virus type I (HIV-1) activities were reported of four sulfated polysaccharides: dextran sulfate, pentosane polysulfate, chondroitin sulfate, and heparin sulfate. In the present study, the anti-HIV-1 activities of several other sulfated polysaccharides, monosaccharides, neutral polysaccharides, and polypeptides were evaluated. Anti-HIV-1 activities of these various agents were measured by four different assays: (1) HIV-1-induced syncytia formation; (2) infectivity of cell-free HIV-1 after preincubation with the putative anti-HIV-1 agent; (3) protective ability of the agents for target CD4+ cells, and (4) anti-reverse transcriptase activity. In addition, potential toxicity of the putative anti-HIV-1 agents was measured by their effects on cellular proliferation, cytotoxic effects, and effects on coagulation processes. These data indicate that only sulfated polysaccharides and one sulfated monosaccharide, glucosamine 6-sulfate, have significant anti-HIV-1 activity. The therapeutic potentials of these agents are also discussed, with special reference to absorption of glucosamine 6-sulfate through the gastrointestinal tract.

Blood Coagulation↗
PubMed1989

Effects of alcohol ingestion on in vitro susceptibility of peripheral blood mononuclear cells to infection with HIV and of selected T-cell functions.

A role for the biological effects of alcohol is postulated in the increased risk of AIDS known to be associated with chronic alcohol abuse and alcohol consumption during sexual activity. In pilot experiments peripheral blood mononuclear cells from healthy volunteers were studied before and after a single ingestion of 0.7 to 3.1 liters of beer or an equivalent dose of ethanol in other beverages. After moderate alcohol consumption there was increased human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cells during 28 days of culture without mitogen stimulation as indicated by overnight syncytium formation with SUP-T1 indicator cells and by increased levels of HIV p24 antigen in the culture supernates. There was also decreased ability of lymphocytes to produce interleukin 2 and soluble immune response suppressor activity after stimulation with concanavalin A, the former, possibly both, for over 4 days after alcohol ingestion. These preliminary data extend well-known immunosuppressive effects of chronic alcohol ingestion to acute ingestion and raise the question: Could even casual alcohol consumption enhance HIV infectivity and/or enhance the progression of latent HIV infection?

Acquired Immunodeficiency Syndrome↗
PubMed1989

Functional analysis of lymphocytes subpopulations in experimental cocaine abuse. I. Dose-dependent activation of lymphocyte subsets.

The potential role of substance abuse, especially cocaine and alcohol as co-factor in HIV infection and in the development and expression of AIDS has been suggested, but the possible biological role of substance abuse in the development of AIDS is not known. In order to better understand immune system function in chronic cocaine abuse, we have assessed primary B cell responses to helper T-cell independent (TI) and dependent (TD) antigens in inbred Fisher male rats injected with 1.25-5 mg cocaine/kg body weight for 10 days. The ability of cocaine-exposed animals to mount primary in vivo splenic plaque-forming cell (PFC) and serum antibody responses to the TI antigen, pneumococcal polysaccharide type III (SIII), was elevated several-fold when compared with controls. The degree of elevation of humoral antibody responses seemed to be directly related to the dose of cocaine. Primary in vivo B cell responses to the TD antigen, sheep red blood cells (SRBC), was elevated at lower concentrations of cocaine (1.25-2.5 mg/kg) and was found to be significantly suppressed after chronic exposure to the higher concentration (5.0 mg/kg). The elevated primary splenic immunostimulation to TI (SIII) may be attributed to a combination of loss of T suppressor cell control and direct B cell stimulation. Elevated immune responses to SRBC at lower concentrations were attributed to stimulation of T helper cells as well as loss of T suppressor cells. Immunosuppression to SRBC observed in response to 5.0 mg/kg of cocaine was most probably due to loss of T helper cell subset functions. These findings were further tested by in vitro methods, where splenic lymphocytes from cocaine-exposed animals were examined for their ability to respond to concanavalin A (Con A) in terms of the induction of antigen non-specific suppressor T cells. The addition of Con A-stimulated splenic lymphocytes from cocaine-treated animals did not inhibit the primary antibody responses of SRBC as compared with saline-treated controls, indicating that suppressor T cells malfunction after cocaine exposure. Lymphocyte subpopulation analysis using fluorescein-labelled monoclonal antibodies showed a significant increase in the B cell populations at doses of 1.25-5 mg/kg. A reciprocal change in T cell populations also took place. No significant numerical change in macrophage (NSE+) and T cell subset, T helper and T suppressor was noticed, suggesting that cocaine probably directly effects mature T cell subset functions but does not affect their differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Macrophage function in chronic experimental alcoholism. I. Modulation of surface receptors and phagocytosis.

In the present study, we have assessed peritoneal, alveolar and splenic macrophages for expression of Fc and C3b surface receptors and their ability to function in immunophagocytosis. We have also measured their oxidative burst response by the nitroblue tetrazolium dye (NBT) reduction method. Our studies revealed that macrophages harvested from chronic alcoholic rats expressed surface C3b and Fc receptors, with significantly higher surface density than macrophages of litter-mate controls (matched for sex and nutritional calories). However, the ability of macrophages from alcoholic rats to phagocytize through C3b and Fc receptors was significantly impaired. In addition, the ability of peritoneal macrophages from alcoholic animals to ingest non-opsonized Candida albicans and to reduce NBT dye was markedly compromised. Abnormalities of macrophage function may, at least in part, account for an increased susceptibility of alcoholic patients to infection.

Alcoholism↗
PubMed1988

Interaction of human immunodeficiency virus with human sperm in vitro.

Transmission of human immunodeficiency virus (HIV) in semen by sexual intercourse is believed to be a major etiological factor in the spread of the disease. In order to explore the role of sperm in this transmission, cell-free HIV-1(IIIB) was coincubated with human sperm for 5 h. After incubation, unattached HIV-1 was extensively washed off the cells and the presence and location of HIV-1 in or on the sperm was determined by electron microscopic (EM) and immunofluorescence methods. Examination of sperm at the EM level showed that HIV-1 attaches to the sperm surface and enters the sperm through the intact cell membrane. Immunofluorescence studies, using polyvalent anti-HIV antibodies, demonstrated the presence of small round fluorescent particles in 5-10% of sperm heads after 5 h of incubation. A search for HIV-1 receptors (CD4 epitopes) revealed the presence of OKT4 epitopes, including OKT4A, B, D, and F on 5-10% of sperm by epifluorescence microscopy and on 10-20% of sperm by flow-cytometric analysis. These in vitro data suggest that human sperm may be the primary cellular element in the transmission of HIV by semen.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Activation of factor B of the alternative pathway of complement. Assessment by rocket immunoelectrophoresis.

During activation of the alternative pathway of complement, Factor B is cleaved into a smaller fragment Ba and a larger fragment Bb. The Ba in plasma was quantitated by one-dimensional rocket immunoelectrophoresis after precipitating plasma B and Bb with 21% polyethyleneglycol. This method was much more sensitive and faster than other technics with which it was compared. Fragment Ba was detected in 22 of 28 rheumatoid arthritis plasma samples and in 12 of 15 systemic lupus erythematous samples but in only 8 of 68 samples obtained from healthy volunteers. The traditional approach of measuring total Factor B for the assessment of activation of the alternative pathway showed values that were even higher than normal in these diseases. The measurement of plasma Ba promises to be a valuable means of assessment of the activation of Factor B and the alternative pathway of complement in clinical disorders.

Arthritis, Rheumatoid↗
PubMed1987

Functional analysis of T-cell subsets in chronic experimental alcoholism.

In order to obtain a better understanding of immune system function in chronic alcoholism, we have assessed primary B-cell responses to helper T-cell independent (TI) and dependent (TD) antigens in chronic alcoholic Sprague-Dawley male rats fed totally liquid diet containing ethanol. Pair-fed littermates received the same diet except that carbohydrates isocalorically replaced ethanol, which accounted for 36% of the total calories. The ability of alcoholic animals to mount primary in vivo splenic plaque-forming cell (PFC) responses to TI pneumococcal polysaccharide type III (SIII) was elevated throughout 50 days of observation when compared to pair-fed controls; serum antibody responses to SIII paralleled the enhanced PFC responses. Primary in vivo B-cell responses to antigen sheep red blood cells (SRBC), a TD antigen, were initially elevated but were found to be significantly suppressed 30 days after chronic ethanol consumption. The degree of immunosuppression increased with length of chronic ethanol consumption. The elevated primary splenic PFC responses to TI (SIII) may be attributed to loss of T-suppressor cell control, since alcoholic rat spleen cells did not respond to low-dose priming with SIII. We suggest that either loss of function and/or actual depletion of accessory and regulatory cells (T-suppressor and T-helper) may be responsible for irregularities in B-cell function observed during chronic alcoholism. T-cell subset enumeration using fluorescein-labelled monoclonal antibodies revealed that a sequential T-helper and T-suppressor loss occurred several days following dysfunction of these T-cell subsets in splenic populations, suggesting that a combination of numerical and dysfunctional changes in lymphocyte subpopulations may be responsible for the immunological alterations observed in chronic alcoholics.

Alcoholism↗
PubMed1986

Irradiation- and cyclophosphamide-induced alterations in Syrian hamster T-cell population activity.

The treatment of hamsters with either irradiation (IR) or cyclophosphamide (CYP) markedly alters select aspects of their cellular immune functions in a dose-related manner. One mechanism that may be responsible for this activity appears to be the dimunition of a T-lymphocyte subpopulation that exerts suppressive influence upon the B-lymphocyte reactivity toward antigens. This study shows that in the hamster, immune susceptibility is affected by the magnitude and orientation of these agents (ie, IR, CYP) as they temporally relate to immunization and/or challenge with the antigen. Moreover, there is evidence that T-independent as well as T-dependent responses are affected by these treatments. Therefore, cyclophosphamide and irradiation modalities can be employed to modify the cellular immune responses in the hamster.

Animals↗
PubMed1986

Treponemal infection specifically enhances node T-cell regulation of macrophage activity.

Hamsters experimentally inoculated in the inguinal region with Treponema pallidum subsp. endemicum develop considerable pathology at that site. We examined the cell populations from these inguinal lymph nodes to determine their intercellular responses to infection. In vitro, syphilitic-node T cells markedly suppressed C3b receptor-mediated ingestion (C3bMI) in syphilitic macrophages derived from sites both proximal and distal to the inoculation. This activity was more pronounced when node T cells rather than peritoneal T cells were used. When treponemal preparations or live treponemes were added to the coculture system, the suppression was specifically enhanced, whereas the addition of heterologous agents did not promote this effect. Syphilitic macrophages from either compartment cultured alone showed no significant inhibition of C3bMI. In parallel studies on syphilitic macrophages, we observed that the expression of Ia quickly became elevated and was sustained throughout the infection. Moreover, in vitro culturing of the syphilitic-node T cells with these macrophages did not alter this function. These observations suggest that the syphilitic node contains a subpopulation of T cells that can selectively suppress macrophage C3bMI activity and concurrently regulate their cellular response to treponemal infection.

Animals↗