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Biomedical subjects

S Specter

Publications and source records attributed to S Specter.

At least 55 records · Page 3Linked to original sources
PubMed1993

Identification of a linear neutralization site within the third variable region of the feline immunodeficiency virus envelope.

Synthetic peptides have been used to map linear B-cell epitopes of the third variable (V3) region of the feline immunodeficiency virus (FIV) external membrane glycoprotein gp120. The analysis of sera from naturally and experimentally FIV-infected cats by Pepscan and enzyme immunoassay with four partially overlapping peptides evidenced three antibody-binding domains, two of which mapped in the carboxyl-terminal half of V3. In particular, the V3.3 sequence (Gly-392-Phe-413) turned out to be important for in vitro neutralization of the virus in that the peptide inhibited the FIV-neutralizing activity of pooled immune cat sera, and on the other hand, cat sera raised against this peptide effectively neutralized FIV infectivity for Crandell feline kidney cells.

Amino Acid Sequence↗
PubMed1992

Inhibition by delta-9-tetrahydrocannabinol of tumor necrosis factor alpha production by mouse and human macrophages.

Suppression by delta-9-tetrahydrocannabinol (THC) of tumor necrosis factor (TNF) production by macrophages has not been reported previously. The present study evaluated the effect in vitro of THC on soluble TNF-alpha production by cultured murine peritoneal macrophages. THC at 5 or 10 micrograms/ml added to medium [RPMI 1640 containing 10 ng LPS/ml, mouse IFN-gamma (100 u/ml), and 0.5% bovine serum albumin (BSA)] used to induce TNF significantly decreased TNF-alpha production by BALB/c mouse macrophages. Macrophages pretreated with THC at 0.1, 0.5, or 1.0 micrograms/ml in protein-free medium for 3 h at 37 degrees C, prior to TNF induction, also showed a decreased ability to produce TNF-alpha in a dose-dependent manner. Increasing the protein concentration from 0.5 to 5% BSA in the medium which was used to induce TNF prevented the inhibitory activity of THC. Human peripheral blood adherent cells treated with THC-containing medium produced less TNF-alpha than controls that were not exposed to THC. Thus, our data provide evidence that THC can inhibit TNF production by mouse and human macrophages. The drug's activity is concentration dependent and is related to the amount of serum protein in the medium used to induce this cytokine.

Animals↗
PubMed1992

Marijuana and immunity: tetrahydrocannabinol-mediated inhibition of growth and phagocytic activity of the murine macrophage cell line, P388D1.

The effects of delta-9-tetrahydrocannabinol (THC) on the growth, DNA synthesis and phagocytic activity of P388D1, a murine macrophage cell line, were investigated. Incubating cell cultures with THC resulted in a dose-dependent inhibition of cell propagation and DNA synthesis. The magnitude of these effects was dependent upon the number of cells in the culture as well as the protein content in the culture medium. As the cell number increased, the THC effect decreased. Using cell cultures in which the cell concentration was standardized, THC (greater than or equal to 5 micrograms/ml) produced pronounced inhibitions of cell growth and DNA synthesis, while lower THC concentrations (less than or equal to 3 micrograms/ml) were less effective. Studies examining the phagocytic activity of the P388D1 cells indicating exposure to THC (5 micrograms/ml for 2 h) only marginally affected the association of latex beads with the external surface of the plasma membrane. However, the ability of these THC-treated cells to internalize the latex particles was severely depressed. Thus, the data indicate that THC inhibited the growth and functional activity of murine macrophages in vitro and suggests that the P388D1 cell line is a useful model to study the effects of cannabinoids on the phagocytic process.

Animals↗
PubMed1992

Methyl inosine monophosphate: a potential immunotherapeutic for early human immunodeficiency virus (HIV) infection.

MIMP is a new thymomimetic purine under development for immunorestorative therapy. Lymphocytes were obtained from eight patients with acquired immunodeficiency disease (AIDS), eight with symptomatic pre-AIDS (ARC), and 22 normal controls and were stimulated in vitro with phytohemagglutinin (PHA). AIDS patients (mean CD4 counts of 40) showed PHA responses less than 10% of control while ARC patients (mean CD4 counts of 544) showed responses approximately 50% of the control responses. MIMP (0.1, 1, 10 and 100 micrograms/ml) progressively augmented the PHA responses in all these groups. The augmentation of the responses of the leukocytes of AIDS patients while statistically significant was minimal. The augmentation of the responses of ARC patients was significant and their maximal responses approached control levels. The effect of 1 micrograms/ml MIMP was comparable with that observed with indomethacin (10(-6) M) and interleukin-2 (IL2 - 4 units/ml) and was additive with each of these stimulants. In a parallel manner, MIMP restored the suppression of control lymphocytes induced by the immunosuppressive 17 amino acid fragment of the P41 peptide of HIV. In vivo experiments showed that MIMP significantly delayed death in a murine FLV AIDS model at a dose of 1 mg/kg by the oral or parenteral route. MIMP is under preclinical development for early HIV disease to forestall progression to AIDS by attenuating virus-induced immunosuppression.

Adjuvants, Immunologic↗
PubMed1992

Further characterization of the biological and pathogenic properties of erythromelalgia-related poxviruses.

Six isolates of erythromelalgia-related poxvirus (ERPV) were characterized with respect to host range, c.p.e. and inclusions, pock formation on chorioallantoic membrane (CAM), morphogenesis, serological reactivity, pathogenesis in animals and DNA restriction fragment profile. The results suggest that ERPV is either a new member of the Orthopoxvirus genus or a subspecies of ectromelia virus. Evidence is provided that (i) ERPV has a wide host range in vitro in which characteristic viral c.p.e. and inclusion bodies are induced; (ii) ERPV, unlike ectromelia virus, causes the formation of tiny greyish-white pocks on CAM both at 34 degrees C and 39 degrees C; (iii) eosinophilic A-type inclusions of ERPV do not contain viral particles; (iv) ERPV isolates are neutralized by both rabbit anti-vaccinia virus and mouse anti-ectromelia virus sera, but not vice versa; (v) young rabbits are not susceptible to ERPV by skin and/or corneal scratch infection even though ERPV is lethal for mice by intraperitoneal inoculation; (vi) the HindIII and SalI fragment profiles of ERPV P-4 DNA are similar to, but obviously different from, those of Chinese ectromelia virus. These biological and pathogenic characteristics of ERPV are distinguishable from those of other members of the genus Orthopoxvirus currently described in the literature.

Animals↗
PubMed1992

The influence of cell culture and storage conditions on HIV-1 infectivity and fusogenic activity.

We have previously demonstrated that acidic medium inhibits the replication of HIV-1. The present study was designed to examine the effects of other growth conditions and infection of fibroblasts by coculture with HIV infected lymphoid cells. Several lymphoblastoid cell lines normally grown in RPMI-1640 were grown in Eagle's MEM. These cells supported virus replication to higher titres than did RPMI-1640. Peak viral titres were achieved within 24-48 h after newly infected or chronically infected cells were placed in fresh medium. When virus was stored in liquid medium either frozen or at higher temperatures, virus titres were retained for several months while frozen but decreased upon storage at 4 degrees C or higher. If cells were passaged after trypsinization in Ca(++)-depleted medium, then a decreased susceptibility of cells for HIV-1 by 2 log10 at 24 h post infection was observed. Infectivity of cell-free and cell-associated HIV-1 was measured using syncytium formation, reverse transcriptase activity and p24 antigen. No fusion between HIV-1 infected CD4+ lymphoblasts and CD4- fibroblasts was observed but HIV-1 infected lymphoid cells, even in the absence of syncytium formation, exerted a strong toxic effect on fibroblasts. This study extends previous findings that medium acidity was inhibitory to virus replication and survival. Thus, conditions for study of HIV must be well controlled in buffered medium so that misleading results are not obtained regarding virus multiplication and possibly regarding transmission to and pathogenesis in CD4- cells.

Animals↗
PubMed1991

Suppression of human macrophage function in vitro by delta 9-tetrahydrocannabinol.

The ability of macrophages to function in the presence of delta 9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, was evaluated. THC added to macrophage cultures prepared from human peripheral blood inhibited macrophage spreading and phagocytosis of yeast. The effects of THC were concentration dependent, with inhibitory effects observed from 10 to 1 micrograms/ml or lower. These results suggest that macrophages are more sensitive to THC than are lymphocytes because macrophage functions were inhibited by THC at concentrations that did not affect lymphocyte function. Thus, inhibition of lymphocyte function(s) by THC could be attributed to a direct effect of the drug on macrophages which indirectly results in lowered lymphoid cell activity.

Adolescent↗
PubMed1991

Delta-9-tetrahydrocannabinol augments murine retroviral induced immunosuppression and infection.

Delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, and the murine retrovirus, Friend leukemia virus (FLV), have been demonstrated to depress cellular immune function, including lymphocyte blastogenic transformation and natural killer cell activity. The present study demonstrates tht the two agents can work in concert to depress these immune activities more severely than either agent administered by itself. When 7.5-10 micrograms/ml THC was added in vitro to spleen cells from mice infected 2-4 weeks earlier with FLV there was a noticeable decrease, beyond that seen with the drug or virus alone, for both lymphocyte blastogenesis and natural killer cell cytotoxicity. In addition, when both FLV and THC were administered to mice concurrently with infection by herpes simplex virus (HSV), mortality attributed to the retrovirus infection occurred significantly more rapidly than in the absence of the drug and HSV. The data indicate that THC acted in the presence of a HSV infection to enhance the FLV induced mortality. By extrapolation to the human condition, these results suggest that marijuana could serve as a cofactor, possibly in conjunction with opportunistic pathogens, in the progression of infection due to the human immunodeficiency virus from latency to overt acquired immunodeficiency syndrome.

Animals↗
PubMed1991

Suppressive effect of delta-9-tetrahydrocannabinol on herpes simplex virus infectivity in vitro.

Delta-9-Tetrahydrocannabinol (THC) was found to reduce the infectivity of herpes simplex virus and was without effect against adenovirus type 2 or poliovirus. The effective THC concentration resulting in an 80% decrement in virus viability was dependent upon the presence or absence of serum in the incubation mixture, as a 5% serum concentration decreased the drug activity by approximately 50-fold. THC-mediated inactivation of herpes simplex virus was both time and dose dependent and did not result in virion disassembly or clumping. The THC-related effect was not influenced by the pH of the suspending medium, suggesting that the mechanism of inactivation differed from that associated with the thermal inactivation of the virus. Thus, the data suggest that THC preferentially reduces the infectivity of the enveloped herpes simplex virus, and that this activity is modulated by the presence of serum proteins.

Adenoviridae↗
PubMed1990

Production of tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) by murine pre-B and B cell lymphomas.

Media from murine pre-B and B lymphoma cell cultures, but not from myeloma cell cultures, was cytotoxic to WEHI 164 cells, causing these TNF-sensitive targets to release 51Cr. The cytotoxic activity in the culture medium reached maximum levels approximately 4 days after the cell culture was initiated. The constitutive production of the factors was not influenced by depletion of serum from the medium or by the addition of either phorbol ester or bacterial endotoxin. The factor has a Mr greater than 10 kDa, and its cytotoxicity was abolished by anti-serum against murine TNF. Northern blot analysis with the use of cDNA probes to murine tumor necrosis factor (TNF-alpha) and lymphotoxin (LT, TNF-beta) showed high levels of TNF-mRNA in the pre-B cell lines, lower levels in the mature B cell lines and no TNF-mRNA in the myeloma cell lines. LT mRNA was present in pre-B cell lines, at a much lower concentration in only one of the B cell lines, and was not present in three other B lymphomas or in the myelomas tested. The results show a positive correlation between the presence of TNF and/or LT mRNA and the 51Cr-releasing activity present in the cell culture medium. Our data indicate that TNF and LT can be produced by murine B cells and that the synthesis of these cytokines may be restricted to certain differentiation stages of the B cell lineage.

Animals↗
PubMed1990

Immunoadjuvanticity of endotoxins and nontoxic derivatives for normal and leukemic immunocytes.

Studies with FLV infected mice, a model for retrovirus induced acquired immunodeficiency, showed that intact lipopolysaccharide rich extract from Serratia marcescens as well as the nontoxic polysaccharide derivative free of lipid A were equally adjuvantic in enhancing antibody formation to sheep erythrocytes, both in vivo and in vitro. The PS-rich endotoxin derivative had little or no toxic activity in leukemic animals as occurred with intact endotoxin. The adjuvanticity of both the nontoxic polysaccharide derivative as well as the intact endotoxin in enhancing antibody formation in FLV infected mice was evident also in vitro when spleen cells from infected animals were immunized with sheep erythrocytes simultaneously with the polysaccharide in comparison with the LPS. Supernatants from normal spleen cells treated in vitro either with the polysaccharide or the intact endotoxin showed immunoenhancing helper activity for both normal and FLV infected spleen cells and this enhancing activity was due to IL-1 induced by either bacterial product. Thus the immunoenhancing soluble mediator, i.e., IL-1, is induced equally by PS or LPS and has immunorestorative activity for FLV infected animals. The potential value of the nontoxic PS as an immunoadjuvant in retrovirus immunosuppressed lymphoid cells is evident. The results of these studies suggest that further investigations concerning the nature and mechanism involved in such adjuvancticity is warranted.

Adjuvants, Immunologic↗
PubMed1990

Auranofin-induced suppression of autoimmune antibody production and inflammation in genetically autoimmune-prone mice.

The gold compound auranofin and lobenzarit (CCA) were compared in regard to effects on development of an autoimmune-like disease in MRL/1 mice, which normally develop elevated levels of serum anti-DNA antibodies and rheumatoid factor as well as joint lesions similar to those seen in patients with rheumatoid arthritis. MRL/1 mice, which are genetically prone to development of autoimmune disease, were given auranofin or lobenzarit by gavage for 15 weeks, starting at 6 weeks of age. Mice were examined periodically for immunological abnormalities as well as histologic changes in articular joints. The auranofin-treated mice showed marked diminution in development of anti-DNA antibodies and serum rheumatoid factor as compared to control animals. Although higher than in the auranofin-treated animals, CCA-treated mice also had lower levels of serum autoantibodies than those seen in the control animals. Examination of limb joints for histopathologic changes indicated that the auranofin-treated animals developed only the slightest evidence of lesions as compared to control animals. CCA-treated mice also had a lessening of lesion development compared to control animals, but lesions were more developed than in auranofin-treated mice. This study indicates that auranofin is more effective than CCA in diminishing development of autoimmunity in MRL/1 mice.

Administration, Oral↗
PubMed1990

Marijuana and immunity: tetrahydrocannabinol mediated inhibition of lymphocyte blastogenesis.

The effects of delta-9-tetrahydrocannabinol (THC) and its major metabolite, 11-OH delta-9-tetrahydrocannabinol (11-OH THC) on mitogen driven lymphocyte blastogenic transformation (LBT) were studied. THC inhibited LBT responses to the T lymphocyte mitogens phytohemagglutinin and concanavalin A but not the B lymphocyte stimulant pokeweed mitogen. The metabolite 11-OH THC caused a comparable, but less significant, inhibition of LBT responses to the T cell mitogens. These inhibitions were dependent upon the drug doses and the time of incubation with the lymphocytes. There was no significant inhibitory activity of THC to the LBT when it was added 24 or 48 h after mitogen. In addition, exposure of lymphocytes to THC for 3 h, followed by removal of the drug prior to addition of mitogen had no effect on the cells' ability to respond to the mitogen. Thus, there appears to be a specified temporal period during which exposure of lymphocytes to THC results in an inhibition of blastogenesis. Interleukin 2 (30 units/ml) could not preclude the THC induced inhibition of lymphocyte blastogenesis. We conclude that THC and 11-OH THC inhibit T lymphocyte blastogenesis. However, unlike the THC mediated inhibition of natural killer cell activity (as shown previously), the process is not responsive to the cytokine interleukin 2.

Concanavalin A↗
PubMed1990

Acid sensitivity of cell-free and cell-associated HIV-1: clinical implications.

Infectivity of free and cell-associated human immunodeficiency virus type 1 (HIV-1) treated in vitro at pH 7.4 to 4.9 for 2 hours was assessed on susceptible CEM-ss cells. Viral activity was monitored by cytopathology and production of reverse transcriptase and p24 antigen. The infectivity of cell-free virus was gradually inactivated and at pH 5.4 was completely lost, with or without subsequent adjustment of pH to neutral. Virus-producing cells also gradually lost their ability to infect as the pH decreased; however, restoration of neutral pH resulted in regained infectivity. Since the pH values used in the study are similar to those found at various entry sites of the human body, the data may be relevant to the mode of transmittal of HIV.

Cell Line↗