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Biomedical subjects

T C Chanh

Publications and source records attributed to T C Chanh.

At least 37 records · Page 2Linked to original sources
PubMed1990

Monoclonal anti-idiotype induces protection against the cytotoxicity of the trichothecene mycotoxin T-2.

An IgG1 mAb, designated HD11, specific for the trichothecene mycotoxin T-2 and capable of neutralizing its cytotoxicity was used to generate a syngeneic monoclonal anti-Id antibody. The generated anti-Id mAb, designated DE8, specifically bound to HD11 anti-T-2 mAb, and not to IgG1 mAb of irrelevant specificity or to normal mouse Ig. DE8 inhibited the binding of HD11 anti-T-2 to T-2-BSA-coated plates, whereas a control anti-Id mAb did not, suggesting recognition of an Id determinant associated with the T-2 binding site of HD11. Moreover, the binding of HD11 to DE8 and that of DE8 to HD11 were specifically inhibited by free T-2 mycotoxin. DE8 mAb was efficient in abrogating the protective effect of HD11 in the cytotoxicity of T-2 on the human epidermoid carcinoma cell line Hep-2. In vivo immunization of BALB/c mice with DE8 conjugated to KLH induced an anti-T-2 antibody titer comparable to that obtained with T-2-OVA immunization, whereas immunization with unconjugated DE8 resulted in a lower titered anti-T-2 response. Immunization with DE8-keyhole limpet or with unconjugated DE8 induced anti-T-2 antibody responses characterized by expression of "HD11-like" Id and by protection against T-2 cytotoxicity. However, the T-2-OVA-induced anti-T-2 response lacked the HD11+ Id and was only partially protective against T-2 cytotoxicity. This represents the first demonstration of the use of an anti-Id based vaccine in the in vivo induction of a protective antibody response against the cytotoxicity of a nonproteinaceous, small m.w. biologic toxin, whose very toxic nature precludes its use as the immunogen.

Animals↗
PubMed1990

A rapid method for quantitating lymphocyte receptor capping: capping defect in AIDS patients.

Capping of concanavalin A (Con A) and anti-Leu-8 (L8) receptors on human peripheral blood mononuclear (PBM) membranes was studied utilizing fluorochrome-conjugated ligands and flow cytometric analysis. Histogram profiles of fluorescent intensities consistently revealed a time-dependent decrease in numbers of brightly fluorescing events concurrent with an increase in numbers of dimly fluorescing events when capping occurs. Differences in fluorescence profiles were detectable by flow cytometric analysis as early as 5 min after capping conditions were initiated. A pronounced defect in receptor capping of PBM cells from AIDS patients was observed. This technique represents a rapid and reproducible means for detecting early changes in cell membrane receptor mobility.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Inhibition of lymphokine-activated killer activity during HIV infection: role of HIV-1 gp41 synthetic peptides.

Lymphokine-activated killer (LAK) activity was analyzed in 31 human immune deficiency virus 1 (HIV-1)-infected patients. It was found to be reduced in all groups of patients, being more pronounced in those with acquired immune deficiency syndrome (AIDS) and AIDS-related complex compared to HIV-1-seropositive, asymptomatic individuals. Only high doses of interleukin-2 were able to restore LAK activity comparable to that of normal controls. In addition, HIV-1 gp41 synthetic peptide sequences 735-752 and 846-860 were able to significantly inhibit normal LAK activity at all the effector:target ratios tested. HIV-1-positive serum and the supernatant fluids from cultured peripheral-blood mononuclear cells from HIV-1-infected patients had the same inhibitory effect on normal LAK activity. These data provide evidence that (1) LAK activity appears to be impaired during the course of HIV-1 infection and (2) HIV-1-positive serum and HIV-1 components could exert a profound inhibition of this functional activity.

Adult↗
PubMed1989

Anti-idiotypic antibodies against a monoclonal antibody specific for the trichothecene mycotoxin T-2.

A BALB/c murine monoclonal antibody against the trichothecene mycotoxin T-2 was generated. The antibody, designated HD11, specifically bound T-2 mycotoxin. The binding of HD11 to T-2 conjugated to bovine serum albumin was inhibited by free T-2 toxin but not by the water-soluble heterocyclic guanidines saxitoxin and tetrodotoxin. The T-2 detection limit in an enzyme-linked immunosorbent assay with HD11 was in the nanogram range. The in vitro cytotoxicity of T-2, as measured by the inhibition of radiolabeled leucine uptake of the human epidermoid carcinoma Hep-2 and KB cell lines, was completely reversed by the addition of HD11. Rabbit anti-idiotypic antibodies specific for HD11 were generated and characterized.

Antibodies, Anti-Idiotypic↗
PubMed1989

Photodynamic inactivation of simian immunodeficiency virus.

A photodynamic flow system employing a dihematoporphyrin ether (DHE) was tested for its ability to inactivate the in vitro infectivity of simian immunodeficiency virus (SICMac) at 630 +/- 5 nm with a light fluence of 5 J/cm2. Cell-free SIVMac was inactivated by photoactivated hematoporphyrin derivative in a dose-dependent fashion. Since SIVMac is closely related to human immunodeficiency virus type 2 (HIV-2) and we have previously reported the successful photodynamic inactivation of HIV-1 in cell-free medium as well as in whole human blood, this technology has the potential for the eradication of transfusion-associated acquired immunodeficiency diseases caused by the above-mentioned retroviruses.

Antiviral Agents↗
PubMed1989

In vitro and in situ inhibition of the sodium channel blocker saxitoxin by monoclonal antibodies.

The sodium channel blocker saxitoxin (STX) was conjugated to keyhole limpet hemocyanin (KLH) and used to immunize BALB/c mice. Anti-STX antibodies were detected in serum by an enzyme-linked immunosorbent assay (ELISA) within a week or two after the first immunization. Spleens from immunized mice were fused with NS-1 myeloma cells and approximately 7000 resultant hybrids were screened by ELISA for reactivity to STX. Two stable hybrids were isolated, subcloned, and characterized. These hybrids, termed S1A5 and S3E.2, secreted specific anti-STX antibodies that did not recognize the closely related toxin tetrodotoxin (TDT), as determined by competition ELISA. The S1A5 monoclonal antibody (mAb) was of the IgMk class and S3E.2 of the IgG1k subclass with affinity constants (Ka values) of approximately 10(6) M-1. The protective ability of these antibodies was tested by a competitive displacement assay for [3H]STX binding on rat brain membranes. Purified S3E.2 strongly displaced [3H]STX binding, whereas S1A5 weakly inhibited [3H]STX binding to membranes. One nanomole of S3E.2 or S1A5 was able to bind 0.03 nmol or 0.005 nmol, respectively, of STX. The S3E.2 mAb offered partial protection against STX-induced reduction of peripheral nerve action potential in rat tibial nerve when administered in situ at concentrations 10- to 30-fold greater than STX. The S1A5 mAb, despite its ability to inhibit STX binding in vitro, was completely ineffectual in situ. These antibodies, particularly S3E.2, thus represent potentially useful reagents for neurobiologic research, detection of toxin contamination, and diagnosis of poisoning, and may provide protection against the toxicity of STX in vivo.

Action Potentials↗
PubMed1989

Protection against nerve toxicity by monoclonal antibodies to the sodium channel blocker tetrodotoxin.

The sodium channel blocker, tetrodotoxin (TDT), was conjugated to keyhole limpet hemocyanin (KLH) and used to immunize BALB/c mice. Anti-TDT antibodies were detected in serum by ELISA and reached stable levels 4-5 wk after the first immunization. Spleens from immunized mice were fused with NS-1 mouse myeloma cells and approximately 9,329 resultant hybrids were screened by ELISA for reactivity to TDT. Two stable hybrids were isolated, subcloned, and characterized. These hybrids, termed TD13a1 and TD2C5, secreted specific anti-TDT antibodies that recognized TDT but not the related sodium channel blocker, saxitoxin (STX), as determined by competition ELISA. Both antibodies were of the IgG1k subclass with Ka's approaching 10(7) M-1. The inhibitory ability of these antibodies was tested by a competitive displacement assay for [3H]STX on rat brain membranes. Both antibodies strongly inhibited TDT binding to membranes. A nanomole of TD2C5 was able to bind approximately 1.8 nmol of TDT, whereas a comparable amount of TD13a1 bound half as much. Furthermore, TD2C5 was able to protect against TDT-induced reduction of peripheral nerve action potentials in rat tibial nerve when administered in situ. These antibodies thus represent potentially useful reagents for neurobiologic research, detection of toxin contamination and diagnosis of poisoning, and may provide protection against the toxicity of TDT in vivo.

Action Potentials↗
PubMed1988

Synthetic peptides homologous to HIV transmembrane glycoprotein suppress normal human lymphocyte blastogenic response.

Human immunodeficiency virus (HIV) envelope glycoprotein is synthesized as a polyprotein precursor of 160 kDa (gp 160) and is subsequently cleaved into an amino terminus subunit, gp 120, and a carboxyl terminus transmembrane subunit, gp 41. Two synthetic peptides corresponding to amino acid sequences 735-752 and 846-860, respectively, as deduced from the nucleotide sequence of HTLV-IIIB gp 160 were synthesized and used to assess their effects on normal human lymphocyte blastogenesis. Peptides 735-752 and 846-860 conjugated to protein carriers, but not free peptides, exerted a pronounced suppression of the normal human lymphocyte proliferative response to concanavalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM), and alloantigens. A synthetic peptide homologous to a 17 amino acid sequence of the gene product of HIV trans-acting transcriptional (TAT III) gene had no suppressive effects. Peptides 735-752 and 846-860 also inhibited the IL-2-dependent proliferation of the murine CTLL-2 cell line and the PHA-induced proliferation of normal mouse spleen cells. HIV peptide-induced suppression of human blastogenesis required a 2- to 3-day incubation of responder cells with peptides, suggesting that binding of peptides to the cell membrane was not sufficient for suppression. These results suggest that, in addition to the selective cytopathic effects of HIV, the etiological agent of the acquired immunodeficiency syndrome (AIDS), on the T-helper/inducer lymphocyte subset, viral peptide-mediated immunosuppression may also play an important role in the pathogenesis of the disease. Moreover, these data clearly indicate the need to address the potential immunosuppressive property of HIV antigens in the effort to select and develop effective prophylactic means against AIDS.

Glycoproteins↗
PubMed1988

Inhibition of normal human natural killer cell activity by human immunodeficiency virus synthetic transmembrane peptides.

The inhibitory effect on normal natural killer (NK) cell activity of two synthetic peptides corresponding to amino acid sequences 735-752 and 846-860, respectively, as deduced from the amino acid sequences of HTLV-IIIB gp160, was assessed. Sequences 735-752 and 846-860 correspond to regions located within the HIV transmembrane gp41, the carboxy terminus of HIV gp160. These two synthetic peptides have been shown previously to suppress the mitogen- and alloantigen-induced normal human lymphocyte blastogenic responses. Peptides 735-752 and 846-860 conjugated to protein carriers exerted a significant inhibition on the normal NK cell activity assayed against K562 tumor target cells in an in vitro 51Cr-release cytoltoxicity assay. At variance, control peptides similarly conjugated had no effect on NK activity. Addition of exogenous recombinant human interleukin-2 (IL-2) resulted in a partial restoration of the suppression of NK cell activity exerted by both peptides. Binding experiments indicated that peptides 735-752 and 846-860 did not affect the formation of effector cell-target cell conjugates, suggesting inhibitory effect(s) subsequent to the formation of the lytic complex as one potential mechanism of the observed NK suppression. These results suggest that peptides 735-752 and 846-860 homologous to sequences within the HIV transmembrane gp41 may play an important role in the pathogenesis of the defective NK cell activity observed in patients with acquired immunodeficiency syndrome (AIDS).

Adult↗
PubMed1988

Neutralization of diverse HIV-1 strains by monoclonal antibodies raised against a gp41 synthetic peptide.

Three IgM monoclonal antibodies raised against synthetic peptide analogs of a hydrophilic region of the gp41 transmembrane env protein of HIV-1 neutralize different HIV-1 isolates but not HIV-2 isolates, as determined by HIV titration and by syncytial inhibition assays. VSV (HIV-1) pseudotypes, however, were not neutralized, indicating that gp41 was not accessible to these antibodies on the pseudotype particles. The antibodies affect early steps in adsorption and penetration of HIV-1.

Antibodies, Monoclonal↗
PubMed1987

Neutralisation of HIV isolates by anti-idiotypic antibodies which mimic the T4 (CD4) epitope: a potential AIDS vaccine.

Polyclonal anti-idiotypic antibodies were raised in mice against anti-Leu3a, a mouse monoclonal anti-human T4 (CD4) antibody that blocks the in-vitro binding of human immunodeficiency virus (HIV) to the CD4 molecule. The anti-idiotypes recognized anti-Leu3a but not OKT4, an anti-human T4 antibody that does not inhibit HIV binding to CD4. The anti-idiotypes specifically reacted with the HIV envelope glycoprotein in solid-phase immunoassays. More importantly, the anti-idiotypes neutralised three distinct isolates of HIV-1 and one isolate of HIV-2 in a syncytial inhibition assay. These results have implications for a potential AIDS vaccine of anti-CD4 preparations to induce an anti-idiotypic response with the capacity to bind HIV at its receptor site.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Immune response to human immunodeficiency virus. In vivo administration of anti-idiotype induces an anti-gp160 response specific for a synthetic peptide.

Anti-idiotypic antibodies (anti-Id) to chimpanzee antibodies directed against a synthetic peptide corresponding to a native epitope associated with gp41 of human immunodeficiency virus (HIV) envelope glycoprotein were produced in rabbits. The peptide was analogous to amino acid sequences 735 to 752 from the human T cell leukemia virus-IIIB isolate of HIV. Characteristics of the anti-Id preparation included: 1) detection of a shared determinant present on a second chimpanzee and one of three rabbit antibody preparations directed against the synthetic peptide, 2) failure to recognize an idiotype (Id) in BALB/c mouse antisera to the peptide, and 3) partial inhibition of the homologous chimpanzee Id preparation from binding either peptide or a recombinant HIV gp160 preparation. Immunization of BALB/c mice with the anti-Id induced an antipeptide response which bound a recombinant gp160 preparation without subsequent peptide or gp160 exposure. The anti-gp160 containing sera from mice immunized with anti-Id were able to inhibit the Id-anti-Id reaction indicating that an Id-positive antibody response was induced. This Id is not normally expressed in the murine anti-gp 160 immune response to the synthetic peptide and suggests that this anti-Id may activate normally silent clones. This study indicates that Id networks may be operational during the immune response to HIV epitopes. Alternatively, anti-Id may be useful in altering the serologic characteristics of an antibody response to HIV and may offer potential for modulating the immune response in this viral infection.

Animals↗
PubMed1987

Use of a resin-bound synthetic peptide for identifying a neutralizing antigenic determinant associated with the human immunodeficiency virus envelope.

A polyamide-based solid-phase support containing an acid-stable p-(oxymethyl)benzoic acid handle to anchor the COOH-terminal amino acid was utilized in the production of synthetic peptides analogous to amino acid sequences 503-532 from the human immunodeficiency virus (HIV) envelope glycoprotein. The resin-bound peptide was used to induce an antibody response to the native form of glycoprotein 120 in both rabbits and mice. This epitope was detected on the surface of HIV-infected cells and was capable of inducing an in vitro neutralizing HIV antibody response. In addition, sera from some individuals exposed to HIV react with this peptide bound to the resin in a solid-phase immunoassay. These data indicate that we have identified a neutralizing antigenic determinant present on the amino-terminal glycoprotein 120 subunits of HIV by utilizing resin-bound synthetic peptides.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Monoclonal anti-idiotypic antibody mimics the CD4 receptor and binds human immunodeficiency virus.

A monoclonal anti-idiotypic (anti-Id) antibody, HF1.7, was generated against anti-Leu-3a, a mouse monoclonal antibody (mAb) specific for the CD4 molecule on human helper/inducer T lymphocytes. The anti-Id nature of HF1.7 was demonstrated by the following properties. (i) It reacted in a solid-phase immunoassay with anti-Leu-3a and not with a panel of irrelevant mouse mAbs. (ii) It partially inhibited the binding of anti-Leu-3a to CD4+ T cells. (iii) It detected a common idiotype present on various anti-CD4 mAbs. Because the CD4 molecule represents the receptor site for human immunodeficiency virus (HIV), the etiologic viral agent of acquired immunodeficiency syndrome, we examined the ability of the anti-mAb HF1.7 to mimic CD4 and bind HIV. This anti-Id mAb reacted with HIV antigens in commercial HIV ELISAs and recognized HIV-infected human T cells but not uninfected cells when analyzed by flow cytofluorometry. Attesting further to the HIV specificity, the anti-Id mAb reacted with a recombinant gp160 peptide and a molecule of Mr 110,000-120,000 in immunoblot analysis of HIV-infected cell lysates. The anti-Id mAb also partially neutralized HIV infection of human T cells in vitro. These results strongly suggest that this anti-Id mAb mimics the CD4 antigenic determinants involved in binding to HIV.

Animals↗
PubMed1987

Human immunodeficiency virus neutralizing antibodies recognize several conserved domains on the envelope glycoproteins.

Serum neutralizing antibodies against the human immunodeficiency virus were frequently detected in infected individuals, and low or absent serum neutralizing titers correlated with poor prognosis. Multiple diverse human immunodeficiency virus isolates were found to exhibit similar susceptibility to neutralization by a panel of human seropositive sera, suggesting that neutralizing antibodies are largely directed against conserved viral domains. Furthermore, utilizing antisera raised against a library of synthetic env peptides, four regions which are important in the neutralization process have been identified within both human immunodeficiency virus envelope glycoproteins (gp41 and gp120). Three of these are in conserved domains and should be considered for inclusion in a candidate vaccine.

AIDS-Related Complex↗