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Biomedical subjects

J C Chermann

Publications and source records attributed to J C Chermann.

At least 109 records · Page 6Linked to original sources

Peripheral blood adherent cells from AIDS patients inhibit normal T-colony growth through decreased expression of interleukin 2-receptors and production of interleukin 2.

Adherent cells display an important accessory role on normal T-cell colony formation. Since the in-vitro proliferation of T colony-forming cells (T-CFC) from AIDS patients is extremely impaired we studied the effect of patients' adherent cells on T-CFC growth. Patients' peripheral blood mononuclear cells (PBMC) were fractionated on the basis of rosette formation with sheep red blood cells and complement-mediated cytotoxicity with OKT3 monoclonal antibody (E-T3-). Both mature (E+) T cells and E-OKT3- cell fractions failed to generate T-cell colonies although colony growth could be obtained from unfractionated PBMC. In five out of 12 AIDS patients, adherent cell-depletion of PBMC enhanced the plating efficiency. Moreover, patients' but not normal adherent cells could inhibit normal T-cell colony growth in a dose-dependent manner. Media conditioned by patients' unstimulated adherent cells (LCM-A+p) also inhibit normal T-cell colony formation. In addition, LCM-A+p were capable of inhibiting interleukin 2-receptor (IL2-R) expression and interleukin 2 (IL2) production by normal mitogen-stimulated T cells. These LCM-A+p did not contain detectable reverse transcriptase activity nor could they infect the CEM T-cell line which is permissive to human immunodeficiency virus (HIV). Conversely, this adherent cell-derived inhibitory activity could be abrogated by heating or treatment with proteolytic enzymes. These findings indicate that the low T-cell colony formation in some AIDS patients could be due to adherent cell-derived inhibitory activity(ies).

Acquired Immunodeficiency Syndrome↗

Detection and titration of neutralizing antibodies to HIV using an inhibition of the cytopathic effect of the virus on MT4 cells.

An assay for determining neutralizing antibodies in sera from individuals infected with HIV was developed. This assay is based on an inhibition of the cytopathic effect observed after HIV superinfection of the HTLV-1-positive cell-line MT4. Only about 10% of asymptomatic seropositive donors exhibit a high titre over 1/500 up to 1/2000 while in 60% of sera, neutralizing antibodies were not detected. The assay reported here can also be used for the comparison of the biological properties of the different strains of HIV.

Antibodies, Viral↗

Risk factors for AIDS and HIV seropositivity in homosexual men.

The authors compared cases of acquired immunodeficiency syndrome (AIDS) diagnosed in San Francisco, California, during 1983-1984 with human immuno-deficiency virus (HIV) antibody-negative neighborhood and clinic controls, looking for risk factors for clinical AIDS. They also compared antibody-positive with antibody-negative neighborhood and clinic controls for risk factors for HIV infection. Odds ratios were 52.0 for AIDs and 7.8 for seropositivity for more than 100 sexual partners versus 0-5 partners when antibody-negative neighborhood controls were compared with cases and with antibody-positive neighborhood controls, respectively. Odds ratios were only 2.9 and 3.4 when antibody-negative clinic controls were compared with cases and with antibody-positive clinic controls, respectively. Odds ratios of 4.6-7.3 for rectal receptivity with most or all partners versus none or one partner were statistically significant, independent of the number of partners. Douching before sex was independently associated with odds ratios of 2.2-2.8. There was no evidence for oral-genital, oral-anal, or other sexual transmission of AIDS. In multivariate analysis, independent odds ratios of 2.4-6.0 for prior syphilis and 10.8-27.9 for prior giardiasis were statistically significant or marginally significant in all comparisons. There was a moderate association with nitrite use. No other drugs were consistently associated with clinical AIDS or HIV seropositivity. Odds ratios associated with AIDS and seropositivity were closely comparable except for number of partners.

Acquired Immunodeficiency Syndrome↗

Clinical and immunological restoration in patients with AIDS after marrow transplantation, using lymphocyte transfusions from the marrow donor.

The diagnosis of transfusion-associated acquired immunodeficiency syndrome (AIDS) was made in 2 patients who developed delayed opportunistic infections and severe cytopenias--56 months for the former (patient 1) and 22 months for the latter, (patient 2) following bone marrow transplantation (BMT) for aplastic anemia. In the third case, grafting for acute leukemia (patient 3) (HIV) infection was probably responsible for the failure of hematological and immunological reconstitution 8 months after allogeneic BMT. Each patient received 6 lymphocyte transfusions from the marrow donor for 3 weeks, combined with a 3-month course of low-dose recombinant alpha interferon. This treatment was followed by recombinant gamma interferon for 3 months. We showed that these 3 patients could resume a normal life for 9 months, at least, and that hematological restoration was observed. Our treatment succeeded in correcting the defect of proliferative response to Candida and the impairment of gamma interferon generation for 4 months in one patient and for more than 12 months in the other two recipients. Nevertheless T4 lymphocyte levels increased only slightly and HIV can still be isolated from the patients' blood. At the time of writing, patients 1 and 3 remain in good health with a partial immunological restoration while patient 2 has died of neurological impairment 2 years after the AIDS diagnosis. Although we cannot generalize this successful therapeutic approach to all patients with AIDS, the results may provide an interesting model of the potential effect of lymphocyte transfusions and the role of interferon therapy.

Acquired Immunodeficiency Syndrome↗

Genetic comparison of LAV-related isolates.

LAV/HTLV-III has been found to be the etiological cause of AIDS. This new human retrovirus has a selective tropism for T lymphocytes of the OKT4/leu 3 subset, in which it induces a cytopathic effect. We have compared Southern blot patterns of integrated proviral DNAs from different individuals at risk or not using a nick-translated LAV probe. We find that LAV/HTLV-III is very similar to our Haitian isolate and close to an isolate from an early-recognized (in 1982) AIDS case in New York. More variation is apparent with Zaïrian isolates as well as an isolate from a nonhigh-risk group when we used Hind III or Bgl II Sac-digested fragments. We also looked at virus isolated from a Sicilian child who developed AIDS after allogenic bone marrow transplant and transfusion. This isolate shows two forms: One is similar to the prototype LAV, the second much different.

Acquired Immunodeficiency Syndrome↗

A monoclonal antibody against LAV gag precursor: use for viral protein analysis and antigenic expression in infected cells.

A murine monoclonal antibody (MAb), named C.V.K., was produced after immunization with highly purified and sonicated lymphadenopathy-associated virus (LAV). No monoclonal antibody was observed with intact virus used as immunogen. C.V.K. MAb recognizes an epitope present on the precursor gag protein of 55 kilodaltons. Western blot analysis and pulse-chase experiments support the interpretation that after p55 cleavage into p25, p18, and p13, only p18 expresses this epitope. C.V.K. MAb selectively stained only LAV-infected lymphocytes. This intracytoplasmic staining appears 3 days after the infection and is correlated with reverse transcriptase activity. Neither membrane immunofluorescence of infected lymphocytes nor neutralizing activity was observed with C.V.K. MAb. These facts suggest that p55 and p18 are not expressed at the cell membrane or on the viral envelope. C.V.K. MAb should prove useful not only in the purification of core proteins but also for detecting infected cells producing the virus in suspension or on histologic sections.

Acquired Immunodeficiency Syndrome↗

Transmission of lymphadenopathy-associated virus/human T lymphotropic virus type III in sexual partners. Seropositivity does not predict infectivity in all cases.

To investigate transmission of lymphadenopathy-associated virus (LAV)/human T lymphotropic virus type III (HTLV-III) in long-term sexual partners, and the relationship between lymphadenopathy-associated virus seropositivity and transmission, nine couples (five heterosexual and four homosexual) at increased risk for acquired immune deficiency syndrome (AIDS) were studied. In two heterosexual couples, transmission of lymphadenopathy-associated virus from a seropositive man at increased risk to his monogamous wife occurred. In one couple, the wife of a man with hemophilia had lymphadenopathy-associated virus antibody and decreased T helper cells; in the other couple, the wife of a bisexual intravenous drug-user had AIDS. Neither woman had a recognized AIDS risk except marriage to a seropositive man at increased risk. However, study of the other couples revealed that regular sexual contact with seropositive persons over long periods did not always lead to evidence of lymphadenopathy-associated virus infection. This study suggests that presence of lymphadenopathy-associated virus antibody does not always indicate a high degree of infectivity.

Acquired Immunodeficiency Syndrome↗

Seropositivity to LAV/HTLV-III in 11 European countries.

The ECP Working Group on AIDS has evaluated data on seropositivity to LAV/HTLV-III supplied by members in II Western European countries. The period covered is 1981-84. The rise in LAV/HTLV seropositivity parallels the incidence of cases of AIDS in the different countries. LAV/HTLV now spreads freely within Europe and spread has become less dependent upon promiscuity. The epidemic is about to enter Eastern Europe. Intravenous drug abusers appear to be the risk group experiencing the most rapid spread at present. Furthermore, seropositivity in males and females outside the traditional risk groups seems on the rise, and as in the US the percentage seronegative in individuals with PGL is quite high. AIDS is rapidly becoming a major cause of cancer in young adults. A coordinated European preventive effort is urgently needed.

Acquired Immunodeficiency Syndrome↗

Genomic variability of selected LAV-related AIDS retroviruses.

All AIDS retroviruses isolated from different patients have shown degrees of heterogeneity as defined by restriction fragment polymorphisms. Despite this variability, all these virus isolates share a number of structural features, including immunological cross-reactivity of virally encoded proteins. In this paper, we compare restriction patterns of integrated proviral DNA from viral isolates of patients belonging to different geographical groups, at risk or not for the disease. We confirm the existence of different clones in the same isolate of the Lymphadenopathy-associated virus (LAV) and of Human T lymphotropic virus (HTLV-III), which are identical. One of these forms is very similar to a Haitian isolate, as well as to an isolate from an early recognized New York case, suggesting a common origin for these viruses. More variation is apparent with Zairian viral isolates, and one of two clones found in a virus from a child who received an allogeneic bone marrow transplant. Greater disparity was also found in the restriction pattern of an isolate from an individual belonging to none of the so-called high-risk groups. We also show that this variation occurs mainly but not only in the env region of the genome, as previously described.

Adult↗

[Infection of insect cell lines by the HIV virus, an agent of AIDS, and a demonstration of insects of African origin infected by this virus].

The etiological agent of AIDS known as HIV has been shown to bind on different insect cell lines including Drosophila, Mosquito, Ceratitis; and his DNA to be integrated in the cellular genome, but no expression of the viral genome was detected in those cells. None of the human lymphocytes markers is expressed at the surface of the insect cells. HIV proviral DNA has been also found in various insects from Central Africa (Zaïre and Central Africa Republic) but not similar insects from the Paris area. These data suggest that insects could be a reservoir or a vector for the AIDS virus.

Acquired Immunodeficiency Syndrome↗