[Natural history of human transmissible subacute spongiform encephalopathies].

Transmissible spongiform subacute encephalopathies are rare fatal diseases which comprise in humans Creutzfeldt-Jakob disease (CJD), Kuru, Gerstmann Straüssler Scheinker, and Fatal Familial Insomnia (FFI). Their etiologic agents (Prions or TSA, for transmissible spongiform encephalopathy agents) are still unknown. TSA/prions resist all the physico-chemical procedures which are efficient against the other micro-organisms.

[Quality of life analysis in patients treated for breast cancers].

Objectives: Evaluate the different quality of life parameters in treated breast cancer patients.

Type Of Study: Retrospective analysis from 1977 to 1987.

Study Site: Bichat, Lariboisière and Tenon Hospitals.

Four cross-linked HIV Gag peptides prime the immune response to HIV proteins in mice.

The functional help provided by four cross-linked synthetic peptides from HIV-1 Gag structural proteins was investigated in the mouse model. These peptides, selected upon non-self-criteria, are not predicted as T epitopes by classical prediction methods such as the Rothbard consensus or the amphipathy rule. Priming mice with these peptides allows the enhancement of the antibody response to HIV-1 Gag proteins (p55, p18, p24) given in the viral particle form.

Recombinant human growth hormone and insulin-like growth factor I induce PrP gene expression in PC12 cells.

Growth factors like NGF are known to increase the expression of PrP gene, a housekeeping gene which is responsible for susceptibility to transmissible spongiform encephalopathies. We evaluated in vitro the effect of recombinant human growth hormone (hGH) and one of its in vivo effectors, the insulin-like growth factor I (IGF-I), on PrP gene expression in PC12 cells. We observed a 30% increase of PrP mRNA level after 7 day treatment by hGH at 10 micrograms/ml and potentiation of NGF effect (reaching four times baseline expression as opposed to three times baseline with NGF alone).

Correlation between HIV provirus burden and in utero transmission.

Objective: No predictive parameters of in utero or perinatal vertical transmission of HIV to newborns are known at present. Vertical transmission may be related to several biological parameters of maternal HIV infection: (1) immunological parameters (neutralizing antibodies); (2) the concentration of viral particles and/or infected cells; and (3) the selection of HIV subspecies of particular cellular tropism. The present study was designed to examine the relationship between cellular viral burden and transmission, and between maternal viral burden and CD4+ cell count and clinical status at delivery.

MRI in 31 patients with Behçet's disease and neurological involvement: prospective study with clinical correlation.

Thirty one patients with Behçet's disease and neurological manifestations were prospectively studied with MRI. Cerebral venous thrombosis was diagnosed in 10 patients. MRI performed during the acute illness in eight patients showed an abnormally high signal on the T2 weighted sequences in the occluded sinus.

Complement and virus-specific antibody-dependent infection of normal B lymphocytes by human immunodeficiency virus type 1.

We tested the susceptibility of human purified, normal B lymphocytes to human immunodeficiency virus type 1 (HIV-1) infection, in the presence or absence of complement-sufficient serum and of virus-specific antibodies. Virus replication was detected when cells were infected in the presence of both complement and anti-HIV antibodies (C'-ADE conditions), by day 2 postinfection. Similar results were obtained when B lymphocytes were purified either from peripheral blood (three healthy donors) or from tonsils (four individuals with chronic tonsillitis).

In vitro infection of human macrophages with human T-cell leukemia virus type 1.

The tropism of the human T-cell leukemia virus type 1 (HTLV-1) for the cells of monocyte-macrophage lineage was evaluated by the coculture of blood monocyte-derived macrophages, with irradiated cells of HTLV-1 producing cell lines MT2 or C91/PL. The susceptibility to HTLV-1 was assessed by the detection of viral DNA using the polymerase chain reaction method. HTLV-1 gene expression in the cells was detected using in situ hybridization and by immunofluorescent staining of viral antigen.

[Role of neutralizing antibodies in protection of the fetal from an HIV positive mother].

The goal of this study is to compare serum Titers of Neutralizing antibodies in HIV 1 infected mothers to the virological status of their newborns. 38 infant-mothers couples were tested. Serum Neutralizing antibodies Titers of the mothers were tested the day of birth.

[Bone sterilization by radiation and the HIV virus].

An experimental study was performed to investigate the efficacy of irradiating HIV-contaminated allografts. Irradiation was achieved using an accelerator delivering 6.3 MeV electrons, and the viral strain was HIV-1/LAV-1.

MRI in neurosarcoidosis.

Nine patients with neurological manifestations of sarcoidosis were explored by MRI and, in some cases, CT. The MRI examinations were performed in T1- and T2-weighted spin-echo sequences in all patients, with gadolinium injection in seven. Several non-specific lesions were demonstrated, the most frequent of them showing on T2-weighted sequences as high-intensity signals in the periventricular white matter and the semi-oval centres.

Bispecific antibody targeting of human immunodeficiency virus type 1 (HIV-1) glycoprotein 41 to human macrophages through the Fc IgG receptor I mediates neutralizing effects in HIV-1 infection.

Human monocyte-derived macrophages that express the CD4 molecule and the Fc receptor for IgG (Fc gamma R) play a major role in the pathogenesis of human immunodeficiency virus (HIV) infection. To explore this possibility further, human monoclonal antibody to glycoprotein 41 (gp41) was produced, and a heterobifunctional antibody composed of F(ab') x F(ab')2 fragments of monoclonal anti-gp41 and anti-Fc gamma RI 22.2 were constructed.

Variations in prion protein and glial fibrillary acidic protein mRNAs in the brain of scrapie-infected newborn mouse.

To begin to understand the molecular basis of cases of Creutzfeldt-Jakob disease recently described in young children, the expression of prion protein and glial fibrillary acidic protein (GFAP) mRNAs was investigated during the development of the brain of scrapie-infected newborn mice. Changes in the time course of expression were identified by Northern blot quantification between days 1 and 172. Although scrapie-infected and control animals showed no detectable changes in brain development (first 56 days of life), GFAP mRNAs were found to increase significantly as early as day 84.

Identification of a neutralizing domain in the external envelope glycoprotein of simian immunodeficiency virus.

Two murine monoclonal antibodies (MAbs), designated MATG2014 and MATG2033, were generated. They are reactive with the external envelope glycoprotein gp130 of the simian immunodeficiency virus of macaque monkey (SIVmac251), and display a cell-free virus neutralizing activity in vitro. In addition, MATG2014 cross-reacts with HIV-2Rod gp140.

Differential human immunodeficiency virus expression in CD4+ cloned lymphocytes: from viral latency to replication.

By using cloning methodology, 13 CD4+, CD8-, CD45RO+, and CD29+ clones, isolated from human immunodeficiency virus (HIV)-negative donors, have been characterized and tested regarding their susceptibility to two strains of HIV type 1 (HIV-1). Infected clones possess integrated provirus. Only six are able to replicate HIV-1, while seven may normally grow without cytopathic effect and without viral replication.

Human immunodeficiency virus type 1 major neutralizing determinant exposed on hepatitis B surface antigen particles is highly immunogenic in primates.

Hepatitis B surface antigen (HBsAg) produced by recombinant DNA technology is now widely and safely used worldwide for hepatitis B vaccination. We used the HBsAg particle as a carrier molecule for presentation of selected human immunodeficiency virus type 1 (HIV-1) determinants to the immune system. Immunization of rhesus monkeys with an HBsAg chimera carrying the HIV-1 envelope major neutralizing determinant allowed us to generate proliferative T-cell responses and, in some cases, neutralizing antibodies and antibody-dependent cellular cytotoxicity.

Frequency of central lesions in polyneuropathy associated with IgM monoclonal gammopathy: an MRI, neurophysiological and immunochemical study.

CNS lesions were studied in polyneuropathy associated with IgM monoclonal gammopathy. Eleven out of 12 patients with IgM MGUS and one patient with Waldenstrom's disease had clinical and electrophysiological features indicating a demyelinating polyneuropathy. MRI showed CNS white matter lesions in two cases.

[Complications of intraperitoneal chemotherapy by the needle technique. Evaluation after ten years].

A hundred and twenty three patients with intraperitoneal cancer (mostly ovarian) were treated between 1980 and 1990 with intraperitoneal chemotherapy administered through a "needle". Local complications were infinitely fewer and less serious than those observed with materials implanted for months. General complications depended on which protocols were being used.

Functional consequences of monocyte/macrophage infection by HIV1.

Monocyte/macrophage infection by human immunodeficiency virus type 1 (HIV1) was studied for its effects on the production of tumour necrosis factor alpha (TNF alpha) and the expression of the manganese superoxide dismutase (MnSOD) gene. For this purpose, human peripheral blood monocytes were obtained from healthy HIV1-seronegative donors by centrifugal elutriation and infected with either the HIV1/LAV1 strain or with the primary HIV1/DAS isolate. The results showed that (1) HIV1/LAV1-infected macrophages did not produce any biologically detectable TNF alpha during the few hours following lentiviral infection, despite rises in the TNF alpha mRNA level; (2) MnSOD gene transcription in the macrophages increased, as measured 2 and 4 h after infection; (3) the level of the MnSOD gene expression declined during the late phases of lentiviral infection, but TNF alpha synthesis and gene expression rose; and (4) bispecific antibody comprised of anti-Fc gamma RI (anti-CD64) and anti-gp41 monoclonal antibodies inhibited the in vitro infection of monocyte-derived macrophages by HIV1/DAS.

Clinical and virological aspects of HIV2 infection in rhesus monkeys.

To establish an animal model of AIDS, two different "wild" or "adapted" HIV2 Rod and Eho strains were cultivated on monkey cells from different species (baboons, cynomolgus, Rhesus monkeys). Five different available strains were then injected both by intravenous (i.v.

Specific and non-specific immunity and protection of macaques against SIV infection.

The simian immunodeficiency virus is a retrovirus closely related to the human immunodeficiency viruses; it induces an AIDS-like disease in macaques, and provides therefore an obvious animal model for anti-lentiviral drug and vaccine strategy assessments. In our experiment, we immunized rhesus macaques with a purified and formalin-inactivated whole SIVmac251 antigen preparation. Most of these monkeys were still protected for more than 4 months following a heterologous SIVsm intravenous challenge.

[Creutzfeldt-Jakob disease in 4 children treated with growth hormone].

Creutzfeldt-Jakob disease was diagnosed in four growth hormone recipients at the age of 10, 11, 18 and 19 years. To our knowledge, the two first cases are the first instances of Creutzfeldt-Jakob disease recorded in children. Three of them were still being treated with synthetic hormone at the onset of the disease.