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Biomedical subjects

D Dormont

Publications and source records attributed to D Dormont.

At least 307 records · Page 17Linked to original sources

Early viral replication in the brain of SIV-infected rhesus monkeys.

To investigate the mechanism of simian immunodeficiency virus (SIV) entry into the central nervous system (CNS) and the initial events leading to neuropathogenesis, SIV replication was studied by in situ hybridization in the CNS of 5 Rhesus macaques at 7 days, 1, 2, and 3 months after SIV intravenous inoculation. CNS infection was found to be a frequent and early event, as SIV was detected in the CNS of all the animals studied and as early as 7 days postinoculation. At the earliest stage, the infection localized mainly to perivascular cells. Using combined immunohistochemistry and in situ hybridization, infected cells were shown to express the CD68 marker, suggesting that infected mononuclear phagocytes crossing the blood-brain barrier represent the main source of virus in the CNS. Early viral replication coincided with neuropathologic changes, consisting in gliosis, perivascular infiltrates and rare glial nodules. Immunophenotyping of brain tissue showed that increased macrophage infiltration, microglial reactivity and MHC class II induction occurred within the first week of infection, indicating a possible immunopathologic mechanism in early CNS pathogenesis.

Animals↗

Intracerebral stenosing arteriopathies. Contribution of three radiological techniques to the diagnosis.

Fifty-one patients with intracerebral stenosing arteriopathy were studied by computerized tomography (CT), magnetic resonance imaging (MRI) and cerebral arteriography. Clinical symptoms were varied, included impaired cognitive functions, progressive neurological deficit, headache and vomiting, and were sometimes not suggestives of the diagnosis. CT scans of the brain were normal in 25 percent of the cases or they were not probative because of various and non-specific abnormalities (hypodensity of various types or haemorrhagic hyperdensity). MRI always showed abnormalities but in many cases the lesions observed on T2-weighted images consisted of non-specific focal areas of high-intensity signal in the white matter. High-intensity signals in both white matter and cortex seemed to be more suggestive of the diagnosis. In this as in other studies, arteriography therefore remains the reference examination for stenosing arteriopathies. Inflammatory, infectious and atheromatous processes are the main causes of these arterial lesions. The aetiological value of radiological examinations is poor, and in most cases the morphology and distribution of the lesions does not point to any specific origin. However, herpes zoster arteritis usually affects the proximal segments of the anterior and middle cerebral arteries and spares the carotid siphon.

Adult↗

Early SIV encephalopathy.

SIV encephalopathy was studied in rhesus macaques early after intracerebral (IC) or intravenous (IV) inoculation. Although SIV was detected in the brain of all IC-inoculated animals, the CNS showed moderate neuropathological changes. IV-inoculated animals presented a spectrum of brain changes ranging from perivascular infiltrates to multinucleated giant cells. CNS infection was detected as early as seven days post-IV-inoculation, mostly in a perivascular localization. Using combined immunohistochemistry and in situ hybridization, infected cells were shown to express macrophage markers.

AIDS Dementia Complex↗

Antibody-dependent enhancement and neutralization pattern of sera from SIV-infected or HIV-2-vaccinated rhesus monkeys.

Neutralizing and enhancing activities in sera were detected by using an in vitro infection assay of HUT78 cells. Ten animals were vaccinated with HIV-2ROD recombinant vaccinia viruses and respective purified proteins. Only sera from monkeys vaccinated with env elicited neutralizing antibodies. No antibody-dependent enhancement (ADE) properties were detected in all the tested sera. Six other macaques were infected with SIV-mac251. All of them had detectable ADE properties in their sera. No major neutralizing activity was detected.

AIDS Vaccines↗

[Spinal infarction in the anterior spinal territory with possible relation with bilharziasis].

We report a case of spinal cord infarction in the anterior spinal artery territory with selective involvement of the anterior horns. A 35-year-old Mauritanian woman was hospitalized because of an acute and severe flaccid paraplegia without any sphincter dysfunction or sensory disturbance. MRI abnormalities (hypersignal on T2-weighted sequences) were restricted to the anterior horns of the lower thoracic spinal cord and conus medullaris. Adamkiewicz's artery appeared abnormally thin at arteriography. The infarction was probably related to vasculitis of schistosomal origin.

Adult↗

[Adult T-cell leukemia and non-malignant adenopathies associated with HTLV I virus. Apropos of 17 patients born in the Caribbean region and Africa].

Adult T-cell leukaemia is the first blood disease caused by a retrovirus: HTLV-1. The authors report the first French series of 15 patients, of whom 9 came from the classical endemic areas--the Antilles and outer Caribbean Islands--and 6 from Africa where the serological prevalence of HTLV-1 is high but few cases of adult T-cell leukaemia have been reported. Emphasis is laid on the importance of immunodeficiency (refractory strongyloidiasis, Pneumocystis carinii pneumonia, polyclonal B lymphoproliferative syndrome) and of other pathologies associated with the retrovirus (polyarthritis, lymphocytic interstitial pneumonia). The authors also describe the presence of adenopathy in healthy carriers: either adenitis suggestive of retroviral infection, or Castelman's disease adenopathy. These clinical presentations are similar to those described in lymphadenopathy syndromes due to the human immunodeficiency viruses. Aggressive lymphomas require chemotherapy, but sooner or later resistance develops, and the prognosis is very poor. The indications for allogeneic bone marrow transplantation are still to be determined. The diagnosis of adult T-cell leukaemia must be considered in all patients with blood disease coming from the endemic areas.

Adult↗

Chemotherapy by the intravenous and intraperitoneal routes combined in ovarian cancer.

Intraperitoneal (ip) administration allows delivery of concentrations of cytotoxic drugs to the site of tumor development that could not be attained by the intravenous (iv) route. Rather than leaving ip delivery systems (Tenckhoff catheter, Port à Cath, etc.) in position for several months, with the attendant risk of complications, we prefer to use a simple needle for lumbar puncture and leave it in place between 1 and 2 hr at each infusion of chemotherapy. Results observed at second-look laparotomy in 31 patients with stage III (FIGO) common epithelial carcinoma, treated from January 1980 to December 1986, are reported after six to ten courses of ip and iv chemotherapy combined. In five patients in whom complete surgical excision had been possible, there was still complete remission (CR). In 26 patients in whom initial surgical excision had been incomplete, there was complete remission in 20 (76%). In the other 6 cases, there were small residual masses (incomplete remission), which could readily be excised by the surgeon. Following second-look laparotomy, these 6 patients received ip maintenance chemotherapy for a further 6 months. During follow-up periods of 22 to 105 months (average 45 months), 8 recurrences were observed (4 of them died); 23 of 31 patients are disease free. At 4 years, actuarial survival was 81.5% and actuarial disease-free survival was 66.2%.

Adult↗

T- and B-lymphocyte responses to human immunodeficiency virus (HIV) type 1 in macaques immunized with hybrid HIV/hepatitis B surface antigen particles.

Recombinant human immunodeficiency virus (HIV)/hepatitis B surface antigen (HBsAg) subviral particles of dual antigenicity and immunogenicity were obtained by fusing 84 amino acids of the HIV type 1 external envelope glycoprotein within the pre-S2 part of the hepatitis B middle protein (M.-L. Michel, M. Mancini, E. Sobczak, V. Favier, D. Guétard, E.-M. Bahraoui, and P. Tiollais, Proc. Natl. Acad. Sci. USA 85:7957-7961, 1988). We now describe the humoral and cellular immune response of rhesus monkeys immunized with these hybrid particles. Macaque antisera raised by subcutaneous injections of the HIV/HBsAg particles were shown to be specific for HIV in peptide-binding assays. Moreover, we were able to generate in these vaccinated animals a T-cell-proliferative response to both parts of the hybrid particle, i.e., HIV and HBsAg. These results establish the presence of a T-cell epitope in this HIV segment, which has been shown previously (L.A. Lasky, G. Nakamura, D. H. Smith, C. Fennie, C. Shimasaki, E. Patzer, P. Berman, T. Gregory, and D. J. Capon, Cell 50:975-985, 1987) to be an important domain involved in the binding of the virus to its cellular receptor, the CD4 molecule. This work demonstrates the feasibility of using the HBsAg subviral particle as a carrier protein for the presentation of foreign immunogenic epitopes to the immune system.

Animals↗

[Primates as a model for the study of lentiviruses and AIDS].

Neither vaccine nor therapy are, to date, available against human HIV infections. Because few is known on human pathogenesis, a standardized animal model is urgently required. Today, different models have been available: 1) "partial models" of the human infection (murine retrovirus, infection of SCID or transgenic mice with HIV, sheep infection with Visna, rabbits infected with HIV1, etc.). These models cannot be used in testing vaccine strategies, but may help in evaluating some particular stages of the pathogenesis of the disease, and the targets of antiretroviral drugs. 2) Disease models, such as cats infected with FIV, and, above, primates infected with HIV or SIV (SIV infected macaques, and, perhaps, HIV2 rhesus monkeys). Primate models are the only possibility to day in testing vaccine procedures before screening among a large population of seronegative humans, and determining drug combination which might be useful in HIV specific therapy. The best primate model is today the SIVMAC251 infected rhesus monkey model, which standardization is now on progress.

Acquired Immunodeficiency Syndrome↗

Lack of permissivity of human monoclonal CD4+ lymphocytes to HIV.

Although knowledge has accumulated about GP110-CD4 interaction, viral penetration into human CD4+ lymphocytes remains unclear, in spite of the fact that all studies on HIV infection were performed on cell-transformed lineages, or on human polyclonal CD4+ cells. In order to investigate this viral entrance into susceptible cells, we studied the permissivity of 13 human monoclonal CD4+ lymphocytes by means of reverse transcriptase (RT) assay and immunocapture. We demonstrated a differential susceptibility to HIV of these CD4+ clones. In a second experiment, HIV infection was studied: (1) sequentially by RT assay and P24 immunocapture on several clones; (2) by cocultivation of infected clones with umbilical cord lymphocytes. These experiments suggested existence of permissive and "nonpermissive" CD4+ monoclonal lymphocytes. Slot blot, then PCR, revealed that proviral DNA sequences were detectable in all clones, but were present at lower levels in nonpermissive clones.

Antibodies, Monoclonal↗

[Subacute brainstem hematoma. A surgically treated case].

We report a case of pontine haemorrhage in which symptoms and signs developed over a 2-months period. Surgery was successful but the patient subsequently died. The pathophysiology of subacute and chronic symptoms and signs is discussed.

Adult↗

MR visualization of CSF flow through a ventriculo-cisternostomy.

The MRI findings in a 6-year-old boy with an astrocytoma of the mesancephalon are reported. A ventriculocisternostomy had been performed in order to reduce the hydrocephalus. At the site of the ventriculocisternostomy, the T2-weighted images showed a low signal in the anterior part of the third ventricle, the interpeduncular and the pontine cistern. This was attributed to CSF flow void. We conclude that MRI can provide information about the precise location and normal functioning of a ventriculocisternostomy.

Astrocytoma↗