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Biomedical subjects

D Dormont

Publications and source records attributed to D Dormont.

At least 361 records · Page 20Linked to original sources
PubMed1984

Characterization of the RNA dependent DNA polymerase of a new human T-lymphotropic retrovirus (lymphadenopathy associated virus).

We described here the characteristics of the Reverse Transcriptase activity associated with the Lymphadenopathy Associated Virus ( LAV ). A critical concentration of non ionic detergent, all four deoxyribonucleosides triphosphates and the divalent cation Mg2+ are required for optimal endogenous enzyme activity. The endogenous reaction product is digested by DNase and not by RNase and its synthesis is only slightly inhibited by actinomycin D. Exogenous reactions are optimal using poly A oligo dT12 -18 or poly Cm oligo dG12 -18 as template primer and Mg2+ as divalent cation. This enzyme can be distinguished from other cellular DNA polymerases activities and from Terminal deoxynucleotidyl Transferase (TdT) by purification from LAV infected T lymphocytes using phosphocellulose column.

Chemical Phenomena↗
PubMed1983

In vitro propagation of the scrapie agent. I. Transformation of mouse glia and neuroblastoma cells after infection with the mouse-adapted scrapie strain c-506.

Seven cell lines including glia cells from mouse brains and mouse neuroblastoma cells were infected with the mouse-adapted scrapie strain c-506. During the early in vitro passages, a stimulation of growth was already observed but cellular morphology and differentiation did not alter. Later on, after 12-16 passages, six of the seven infected lines displayed cell proliferation and morphological alterations, suggesting an in vitro morphological transformation. At this stage, differentiation was no longer observed in the scrapie-infected neuroblastoma cells and all the scrapie-infected cells formed two to four times more colonies in liquid medium than the controls, and developed large tridimensional colonies in agar. The part played by the scrapie agent in these changes is discussed.

Animals↗
PubMed1982

Initial chemoimmunotherapy in inflammatory carcinoma of the breast.

Fifteen patients with clinical primary inflammatory carcinoma of the breast were treated with initial chemoimmunotherapy between September 1974 and May 1977. The protocol was a combination of Adriamycin, vincristine, 5-fluorouracil, and methotrexate given by I.V. push, and melphalan per os. Thermographic cooling was taken as the criterion of operability. Initial chemotherapy was resumed after surgery up to a total of ten courses and followed by maintenance chemotherapy for a minimum of one year. Immunotherapy using I-BCG-F. Pasteur was routinely associated with the antimitotic agents. The median survival for our 15 patients has not been reached and exceeds 56 months. These results correspond to an obvious therapeutic benefit compared with recent attempts in which similar chemoimmunotherapy protocols were used; this benefit seems to be the consequence of the adaptation of the length of initial chemotherapy to the data given by plate-thermography.

Aged↗
PubMed1982

[In vitro modification of the morphology and the growth of cells infected with scrapie (author's transl)].

Seven cell lines originated either in brains or in neuroblastomas of Mice, were infected with Scrapie. After 12 to 16 in vitro passages, 6 lines out of 7 showed changes of their morphology, and of their growth, resembling those occurring in the course of a malignant transformation. The Scrapie infected cells acquired the capacity to form 2 to 4 times more colonies in liquid medium than the controls, and to develop large tridimensional colonies in semisolid medium. The role of Scrapie in these changes is discussed.

Animals↗
PubMed1982

[Cancer of the ovary: the usefulness of Cul-de-sac aspiration and the level of carcino-embryonic antigen in the peritoneal fluid].

While it is useful to carry out aspiration from the Pouch of Douglas for screening for cancer of the ovary, the technique is irreplaceable for the follow-up of tumours that have been operated on or irradiated or treated with chemotherapy. We have carried out 1,353 aspirations: 189 of these which were done routinely have been equivocal. 380 aspirations that were carried out because of abnormal symptoms led to the discovery of 26 cancers of which 2 were very early ones. 784 aspirations were carried out for follow-up. There were in all 4.8% blank aspirations, 0.5% false positives and 1.6% false negatives, which is an indication of the reliability of the method so long as certain points in the technique are carefully followed. These figures, which are quoted as a percentage of the total number of aspirations, however, become more important when considered as a percentage of the number of cancers that were diagnosed (5.5% false positive and 18% false negatives). Furthermore, the level of C.E.A. in peritoneal fluid is a method which can be added to cytology in following up the progress of the disease which is not to be dismissed.

Adolescent↗
PubMed1981

[Trials of in vitro propagation of the scrapie agent in mouse nerve cells].

We attempted to propagate the Scrapie agent in vitro in glia and neuroblastoma cells of Mice. Four out of seven assays of infection were positive, i.e. after several passages in vitro yielding at most a 10(9) fold final dilution of the original material, the extracts of each of the four cultures, when injected intracerebrally into CD1 Mice, produced a deadly disease displaying the clinical and pathological signs characteristic of Scrapie.

Animals↗
PubMed1981

[Creutzfeldt-Jakob disease in the squirrel monkeys].

Four different strains of Creutzfeldt-Jakob disease virus (2 primary and 2 passaged in primates or mice) were inoculated intra-cerebrally into squirrel monkeys implanted with continuously-recording indwelling electrodes. Simultaneous EEC and videotape recordings were made on unrestrained animals. In addition EEG recordings were made of evoked visual potentials on restrained animals. EEG abnormalities appeared in every animal before the first clinical signs (6 to 20 months after inoculation) and included generalized slowing, epileptiform patterns and occasional episodes of pseudo-periodic activity. Abnormal evoked visual potentials and disturbances of consciousness were also noted. All viral strains produced similar disorders and the death of inoculated animals. The relative frequency of epilepsy seen in the CJD-inoculated squirrel monkey contrasts with its irregular occurrence in most other monkey species, and its total absence in the spider monkey. This could be related to the lesser complexity of neo-cortical evolution in the squirrel monkey and a less pronounced development of inhibitory CNS mechanisms under the general control of GABA-ergic neurons.

Animals↗
PubMedDate not supplied

In vitro infection of macrophages by HIV: correlation with cellular activation, synthesis of tumour necrosis factor alpha and proteolytic activity.

Macrophages were obtained after differentiation of healthy donor monocytes. Seven to 9 days after isolation, cells were infected with HIV1. Tumour necrosis factor alpha (TNF alpha) biological activity, TNF alpha- and 1-6-fructose-diphosphatase-gene expression and gelatinase activity were sequentially determined and correlated with viral infection and replication. TNF alpha was only detectable when mature viral particles were isolated in cell culture supernatants; 1-6-fructose diphosphatase mRNA was hyperexpressed in infected cells and its proteolytic activity was tremendously decreased during the early days postinfection. These results would seem to indicate that in human macrophage activation, cytokine secretion and microbicidal proteolytic activity are strongly modified by HIV infection.

Blotting, Northern↗
PubMedDate not supplied

B-cell continuous epitopes of the SIVmac-251 envelope protein in experimentally infected macaques.

The humoral immune response of 34 macaques experimentally infected with SIVmac-251 was studied using a combination of an epitope library and synthetic peptides. The course of the immune response was checked for up to 9 months postinfection with a panel of clones expressing SIV fragments. A systematic study was performed with synthetic peptides covering the whole transmembrane (TM) and external (SU) envelope proteins. Seven major immunodominant epitopes were characterized. Four are localized in the SU protein: one in the V1 region (111-130), one in the Cys loop of the V3 region (311-330) and two in the C-terminal end (501-520 and 511-530). Three are localized in the TM protein: one in the extracellular domain (601-619), one in the anchor domain (731-750) and one in the intracytoplasmic domain (861-881). Among these epitopes, only one, 601-619, was found to be reactive with all sera and can be defined as the principal immunodominant epitope.

Amino Acid Sequence↗
PubMedDate not supplied

Differential effects of a new amphotericin B derivative, MS-8209, on mouse BSE and scrapie: implications for the mechanism of action of polyene antibiotics.

Mice were infected intracerebrally with the bovine spongiform encephalopathy (BSE) or the scrapie agent and treated during 8 weeks postinfection to test the protective effect of a new amphotericin B (AmB) derivative, MS-8209, in experimental transmissible spongiform encephalopathies. The results show that (i) the treatment prolonged the incubation period of both BSE-infected and scrapie-infected mice, (ii) MS-8209 and AmB were much more efficient in delaying the onset of scrapie than that of BSE, and (iii) a delay in Prp-res (proteinase K-resistant prion protein) and GFAP (glial fibrillary acidic protein) accumulation was observed in the brains of scrapie-infected mice, but was not significant in BSE-infected mice. The analysis of the molecular and clinical results strongly suggests a common mechanism of action of this category of drugs on the different transmissible spongiform encephalopathy strains. This could be due to an interaction with the PrP transconformation process leading to the formation of PrP-res.

Amphotericin B↗
PubMedDate not supplied

Treatment of human monocyte-derived macrophages with a TNF alpha synthesis inhibitor prior to HIV1 infection: consequences on cytokine production and viral replication.

Human monocyte-derived macrophages (MDM) were infected with the viral strain HIV1/Ba-L and with the clinical isolates HIV1/DAS and HIV1/PAR. Kinetics of tumour necrosis factor alpha (TNF alpha) and interleukin-6 (IL6) production were investigated for 28 days after infection. At the early stages of infection we observed significant TNF alpha and IL6 secretion 2 to 10 h after infection, whatever the viral strain we used. During the late events of MDM infection, TNF alpha and IL6 were detected over 16 to 21 days following HIV1 infection, at the time of high viral replication. Pretreatment of MDM with a TNF alpha synthesis inhibitor, RP 55778, 4 h prior to HIV infection induced a modified cytokine pattern during the first ten hours of infection: TNF alpha production was totally inhibited despite comparable amounts of IL6. At the late phases of the cell culture, a decrease in magnitude of both viral and cytokine production as well as a delay in the appearance of reverse transcriptase activity and cytokine secretion peaks were observed in RP-55778-pretreated and HIV1-infected MDM cultures. Similar results were obtained after pretreatment of HIV1/DAS-infected MDM cultures with an anti-TNF alpha monoclonal antibody.

Antibodies, Monoclonal↗
PubMedDate not supplied

Variation in virological parameters and antibody responses in macaques after atraumatic vaginal exposure to a pathogenic primary isolate of SIVmac251.

We developed an animal model for the male-to-female transmission of human immunodeficiency virus, consisting of an atraumatic vaginal application of simian immunodeficiency virus onto the intact vaginal mucosa of cynomolgus macaques. Different doses of a pathogenic isolate of SIVmac251, with or without seminal plasma, were infused into the vaginas of female macaques. Infection of macaques could be achieved after a single exposure to the virus. Two patterns of infection were underscored with no relation to the virus dose inoculated: in 50% of the monkeys, SIV was persistently recovered and a strong antibody response to SIV was evidenced in blood and vaginal secretions. In the other infected animals, SIV infection was only transiently evidenced and a weak systemic antibody response was detected. It appeared that the presence of seminal plasma may be implicated in this variability only when low doses of virus are inoculated. Sequence analysis of the env gene of SIV revealed that most of the persistently viraemic animals were infected with a viral variant different from that of transiently viraemic macaques.

Amino Acid Sequence↗
PubMedDate not supplied

Nitric oxide synthesis during acute SIV mac251 infection of macaques.

During HIV1 infection, nitric oxide (NO) could significantly contribute to immune dysregulation by its multiple effects on the modulation of the host immune response. The in vivo regulation of NO production is attributable to several nitric oxide synthases, one of which is a cytokine-inducible enzyme (iNOS). In vitro experiments suggest that iNOS expression in macrophages may be directly modulated by HIV infection. Acute infection of macaques with a pathogenic strain of the simian immunodeficiency virus (SIV) represents a relevant animal model for the in vivo study of the relationships between iNOS expression and lentiviral replication. Indeed, acute infection in this model is characterized by high rates of viral replication associated with early cytokine dysregulations, in the absence of opportunistic infection. In our experiment, two cynomolgus macaques were inoculated intravenously with a pathogenic isolate of SIVmac251, and iNOS gene expression was investigated ex vivo during acute infection in mononuclear cells obtained from bronchoalveolar lavage (BALMCs). An enhancement of this gene expression was observed as early as the second week of infection, at the time of peak of systemic viraemia, and increased until day 31 p.i. This overexpression was concomitant with a marked linear increase in IFN gamma expression in BALMCs. At the time of systemic viral load peak, the production of NO in plasma of these two monkeys was evidenced by the detection of large amounts of nitrate.

Acute Disease↗