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Biomedical subjects

P Sansonetti

Publications and source records attributed to P Sansonetti.

At least 55 records · Page 3Linked to original sources
PubMed1995

Gag-specific cytotoxic responses to HIV type 1 are associated with a decreased risk of progression to AIDS-related complex or AIDS.

The duration of human immunodeficiency virus (HIV-1) infection prior to the development of AIDS is variable, and for most patients the exact time of infection is not known. A group of 38 HIV-1-infected subjects was tested while asymptomatic for comparative cytotoxic lymphocyte responses to the Gag and envelope antigens of HIV-1. Twenty of the 38 patients had no detectable primary cytotoxic T lymphocyte (CTL) response to Gag, and this was associated with a relative risk of 1.89 for progression to ARC or AIDS during the subsequent 3 to 40 months of observation when compared with patients who had Gag-specific CTL activity at the beginning of the observation period. In contrast, no significant association was observed between envelope-specific cytotoxic activity and disease progression. Other patient characteristics, including CD4+ T lymphocyte counts and antibody levels to the p24gag protein, measured at the start of observation, did not correlate with disease progression during the observation period. This suggests that the anti-Gag CTL response may be protective during HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Myosin II is involved in capping and uroid formation in the human pathogen Entamoeba histolytica.

The redistribution and capping of surface receptors on the human pathogen Entamoeba histolytica was observed in the presence of concanavalin A (ConA). Capping was correlated with plasma membrane folding towards the rear of the amoeba and with uroid formation. The uroid is thought to play a role in the escape of amoebae from the host immune response. To localize myosin II during capping, amoebae were incubated in the presence of ConA and then analyzed by microscopy. Myosin II was three times more concentrated within the uroid compared with the rest of the cell, suggesting that the release of caps may depend upon mechanical contraction driven by myosin II activity. The use of drugs that disrupt cytoskeletal structure or that inhibit myosin heavy chain phosphorylation demonstrated that inhibition of capping prevents uroid formation. Biochemical analysis allowed the identification of two ConA receptors which have been previously described as major pathogenic antigens of this parasite: the 96-kDa antigen, which carries alcohol dehydrogenase 2 activity and binds extracellular matrix proteins, and the Gal-GalNAc-inhibitable surface lectin, which is involved in amoeba-cell interactions and in the degradation of complement particles attached to the parasite.

Amino Acid Sequence↗
PubMed1994

[Prevention of Pneumocystis carinii pneumonia associated with HIV infection using pentamidine aerosols. Retrospective study of 465 cases].

OBJECTIVES: At least 80% of human immunodeficiency virus (HIV)-positive patients not given prophylaxis therapy against Pneumocystis carinii develop pneumonia, a major cause of morbidity and mortality. We therefore retrospectively evaluated prophylaxis protocols given from March 1988 to July 1991 at the Pasteur Institute Hospital. METHODS: Pentamidine aerosols were prescribed for 456 HIV-positive patients as primary or secondary prophylaxis. From March 1988 to November 1989 the dose was 4 mg/kg pentamidine mesylate once a month for primary prophylaxis and 4 mg/kg twice a month for secondary prophylaxis. From November 1989 pentamidine isethionate was given at the dose of 300 mg once a month. RESULTS: Tolerance was generally good, treatment had to be discontinued in only 2 of the 456 patients due to side effects. Pneumocystis carinii pneumonia was diagnosed in 4.9% of the treated patients, but in only 2.9% of those who were compliant. Pneumocystis carinii pneumonia occurred in very immunodepressed patients and radiologically appeared as an interstitial or alveolo-interstitial syndrome, often with a macronodular element, in 65% of the patients. CONCLUSION: The results of this retrospective study confirm the prophylactic value of pentamidine aerosols given after trimethoprim-sulfamethoxasol.

AIDS-Related Opportunistic Infections↗
PubMed1994

The secretion of the Shigella flexneri Ipa invasins is activated by epithelial cells and controlled by IpaB and IpaD.

Shigella species are enteropathogens that invade epithelial cells of the human colon. Entry into epithelial cells is triggered by the IpaB, IpaC and IpaD proteins which are translocated into the medium through the specific Mxi-Spa machinery. In vitro, Shigella cells secrete only a small fraction of the Ipa proteins, the majority of which remains in the cytoplasm. We show here that upon interaction with cultured epithelial cells or in the presence of fetal bovine serum, S.flexneri release pre-synthesized Ipa molecules from the cytoplasm into the environment. Evidence is presented that IpaB and IpaD are essential for both blocking secretion through the Mxi-Spa translocon in the absence of a secretion-inducing signal and controlling secretion of the Ipa proteins in the presence of a signal. Subcellular localization and analysis of the molecular interactions of the Ipa proteins indicate that IpaB and IpaD associate transiently in the bacterial envelope. We propose that IpaB and IpaD, by interacting in the secretion apparatus, modulate secretion.

Adhesins, Bacterial↗
PubMed1994

Extracellular association and cytoplasmic partitioning of the IpaB and IpaC invasins of S. flexneri.

Shigella species cause bacillary dysentery in humans by invading colonic epithelial cells. IpaB and IpaC, two major invasins of these pathogens, are secreted into the extracellular milieu. We show here that IpaB and IpaC form a complex in the extracellular medium and that each binds independently to a 17 kDa polypeptide, IpgC, in the bacterial cytoplasm. The IpgC polypeptide was found to be necessary for bacterial entry into epithelial cells, to stabilize the otherwise unstable IpaB protein, and to prevent the proteolytic degradation of IpaC that occurs through its association with unprotected IpaB. We propose that IpgC, which is not secreted and thus acts as a molecular chaperone, serves as a receptor that prevents premature oligomerization of IpaB and IpaC within the cytoplasm of Shigella cells.

Adhesins, Bacterial↗
PubMed1993

Identification and characterization of a myosin heavy chain gene (mhcA) from the human parasitic pathogen Entamoeba histolytica.

The mhcA gene from the human pathogen Entamoeba histolytica was identified using the polymerase chain reaction. It is a single copy gene expressed as a 6.4-kb mRNA. The deduced MhcA protein sequence is highly similar to myosin II from both Dictyostelium discoideum and Acanthamoeba castellanii. The globular head domain of MhcA contains the specific regions involved in ATP binding, actin binding, and interaction with myosin light chain. The tail domain is organized in an alpha-helical coiled coil structure, which suggests that MhcA is an alpha-fibrous protein. The coiled coil is interrupted by two prolines indicating that like other myosins, either from smooth muscle or from non-muscle cells, the tail of MhcA folds twice on itself. In addition, MhcA presents sequence similarities with the heavy chain phosphorylation sites of smooth and non-muscle vertebrate myosins.

Amino Acid Sequence↗
PubMed1993

Infection due to Klebsiella rhinoscleromatis in two patients infected with human immunodeficiency virus.

Two cases of rhinoscleroma in patients infected with the human immunodeficiency virus (HIV) who had stayed in an area of endemic Klebsiella rhinoscleromatis are reported. One of the patients presented with oropharyngeal lesions, an unusual clinical picture. Both patients suffered from a major cellular immune deficiency. The importance of Klebsiella rhinoscleromatis infection in AIDS-related oropharyngeal pathology and the possible treatment of such infection in HIV-positive patients are not yet clearly established.

AIDS-Related Opportunistic Infections↗
PubMed1993

Localization of myosin heavy chain A in the human pathogen Entamoeba histolytica.

To recognize myosin II in trophozoites of the human pathogen Entamoeba histolytica, a specific antimyosin polyclonal serum was raised against a fusion protein consisting of a 146-amino-acid fragment of the myosin II heavy chain A of E. histolytica (MhcA) fused with beta-galactosidase. The hybrid protein was encoded by a chimera gene formed by a DNA fragment, from the mhcA gene, amplified by polymerase chain reaction and fused with the lacZ gene of Escherichia coli. Polymerase chain reaction-amplified DNA is located within the region encoding the tail domain of myosin. This antibody recognized a 250-kDa protein in extracts of E. histolytica trophozoites. Confocal microscope analysis of antibody-labelled trophozoites indicated that MhcA localizes at the posterior pole of locomoting cells and concentrates within the uroid. These results might indicate that MhcA is involved in movement and in the uroid formation which help amoebas to escape the host immune response. These data are the first evidence indicating that myosin exists in E. histolytica. In addition, two other peptides were found in myosin-enriched extracts of amoebas, indicating that other myosins may be present in this parasite.

Amino Acid Sequence↗
PubMed1993

Characterization of B-cell epitopes on IpaB, an invasion-associated antigen of Shigella flexneri: identification of an immunodominant domain recognized during natural infection.

The invasion plasmid antigen B (IpaB), a 62-kDa plasmid-encoded protein associated with the ability of shigellae to invade epithelial cells, is the bacterial antigen most strongly and consistently recognized by the host during infection. The strong systemic and mucosal immune responses observed against this invasin prompted us to map its B-cell epitopes. For this purpose, IpaB was first overexpressed in Shigella flexneri and used to raise rabbit polyclonal antiserum and murine monoclonal antibodies, which were subsequently used to screen a lambda gt11 ipaB library. Inserts of recombinant DNA clones that were specifically recognized by the antisera and antibodies were sequenced, and three distinct determinants were identified. Further characterization of these determinants showed that they were recognized by sera from patients convalescent from shigellosis, suggesting that they are relevant to the humoral response during natural infection. Moreover, the IpaB region comprising the three determinants was systematically recognized by all sera from infected patients that we tested, whereas other regions of the protein were not. These data suggest that this region, located between amino acid residues 147 and 258, is the major immunogenic domain of the invasin in the course of natural infection.

Animals↗
PubMed1992

[Lung abscess caused by Rhodococcus (Corynebacterium) equi in HIV infection. Two cases].

Rhodococcus (Corynebacterium) equi is a well-known Gram positive bacillus which is usually pathogenic in farm animals but rarely causes diseases in humans. Only 30 cases of human infection have been reported in the literature. R. equi has recently been added to the list of opportunistic agents in severe HIV infection. Its most common manifestation in immunocompromised is a slowly progressive pneumonia which may cavitate. R. equi pulmonary infections are difficult to treat: they usually require prolonged parenteral antibiotic therapy and often need surgical treatment. Two cases of cavitary pneumonia in patients with severe HIV infection are reported here. In one case the disease was associated with pulmonary Kaposi sarcoma and pneumocystis pneumonia; the other case was the first opportunistic infection in the course of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Enhancement of HIV-specific cytotoxic T lymphocyte responses by zidovudine (AZT) treatment.

Zidovudine or 3'-azido-2'-3'-dideoxy-thymidine (AZT) is an antiviral drug widely used to treat HIV-infected patients. Because cytotoxic T lymphocytes (CTL) are thought to contribute actively to resistance against HIV-induced disease, we studied sequentially 10 HIV-infected individuals under zidovudine treatment for a period of 6-12 months. For a given patient all lymphocyte suspensions corresponding to the complete zidovudine therapy period were tested on the same day and on the same target cells. Patients were selected for expression of HLA-A2 and/or HLA-A3 class I transplantation antigen. HLA-restricted cytotoxicity specific for env, gag and nef HIV proteins was quantified for each patient at 6 week intervals. The data clearly indicated that zidovudine has a beneficial effect on the CTL response during the first 6-12 weeks of treatment, inducing cytotoxicity levels up to 100-fold stronger than base line. This effect was usually short lived. However, patients who maintained strong levels of cytotoxicity had better clinical and survival outlook than patients who had lost all detectable cytotoxic lymphocytes. It is proposed that AZT, among other effects, delays the onset of disease in HIV-infected patients by contributing to the stimulation of the HIV-specific CTL response.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Identification of a myosin heavy chain gene from Entamoeba histolytica.

The myosin heavy chain gene A, mhcA, from E. histolytica was identified by polymerase chain reaction. There is only one copy of this gene on the ameba genome. The mhcA gene encodes a 6 kb messenger RNA. The predicted protein sequence is homologous to myosin II from both, Dictyostelium discoideum and Acanthamoeba castellanii. Specific areas of the N-terminal region of myosin II are highly conserved reflecting a similarity in functional domains, like the ATP or the actin binding sites.

Acanthamoeba↗
PubMed1990

Detection of primary cytotoxic T lymphocytes specific for the envelope glycoprotein of HIV-1 by deletion of the env amino-terminal signal sequence.

A heterogenous population of envelope glycoprotein-specific cytotoxic effector cells are found in the peripheral blood of individuals infected with HIV-1, and in many cases env-specific lysis is not restricted by MHC molecules and is not blocked by antibody to CD3 (Rivière, Y. et al., J. Virol. 1989, 63:2270). In order to detect env-specific cytotoxic T lymphocytes (CTL) in fresh peripheral blood mononuclear cells of HIV-1-infected donors, a mutant env gene with deletion of the amino-terminal signal sequence was inserted into vaccinia virus. This deletion of the amino-terminal signal sequence was inserted into vaccinia virus. This deletion results in synthesis of an envelope protein that is not glycosylated and not expressed at the surface of infected cells. Target cells infected with this recombinant vaccinia virus are not lysed by antibody-mediated cellular cytotoxicity, but they are recognized by secondary CTL. Comparing lysis of target cells expressing gp160 of HIV-1 and the signal peptide deletion mutant, primary env-specific CTL were detected in some individuals infected with HIV-1.

Amino Acid Sequence↗
PubMed1990

Immunodetection of lipopolysaccharide in macrophages during the processing of non invasive Shigella dysenteriae.

The location of lipopolysaccharide (LPS) was studied by immunofluorescence and immunoelectron microscopy in macrophages infected with a non-invasive Shigella dysenteriae 1 strain. Bacterial degradation began only 3 h after the end of infection. The first visible sign of degradation was detected by immunogold labelling at the level of LPS which detached from the bacterial surface and was transferred to the perinuclear lysosomes. After a few hours, it was found in small vesicles spread over the whole macrophage cytoplasm in which it remained visible for 72 h. These vesicles seemed to belong to a compartment in which slowly or non-degradable compounds are stored. LPS separation from the bacterial surface was immediately followed by the degradation of the intrabacterial constituents. The long lag period observed before initiation of bacterial degradation was not due to a lack of phagosome acidification, since DAMP, a lysosomotropic drug was found in all phagosomes at the end of the ingestion period. The frequency of phagosome-lysosome fusion was 30% for S dysenteriae and 72% for B subtilis used as a reference of high fusion frequency. The low frequency of fusion of S dysenteriae may play an important role in the survival of the virulent strains in macrophage by providing bacteria enough time to lyse the phagosome membrane before lysosome fusion occurs.

Adamantane↗
PubMed1990

Immunolabelling of Shiga toxin in macrophages infected with Shigella dysenteriae 1.

Immunolabelling of Shiga toxin in macrophages infected with a non-invasive Shigella dysenteriae 1 isolate showed that bacteria remained alive for 3 h after ingestion within the phagocytic vacuole and synthesized Shiga toxin. The normal process of toxin secretion was, however, impaired by the phagosomal environment and toxin molecules accumulated within the bacterial cytoplasm.

Bacterial Toxins↗
PubMed1990

Primary cytotoxicity against the envelope glycoprotein of human immunodeficiency virus-1: evidence for antibody-dependent cellular cytotoxicity in vivo.

Fresh peripheral blood mononuclear cells from human immunodeficiency virus-1 (HIV-1) seropositive donors can lyse target cells expressing the envelope glycoprotein in vitro. In most cases, this antigen-specific lysis is not mediated by T lymphocytes. Lymphoblastoid cell lines infected with recombinant vaccinia viruses expressing different forms of the envelope protein of HIV-1 were used as target cells in chromium-release assays of primary cytotoxic effector cells and of antibody-dependent cellular cytotoxicity (ADCC). By depleting effector cells of CD16+ lymphocytes, or by blocking target cell lysis with an anti-human IgG serum, primary env-specific lysis was found to be due to ADCC, the effector cells being armed in vivo with specific, cytophilic antibodies. This phenomenon is dependent on cell surface expression of the envelope protein and is directed against both gp120 and gp41. Human HIV-1 antibody-positive sera are able to mediate ADCC against HIV-infected CD4+ T lymphocytes, suggesting a possible role of ADCC in the natural infection.

Antibody-Dependent Cell Cytotoxicity↗