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Biomedical subjects

M Mojon

Publications and source records attributed to M Mojon.

At least 19 recordsLinked to original sources

Detection of Pneumocystis carinii DNA by PCR amplification in various rat organs in experimental pneumocystosis.

Pneumocystosis is usually a disease of the lungs, but the number of cases of extrapulmonary pneumocystosis has greatly increased during the AIDS epidemic. Much remains unknown about the frequency and mechanisms of dissemination. In the present study, a systematic search for Pneumocystis carinii by PCR with primers specific for mitochondrial rRNA was performed in the lung, liver, spleen and kidney of 12 immunosuppressed rats and two immunocompetent rats. The amplified products were analysed by Southern hybridisation with a digoxigenin-11-dUTP labeled probe. P. carinii DNA was found in lungs in all 14 rats and in at least one organ other than lung in 11 immunosuppressed rats and the two control rats. We suggest that extrapulmonary dissemination may not be an exceptional phenomenon in the course of pneumocystosis, but rather part of the natural evolution of the disease.

Animals↗

Enterocytozoon bieneusi as a cause of chronic diarrhea in a heart-lung transplant recipient who was seronegative for human immunodeficiency virus.

Enterocytozoon bieneusi is a major cause of chronic diarrhea and malabsorption in patients with AIDS. We report what we believe is the first case of intestinal infection due to E. bieneusi in a heart-lung transplant recipient who was seronegative for human immunodeficiency virus (HIV). The clinical presentation and the evolution of the disease were identical to those usually observed in patients with AIDS and included diarrhea, massive weight loss, and persistent infection despite treatment with albendazole. E. bieneusi was identified in the patient's duodenal mucosa by electron microscopy. No other etiologic agent was detected. We conclude that E. bieneusi may be responsible for serious intestinal infections in patients whose immunosuppression is not related to HIV.

Animals↗

Inhibition of human peripheral blood mononuclear cell proliferative response by glycosphingolipids from metacestodes of Echinococcus multilocularis.

The effect on human peripheral blood mononuclear cells (PBMCs) of neutral glycosphingolipids extracted from metacestodes of the parasite Echinococcus multilocularis was investigated. Neutral glycosphingolipids inhibited [3H]thymidine uptake by human PBMCs upon stimulation by mitogens such as phytohemagglutinin A and pokeweed mitogen or by allogeneic Burkitt B cells. This effect was dose dependent and was related to a decrease in interleukin 2 (IL-2) synthesis, the expression of IL-2 receptors (CD25) being unmodified. Addition of exogenous recombinant IL-2 restored the cell proliferation. Partial inhibition of immunoglobulin G (IgG), IgA, and IgM synthesis was observed in the supernatant of cell culture in association with the inhibitory effect. Identification of active subfractions contained in the neutral glycosphingolipid fraction was also studied in relation to cell viability. The free ceramide fraction had an inhibitory effect, in part related to cell lysis, particularly at high concentration, while the monogalactosylceramides had a paradoxical effect: as an activator at low concentrations and as an inhibitor at high concentrations, with limited cell survival. The immunogenic neutral glycosphingolipids containing at least two carbohydrate residues, all having a structure based on Gal beta 1-->6Gal, were inhibitors of PBMC proliferation and showed good cell survival. These results suggest that parasite neutral glycosphingolipids may play an immunologically relevant role in alveolar hydatid disease.

Animals↗

Free ceramides of Echinococcus multilocularis metacestodes.

Free ceramides were isolated and purified from the metacestodes of Echinococcus multilocularis. Two different fractions were obtained by preparative thin-layer chromatography. Their structure was determined by gas chromatography and electron impact mass spectrometry of trimethylsilylated derivatives. The ceramide with the higher thin-layer chromatographic migration rate contained exclusively erythro-sphinganine associated with saturated C16, C18 and very-long-chain fatty acids (up to C30) and unsaturated C24 fatty acid. The second ceramide contained 90.3% sphingosine and 9.7% sphinganine associated with saturated C16 and C24 and unsaturated C18 and C24 fatty acids. These findings were discussed with regard to the structure and metabolic pathway of neutral and acid glycosphingolipids found in the metacestodes.

Animals↗

[Halofantrine: for new rules of prescription].

Halofantrine is an antimalarial drug widely prescribed for chloroquine-resistant strains of Plasmodium falciparum. It has been recognized to cause serious deleterious effects which have dampened early enthusiasm for this compound. Basically, the adverse effects involve lengthening of the QTc interval, torsade de pointes and induction of late ventricular potentials. These side effects are related to the quinidine-like effect of the drug which has a chemical structure similar to quinine and quinidinic drugs. More recently, severe haemolytic accidents have been reported suggesting an autoimmunization mechanism. These side effects imply new rules for prescription and more prudent use of halofantrine, especially for prophylaxic therapy against malarial attacks in travellers.

Antimalarials↗

Good immunogenicity of GBM strain inactivated hepatitis A vaccine in healthy male adults.

A formalin-inactivated aluminium hydroxide adsorbed hepatitis A vaccine was evaluated in a dose-response study on 195 healthy male adults (age range: 18-31 years) in two French hospitals (Lyon, Rouen). Four doses (20, 40, 80, 160 RIA antigen units) were administered intramuscularly (i.m.) in two injections over a 6-month period. At the time of the first vaccine injection, 32 subjects (16.4%) were found positive (> 20 mIU ml-1) for HAV antibody (total Ig RIA HAVAB assay, Abbott Laboratories) and were excluded from the analysis of immunogenicity criteria. Fourteen days after the first vaccine injection, 78.1% (95% confidence interval (CI): 62-90) of seronegative subjects who received the 160 RIA antigen unit dose seroconverted with a geometric mean titre (GMT) of 43 mIU ml-1 (95% CI: 33-56). Seroconversion was 100% (95% CI: 91-100) at 1 month with a GMT of 95 mIU ml-1 (95% CI: 79-112). Statistical analysis revealed a significant dose-related effect (p < 0.0001) on GMT by multivariate regression analysis of the results after the first injection. Biological safety was evaluated and alanine aminotransferase and aspartate aminotransferase levels were similar prior to and 14 days after the first injection in the four groups. Reactions after injection were similar in the four dosage groups: 6.2% of subjects reported immediate reactions after first vaccination (feeling sick, spontaneous pain, headache), 8.9% reported local reactions at the site of injection (spontaneous pain, haematoma, local adenopathy) and 13.5% reported general reactions ('flu-like' syndrome, gastrointestinal tract disorders, fatigue, headache).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Congenital toxoplasmosis, evaluation of the prevention policy].

OBJECTIVES: This study was performed to assess the effect of a prevention programme against congenital toxoplasmosis conducted as part of the French health policy developed in the Rhône department. METHODS: A descriptive epidemiological survey was conducted in 1991 including 806 post-partum women who were hospitalized in 22 maternities in the Rhône department. RESULTS: Forty-nine percent of the women had negative serology tests. French legislation requiring detecting non-immunized women at diagnosis of pregnancy was applied satisfactorily by the attending physicians. Inversely, women at risk were insufficiently informed: only 17% of the women at risk were aware of the three main routes of contamination; 63% believed vaccination is possible and 11% though they had been vaccinated. Deficient information was probably the cause of poor compliance to preventive measures as observed in this sample: only 17% of the serologically negative women stated they had applied anti-toxoplasmosis prophylaxy measures. CONCLUSION: Women at risk must be informed to convince them to modify their behaviour during pregnancy. The role of the attending physician and biologist is of major importance.

Adult↗

Gangliosides of Echinococcus multilocularis metacestodes.

Gangliosides, glycosphingolipids with sialic acid, were found in metacestodes of Echinococcus multilocularis in low quantities. All gangliosides were resolved after preparative high-performance thin layer chromatography into four fractions. Cholera toxin was specifically bound to the major ganglioside, allowing the identification of it as a GM1. Precise structure of the four fractions was determined by sequential degradation by exoglycosidases, gas chromatography, electron impact mass spectrometry and liquid secondary ion-mass spectrometry. Beside GM1, the other fractions were GM3, GD1a and, at a lesser percentage, GM2, all belonging to the same a-ganglio-series. The ceramide part of these parasite gangliosides contained sphingosine associated to unsaturated n24, saturated n24 and n16 fatty acids.

Animals↗

Fusarium infections in immunocompromised patients: case reports and literature review.

Five cases are reported of Fusarium infection in patients with aplasia following chemotherapy of leukemia. The clinical signs, diagnosis and course of the infection during treatment are outlined and discussed in conjunction with the characteristics of other cases already reported in the literature. Sixty-three cases of Fusarium infection have been reported in immunocompromised patients, 44 cases since 1985. These included patients with hematological malignancies (58 cases), especially acute leukemia (43 cases). The main sites of infection were the skin (46 cases), blood (28 cases) and lungs (13 cases). The infection was mostly diagnosed by means of skin biopsy but also by means of positive blood cultures. Forty-three strains were identified, 19 of which were Fusarium solani. Amphotericin B treatment was given in 55 cases, often combined with other antifungal agents, leukocyte transfusions or granulocyte-macrophage-colony stimulating factor. The outcome was fatal in 36 of the 63 cases reported, often due to resistance of the strain to antifungal agents, particularly amphotericin B (20 of 33 strains tested). The most important risk factor seems to be profound and prolonged aplasia. Deep mycoses due to Fusarium species thus pose an important problem and are occurring in increasing numbers in immunocompromised patients. Treatment of these infections is difficult and the prognosis is poor.

Adult↗

[Human angiostrongyliasis caused by Angiostrongylus costaricensis].

Angiostrongylus costaricensis was discovered by Morera and Céspedes in 1971, in a man suffering from an abdominal syndrome. Upon surgery, worms were observed in the cranial mesenteric artery. These worms were assigned to the metastrongylid strongyles and to the genus Angiostrongylus, which was already known, in man medicine, by the species A. cantonensis, the causative agent of an eosinophilic meningitis. Morera's parasite was named Angiostrongylus costaricensis from the place where it was described. A costaricensis is a dixenic parasite, the definitive hosts (D.H.) of which are the cotton-rat (Sigmodon hispidus) and some other rodents. Experimentally, carnivora (Nasua spp: procyonidae) and monkeys (Saguinus mystax: hapalidae) are receptive, same as dogs. The intermediary hosts (I.H.) are slugs belonging to the Veronicellidae family (order gymnophila), mainly Vaginulus plebeius. In the D.H., the parasite produces eggs that hatch into first stage larvae (L1), which are expelled with faeces, eaten by slugs and become infective third stage larvae (L3). L3 are then expelled through mucoïd secretions of the slug and pollute soil and vegetables. D.H. and man get infected with consuming polluted vegetables or even the infected slugs themselves. L3 migrate through lymphatic system and arrive inside the mesenteric artery, where they become adults. In man, the worm can reach this adult egg-laying stage, but larvae are trapped inside granulomas in the intestinal wall and cannot evolve. So, man is a dead-lock for A. costaricensis. Angiostrongylosis costaricensis is an illustration of an hemi-zoonosis (the parasite cannot go back from man to animals) of the biological pattern.

Angiostrongylus↗

Prevalence of intestinal protozoans in French patients infected with HIV.

To assess the prevalence of intestinal protozoans in French HIV-infected patients, stool samples, duodenojejunal biopsies, and/or colorectal biopsies from 81 patients were studied for parasites, viruses, and bacteria. Pathogens were found in 70.6% of AIDS patients with diarrhea or malabsorption. The respective prevalence of protozoa in AIDS patients with diarrhea was Cryptosporidium sp.: 37.3%, Blastocystis hominis: 13.7%, Giardia intestinalis: 5.8%, Isospora belli: 2%, Enterocytozoon bieneusi: 2%. Microsporidia were noted in one patient with severe malabsorption but no diarrhea. Other pathogens included cytomegalovirus in 27.4% and Mycobacterium avium in 5.8%. Patients with identified pathogens were more immunosuppressed and more severely malnourished than those with unexplained diarrhea. Multiple pathogens were found in 13 of 81 patients (16%). Twenty-six of 66 identified pathogens (40%) were diagnosed only on biopsy specimens. Chronic diarrhea in HIV patients could be explained in the vast majority by appropriate gastrointestinal investigations. Cryptosporidia played a major role, while microsporidia appeared to be less common.

Acquired Immunodeficiency Syndrome↗

Glycosphingolipids with Gal beta 1----6Gal sequences in metacestodes of the parasite Echinococcus multilocularis.

Neutral glycosphingolipids of the metacestodes of Echinococcus multilocularis, an animal and human parasite, were resolved by high performance thin layer chromatography into 12 fractions. Nine of these fractions were permethylated, analyzed by electron impact-mass spectrometry, and submitted to methylation analysis by gas chromatography-mass spectrometry. Native fractions were analyzed by liquid secondary ion-mass spectrometry and degraded sequentially by exoglycosidases. In addition to a previously described galactosylceramide, a di-, a tri-, and a tetragalactosyl-ceramide having Gal beta 1-6Gal internal linkages were characterized. This type of carbohydrate chain has been described in glycolipids of a marine mollusk, Turbo cornutus (Matsubara, T., and Hayashi, A. (1981) J. Biochem. (Tokyo), 89, 645-650). In addition two novel fucolipids were found with the following structures: Fuc alpha 1-3Gal beta 1-6Gal-Cer and Gal beta 1-6(Fuc alpha 1-3)Gal beta 1-6Gal-Cer. Ceramides contained sphinganine and either nonhydroxy fatty acids with 16, 18, 26, and 28 carbon atoms, or hydroxy fatty acids, with 16 and 18 carbon atoms. Di-, tri-, and tetragalactosylceramides containing the Gal beta 1-6Gal disaccharide were found to be immunogenic in humans.

Animals↗

Production and characterization of monoclonal antibodies to human Pneumocystis carinii for the diagnosis of P. carinii pneumonia.

OBJECTIVES: Monoclonal antibodies against human Pneumocystis carinii were produced by fusion of myeloma cells (X63-AG8.653) with splenocytes from Biozzi mice that had been immunized against P. carinii cysts isolated from infected human lung. The aim of this study was to evaluate the usefulness of these monoclonal antibodies for the diagnosis of P. carinii pneumonia by indirect immunofluorescence in comparison with a modified silver stain method and commercial kits. METHODS: One hundred fifty-seven specimens from 87 patients, infected or non-infected with human immunodeficiency virus, were examined for the presence of P. carinii. Specimens were either induced sputum samples or bronchoalveolar lavage fluids. Indirect immunofluorescence was performed with six stable clones obtained by limiting dilution. Four of the monoclonal antibodies were IgG1 isotypes, one was an IgG3 and one was an IgM. Their isoelectric points varied from 6.5 to 8.3. Tests were also performed with silver methenamine staining and with two commercially available monoclonal antibodies (Monofluo kit from Diagnostics Pasteur and MAb from Dako). RESULTS: The 6 antibodies all recognized P. carinii cysts in indirect immunofluorescence. No cross reactivity was observed with yeast or host cells. P. carinii antigens could not be identified with western immunoblotting suggesting that the monoclonal antibodies recognized native antigens. This result was confirmed by dot blot analysis. Spots were observed with native but not with denatured antigens. Inhibition studies showed that these 6 antibodies recognized the same or overlapping sites. The sensitivities of detection of P. carinii in sputum were 87% by silver stain and from 93.5 to 96.7% by immunofluorescence. The sensitivities of detection in bronchoalveolar lavage were 67.3% by silver stain and from 75.7% to 76.8% by immunofluorescence. CONCLUSION: Immunofluorescence was more sensitive than silver staining and the best results were obtained with E5-8 and A8-13 monoclonal antibodies and with Monofluo kit.

Animals↗

Detection of antibodies against glycolipids of Echinococcus multilocularis metacestodes in sera of patients with alveolar hydatid disease.

Glycosphingolipids extracted from Echinococcus multilocularis metacestodes were tested against sera from patients with alveolar hydatid disease (AHD). The tests were performed first by ELISA then by immunostaining on thin layer chromatography. A binding between the parasite glycolipids and antibodies of AHD human sera was observed by ELISA. The glycolipids related to this binding were specifically parasite neutral glycosphingolipids. No reaction was observed with parasite acid glycolipids nor with neutral glycolipid extracts from human or mongolian gerbil erythrocytes. Comparison between absorbance values of 25 AHD sera and 20 control sera showed significant differences. Similar results were obtained with sera from hydatid cyst patients. Sera from patients with other parasitoses (schistosomiasis, strongyloidosis or paludism) were also tested. The reactive fractions were identified by immunostaining on thin layer chromatography with AHD sera, they were neutral glycosphingolipids containing at least two carbohydrate residues. These results were compared with chromatograms obtained with hydatid cyst human sera and discussed.

Animals↗

Glycosphingolipids of Echinococcus multilocularis metacestodes.

Neutral and acid glycosphingolipids of Echinococcus multilocularis metacestodes that were obtained after intraperitoneal infection of Meriones unguiculatus have been analyzed by thin layer chromatography. Neutral and acid glycosphingolipids accounted for 95% and 5% of total glycosphingolipids, respectively. 12 different fractions were observed in the neutral glycosphingolipids extracts of the parasite. The most important was a monohexosylceramide fraction accounting for 56.4% of neutral glycosphingolipids. 9 different fractions were detected in gangliosides (acid glycosphingolipids). The fact that these glycosphingolipids were specific to the parasite was established by the analysis of different cell populations of the host. Glycosphingolipids were purified from control and parasite-infected gerbil blood cells as well as from peritoneal exudate cells of healthy gerbils after a non-specific immunostimulation. The chromatograms obtained with these extracts were totally different from the parasite. In addition, parasitosis was found to have no effect on the host blood cell glycosphingolipids.

Animals↗