HIV-1 group O sensitivity to antiretroviral drugs.
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Biomedical subjects
Publications and source records attributed to F Simon.
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The prognosis inflammatory and nutritional index (PINI) is a score based on albumin, glycoprotein acid and C-reactive protein levels. PINI was developed to evaluate nutritional and inflammatory status of patients presenting inflammatory syndromes with or without denutrition. In the present study conducted over a period of 6 days in the Pediatric Department of Bambri Hospital in the Central African Republic, we evaluated the usefulness of PINI for follow-up of 25 undernourished Central African children presenting marasmus (n = 15) or kwashiorkor (n = 10) associated with a laboratory documented inflammatory process. All children received nutritional support. We assessed the influence of inflammatory and nutritional factors on PINI values. Data measured in blood samples taken from 16 patients who also presented documented inflammatory manifestations but were not undernourished. A parallel decrease in C-reactive protein and PINI was observed from D0 to D6 and an increase in albumin and prealbumin from D3. There was a positive correlation between C reactive protein values and PINI on D0, D3 and D6. There was no significance difference between PINI and C reactive protein levels in the two study groups. In contrast, a significant difference was observed between albumin and prealbumin. These findings indicate that PINI is of little value for evaluation of inflammatory processes associated with malnutrition. The two main drawbacks of PINI are first that it is more sensitive to the inflammatory than nutritional factors and second that the physical and pharmakinetic parameters used for its calculation are too different.
Nine patients with atypical HIV-1 western blot profiles were diagnosed as having HIV-1 subtype O infection. All the patients were living in France; eight originated from Cameroon and one from France. Lymphocyte DNA amplification by the polymerase chain reaction was only positive when HIV-1 subtype O specific primers were used. Preliminary sequence analysis of amplified products and serological reactivity against a specific subtype O synthetic env peptide confirmed HIV-1 subtype O infection. HIV-1/HIV-2 enzyme-linked immunosorbent assays, especially those based on env peptides or on the sandwich format, can be negative in HIV-1 subtype O infection.
Monoclonal antibodies A33/22 and La11G7 have been used to study the distribution of the corresponding antigens, PwA33 and La, on the lampbrush chromosome loops and nucleoplasmic structures of P. waltl oocytes, using immunofluorescence, confocal laser scanning microscopy and immunogold labeling. The results obtained with these antibodies have been compared with those obtained with the Sm-antigen-specific monoclonal antibody Y12. All these monoclonal antibodies (mAbs) labeled the matrices of the majority of normal loops along their whole length. Nucleoplasmic RNP granules showed a strong staining with the mAbs La11G7 and Y12 throughout their mass, but with the mAb A33/22, they showed only a weak peripheral labeling in the form of patches on their surface. This patchy labeling was confirmed by confocal laser scanning microscopy. Electron microscopy revealed that this patchy labeling might be due to a hitherto undescribed type of submicroscopic granular structure, around 100 nm in either dimension, formed by 10-nm particles. Such granules were observed either attached to the RNP granules or free in the nucleoplasm, but rarely in relation with the normal loop matrices. These 100-nm granules may have a role in the movement of proteins and snRNPs inside the oocyte nuclei for storage, recycling, and/or degradation. Our results also suggest that all the microscopically visible free RNP granules of the nucleoplasm of P. waltl oocytes correspond to B snurposomes. The granules forming the B (globular) loops showed a labeling pattern similar to that of B snurposomes; their possible relationship is discussed.
We report the clinical and biological course of infection with human immunodeficiency virus (HIV) type 1 in 11 liver transplant recipients who acquired this infection between 1985 and 1987. Eight patients were infected by blood or blood products from graft-related transfusions and one by the graft itself; the remaining two patients were infected after transplantation and had independent risk factors. All patients received a triple-drug immunosuppressive regimen including cyclosporine. The mean duration of follow-up after liver transplantation was 52 months (standard error, +/- 32 months). Chronic graft rejection was documented in four cases. The cumulative incidences of HIV-related complications and HIV-related deaths were 82% and 27%, respectively. Three patients died rapidly of HIV disease. The survival rate 7 years after transplantation was 36% among the 11 HIV-infected patients, whereas it was approximately 70% among HIV-negative liver transplant recipients during the same period. The course of HIV infection in the four survivors did not appear to differ from that in other patients infected by blood transfusion.
OBJECTIVE: To determine plasma cytokine levels [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6] in African patients infected with HIV-2 relative to values in HIV-1-infected patients, and their relation to immunologic and clinical status. DESIGN: Questions about the observed differences in the pathogenesis of HIV-2 and HIV-1 remain unanswered. Cytokines, especially TNF-alpha, are involved in the regulation of HIV-1 replication, and can be found in the plasma of HIV-1-infected individuals. Therefore, we evaluated TNF-alpha, IL-1 beta and IL-6 levels in the plasma of African patients with different stages of HIV-2 disease. This was a 3-year prospective follow-up study. METHODS: Cytokine plasma levels were assayed in 40 HIV-2- and 51 HIV-1-infected patients from Africa. Nineteen of the 40 HIV-2-infected-patients underwent serial assays every 4 months for 3 years. Data were analysed in relation to the number of CD4+ and CD8+ cells, viral load and clinical status. RESULTS: Plasma levels of TNF-alpha and IL-1 beta were significantly higher in all the HIV-1- and HIV-2-infected patients than in healthy controls; IL-6 levels were around the detection limit for all patients. TNF-alpha levels were lower in the HIV-2-infected than in the HIV-1-infected patients at all Centers for Disease Control and Prevention (CDC) disease stages, including the asymptomatic phase. The CD4+ cell count was always higher in the HIV-2-infected patients, regardless of CDC stage. The prospective follow-up showed that TNF-alpha levels remained stable during the course of HIV-2 disease, as did the CD4+ cell count and virus load. CONCLUSION: Lower and stable plasma TNF-alpha levels in African patients infected with HIV-2, associated with lower viral load and higher CD4+ cell count, suggests the existence of a more appropriate and efficient immune response to HIV-2 than to HIV-1.
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The authors report a case of disseminated African histoplasmosis with bone and joint involvement in a black 28-year-old citizen of the Central African Republic who presented with a 17-month history of multiple osteoarticular lesions (sternoclavicular joints, humerus, ribs), cutaneous lesions (face, scalp, thorax), and lymphadenopathy. Clinical manifestations resolved rapidly under treatment with ketoconazole (600 mg/d for 10 days then 400 mg/day for nine months). Persistent yeast cells were then found upon examination of a lymph node biopsy specimen. The characteristics and diagnosis of osteoarticular lesions due to African histoplasmosis are discussed on the basis of a review of the literature. Bone and joint lesions due to African histoplasmosis have not yet been reported in patients with the acquired immunodeficiency syndrome. However, the expanding epidemic of human immunodeficiency virus infection in Africa can be expected to result in an increase in the incidence of African histoplasmosis. Imidazole derivatives are easier to use on a long-term basis than amphotericin B and have significantly improved our ability to treat African histoplasmosis.
One case of aortoesophageal fistula is presented. This pathology is rare: most of aortoenteric fistulas are in the duodenojujunum. Clinical presentation is rarely as clear as the Chiari triad describes it: mild thoracic pain, sentinel arterial hemorrhage and exsanguination. Esophagoscopy, computed tomography and arteriography are helpful for diagnosis. Issue is fatal without surgery but patients are often too old to tolerate it.
On the African continent, rhinophycomycosis entomophtorae, a deep mycosis due to Conidiobolus coranatus, has been encountered mainly in wet forest areas. Only one case, which involved a Tchadian, has been reported in a dry zone. The present report describes a case observed in a 30-year-old Somalian, who lived all his life in the rural zone of Dinsoor where the climate is hot (temperature between 22 degrees C and 30 degrees C) and dry (annual rainfall less than 400 mm). In this patient, diagnosis was based on the presence of a characteristic bifocal deformation of the central region of the face and on histological findings typical of rhinophycomycosis entomophtorae. This case underlines the fact that this deep mycosis can occur outside of wet forest areas in Africa. Thus practitioners should not rule this diagnosis out simply on the basis of climatic conditions.
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The stable expression of the human cytochrome CYP2E1 (P450 alcohol) was performed in the mammalian cell line PC-12. This cell line expressed cytochrome b5 (58 +/- 12 pmol/mg microsomal protein vs 528 +/- 80 pmol/mg in microsomal human liver) and a high level of NADPH: cytochrome P450 reductase (140 +/- 20 nmol.min-1.mg microsomal protein-1 vs 68 +/- 48 nmol.min-1.mg-1 in microsomal human liver). An expression plasmid was constructed using the cDNA for the human CYP2E1 mRNA and the Rous sarcoma virus (RSV) promoter. This plasmid was co-transfected with the plasmid RSVneo into PC-12 cells. Clones were selected for resistance to the neomycin analog, G418, and then screened for expression of the CYP2E1 isozyme by testing for 6-hydroxylation of chlorzoxazone, a specific substrate for CYP2E1. Expression of CYP2E1 was confirmed in one clone, DB-7, by Western blot analysis and by measurement of monooxygenase activities which were not detectable in PC-12 cells. Chlorzoxazone 6-hydroxylation, n-butanol oxidation and dimethylnitrosamine N-demethylation were localized in microsomes (62, 60 and 63 pmol.min-1.mg microsomal protein-1, respectively) and were inhibited by carbon monoxide and diethyldithiocarbamate, both inhibitors of P450 enzymes. Although the level of the enzyme activities was about a tenth of that measured in human liver microsomes, CYP2E1 expressed in DB-7 cells has catalytic competence similar to human liver CYP2E1. DB-7 cells metabolized acetaminophen and this metabolic activation was shown to be toxic to these cells by release of lactate dehydrogenase. Construction of recombinant cell lines expressing CYP2E1 provides a useful tool for studying the catalytic properties of this enzyme and the consequent cytotoxic effects of substrates metabolized by this enzyme.
OBJECTIVE: To determine circulating viral load in HIV-2-infected individuals. METHODS: Viral load was determined in 40 HIV-2-infected adults using standardized quantitative cell and qualitative plasma viraemia assays. We also tested for proviral HIV-2 DNA using single and nested polymerase chain reaction (PCR) in fresh lymphocytes from 27 subjects. The results were compared, on the basis of the CD4+ lymphocyte count, with our published data for HIV-1 infection. RESULTS: HIV-2 was isolated from peripheral blood mononuclear cells (PBMC) from 19 individuals and plasma from four patients. The rate of cell and plasma viraemia positivity correlated with the CD4+ cell count and HIV-2 virus load increased as the CD4+ cell count fell. The cellular HIV-2 load in the patients with a CD4+ count < 200 x 10(6)/l was similar to reported values for HIV-1, but the HIV-2 isolation rate from the plasma of these individuals was significantly lower than for HIV-1. When the CD4+ count was between 200 and 500 x 10(6)/l, the rate of HIV-2 isolation from plasma and the cellular virus load were both significantly lower than for HIV-1. When the CD4+ count was > 500 x 10(6)/l, HIV-1 and HIV-2 were undetectable in plasma and HIV-1 was isolated from PBMC in significantly more cases than HIV-2. By single PCR, amplification were positive in 14 out of 27 subjects and there was a correlation between positivity and CD4+ cell count. By nested PCR, only four of the 27 subjects, all with a high CD4+ count, remained negative. CONCLUSIONS: Differences in viral load between individuals infected with HIV-2 and those infected with HIV-1 could partly account for reported differences in the pathogenicity of the two viruses.
Comparison of the original edition of anatomical nomenclature published in 1955 with its revised version dating from 1965, 1975 and 1985 confirmed the distinct trend of preferring the concordant attribute over the nonconcordant one in the later editions, i.e. adjectives rather than the genitive. Some changes, however, defy explanation and neither can the further development be predicted. The author considers it as unfavorable that the unwritten rule on using the adjective or the genitive in expressing localization in anatomical nomenclature is being abolished. (Ref. 9).