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Biomedical subjects

L Belec

Publications and source records attributed to L Belec.

At least 37 records · Page 2Linked to original sources
PubMed1999

Increased Ed-B fibronectin plasma levels in spondyloarthropathies: comparison with rheumatoid arthritis patients and a healthy population.

OBJECTIVE: To determine, for the first time, plasma levels of general fibronectin (Fn) and two spliced isoforms, Ed-A and Ed-B, in patients with spondyloarthropathy (SpA) in comparison with rheumatoid arthritis (RA) patients and healthy volunteers (HV). METHODS: Plasmas (EDTA) as well as clinical data, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were collected in two groups of 10 patients fulfilling the European Spondylarthropathy Study Group criteria for SpA or the 1987 American College of Rheumatology criteria for RA. Plasmas of 21 blood donors served as controls. Plasma levels of Fns were determined by using an in-house immunocapture ELISA, using monoclonal antibodies (MAbs) against general Fn and its isoforms. RESULTS: Total Fn plasma levels were significantly higher in the SpA group (mean+/-S.D.=1387+/-569 mg/l) than in the RA group (684+/-196 mg/l; P=0.02) and in HV (303+/-211 mg/l; P<0.0001). Ed-A Fn levels appeared higher in SpA (23+/-10.4 mg/l) and RA (32.5+/-16.5 mg/l) groups than in the HV group (2.8+/-0.9 mg/l; P=0.0003 and P<0.0001, respectively), without a significant difference between SpA and RA groups. Ed-B Fn levels were higher in SpA (6.9+/-2.1 mg/l) than in RA (3.2+/-1.9 mg/l; P=0. 02) and HV (1.1+/-0.8 mg/l; P=0.0003) groups. No significant correlation was observed in SpA patients between each Fn level and clinical activity, ESR or CRP levels. CONCLUSIONS: This study showed an increase in plasma levels of Fn and Ed-B Fn in SpA patients compared with RA patients and HV, which could not be attributed solely to systemic inflammation. It may be hypothesized that Ed-A and Ed-B Fn might reflect local turnover in inflamed tissues, and that Ed-B Fn might be particularly involved in the musculoskeletal inflammatory process of SpA.

Adult↗
PubMed1999

[Intrathecal synthesis of anti-Toxoplasma gondii antibodies during cerebral toxoplasmosis associated with African AIDS].

Thirty-four HIV-1-infected in-patients of the Hôpital Central des Forces Armées Congolaises, Brazzaville, Congo, hospitalized for suspected cerebral toxoplasmosis, have been evaluated for integrity of the blood-brain barrier, intrathecal synthesis of total IgG, toxoplasmic serology in blood and cerebrospinal fluid, and for intrathecal synthesis of IgG to Toxoplasma gondii. An empiric scale to gauge the possibility of clinical cerebral toxoplasmosis was used to classify the patients (+, +2, +3). Only an intrathecal synthesis of IgG to Toxoplasma gondii was found to be associated with suspected cerebral toxoplamosis: it was found in about 80% of patients, and more frequently in patients with a higher probability of disease. In contrast, alteration of the blood-brain barrier, intrathecal synthesis of total IgG and toxoplasmic serology in blood as well as in cerebrospinal fluid were not associated with suspected cerebral toxoplamosis. Taken together, these findings confirm that intrathecal synthesis of antitoxoplasmic antibodies of IgG isotype occurs in cerebral toxoplasmosis. Demonstration of intrathecal synthesis of antitoxoplasmic IgG antibodies could be used to confirm clinical diagnosis of cerebral toxoplamosis, especially in an African context, where sophisticated laboratory facilities are often lacking.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Discrepant responses to triple combination antiretroviral therapy in advanced HIV disease.

OBJECTIVES: To determine the clinical, virological and immunological outcome in a cohort of unselected patients receiving triple combination therapy for more than 1 year. METHODS: Prospective follow-up of a cohort of 162 unselected, protease inhibitor-naive, antiretroviral-experienced patients with advanced HIV disease, treated with indinavir combined with two nucleoside analogues. RESULTS: The mean CD4 cell count and plasma HIV RNA level in the study group at baseline were 69+/-5 x 10(6)/l and 4.75+/-0.07 log10 copies/ml, respectively. Five per cent of patients died prematurely or were lost to follow-up. Fifty-seven per cent of patients responded to therapy, as assessed by a sustained increase in CD4 cell counts above 50 x 10(6)/l and a decrease in plasma HIV RNA greater than 1 log10 copies/ml, throughout 12.1 months of follow-up. Seventeen per cent of patients were immunological and virological non-responders. Twenty-one per cent of patients exhibited discrepant virological and immunological responses to treatment, of whom one-half failed to exhibit significant increases in CD4 cells despite a virological response to therapy and one-half exhibited increased CD4 cell counts in the absence of significant decrease in plasma viral load. The incidence of AIDS-defining events in the latter group of patients was similar to that of responder patients, whereas their incidence was higher in patients who failed to exhibit a virological and immunological response and those who failed to increase CD4 cells despite a significant decrease in viral load. CONCLUSION: Our observations of discrepant immunological and virological responses to treatment raise the issue of the significance of persistent elevated levels of plasma HIV RNA and of the relevance of measurements of plasma viral load for assessing the efficacy of antiretroviral therapy in patients whose CD4 cell counts increase despite the absence of significant decrease in plasma HIV viral load.

Adult↗
PubMed1998

The sequential occurrence of pol 215 and pol 41 zidovudine resistance mutations is associated in an additive fashion with low CD4 cell counts and high plasma and cellular HIV viral load.

We report on a cross-sectional study of virological and immunological surrogate markers of HIV infection in 115 patients for whom a determination of the pol 215 and pol 41 zidovudine (ZDV) resistance mutations had been described between January 1995 and February 1996. The patients received ZDV alone or a combination of ZDV and zalcitabine or didanosine. A total of 55, 15 and 45 patients exhibited a wild (W), a mixed (MIX) or a mutant (M) genotype at codon pol 215, respectively; 85, 10 and 20 patients exhibited a W, a MIX or a M genotype at codon pol 41, respectively. Patients exhibiting the pol 215 M genotype had lower CD4 cells, higher plasma viral load and higher proviral burden than patients exhibiting the pol 215 W genotype. Patients who had variants exhibiting both pol 215 M and pol 41 M or MIX genotypes had significantly worsened surrogate marker values than patients having variants only carrying the pol 215 M genotype. These observations demonstrate that the two mutations additively associate with pejorative surrogate markers.

Adult↗
PubMed1998

Intracellular neutralization of HIV transcytosis across tight epithelial barriers by anti-HIV envelope protein dIgA or IgM.

Human immunodeficiency virus, generated during contact between HIV-infected cells and the apical surface of an epithelial cell, can cross a tight epithelial barrier by transcytosis. We show that transcytosis of primary HIV isolates is blocked by dimeric IgA or IgM against HIV envelope proteins. Neutralization occurs intracellularly within the apical recycling endosome, and immune complexes are specifically recycled to the mucosal surface. One epitope involved in neutralization is a conserved sequence of the gp41 HIV envelope protein subunit. Finally, transcytosis also occurs across functional human mucosal tissue in a process inhibited by a serosal internalization of IgM against the HIV envelope protein. These results suggest that induction of mucosal immunity to HIV envelope proteins may impair the transcytotic route of HIV mucosal transmission.

Antigen-Antibody Complex↗
PubMed1998

The specificity patterns of human immunoglobulin G antibodies in serum differ from those in autologous secretions.

The specificity patterns of immunoglobulin G (IgG) antibodies to streptococcal antigens in serum and autologous secretions were compared in order to determine whether IgG found in human secretions is exclusively of serum origin or can also be locally produced irrespective of the systemic immune system. Surface antigens from a type 6 M-protein strain of Streptococcus pyogenes were extracted by cell wall digestion and subjected to sodium lauryl sulfate-polyacrylamide gel electrophoresis under reducing conditions. After being blotted onto nitrocellulose, the antigens were incubated with purified IgG from various body fluids: saliva, cervicovaginal secretions, seminal fluid, and colostrum. Binding was then revealed with labeled antibodies to human Fcgamma fragments. The antibody specificity patterns obtained by computer-assisted analysis were compared with those of paired sera. Major variations were observed between serum and secretions, as well as between different secretions from the same subject. These results are in favor of IgG-associated local immunity within different tissue compartments. This IgG response to mucosal antigens can complement that of secretory IgA in the defense against pathogens and should be taken into account during topical vaccinations.

Antibodies, Bacterial↗
PubMed1997

Peripheral neuropathy in human immunodeficiency virus-infected patients with the diffuse infiltrative lymphocytosis syndrome.

A subset of human immunodeficiency virus (HIV)-infected patients develop persistent CD8 hyperlymphocytosis and a Sjogren's syndrome-like syndrome associated with multivisceral CD8 T-cell infiltration, known as the diffuse infiltrative lymphocytosis syndrome (DILS). Patients with DILS tend to have higher CD4 cell counts, fewer opportunistic infections, and longer survival times than other HIV-infected patients. Peripheral nerve involvement in DILS has been poorly documented. We studied 12 HIV-infected patients with CD8 hyperlymphocytosis, DILS, and clinical signs of peripheral neuropathy. Two of 4 patients who were HLA typed were HLA-DR5 and 1 was HLA-DR6. All patients had the sicca syndrome and multivisceral involvement. The neuropathy was acute or subacute, always painful, and symmetrical in 8 cases. Electrophysiology was consistent with axonal neuropathy in 10 of 12 patients. Nerve biopsy showed marked angiocentric CD8 infiltrates without mural necrosis (12 of 12), and abundant expression of HIV p24 protein in macrophages (12 of 12). The HIV genome was detected by polymerase chain reaction in nerve homogenates. Zidovudine therapy was associated with improvement in 6 of 6 patients and steroid therapy was beneficial in 4 of 5 patients. No T-cell lymphoma was observed during follow-up, but 2 patients developed a primary B-cell lymphoma. We conclude that DILS neuropathy represents HIV-associated neuropathy, characterized by marked CD8 infiltration and abundant HIV in nerve, that improves with zidovudine or steroid therapy, and probably reflects a systemic host-determined and antigen-driven response to HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1997

[Overproduction of tumor necrosis factor-alpha in African patients with HIV-1 infection, cachexia and low tri-iodothyronine syndrome].

Sick euthyroid syndrome characterized by low triiodothyronine (T3) levels is observed in advance stages of HIV infection. The purpose of this prospective study was to determine if proinflammatory cytokines play and role in the pathogenesis of this syndrome in HIV-1-infected patients. Serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta were measured in 40 African patients presenting HIV-1 infection associated with low T3 levels in 20 cases (group I) and normal or elevated T3 levels in 20 cases (group II). Elevation of serum TNF-alpha levels was more common and mean serum TNF-alpha level was significantly higher in group I than group II (116 +/- 39 versus 3.05 +/- 0.04 pg/ml; p < 0.01). Serum IL-1 beta levels were not significantly different between the two groups. These findings are consistent with previous experimental data and suggest that sick euthyroid syndrome in cachectic HIV-1 infected patients may be due to overproduction of TNF-alpha.

AIDS-Related Opportunistic Infections↗
PubMed1996

Human T-lymphotropic virus type I excretion and specific antibody response in paired saliva and cervicovaginal secretions.

Paired sera, salivas, and cervicovaginal secretions from 17 HTLV-I-infected women (10-75 years) were evaluated for total IgA, IgG, IgM, for IgA and IgG to whole HTLV-I lysate, for albumin, and for tax-rex proviral HTLV-DNA. IgG to HTLV-I were constantly detected, with much higher titers in serum (mean titer: 97,800) than in saliva (53) or in cervicovaginal secretions (216). IgA to HTLV-I were detected in only 12 (70%) sera, 6 (35%) salivas, and 8 (53%) cervicovaginal secretions, with higher titers in serum (75) than in saliva (8). Using the relative coefficient of excretion by reference to albumin, as well as the comparison of specific activities, the HTLV-I-specific IgG appeared primarily originating from serum, whereas IgA to HTLV-I were primarily locally produced. Salivary synthesis of IgG to HTLV-I occurred in both patients with a sicca syndrome attesting salivary glands impairment. Local excretions of total IgA, IgG, and IgM evaluated in body fluids were normal. HTLV DNA was detected in 4 (24%) salivas and in 3 (20%) cervicovaginal secretions, always in patients demonstrating local synthesis of HTLV-I-specific IgA or IgG. HTLV-I excretion elicits a weak local immune response to HTLV-I in saliva as well as in cervicovaginal secretions, which could be relevant for HTLV-I transmission via body fluids.

Adolescent↗
PubMed1996

All-trans-retinoic acid in POEMS syndrome. Therapeutic effect associated with decreased circulating levels of proinflammatory cytokines.

Chronically elevated serum levels of proinflammatory cytokines is a feature of the syndrome known as POEMS (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal [M] protein, skin changes). A patient had a POEMS syndrome with thrombocytosis and biclonal gammopathy and was treated as follows: all-trans-retinoic acid (tretinoin) at 90 mg/day for 50 days, no treatment for 70 days, readministration of tretinoin at 75 mg/day for 180 days. Focal bone lesion irradiation was performed from day 26 to day 50. Serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), and IL-1 beta normalized within 7 days after the first administration of tretinoin, transiently increased at the time of radiotherapy, increased again after withdrawal of the tretinoin, and decreased again after its reintroduction. The platelet count and gammopathy paralleled the changes in the cytokine levels. This study documents in vivo the ability of all-trans-retinoic acid to down-regulate the release of IL-6, IL-1 beta, and TNF alpha, and illustrates its potential as a therapeutic agent in conditions associated with chronic overproduction of proinflammatory cytokines.

Cytokines↗
PubMed1996

Acute community-acquired bacterial pneumonia in Human Immunodeficiency Virus (HIV) infected and non-HIV-infected adult patients in Cameroon: aetiology and outcome.

SETTING: Yaounde Central Hospital, Jamot Hospital, Yaounde, and CEBEC Hospital in Douala. OBJECTIVE: To determine and compare the bacterial aetiology and outcome of acute community-acquired pneumonia in adult patients with and those without the Human Immunodeficiency Virus (HIV) infection. DESIGN: We studied 110 consecutive adult patients admitted for pneumonia into three hospitals in Cameroon, from November 1991 to December 1992. Blood cultures, sputum microscopy and cultures as well as pneumococcal antigen detection in sera and sputum were performed. Serological analysis for HIV, Mycoplasma pneumoniae, Coxiella burnetti and Chlamydia pneumoniae was also done. RESULTS: Twenty-eight (25.5%) of the 110 patients were HIV positive. Streptococcus pneumoniae was the most common single bacterial aetiology in the two groups. Bacteremia was observed in 12 (15.0%) of 80 patients on whom blood cultures were done and was significantly more common in HIV seropositive than seronegative patients. Mortality was the same in the two groups. CONCLUSION: There were no differences in aetiology and outcome between HIV seropositive and seronegative patients. However, bacteremia occurred more significantly in the HIV seropositive group.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Pro-inflammatory cytokines: a pathogenic key of POEMS syndrome].

The Polyneuropathy, Organomegaly, Endocrinopathy, M protein, Skin changes (POMEMS) syndrome is a rare multisystem disorder of obscure pathogenesis, associated with osteosclerotic myeloma. Unlike multiple myeloma without neuropathy, circulating levels of proinflammatory cytokines (IL-1 beta, TNF-alpha IL-6) are increased in patients with POEMS syndrome. Sites of IL-1 beta production include lymph node and bone marrow tissues. These data support the view that pleiotropic effects of proinflammatory cytokines released secondary to a strong activation of the monocyte/macrophage system, take part in the multisystemic expression of the disease.

Cytokines↗
PubMed1995

Decreased cervicovaginal production of both IgA1 and IgA2 subclasses in women with AIDS.

Paired sera and cervicovaginal secretions from 35 HIV-1-infected women representing different CDC stages of HIV infection were evaluated for total IgA, IgA1 and IgA2, for IgA, IgA1 and IgA2 to gp160, and for albumin. Age-matched healthy women (n = 45) served as controls. The secretion rates of total IgA, IgA1 and IgA2 were evaluated by calculating their relative coefficients of excretion by reference to albumin. In HIV-infected women, total IgA1 and IgA2 in sera and in cervicovaginal secretions increased proportionately as early as stages II + III and more markedly at stage IV. By contrast, the secretion rates of total IgA IgA1 and IgA2 were markedly reduced in AIDS women, the IgA2 secretion rate decreasing significantly as early as stages II + III. This apparent discrepancy was probably the result of increased transudation of serum-borne immunoglobulins into the vaginal cavity, since albumin levels in cervicovaginal secretions increased significantly according to the stages of disease. HIV-reactive IgA antibodies in serum, as in cervicovaginal secretions, were principally found within the IgA1 subclass. In women at stage IV, a high local production of IgA1 to gp160 occurred in spite of the impairment of cervicovaginal IgA synthesis, probably because of marked genital HIV replication at advanced stages.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Seroprevalence of rickettsial infections of the Boutonneuse fever group or its apparent group in Bangui (Central African Republic)].

115 sera from African individuals, including 66 HIV-1-infected individuals and 49 HIV-seronegative age-matched healthy controls, living in Bangui, Central African Republic, were screened for Rickettsia conorii antibody by indirect immunofluorescent assay; 53 (46%) sera had significant IgG to R. conorii titer, and 5 (4.3%) had significant IgM to R. conorii titer, without significant difference between HIV-positive and negative individuals. These findings indicate a great exposure to spotted fever group rickettsial infections in Bangui.

Adult↗