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Biomedical subjects

J M Besnier

Publications and source records attributed to J M Besnier.

At least 37 records · Page 2Linked to original sources

Tumorigenesis and metastasis of neoplastic Kaposi's sarcoma cell line in immunodeficient mice blocked by a human pregnancy hormone.

Kaposi's sarcoma (KS) occurs more often in men than in women and HIV-1-associated KS has a high occurrence in homosexual men (over 30%). Most cultures of KS tumours yield cells with properties of hyperplastic (not malignant) endothelial cells under the control of several cytokines. The role of HIV-1 may be in promoting high levels of some cytokines and providing stimulation to angiogenesis by the HIV-1 Tat protein, which synergizes with basic fibroblast growth factor in promoting these effects. Here we describe an immortalized AIDS-KS cell line (KS Y-1) and show that these cells produce malignant metastatic tumours in nude mice and are killed in vitro and in vivo (apparently by apoptosis) by a pregnancy hormone, the beta-chain of human chorionic gonadotropin. Similarly, chorionic gonadotropin kills KS SLK, cells from another neoplastic cell line (established from a non-HIV-associated KS), as well as the hyperplastic KS cells from clinical specimens grown in short-term culture, but does not kill normal endothelial cells. These results provide evidence that KS can evolve into a malignancy and have implications for the hormonal treatment of this tumour.

Acquired Immunodeficiency Syndrome↗

Medical treatment of infective endocarditis: general principles.

The main objective of medical treatment of infective endocarditis is to sterilize the vegetative lesions characteristic of the disease. The general principles of treatment are: (1) identification of the causative organism; (2) in vitro determination of its susceptibility, and (3) the choice of a bactericidal treatment. In vitro susceptibility, the minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC) rate, the level of aminoglycoside resistance and in vitro synergy testing are determined according to the organism. Bactericidal therapy requires a combination of antimicrobials with synergistic activity, generally a cell-wall-active agent and an aminoglycoside. Treatment must be instituted parenterally, to ensure complete bioavailability, high serum concentrations and good penetration into the vegetations. The mode of administration depends on the organism, the serum-half-life and the mode of antimicrobial effect whether time or concentration-dependent, and the post-antibiotic effect (PAE). Cell-wall-active antibiotics (beta-lactams and glycopeptides) with a time-dependent activity require concentrations above MIC for as long as possible between administrations, mainly if there is no PAE; conversely, aminoglycosides or fluoroquinolones with a concentration-dependent activity must be used to obtain a peak-concentration five to ten times the MIC. Therapy must be monitored rigorously. The clinical relevance of serum bactericidal titre is poor owing to lack of standardization and its poor predictive value of failure. The duration of therapy must be sufficient (4-6 weeks) to prevent failure or relapse.

Animals↗

[Acute viral meningitis].

Viral meningitis are the most frequent cause of clear cerebrospinal fluid (CSF) meningitis and are usually benign. The viral nature is suggested by clinical arguments (context, associated manifestations) and particularly the analysis of CSF, typically lymphocytic. However, problems of CSF interpretation may occur during the polymorphonuclear reaction at the beginning of such meningitis and after elevated protein or low glucose concentration. The main differential diagnosis are: partially treated bacterial meningitis, the beginning of meningococcal meningitis, listeriosis or tuberculous meningitis which need and urgent and specific treatment. The most common agents are the enteroviruses. The etiology can only be detected through careful virological investigations. These studies may be useful in outbreaks or in epidemiological studies.

Acute Disease↗

Isolated motor control dysfunction related to progressive multifocal leukoencephalopathy during AIDS with normal MRI.

We describe the case of a human immunodeficiency virus-infected 34-year-old man with progressive multifocal leukoencephalopathy (PML). His case displayed unusual features, including a bizarre movement disorder, predominant involvement of the subcortical U fibers on neuropathologic examination, and the absence of MRI abnormalities suggestive of PML. Anatomic-clinical correlations are discussed.

AIDS Dementia Complex↗

Tamponade due to Rhodococcus equi in acquired immunodeficiency syndrome.

Infection with Rhodococcus equi has been described as a cause of cavitary pneumonia in AIDS patients. We report such a case, complicated by bacteremia, tamponade, and possible brain and liver abscesses. Medical treatment was successful with pericardiocentesis and antibiotherapy with teicoplanin, gentamicin, clarithromycin, rifampicin, supplemented by empirical treatment of cerebral toxoplasmosis. Antibiotherapy was terminated after 6 months, without relapse 2 months later.

AIDS-Related Opportunistic Infections↗

[Pulmonary malacoplakia and Rhodococcus equi pneumonia in a patient infected with the human immunodeficiency virus. A case report with review of the literature].

We report a case of pulmonary malakoplakia in a patient suffering from AIDS secondary to a Rhodococcus equi pneumonia. The association between these two pathologies only occurring in the immunodepressed does not seen fortuitous. Deficiency in cellular immunity and macrophage cellular activity as well as failure of intracellular bactericidal and phagolysosomal function are very probably the links. The treatment of this opportunistic germ rests on prolonged poly-antibiotic therapy or indeed surgical excision.

AIDS-Related Opportunistic Infections↗

Enzyme-linked oligosorbent assay for detection of polymerase chain reaction-amplified human immunodeficiency virus type 1.

An enzyme-linked oligosorbent assay (ELOSA) was developed for the detection on microtiter plates of polymerase chain reaction (PCR)-amplified human immunodeficiency virus type 1 (HIV-1) DNA. The denatured PCR product was hybridized with a passively adsorbed oligonucleotide capture probe and a horseradish peroxidase-labeled oligonucleotide detection probe. The sensitivity and specificity of the PCR-ELOSA technique depended to some extent on the nucleotide sequences of the oligonucleotide primer and probe quartet used in the amplification and detection. We evaluated five oligonucleotide quartets located in the gag, pol, vpr, env, and nef regions of HIV-1. DNAs from 39 HIV-1-seropositive individuals and 27 healthy HIV-1-seronegative controls were amplified by the PCR procedure, and the products were detected by ELOSA. Ten copies of HIV-1 DNA against a background of 1 microgram of human DNA were specifically detected by PCR-ELOSA. Specificities and sensitivities were, respectively, 100 and 95% for the gag system, 100 and 97% for the pol system, 100 and 85% for the vpr system, 96 and 95% for the env system, and 100 and 95% for the nef system. The simplicity of ELOSA makes it suitable for automation and applicable to genetic testing and detection of viral and bacterial DNAs or RNAs in most routine laboratories.

Base Sequence↗

[Situations and procedures with risk of bacterial endocarditis (intracardiac surgery excluded)].

Situations which can be considered at risk for infective endocarditis are those causing a bacteremia, which is necessary for the development of an endocarditis. Such situations can be identified by clinical studies evaluating the rate at which a bacteremia occurs after some procedures or because of lesions, then the risk of endocarditis after such a bacteremia. Without considering preexisting cardiac lesion and age, some situations seem to be at risk of subsequent endocarditis: acute bacterial infection for which antibiotherapy is necessary; procedures involving the mouth with the exception of superficial caries and bloodless supragingival prosthetic preparations; oesophageal dilatation, laser endo-oesophageal procedures, sclerosis of oesophageal varices; colonoscopy and sigmoidoscopy for cancer lesions, gastrointestinal procedures on a potentially infected gastrointestinal tract (cholecystectomy, colectomy...); tonsillectomy and adenoidectomy; naso-tracheal intubation; instrumental procedures involving the ureter or kidney, and prostatic or urinary tract biopsies and surgery; procedures performed on infected skin. In cardiac patients at high risk, in addition to the above retrograde cholangiography, colonoscopy and rectosigmoidoscopy, lithotripsy. In these situations the risk of endocarditis is probably linked to the rate of bacteremia, the size of inoculum, and the bacteria, compared with spontaneous bacteremia without any procedure, where the inoculum is low and bacteria is considered as non pathogenic. A prophylaxis has to be discussed in such situations, which are probably involved in less than 10% of endocarditis.

Adenoidectomy↗

Prevalence and persistence of antibody titers to recombinant HIV-1 core and matrix proteins in HIV-1 infection.

Numerous studies have established the correlation between antibodies to the core protein p24 of HIV-1 and the progression of the acquired immunodeficiency syndrome. In this study, we analyzed the immune response to two recombinant gag proteins, p24 and p17, in order to evaluate their diagnostic or prognostic significance. Immune response to the immunodominant domain of the transmembrane glycoprotein gp41 was used as a reference. Sera collected from individuals from France and Burundi (Central Africa) at various CDC stages of HIV-1 infection were tested using three sandwich enzyme-linked immunoassays developed with a synthetic peptide corresponding to the immunodominant domain of gp41, SP gp41, or recombinant p24 and p17 cloned and expressed in Escherichia coli. These assays allowed detection of titer antibodies to the three cited antigens. Antibodies to SP gp41 were detected in every HIV-1-positive patient from France and Burundi, generally at a high and stable level. Results obtained with p24 confirmed the value of antibodies to p24 as a prognostic marker only in European and North American populations, since the African population had very high levels of these antibodies even at an advanced stage of the disease. They also confirmed that initial antibody response to p24 is more predictive of outcome than antibody titer change over time. Although antibodies to p17 decline during progression to AIDS, they are frequently absent in French patients at early, asymptomatic stages and therefore could not be used as a prognostic marker. In contrast, antibodies to p17 are significantly less common in African patients with AIDS when compared with symptomless HIV-1-infected African individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Characterisation and functional aspects of monoclonal antibodies specific for surface proteins of coagulase-negative staphylococci.

Mouse monoclonal antibodies (MAbs) raised against whole cells of Staphylococcus epidermidis strain 354 were characterised morphologically and functionally. Nine MAbs showed strong reactivity with coagulase-negative staphylococci (CNS). Only two MAbs were specific for CNS; both belonged to the IgG1 subclass, and one, MAb 36.4, reacted only with the strain used for immunisation. In immunoblotting, both CNS-specific MAbs 36.3 and 36.4 reacted strongly with cell-wall protein bands of 220 Kda of S.epidermidis strain 354 and weak reactivity was observed with a 110-Kda band. MAb 36.3 reacted also with 220-230 Kda bands of two other S.epidermidis strains (291 and ATCC 35984) and a 160-180 Kda band of S.epidermidis strain 354. Only MAb 36.4 promoted phagocytosis of strain 354 by polymorphonuclear leucocytes (PMNL) and monocytes, whereas MAb 36.3 and the other MAbs lacked this activity. Opsonisation of S. epidermidis with MAb 36.4 in the presence of complement enhanced uptake by PMNL, but not by monocytes. Furthermore, S.epidermidis strain 354 opsonised with MAb 36.4 induced chemiluminescence of PMNL. Immuno-gold electronmicroscopy with both MAbs 36.3 and 36.4 demonstrated a homogeneous distribution of gold particles on the surface as well as close to the surface of S.epidermidis.

Animals↗

Characterization of a proteinaceous adhesin of Staphylococcus epidermidis which mediates attachment to polystyrene.

Coagulase-negative staphylococci (CoNS) have evolved into important agents of foreign body-related infections. Adhesion of causative bacteria to biomaterials is considered to be an essential step in these infections. We and others have shown that adhesion of CoNS to biomaterials may be mediated by protease-sensitive surface constituents. In the present study we expanded on these investigations by characterizing a biomaterial adhesin of Staphylococcus epidermidis 354 by using a strain-specific monoclonal antibody (MAb 36.4). MAb 36.4 was strongly and exclusively reactive with strain 354 in an enzyme-linked immunosorbent assay in which whole bacteria were used as antigens. Immunoblotting of cell wall polypeptides of strain 354 revealed strong reactivity with a 200- to 220-kDa band and a weaker reaction in the 100- to 110-kDa range. Preincubation of strain 354 with MAb 36.4 resulted in a 54 to 91% (mean +/- standard deviation, 74% +/- 14%; n = 10) inhibition of adhesion to polystyrene spheres. Fab fragments prepared from MAb 36.4 also inhibited adhesion effectively, indicating specific blocking of an adhesion antigen rather than aspecific inhibition. Immunogold electron microscopy with MAb 36.4 revealed deposition of gold particles on the cell surface and possibly also on fimbrialike surface projections. It is concluded that a surface-located protein antigen of S. epidermidis 354 recognized by MAb 36.4 acts as an adhesin mediating attachment to uncoated foreign material. It is speculated that this type of adhesion to biomaterials may play an important role in the pathogenesis of foreign body-related infections caused by CoNS.

Antibodies, Monoclonal↗

Successful treatment of acute fascioliasis with bithionol.

Fascioliasis is the parasitic infestation of the liver and biliary tract related to Fasciola hepatica. Bithionol is proposed as the treatment of choice for human fascioliasis without major side effects. However, the efficacy of bithionol has been evaluated in chronic but not in acute fascioliasis. In this study we report on the success of treatment with bithionol in 10 patients with fascioliasis, 8 having acute fascioliasis. The criteria for the diagnosis of fascioliasis were hypereosinophilia, positive immunoelectrophoresis and indirect hemagglutination. Bithionol was given orally to hospitalized patients at the daily dose of 25 mg/kg body wt for 10 days. Three patients with acute fascioliasis received a second course of bithionol 2 or 3 mo after the first because of the recurrence of diarrhea and fatigue in one patient and persistent hypereosinophilia in two patients. All patients were cured. The follow-up period after the first course of treatment was between 16 and 47 mo. No major side effects were observed. We conclude that bithionol is the drug of choice for both acute and chronic fascioliasis. Moreover, its oral administration may allow treatment of fascioliasis in outpatients who do not have serious symptoms.

Acute Disease↗