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Biomedical subjects

C Olivier

Publications and source records attributed to C Olivier.

At least 19 recordsLinked to original sources

Multiple restricted origin of oligodendrocytes.

The plp gene encodes the proteolipid protein and its alternatively spliced product DM-20, major proteins of CNS myelin. In the mouse, plp/dm-20 transcripts are expressed beginning at embryonic day 9.5 (E9.5) by restricted foci of germinative neuroepithelial cells. To determine the identity of the neural precursors expressing plp/dm- 20, a zeomycin resistance gene fused to the lacZ reporter was expressed in transgenic mice under the control of the plp regulatory sequences. In the three different lines generated, the pattern of beta-galactosidase expression was similar and superimposable on the expression pattern of endogenous plp/dm-20. Both in vivo and in vitro, the transgene was expressed by O4(+) pre-oligodendrocytes, and later by RIP+ differentiated oligodendrocytes, but not by neuronal cells, astrocytes, or radial glial cells. After zeomycin selection, a dramatic enrichment in O4(+) pre-oligodendrocytes was observed in cultures derived from E12.5 transgenic embryos. This enrichment indicates the oligodendroglial specification of neural precursors that continuously express plp/dm-20. Early plp/dm-20-expressing precursors, however, appear to be a separate population from previously described PDGFRalpha oligodendrocyte precursors, as shown by the striking differences in their (1) patterns of distribution and (2) responsiveness to PDGF. These data suggest that oligodendrocytes have a plural origin and that early plp/dm-20 defines one of the neural lineages generating oligodendrocytes.

Animals

Signaling of type II oncostatin M receptor.

Oncostatin M (OSM) mediates its bioactivities through two different heterodimer receptors. They both involve the gp130-transducing receptor, which dimerizes with either leukemia inhibitory receptor beta or with OSM receptor beta (OSMRbeta) to generate, respectively, type I and type II OSM receptors. Co-precipitation of gp130-associated proteins, flow cytometry, polymerase chain reaction, and tyrosine phosphorylation analyses allowed the characterization of both types of OSM receptors expressed on the surface of different cell lines. It also allowed the detection of a large size protein, p250, that specifically associates to the type II OSM receptor components and that is tyrosine-phosphorylated after the activation peak of the gp130.OSMRbeta heterocomplex. The restricted expression of type I OSM receptor by the JAR choriocarcinoma cell line, and type II receptor by the A375 melanoma cell line, permitted the characterization of their signaling machineries. Both type I and type II OSM receptors activated Jak1, Jak2, and Tyk2 receptor-associated tyrosine kinases. The information is next relayed to the nucleus by the STAT3 transcriptional activator, which is recruited by both types of OSM receptors. In addition, STAT5b was specifically activated through the gp130.OSMRbeta type II heterocomplex. The signaling pathway differences observed between the common type I LIF/OSM receptor and the specific type II OSM receptor might explain some of the bioactivities specifically displayed by OSM.

Animals

[Syncope with long QT interval in a 39 day-old infant treated with cisapride].

UNLABELLED: Cardiotoxicity of cisapride may increase when this drug is associated with ranitidine. CASE REPORT: A 37-day old term infant, treated with cisapride (1.2 mg/kg/d) and ranitidine for regurgitations, was hospitalized for malaise. A prolonged QT interval (with isolate ventricular extrasystoles), noted at admission, disappeared rapidly after cisapride withdrawal. Linkage to cisapride was probable, promoted by high dosage and cisapride metabolism inhibition by ranitidine, but its plasma concentration was not measured. CONCLUSION: This case report stresses the problem of cisapride dosage in infants and the question of an interaction between cisapride and ranitidine.

Anti-Ulcer Agents

Prophylactic intracavitary treatment with interferon alpha increases interferon gamma production by peripheral blood mononuclear cells in patients with superficial transitional cell carcinoma of the bladder.

The immunomodulatory effect of prophylactic intravesical instillations of interferon alpha 2b (IFN-alpha-2b) on interferon gamma (IFN-gamma) and interleukin 4 (IL-4) production by peripheral blood mononuclear cells (PBMCs) from patients with superficial transitional cell carcinoma (STCC) of the bladder has been analysed. There were no significant differences in the production of IFN-gamma and IL-4 by PBMCs from untreated patients and healthy control subjects after 24 h of phytohaemagglutinin (PHA) stimulation. However, between 3 and 6 months after finishing the prophylactic intracavitary treatment with IFN-alpha-2b, PHA-stimulated PBMCs from patients with STCC of the bladder showed a significantly enhanced production of IFN-gamma and a significantly decreased production of IL-4. Both IFN-gamma and IL-4 returned to pretreatment levels 1 year after ending the treatment. In conclusion, prophylactic intravesical instillations of IFN-alpha-2b in patients with STCC of the bladder have an immunoregulatory effect on the production of IFN-gamma and IL-4 by PBMCs.

Adjuvants, Immunologic

[Pulmonary manifestations of tuberculosis in children].

The occurrence of tuberculosis in children is dependent on a contagious bacillus carrying adult. Among 500 cases notified annually, perhaps 5 or 6% of the total infectious reservoir in France, 75% have parenchymal pulmonary disease and/or lymph nodes. These tuberculous diseases only represent 10% of the pulmonary disorders: 90% remain primary infections (PI active) or latent infections. These are most often asymptomatic (PI Latent) or of low grade activity (PI active). The CT scanner and fibreoptic bronchoscopy are indispensable complementary investigations in tuberculous disease. Whatever the clinical picture the diagnosis rests on bacteriological confirmation (but only 30% of cultures are positive) and most often rests on a body of evidence: for example a contagious adult living in proximity or a contagious family, or other risk factors are present. The evidence of a child with whatever form of pulmonary tuberculosis, even a latent primary infection, requires treatment which is adapted in such a way to enable a cure and to protect against subsequent endogenous re-activation. A coherent system of co-operation between the hospital and community service and between paediatricians and adult physicians is indispensable to find the index adult case to break the chain of contagion. There are two specific aspects in children, first congenital tuberculosis when a diagnosis is difficult and secondly tuberculosis in a child who is HIV positive when the management can be delicate.

AIDS-Related Opportunistic Infections

[Traveling with small children].

Traveling with children especially in the tropics requires special planning. Contraindications are rare but care providers should obtain information about medical and transfusional facilities at the destination. Children should receive all vaccinations required for international travel and for specific countries, taking into account age, location, duration of stay, and purpose of trip. A first aid kit should be packed containing a thermometer, bandages, antiseptic agents, a total sunscreen preparation, a mosquito net, sterile compresses, tablets for water disinfection, and indispensable medications (antimalarial agents, antipyretics, oral rehydration solutions, antiemetics, and eye wash). The main indication for chemoprophylaxis is malaria. Chloroquine is recommended for most locations but proguanil may be necessary in areas of resistance. Special attention must be paid to skin care in infants: maintaining cleanliness, avoiding cuts insofar as possible, and treating any wounds. Clothing must be carefully laundered and adequate to prevent overexposure to sunlight and insect bites. Insect bites must also be prevented by applying repellents, using mosquito nets, and wearing insecticide-treated garments. Handwashing by people who prepare meals and by the children before eating is important to prevent food poisoning. Breast feeding is advisable for infants. Thorough cooking of meats, rinsing of fresh produce, drinking of bottled beverages, and sterilization of water are also important food safety measures. These precautions are usually adequate to allow safe travel with children.

Child

Alanine substitution for Thr268 and Asp269 of soluble ciliary neurotrophic factor (CNTF) receptor alpha component defines a specific antagonist for the CNTF response.

Ciliary neurotrophic factor (CNTF) associates with an alpha subunit (CNTFRalpha) of the receptor complex to initiate signal transduction by facilitating heterodimerization of the gp130 transducing protein and the leukemia inhibitory factor receptor (LIFR) beta. CNTFRalpha is anchored to the membrane by a glycosylphosphatidylinositol linkage; however, a soluble form of the alpha subunit can still bind CNTF to recruit the signal transducing components of the receptor complex. In the present study we show that alanine substitution for residues Thr268 and Asp269 of the CNTFRalpha subunit results in a mutated receptor subunit (R3), which can bind CNTF with an affinity similar to that of the wild type CNTFRalpha but, when expressed as a soluble receptor subunit, lowers the binding of CNTF to its tripartite receptor. In addition, CNTFR3alpha inhibits the proliferation of the TF1 hematopoietic cell line triggered by CNTF plus soluble wild type CNTFRalpha but not by IL-6 or oncostatin M. Similarly, CNTFR3alpha specifically antagonizes the induction of gp130 and LIFRbeta tyrosine phosphorylation observed in response to CNTF and wild type soluble CNTFRalpha in the HepG2 hepatoma cell line, as well as the subsequent events leading to haptoglobin synthesis. Positions 268 and 269 of CNTFRalpha appear to be critical for its interaction with gp130 and LIFRbeta, whereby alanine substitution of the residues at these positions results in antagonism of the CNTF-induced response.

Alanine

[Pelvic Castleman's disease: apropos of a case].

Castleman's disease (CD) is a enigmatic lymphoid disease of unknown etiology which rarely manifest itself as an isolated pelvic mass. We report a case of pelvic Castleman's disease masquerading as a uterine myoma. The patient presented symptoms related to compression of adjacent structures, splenomegaly and abdominal lymphadenopathy, the laboratory data revealed positive Epstein-Barr virus serology, elevated beta 2-microglobulin level and presence of antinuclear antibodies. The intraabdominal involvement, histological patterns and clinical forms of this condition are reviewed. Likewise etiopathogenic, radiologic and therapeutic aspects related with this entity are discussed. We suggest that pelvic Castleman's disease should be included in the differential diagnosis of females presenting a pelvic mass containing calcifications.

Antibodies, Antinuclear

Clinical evaluation of Amplicor HIV-1 test for detection of human immunodeficiency virus type 1 proviral DNA in peripheral blood mononuclear cells.

We report here the clinical evaluation of Amplicor polymerase chain reaction (PCR) assay for the detection of the human immunodeficiency virus type 1 (HIV-1) in peripheral blood mononuclear cells (PBMCs). Results obtained with Amplicor HIV-1 test were compared to serological status and a standard PCR assay using SK38/SK39 and oligomer hybridization with SK19. A panel of 208 well-characterized specimens was analyzed, including PBMC lysates from 47 antibody-negative high-risk individuals, eight antibody-negative low-risk subjects, two subjects with acute retroviral disease, 35 asymptomatic seropositive subjects (59 samples) with CD4 counts > 400/mm3, 31 patients (46 samples) with AIDS-related complex (ARC), 30 patients (40 specimens) with AIDS, and six seropositive patients with unknown clinical status. Amplicor demonstrated a specificity of 100% and a sensitivity of 98.7%. Of the two false-negative samples with Amplicor, one was negative for beta-globin amplification, whereas a dilution of the other sample turned positive for HIV-1. Inhibitors of Taq polymerase were thus believed to be responsible for the negative results. This study demonstrates that commercialized nonisotopic PCR assays reach adequate levels of sensitivity and specificity for diagnosis of HIV-1 infection and could be considered in clinical situations in which serology is not helpful.

AIDS-Related Complex

Use of intracavitary interferon-alpha-2b in the prophylactic treatment of patients with superficial bladder cancer.

BACKGROUND: The evolution of superficial transitional cell carcinoma (TCC) of the bladder poses a clinical management problem due to its tendency to recur after initial transurethral resection (TUR). Natural Killer (NK) cells are a distinct subset of lymphocytes that possess the ability to lyse tumor cells without prior sensitization in a nonmajor histocompatibility-restricted fashion. These cytotoxic cells constitute a relevant barrier against the local growth and systemic dissemination of neoplastic diseases. METHODS: The immunomodulatory effect, after TUR of the tumor, of the prophylactic treatment with intravesical instillations of interferon-alpha-2b (IFN-alpha-2b) upon the NK activity of peripheral blood mononuclear cells (PBMNC) in 17 patients with superficial TCC of the bladder was analyzed using a 4-hour 51sodium chromate (51Cr)-release cytotoxicity assay against both NK-sensitive, or K562, and NK-resistant, or JY, tumor target cells. RESULTS: There were no significant modifications of the NK activity of PBMNC during the 3 months of IFN-alpha-2b intracavitary treatment (P > 0.05). However, with respect to their levels before treatment, NK activity in PBMNC at 3 months posttreatment was enhanced significantly in the 14 patients who showed no sign of tumor recurrence in the 12 months of follow-up (P < 0.01). Six months after finishing the intracavitary IFN-alpha-2b instillations, the PBMNC NK activity in these patients had returned to the levels found before initiating the therapy (P > 0.05). This temporary enhancement of the PBMNC NK activity was not found in three patients with evidence of tumor recurrence at some time during the 12 months after treatment. In similar experimental conditions, significant enhancement of the NK activity in PBMNC was not observed in nine patients with superficial bladder TCC who were treated with intracavitary instillations of mitomycin C (MMC) after the TUR of the tumor and who were free of recurrence of the disease at 1 year of follow up. CONCLUSION: The prophylactic intracavitary treatment of superficial bladder TCC with IFN-alpha-2b may induce an immunomodulatory effect in the NK activity of PBMNC that appears to be associated with the clinical evolution of the disease.

Administration, Intravesical

Coamplification of HIV type 1 and beta-globin gene DNA sequences in a nonisotopic polymerase chain reaction assay to control for amplification efficiency.

The polymerase chain reaction (PCR) fails to detect HIV-1 sequences in 5% of infected individuals. To screen for false-negative PCR tests, we developed a nonisotopic PCR assay in which sequences from the beta-globin gene and from the HIV-1 vpu-env region were coamplified with biotinylated and fluorescein-labeled primers, respectively. Coamplified products were reacted with specific internal digoxigenin-labeled RNA probes. Hybrids were detected in a microtiter plate coated with streptavidin or anti-fluorescein antibody, with enzyme-labeled anti-digoxigenin antibody. After the optimization of the coamplification conditions, the assay could detect 5 proviral DNA copies in a lysate from 100,000 peripheral blood mononuclear cells. Fifty-seven samples from 55 HIV-1-seropositive patients and 25 samples from 25 seronegative individuals were evaluated. Fifty-two samples from HIV-infected individuals were positive for HIV-1 vpu-env sequences. Three of the 5 PBMC lysates falsely negative for HIV-1 sequences had reactivities for beta-globin (3-23 fu) below that of 100,000 cells (304 fu). Nonisotopic coamplification allowed for the evaluation of the quality of specimens for PCR concurrently with the detection of the presence of viral template sequences.

Acquired Immunodeficiency Syndrome

Defective functional response to membrane stimuli in lymphocytes from patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a local disturbance in the prostate that may involve an inflammatory infiltrate predominantly composed of activated lymphocytes and macrophages. The activation and proliferative response of T lymphocytes to different mitogenic signals has been analysed in peripheral blood mononuclear cells (PBMC) from 45 patients with BPH and 55 healthy controls. The PBMC obtained from the patients showed a significant specific impairment in proliferation, CD25 expression and IL-2 production in response to stimulation with lectins (phytohaemagglutinin (PHA), concanavalin A (Con A)), that was not corrected by the addition of IL-2 or of phorbol esters (phorbol myristate acetate (PMA)). Also, the CD28 response was defective in patient PBMC. Activation with anti-CD3 or anti-CD2 MoAbs was normal, but the addition of PMA to these stimuli provoked a significant defective response. Only the use of transmembrane stimuli (PMA and ionomycin) elicited responses similar to those found in the control group. The results indicate that peripheral T lymphocytes from BPH patients show a functional impairment that is mainly explained by an alteration of membrane signals (PHA, CD28) and is distal to protein kinase C (PKC) activation.

Aged

[Clinical experience with the treatment of metastatic renal cell carcinoma with subcutaneous interleukin-2r (IL-2r) and interferon Alpha-2b (IFN Alfa-2b)].

This work presents our recent clinic experience in the treatment of advanced RCC with IL-2 in association to alpha IFN given subcutaneously. Fifteen patient with histologically confirmed advanced RCC and measurable lesions were entered in the study. Patients were treated in cycles of 7 weeks at a IL-2 dose of 4.8 million IU/m2 (induction phase)-2.4 million IU/m2 (maintenance phase) every 12h five days a week and alpha IFN: 6 million IU/m2 every 24h three days a week, and were afterwards evaluated for response. Responders with localized residual bulk underwent rescue surgery. Seven patient has objective response (3 complete, 2 partial and 2 stable responses). The complete responses were stable and lasted 36 m, 14 m and 8 m, and global survival was of 14.6 m (3-36 m). All patients had toxicity at various degrees but WHO grade II was not exceeded at any time. The association of IL-2 and alpha IFN 2b given subcutaneously, appears to have antitumoral activity against advanced RCC with durable responses and in a proportion similar to other associations in intravenous administration, but with lower systemic toxicity. Surgical resection of residual bulk can be beneficial in selected patient with partial response.

Adult

[The surgical opportunity in metastatic lesions of renal-cell carcinoma after a response to adjuvant immunotherapy].

Surgical resection of primary lesions and single metastasis can be curative, but surgery, used as the only therapeutic option, is not unanimously accepted in patients with multiple metastasis and, apart from other considerations, there are no established clinical criteria to allow us to predict which patients will benefit from a metastectomy. This study evaluates four patients with advanced RCC. Three had multiple pulmonary metastasis at the time of diagnosis and one presented retroperitoneal mass at 36 months of follow-up. All patients were nephrectomized and received adjuvant immunotherapy with an association of IL-2 and 2b alpha-IFN subcutaneously, obtaining partial response of the disease after two treatment courses. Later, the patients underwent debulking surgery. Two patients are still alive and have no evidence of disease progression at 28 months and 8 months of follow-up. This data and that contrasted with other authors, suggests that surgical management would be a reasonable option in patients who have partially responded to immunotherapy, even though the selection of both candidates and surgical strategy should be considered on an individual basis.

Aged