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G Bailly

Publications and source records attributed to G Bailly.

18 recordsLinked to original sources

Direct signal transduction via functional interferon-alphabeta receptors in CD34+ hematopoietic stem cells.

Affinity purified, freshly isolated CD34+ progenitors were shown to express low levels of type I interferon (IFN) receptors (740 +/- 60 binding sites/cell, K(d) 0.7 +/- 0.04 nM) determined by Scatchard's analysis using a radiolabelled, neutralizing, monoclonal antibody directed against the IFNAR1 chain of the human type I IFN receptor. Treatment of freshly isolated (day 0), highly purified (>95% pure) CD34+ cells with recombinant IFN-alpha resulted in rapid tyrosine phosphorylation and activation of STAT1, Tyk2 and JAK1 as shown by Western immunoblotting. Similarly, IFN treatment was shown by confocal microscopy to result in rapid nuclear localization of the transcription factors IRF1 and STAT2, demonstrating the presence of functional IFN receptors on freshly isolated (day 0) CD34+ cells. The number of specific type I IFN receptor binding sites expressed on hematopoietic progenitor cells increased to some 1440 +/- 40 per cell after 11 days of cultivation of CD34+ cells in vitrosuggesting that receptor expression increases with cell differentiation. IFN-mediated signal transduction and the inhibitory effect of IFN-alpha on 7 or 14 days CFU-GM and BFU-E colony formation was abrogated in the presence of the anti-IFNAR1 mAb, indicating that IFN-alpha acts directly on the proliferation of human hematopoietic progenitor cells via receptor activated signal transduction without excluding the induction of other cytokines or growth factors by residual accessory cells.

Active Transport, Cell Nucleus↗

Linear degrees of freedom in speech production: analysis of cineradio- and labio-film data and articulatory-acoustic modeling.

The following contribution addresses several issues concerning speech degrees of freedom in French oral vowels, stop, and fricative consonants based on an analysis of tongue and lip shapes extracted from cineradio- and labio-films. The midsagittal tongue shapes have been submitted to a linear decomposition where some of the loading factors were selected such as jaw and larynx position while four other components were derived from principal component analysis (PCA). For the lips, in addition to the more traditional protrusion and opening components, a supplementary component was extracted to explain the upward movement of both the upper and lower lips in [v] production. A linear articulatory model was developed; the six tongue degrees of freedom were used as the articulatory control parameters of the midsagittal tongue contours and explained 96% of the tongue data variance. These control parameters were also used to specify the frontal lip width dimension derived from the labio-film front views. Finally, this model was complemented by a conversion model going from the midsagittal to the area function, based on a fitting of the midsagittal distances and the formant frequencies for both vowels and consonants.

Cineradiography↗

Localization of a receptor nonapeptide with a possible role in the binding of the type I interferons.

Interferons (IFNs) in common with other cytokines activate Janus tyrosine kinases and latent STAT transcription factors upon binding to their cell surface receptor. Type I IFNs bind to a receptor composed of two transmembrane polypeptides, IFNAR1 and IFNAR2, which belong to the class II cytokine receptor family that also includes the cellular receptors for IFN-gamma, interleukin-10 and coagulation protease factor VII (tissue factor). The extracellular domain of the type I IFN receptor chain IFNAR1, has four fibronectin type-III sub-domains. Human IFNAR1 has intrinsic weak affinity for type I IFNs and plays an essential role in transmembrane signaling, formation of a high affinity complex with IFN and the modulation of ligand specificity. In order to characterise the ligand binding site on IFNAR1 we analysed the epitope recognized by the anti-IFNAR1 mAb, 64G12, which inhibits the binding and biological activities of both IFN-alpha and IFN-beta. The target peptide recognized by the 64G12 mAb was determined by screening a set of 48 overlapping peptides covering the first two subdomains (residues 23-229) of the extracellular region of IFNAR1. The results of this study show that the peptide (FSSLKLNVY), localized within the first sub-domain (residues 89-97) of IFNAR1, which is recognized by the 64G12 mAb, most likely overlaps a site to which both IFN-alpha and IFN-beta bind in the ligand-receptor complex. Thus, since the 64G12 mAb can neutralize the biological activities of all the type I IFNs tested, we suggest that the target peptide recognized by the 64G12 mAb, is a possible anchorage point on IFNAR1, common to binding of both IFN-alpha and IFN-beta.

Amino Acid Sequence↗

Saccade metrics in multiple sclerosis: versional velocity disconjugacy as the best clue?

We studied the parameters (latency, amplitude, peak velocity) of horizontal saccades in 32 patients with multiple sclerosis (MS) and 20 healthy, age matched control subjects. Saccades were recorded by direct-current electro-oculography technique (EOG). The patients were divided in 2 groups according to the absence or the presence of clinical internuclear ophthalmoplegia (INO). In both groups, we found increased latency, hypometria and reduced velocity. The disconjugacy of saccades was measured by calculating the ratio of abduction and adduction peak velocities (the versional disconjugacy index: VDI). Though the absolute value of this index might be dependent on the recording technique, its variation is not. Interestingly, the VDI was significantly increased in the groups of MS patients without clinical INO, indicating a more severe slowing in adduction. We concluded that VDI may be a very useful index in detecting subtle disorders in saccades conjugacy.

Electrooculography↗

Combination of recombinant interferon alpha-2a and vinblastine in advanced renal cell cancer.

Among 40 evaluable patients with metastatic renal cell cancer treated by high-dose interferon alpha-2a in combination with vinblastine, the authors have observed a 42.5% response rate. The 8 months' median duration of remissions is relatively short but some patients experience very long remissions, lasting many months after discontinuation of therapy. The survival of responding patients is significantly longer than the survival of nonresponders. The diverging results of other studies of the same combination are discussed; its efficacy is certainly dependent on the type of interferon, on the dose actually administered, and on the compliance to this often poorly tolerated treatment.

Adult↗

Treatment of superficial bladder tumors with intravesical recombinant interferon alpha-2a.

In a prospective study, the toxicity and efficacy of an instillation therapy with recombinant interferon alpha-2a (rIFN-alpha-2a) were evaluated in 12 patients with superficial bladder tumors. Treatment consisted of 8 weekly instillations of 54 X 10(6) IU rIFN-alpha-2a in 50 ml saline. Two weeks after completion of the instillation therapy, the tumor status was assessed with cystoscopy, biopsy and bladder wash-out cytology. Two partial responses, 1 no change and 2 progressive disease were seen in the 5 patients with TA tumors. In the 4 patients with carcinoma in situ, 1 complete response, 1 partial response and 2 no change were observed. Three patients suffered from carcinoma in situ and superficial papillary tumors, 1 showed complete response of the carcinoma in situ but no change of the TA tumor, the other 2 patients showed progressive disease. Three patients with partial response received a follow-up combination therapy with interferon intravesically and etretinate orally (25 mg/day). These patients presented progressive disease or no change 10 weeks after starting the follow-up combination therapy. During the treatment period, no side effects of interferon or changes of the serum interferon levels were observed. The treatment results are considered unsatisfactory; nevertheless, some activity after intravesical administration of interferon (mainly in patients with carcinoma in situ) could be demonstrated. Since the cytotoxic and antiproliferative effects seem to be dose-dependent, further studies might be done using higher interferon dosages and shorter treatment intervals.

Administration, Intravesical↗

[Treatment of metastatic renal adenocarcinomas with combined recombinant alpha-2a interferon and vinblastine].

The results of treatment of metastatic renal cell carcinoma have so far been very poor. Many phase II studies have shown that interferon alpha therapy is active in a significant proportion of patients (approximately 10 to 15% complete and partial remission). In the hope of improving these results we have conducted a phase I-II study of the combination of interferon alpha-2a and vinblastine in 21 patients with metastatic renal cell cancer. Side-effects were pronounced and the mean tolerated doses were 12.5 x 10(6) U/m2 interferon alpha three times per week and 0.10 mg/kg vinblastine once every three weeks. We observed a 43% response rate, with 1 complete remission, 8 partial remissions, 4 stabilizations and 8 progressions. These very encouraging results need to be confirmed by large scale studies.

Adenocarcinoma↗

[Medical treatment of metastatic cancer of the kidney with a combination of vinblastine and recombinant interferon alpha IIa. Result of a phase I-II trial].

Usual treatments of metastatic renal cell carcinoma are not efficient. Phase II trials using Interferon alpha showed a low response rate (10 to 15%). We have conducted a phase I-II trial using a combination of Vinblastine and Recombinant alpha 2 A Interferon in 21 patients. The response rate is of 43% including 1 complete and 8 partial remissions, 5 stabilizations and 8 progressive diseases. In spite of important side effects, these results are promising.

Adult↗

[Not Available].

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France↗

[Anaerobic gangrene in the edges of a segmental hysterotomy. Severe infectious complication of a cesarean section. Sequelae. Apropos of a recent case].

The infection of the edges of a hysterotomy wound by anaerobic bacteria is a very rare and dangerous complication of Caesarean section. Early surgical intervention with trimming of the edges and the institution of drainage together with suitable antibiotic treatment led to recovery. A second pregnancy, which unfortunately ended with a premature delivery, resulted after this conservative surgical procedure.

Adult↗

[Congenital choledochal cyst. The value of systematic ultrasound screening starting in the second trimester of pregnancy (author's transl)].

Routine obstetrical ultrasound carried out in the 20th week of amenorrhoea made it possible to identify a septate abdominal cyst which was non-urinary in origin and situated in the right hypochondrium. It was difficult, armed with this information, to be sure from which organ the cyst derived. The secondary diagnosis of a congenital cyst of the bile duct was made at laparotomy carried out a few hours after birth.

Adult↗

[Endocrinolgy of estrogens: some recent developments and future applications].

The interaction of oestrogens with their intra-nuclear receptor is now recognized in its tri-dimensional aspects. A new receptor, ER beta, has been cloned and new non-genomic oestrogen effects have been reported. Hence, a better understanding of physiological mechanisms or of pathophysiological aspects, such as phyto- and xeno-oestrogens' influence on the organism, is possible. New compounds, belonging to the SERM family, are being explored. Raloxifene is now available for the prevention of post-menopausal osteoporosis. Tamoxifen has been associated with a beneficial effect for the primary prevention of breast cancer in a high-risk population. The understanding of genetic susceptibility could contribute, to better define women at risk. A dedicated primary prevention strategy in women with a high risk of breast cancer coupled with early detection through mammography will continue to improve the prognosis of this hormono-dependent cancer.

Animals↗