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Biomedical subjects

F Michel

Publications and source records attributed to F Michel.

At least 73 records · Page 4Linked to original sources
PubMed1999

Tyrosine 319, a newly identified phosphorylation site of ZAP-70, plays a critical role in T cell antigen receptor signaling.

Following T cell antigen receptor (TCR) engagement, the protein tyrosine kinase (PTK) ZAP-70 is rapidly phosphorylated on several tyrosine residues, presumably by two mechanisms: an autophosphorylation and a trans-phosphorylation by the Src-family PTK Lck. These events have been implicated in both positive and negative regulation of ZAP-70 activity and in coupling this PTK to downstream signaling pathways in T cells. We show here that Tyr315 and Tyr319 in the interdomain B of ZAP-70 are autophosphorylated in vitro and become phosphorylated in vivo upon TCR triggering. Moreover, by mutational analysis, we demonstrate that phosphorylation of Tyr319 is required for the positive regulation of ZAP-70 function. Indeed, overexpression in Jurkat cells and in a murine T cell hybridoma of a ZAP-70 mutant in which Tyr319 was replaced by phenylalanine (ZAP-70-Y319F) dramatically impaired anti-TCR-induced activation of the nuclear factor of activated T cells and interleukin-2 production, respectively. Surprisingly, an analogous mutation of Tyr315 had little or no effect. The inhibitory effect of ZAP-70-Y319F correlated with a substantial loss of its activation-induced tyrosine phosphorylation and up-regulation of catalytic activity, as well as with a decreased in vivo capacity to phosphorylate known ZAP-70 substrates, such as SLP-76 and LAT. Collectively, our data reveal the pivotal role of Tyr319 phosphorylation in the positive regulation of ZAP-70 and in TCR-mediated signaling.

Amino Acid Sequence↗
PubMed1999

Tight binding of the 5' exon to domain I of a group II self-splicing intron requires completion of the intron active site.

Group II self-splicing requires the 5' exon to form base pairs with two stretches of intronic sequence (EBS1 and EBS2) which also bind the DNA target during retrotransposition of the intron. We have used dimethyl sulfate modification of bases to obtain footprints of the 5' exon on intron Pl.LSU/2 from the mitochondrion of the alga Pylaiella littoralis, as well as on truncated intron derivatives. Aside from the EBS sites, which are part of the same subdomain (ID) of ribozyme secondary structure, three distant adenines become either less or more sensitive to modification in the presence of the exon. Unexpectedly, one of these adenines in subdomain IC1 is footprinted only in the presence of the distal helix of domain V, which is involved in catalysis. While the loss of that footprint is accompanied by a 100-fold decrease in the affinity for the exon, both protection from modification and efficient binding can be restored by a separate domain V transcript, whose binding results in its own, concise footprint on domains I and III. Possible biological implications of the need for the group II active site to be complete in order to observe high-affinity binding of the 5' exon to domain I are discussed.

Base Sequence↗
PubMed1999

Molecular phylogeny of swallowtail butterflies of the tribe Papilionini (Papilionidae, Lepidoptera).

Swallowtail butterflies of the tribe Papilionini number about 225 species and are currently used as model organisms in several research areas, including genetics, chemical ecology and phylogenetics of host plant utilization and mimicry, mechanisms of speciation, and conservation. We have inferred phylogenetic relationships for a sample of 18 species of the genus Papilio (sensu lato) and five outgroup taxa by sequencing two stretches of mitochondrial DNA that correspond to segments 12886-13370 and 12083-12545 of Drosophila melanogaster mitochondrial DNA and consist of sections of the genes for the large ribosomal RNA and subunit 1 of NADH-dehydrogenase. Our data support the monophyly of Papilio and, within it, of several traditionally recognized subgroups. Species belonging to groups that utilize primarily Rutaceae as larval foodplants form two clusters, corresponding to Old World and American taxa, respectively, while two previously recognized clades-of American and South Asian-Austronesian origin-whose members were known to feed mostly on Lauraceae and Magnoliaceae, are observed to form a clade. The sister group of Papilio is found to be the South Asian genus Meandrusa, which also happens to feed on Lauraceae. The latter plant family is therefore the probable larval host of the ancestor Papilio and the shift to Rutaceae (which four-fifths of extant Papilio species use as foodplants) is more likely to have occurred only after the initial diversification of the genus.

Animals↗
PubMed1999

Influence of specific mutations on the thermal stability of the td group I intron in vitro and on its splicing efficiency in vivo: a comparative study.

Group I introns constitute excellent systems for analyzing the relationship between RNA tertiary folding and catalysis. Within a hierarchical framework interpretation of RNA folding, secondary structure motifs subtend RNA three-dimensional (3D) architecture. Thus, mutations in two-dimensional motifs are expected to have effects different from those disrupting 3D contacts. Using UV spectroscopy, we have studied the influence of nucleotide substitutions, in both secondary and tertiary structure elements, on the thermal stability of the tertiary folding of the bacteriophage T4 td group I intron. Further, we present a quantitative analysis of the relationship between the splicing efficiency in vivo and the stability of the intron structure as monitored by UV melting curves. We conclude that the stability of the tertiary structure of a group I intron as measured by UV melting is generally a good indication of its ability to splice in vivo.

Base Sequence↗
PubMed1999

Bone mineral density in men treated with synthetic gonadotropin-releasing hormone agonists for prostatic carcinoma.

PURPOSE: We evaluate the relationship between the use of synthetic gonadotropin-releasing hormone (Gn-RH) agonists and bone loss in men. MATERIALS AND METHODS: Bone mineral density and parameters of mineral metabolism were evaluated in 12 patients with stage C prostatic carcinoma before and after 6, 12 and 18 months of treatment with 3.75 mg. triptorelin intramuscularly every 4 weeks. RESULTS: Of the 12 patients 9 were evaluated after 6, 7 after 12 and 6 after 18 months of therapy. In comparison with month 0, the lumbar and femoral neck bone mineral density tended to decrease at month 6 (-3 and -2.7%, p = 0.31 and 0.17, respectively), at month 12 (-4.6 and -3.9%, p = 0.13 and 0.13) and at month 18 (-7.1 and -6.6%, p = 0.12 and 0.027). A second analysis revealed that the lumbar and femoral neck bone mineral density was significantly decreased on the last evaluation compared to month 0 (p = 0.05 and 0.028, respectively). The serum osteocalcin was increased during treatment, suggesting an accelerated bone turnover in men treated with Gn-RH agonists. CONCLUSIONS: The use of Gn-RH agonists in men may induce an accelerated bone loss. Further studies are needed to confirm these results and to evaluate the incidence of osteoporotic fractures in men treated with Gn-RH agonists.

Adenocarcinoma↗
PubMed1999

Peripheral primitive neuroectodermal tumors of bone. A review of three cases.

The recently individualized and still incompletely understood family of peripheral neuroectodermal tumors encompasses several tumor types, of which some have a predilection for bone. Immunocytochemical studies are essential and usually provide the diagnosis. A t(11;22)(q24;q12) translocation is present in over 80% of cases. Ewing's sarcoma is now viewed as an undifferentiated form of peripheral neuroectodermal tumor, and both tumors require management with combination chemotherapy plus radiation therapy and/or surgery. Contradictory data have been reported regarding the comparative prognosis of peripheral neuroectodermal tumor and Ewing's sarcoma, indicating a need for further studies in large numbers of patients. We illustrate these points by three case-reports, two in girls diagnosed with a vertebral primary at five and nine years of age, respectively, and one in a man diagnosed with a pelvic primary at 29 years of age.

Adult↗
PubMed1999

Refractory arthropathy after intravesical bacillus Calmette-Guérin therapy. Usefulness of isoniazide.

BACKGROUND: Arthritis associated with bacillus Calmette-Guérin immunotherapy usually responds dramatically to nonsteroidal antiinflammatory drug therapy. Isoniazid is generally reserved for other complications such as granulomatous hepatitis. CASE-REPORT: A 73-year-old man was admitted for fever, arthritis of the knees and right temporomandibular joint, an inflammatory swelling over the left Achilles tendon and bilateral conjunctivitis. The symptoms started in the wake of a course of intravesical bacillus Calmette-Guérin immunotherapy. Laboratory tests showed evidence of severe inflammation. Cultures of blood, urine and joint fluid specimens were negative, as were tests for autoantibodies and serologic tests for organisms known to cause reactive arthritis. Nonsteroidal antiinflammatory therapy was ineffective and glucocorticoid therapy produced only a partial response. All the symptoms resolved under isoniazid therapy in a dosage of 300 mg/day for three months. CONCLUSION: Use of antituberculous agents may be required in some cases of arthritis associated with bacillus Calmette-Guérin immunotherapy, most notably those with severe pyrexia.

Adjuvants, Immunologic↗
PubMed1999

[Treatment of ureteropelvic junction stenosis with cold blade retrograde endopyelotomy].

BACKGROUND: The classical treatment of ureteropelvic junction (UPJ) stenosis consists of open surgical resection-anastomosis. Endopyelotomy, a less invasive procedure, allows antegrade or retrograde endoscopic incision of this junction. The authors' experience of cold blade retrograde endopyelotomy (CBRE) is presented and compared with other techniques. MATERIAL AND METHOD: Thirteen patients (3 men and 10 women), with a mean age 55.3 years, underwent CBRE with ureteroscopic and fluoroscopic control for primary (10/13) or secondary (3/13) UPJ stenosis. The clinical and urographic efficacy of the method was assessed retrospectively. RESULTS: Median operating times and hospital stays were 40 min and 4 days respectively. The postoperative complication rate was 15.4% (two urinary tract infections). Eleven of the 13 patients are currently symptom-free with a mean follow-up of 26.5 months. Follow-up urography (mean follow-up: 11.9 months) shows a satisfactorily revascularized junction in 84.6% of cases (1 asymptomatic stenosis, 1 symptomatic stenosis revised by open surgery). CONCLUSION: Compared to the other treatments of UPJ stenoses, CBRE is a simple, minimally invasive technique, which reduces operating time and hospital stay and therefore presents a good cost-efficacy ratio.

Adult↗
PubMed1999

[Treatment of complete rupture of the posterior urethra by endoscopic realignment].

OBJECTIVE: To assess the efficacy and benefit of treatment of complete rupture of the posterior urethra by endoscopic realignment. MATERIAL AND METHODS: Between 1991 and June 1998, 14 men were hospitalised for complete traumatic rupture of the posterior urethra: 13 of them were treated by endoscopic realignment. RESULTS: With a mean follow-up of 29 months, all patients are continent and urinate with a satisfactory urinary stream. Two patients developed an urethral stricture and three others developed two urethral strictures treated by internal urethrotomy (38.4%). Three patients are impotent, one following embolization of both hypogastric arteries (23%). CONCLUSION: Endoscopic realignment of complete rupture of the posterior urethra is a simple, minimally invasive technique, allowing optimal preservation of continence and erection in these young patients. It may induce urethral strictires which can be effectively treated endoscopically and which can be prevented by systematic use of self-calibration of the urethra.

Adolescent↗
PubMed1999

[Pleiotropic effects of garlic].

Garlic as a herbal remedy reduces a multitude of risk factors which play a decisive role in the genesis and progression of arteriosclerosis: decrease in total and LDL-cholesterol, increase in HDL-cholesterol, reduction of serum triglyceride and fibrinogen concentration, lowering of arterial blood pressure and promotion of organ perfusion, and, finally, enhancement in fibrinolysis, inhibition of platelet aggregation, and diminution of plasma viscosity. In a prospective, 4-year clinical trial with primary endpoint 'arteriosclerotic plaque volume' it was proven not only a 9 to 18% reduction and 3% regression in plaque volume of the total collective under the influence of standardized garlic powder dragees (900 mg/die LI 111), but also of some facets of the phytopharmacologic pleiotropy of this herb: decrease in LDL level by 4%, increase in HDL concentration by 8%, and lowering in blood pressure by 7%. The reduction of arterial blood pressure is due to an additional opening of K(Ca) ion channels in the membrane of vascular smooth muscle cells that effects its hyperpolarization. This membrane hyperpolarization closes about 20% of the L-type Ca2+ channels, consequence of which is vasodilatation. In human coronary arteries, the increase in vascular diameter by 4% is closely associated with an improvement of coronary perfusion by 18%. These pleiotropic effects of garlic result in a reduction of relative cardiovascular risk for infarction and stroke by more than 50%.

Arteriosclerosis↗
PubMed1999

Transmission of varicella to a gravida via close contacts immunized with varicella-zoster vaccine. A case report.

BACKGROUND: Varicella-zoster is a highly contagious DNA virus, transmitted by direct contact and respiratory droplets. An attenuated live-virus vaccine has recently become available and is of value for susceptible, nonimmunized people. As with other attenuated vaccines, such as measles, mumps and rubella virus, there is no evidence of transmission by those immunized, and it is generally recognized that these vaccines can be given to the close contacts of pregnant women. CASE: A 32-year-old woman at 39 weeks of gestation presented with generalized pruritic vesicles and pustules. Diagnosis of primary varicella infection was made and confirmed by serologic studies. The patient denied recent or past exposure. The only significant history that the patient could recall was her exposure to her two children, who were vaccinated with the varicella-zoster vaccine eight days prior to her admission but were asymptomatic. CONCLUSION: This is the first report of a pregnant woman contracting the primary varicella infection from exposure to close contacts vaccinated with the varicella vaccine. It may not be as safe as previously thought for seronegative gravidas to be in close contact with people vaccinated with the varicella vaccine.

Adult↗
PubMed1998

Fyn and ZAP-70 are required for Vav phosphorylation in T cells stimulated by antigen-presenting cells.

In T cells, triggering of the T cell antigen receptor or of the co-stimulatory receptor CD28 can direct tyrosine phosphorylation of the signaling protein Vav. We investigated the role played by the protein tyrosine kinases Fyn, Lck, and ZAP-70 in these processes in a T cell hybridoma after physiological stimulation of the T cell receptor (TCR) and CD28. A dominant-negative mutant approach based on overexpression of catalytically inactive alleles of these kinases showed that CD28-induced Vav phosphorylation preferentially requires Fyn, whereas ZAP-70 had no role. Consistently, Vav was strongly phosphorylated in Lck-deficient JCAM-1 cells after CD28 ligation. In contrast, ZAP-70 appeared to control TCR-directed Vav phosphorylation. However, overexpression of ZAP-70 carrying a mutated Tyr315, contained within a motif previously suggested to be a Vav Src homology 2 domain binding site, had little or no effect. Immunoprecipitation assays showed that phosphorylated Vav associated with Fyn after CD28 triggering and that this interaction, likely to involve binding of Fyn Src homology 2 domain to Vav, was more strongly detectable after concomitant CD28 and TCR stimulation. These data suggest that Fyn plays a major role in controlling Vav phosphorylation upon T cell activation and that the mechanism implicating ZAP-70 in this process may be more complex than previously anticipated.

Animals↗
PubMed1998

Gaze discrimination is unimpaired in schizophrenia.

Interpersonal communication is largely dependent on interpretation of facial expression and emotion. Difficulties in face processing, and more specifically in gaze discrimination, have been described in schizophrenic patients. According to Baron-Cohen (Mindblindness. M.I.T. Press, Cambridge, MA, 1995), gaze discrimination relies on the functioning of a specific cognitive module, the Eye Direction Detector (EDD). It has been proposed [Rosse et al. (1994) Gaze discrimination in patients with schizophrenia: preliminary report. American Journal of Psychiatry 151, 919-921] that an impairment in gaze discrimination is present in schizophrenia, and plays a fundamental role in inducing the paranoid symptoms reported by many patients. However, in the previous studies, gaze direction detection and interpretation of gaze have never been completely dissociated. The present experiment attempts to test the schizophrenics' skill in a simple gaze direction detection task. A series of photographic portraits of models looking at different directions have been presented to 22 schizophrenic patients and 36 control subjects. For each portrait subjects were asked to determine whether gaze was directed to the right or to the left by pressing a keyboard key. A forced choice paradigm was used. No differences were reported between schizophrenic patients and control subjects. That is, in the present paradigm, schizophrenic patients did not show any specific impairment in detecting the direction of gaze of the portraits. The results are discussed according to the notion that a dissociation is present in schizophrenia between implicit and explicit processes. The present case illustrates how the more automatic elementary functions, such as the detection of gaze direction, may be spared in schizophrenic patients, whereas explicit cognitive functions are likely more affected.

Adult↗