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Biomedical subjects

G Michel

Publications and source records attributed to G Michel.

At least 91 records · Page 5Linked to original sources
PubMed1999

Differential IL-10 receptor gene expression in acute versus chronic atopic eczema. Modulation by immunosuppressive drugs and cytokines in normal cultured keratinocytes.

OBJECTIVE AND DESIGN: The effects of the anticytokine interleukin 10 (IL-10) are mediated by specific receptors. In this study we examined the role of the IL-10 receptor (IL-10R) in the pathophysiology of atopic eczema. MATERIALS AND METHODS: For this purpose we analyzed the expression of IL-10R in the skin of patients with acute and chronic atopic eczema in comparison to the expression in healthy individuals using in situ binding experiments with fluorescently labeled IL-10 and semiquantitative reverse transcriptase-PCR specific for IL-10R1. In addition, we studied the influence of the Th2-associated cytokine interleukin-4 (IL-4), the Th1-associated gamma-interferon (IFN-gamma), the immunosuppressive drug FK506, the H1-antagonist loratadine and UVA irradiation on the expression of IL-10R1 in cultured normal human keratinocytes. RESULTS: We found that IL-10 receptor mRNA and protein are strongly downregulated in acute phase atopic lesions. Furthermore we could show that IL-4, IFN-gamma, FK506, loratadine and UVA enhance the mRNA levels of the IL-10R1 in vitro in normal cultured keratinocytes. We could also demonstrate restored IL-10R1 mRNA levels in lesional atopic skin of a patient after UVA1 therapy. CONCLUSIONS: Our results demonstrate for the first time that IL-10 receptors may have a role in the pathogenesis of atopic eczema and its upregulation by FK506 and UVA could explain the therapeutic efficacy of these agents.

Acute Disease↗
PubMed1999

Effects of the neuropeptides substance P, calcitonin gene-related peptide and alpha-melanocyte-stimulating hormone on the IL-8/IL-8 receptor system in a cultured human keratinocyte cell line and dermal fibroblasts.

The neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP) and alpha-melanocyte-stimulating hormone (alpha-MSH) are known to be able to regulate the production of cytokines in the skin. Since IL-8 plays an important role in cutaneous inflammation, the effects of SP, CGRP and alpha-MSH on the IL-8/IL-8 receptor (IL-8RA) systems of these cell types were studied. Cultures of human dermal fibroblasts and an immortalized keratinocyte cell line HaCaT were treated with 10-8 M SP, CGRP or alpha-MSH. The results demonstrated that these neuropeptides have different effects on the IL-8 and IL-8RA expressions of the cells. SP and CGRP upregulated the IL-8RA mRNA expression in HaCaT cells, but had no influence on their IL-8 production, whereas, alpha-MSH had no effect on either the IL-8 or the IL-8RA mRNA expression in HaCaT cells. In contrast, alpha-MSH resulted in a time-dependent induction of the IL-8 mRNA expression in dermal fibroblasts. This induction was already detectable after 6 h, and after 12 h there was a 5-fold change in comparison with the controls. The IL-8 content of the supernatant was also increased, with a maximum at 48 h after alpha-MSH treatment. The data established in the present study support the notion that neuropeptides can directly modulate the IL-8/IL-8RA system of keratinocytes and fibroblasts.

Antigens, CD↗
PubMed1999

Prevalence and management of hypertension in type 1 diabetes mellitus in Europe: the EURODIAB IDDM Complications Study.

AIM: To examine the prevalence of hypertension and the rates of hypertension awareness by investigating treatment and control among respondents to the EURODIAB IDDM Complications Study, and to explore the variation in hypertension management by age, sex and end-organ damage. METHODS: A cross-sectional study, examining 3250 randomly selected Type 1 diabetic patients from 31 diabetes clinics in 16 European countries between 1989 and 1990. Mean age was 32.7 years (SD= 10.0) and mean duration of diabetes mellitus (DM) was 14.7 years (SD=9.3). Subjects were asked about a history of high blood pressure (BP) and current prescribed medications were recorded by the subject's physician. Hypertension was defined as having a systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg or current use of antihypertensives. Control was defined as a BP < 130/85 mmHg. RESULTS: Twenty-four per cent of subjects had hypertension, among whom fewer than one-half (48.5%) were aware of a previous diagnosis and a similar proportion (42.2%) were on treatment. Only 11.3% of those with hypertension were both treated and controlled. The majority (81%) of those receiving drug therapy for hypertension were on a single drug, most commonly an angiotensin-converting enzyme inhibitor (47%). CONCLUSION: These data show the extent of undermanagement of hypertension in Type 1 DM across Europe prior to the publication of the St. Vincent Declaration and provide a useful baseline against which future improvements in the management of hypertension can be monitored.

Adolescent↗
PubMed1999

Expression, purification, crystallization and preliminary x-ray analysis of the kappa-carrageenase from Pseudoalteromonas carrageenovora.

A recombinant form of His-tagged kappa-carrageenase from Pseudoalteromonas carrageenovora has been expressed, purified and crystallized. Crystals have been obtained by the vapour-diffusion method using polyethylene glycol (Mr = 4000) as a precipitant. These crystals belong to the space group P212121, with unit-cell parameters a = 58.2, b = 62.8, c = 77.9 A, and diffract to 2.2 A resolution on a rotating-anode X-ray source.

Bacterial Proteins↗
PubMed1999

Assembly of XcpR in the cytoplasmic membrane is required for extracellular protein secretion in Pseudomonas aeruginosa.

A broad range of extracellular proteins secreted by Pseudomonas aeruginosa use the type II or general secretory pathway (GSP) to reach the medium. This pathway requires the expression of at least 12 xcp gene products. XcpR, a putative nucleotide-binding protein, is essential for the secretion process across the outer membrane even though the protein contains no hydrophobic sequence that could target or anchor it to the bacterial envelope. For a better understanding of the relationship between XcpR and the other Xcp proteins which are located in the envelope, we have studied its subcellular localization. In a wild-type P. aeruginosa strain, XcpR was found associated with the cytoplasmic membrane. This association depends on the presence of the XcpY protein, which also appears to be necessary for XcpR stability. Functional complementation of an xcpY mutant required the XcpY protein to be expressed at a low level. Higher expression precluded the complementing activity of XcpY, although membrane association of XcpR was restored. This behavior suggested that an excess of free XcpY might interfere with the secretion by formation of inactive XcpR-XcpY complexes which cannot properly interact with their natural partners in the secretion machinery. These data show that a precise stoichiometric ratio between several components may be crucial for the functioning of the GSP.

Bacterial Proteins↗
PubMed1999

Isolation of Legionella pneumophila by centrifugation of shell vial cell cultures from multiple liver and lung abscesses.

A 7-year-old girl was admitted to the hospital with acute lymphoblastic leukemia and was treated with allogenic cord blood transplantation. At day 30 after graft, she developed a fever and multiple nodular lesions disseminated in the liver and lungs. All bacterial cultures attempted on liver and lung biopsy specimens and blood remained sterile on standard axenic media. However, inoculation of liver and lung biopsy specimens on eukaryotic cell monolayers by the centrifugation-shell vial technique (M. Marrero and D. Raoult, Am. J. Trop. Med. Hyg. 40:197-199, 1989) led to the recovery of a strain of Legionella pneumophila serogroup 1, identified by 16S rRNA gene amplification and sequencing and serotyping. Our findings demonstrate that the centrifugation-cell culture method, which has previously been useful for the isolation of other strictly or facultatively intracellular bacteria, can also serve as a method for the recovery of L. pneumophila from clinical material.

Biopsy↗
PubMed1999

[Thyroglossal duct cysts, surgery and histology].

70 years ago Sistrunck described a specific procedure for the management of thyroglossal duct cysts. However, this surgical procedure is not performed often. In a review on 28 cases, the authors have determined whether the Sistrunck's operation was too extensive in the treatment of thyroglossal duct cysts. 28 surgicals procedures have been performed during five years, 6 Schlange's procedure and 22 Sistrunck's procedure. We have had 17% of complications with only one recurrence, after six months, with Schlange's operation. During the interventions, we have been able to see and feel a duct in only one case. This difficulty in determining the presence of a duct intra-operatively could suggest that there was no duct. So we have undertaken a histological study of all 28 specimens obtained from surgery. Results showed the presence of one or multiple tracts in 72% of cases. Finally, this study show that Sistrunck's procedure is still the best operation for treatment of all cases of thyroglossal duct cysts. All other operations, and particularly Schlange's procedure, are inadequate because they are in contradiction with histological and embryological studies.

Adolescent↗
PubMed1999

[Osteopetrosis: diagnostic and therapeutic management. Apropos of 5 cases].

PURPOSE OF THE STUDY: The purpose of this study was to analyse 5 cases of osteopetrosis: 2 dominant and 3 recessive forms. MATERIAL AND METHODS: Among five cases of children suffering from osteopetrosis. There were three malignant and two benign forms. Three children affected by malignant form, received a bone marrow transplantation. RESULTS: Only one child who received a bone marrow transplantation was still alive and cured (one died due to transplantation complications, the other child died accidentally). The two children presenting a benign form were periodically followed for iterative fractures and did not present serious complications. DISCUSSION: Our analysis compared to literature review allows us to insist on bone marrow transplantation. This is the only possibility for these children who were condemned in the past. The frequency of iterative fractures on children presenting a dominant form necessitates medical and orthopedic follow-up. Narrowness of the medullary canal, bone fragility contra indicates intramedullary nailing when fixation is indicated. CONCLUSION: Osteopetrosis is an autosomal metabolic bone disease caused by an anomaly of osteoclasts action. Two main forms exist: the dominant form which is benign, and the recessive form which is malignant. Actually recessive forms can be treated and cured by bone marrow transplantation and the children who were in the past condemned are saved. Children with dominant form must be followed up by an orthopaedic surgeon because of bone weakness. The increase in number of cases detected in immigrant populations with a high rate of consanguineous marriages led us to present this study.

Bone Marrow Transplantation↗
PubMed1999

Frozen section of lymph nodes in uterine cervical carcinoma.

UNLABELLED: The aim of this study was to evaluate the accuracy of frozen section examination of lymph nodes in cervical cancer. METHODS: This retrospective study was based on 55 patients with stage Ib or IIa invasive cervical carcinoma treated by surgery followed by irradiation. All patients underwent a pelvic lymphadenectomy with frozen section analysis of lymph nodes. RESULTS: A total of 1249 nodes were removed (23 per patient) and 501 nodes (40%) were examined during the frozen section analysis. The sensitivity of frozen sections analysis in detecting metastatic nodes was 89%, its specificity and positive predictive value was 100% and its negative predictive value was 97%. CONCLUSIONS: The frozen section diagnosis of pelvic nodes should be performed in patients with a small cervical carcinoma to avoid systematic para-aortic lymphadenectomy. This is an accurate procedure and should be carried out on obturator, external iliac and common iliac nodes.

Adenocarcinoma↗
PubMed1998

Alternating radiotherapy and chemotherapy for inoperable Stage III non-small-cell lung cancer: long-term results of two Phase II GOTHA trials. Groupe d'Oncologie Thoracique Alpine.

PURPOSE/OBJECTIVE: To report on two consecutive Phase II cooperative trials in which we evaluated the combination of alternating hyperfractionated accelerated radiotherapy and cisplatin-based chemotherapy in inoperable Stage III non-small cell lung cancer (NSCLC). PATIENTS & METHODS: Between February 1986 and September 1989, 65 patients were entered in the first trial (GOTHA I), and between December 1989 and October 1992 67 were enrolled in the second trial (GOTHA II). In both protocols, radiotherapy (RT) was administered twice daily, at 6 h intervals, 5 days a week, to a total dose of 63 Gy in 42 fractions of 1.5 Gy. RT was given during weeks 2, 3, 6, and 7, over an elapsed time of 6 weeks. In GOTHA I, three cycles of cisplatin, 60 mg/m2 day 1, mitomycin, 8 mg/m2 day 1, and vindesin 3 mg/m2 day 1 and the first day of the following week, were given during weeks 1, 5, and 9; in GOTHA II, cisplatin 70 mg/m2 day 1 and vinblastin 5 mg/m2 day 1 and the first day of the following week were given during weeks 1, 5, 9, 13, 17, and 21. RESULTS: With a minimum follow-up of 3 years, the 1-, 2-, 5-, and 8-year overall survival probability was 56% (95% CI 47-64%), 27% (20-35%), 12% (7-18%) and 9% (3-16%), respectively, with a median survival of 13.6 months (11.4-16.8). Median follow-up for survivors was 6 years (3.3-9.9). There were no survival differences between Stages IIIA and IIIB (p = 0.84), performance status 0, 1, 2 (p = 0.87), sex (p = 0.45) or between the two treatment protocols. At this time, 14 patients are alive, and 118 have died: 102 from NSCLC, 4 from acute toxicity, 2 from secondary surgery, 4 from other medical causes, and 6 from unknown causes. Correlation between response and long-term survival was poor, since of the 24 patients who survived 3 years or more, only 6 (25%) were classified as having a complete response; the remainder having either a partial response (11, 46%), no change (6, 25 %), or "progressive disease" (1, 4 %). First site of relapse was local in 31% of these cases, distant in 43%, local and distant in 15 %, and unknown in 11%. Main grade 3-4 acute toxicities were nausea-vomiting (17%), mucositis (15%), leukopenia (41%), and thrombocytopenia (11%). Eight patients presented with grade 3-4 symptomatic lung radiation pneumopathy. CONCLUSION: Based on this experience with 132 patients, this combination of alternated RT and chemotherapy (CT) for inoperable Stage III NSCLC is feasible with acceptable toxicity, and long-term results suggest a gain in survival when compared to those obtained with conventional RT alone. However, the still high local and distant failure rates indicate that both local and systemic therapies need to be improved.

Adult↗
PubMed1998

Differential modulation of pro- and anti-inflammatory cytokine receptors by N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxy-crotonic acid amide (A77 1726), the physiologically active metabolite of the novel immunomodulator leflunomide.

N-(trifluoromethylphenyl)-2-cyano-3-hydroxy-crotonic acid amide (A77 1726), the physiologically active metabolite of leflunomide, has been described to exert antiproliferative effects in vitro and anti-inflammatory actions in several animal models. Currently, its use is being evaluated in clinical trials in psoriasis, which is characterized by epidermal hyperproliferation and infiltration of inflammatory cells. We studied the effects of A77 1726 on growth and gene expression in cultured epidermal cells by 5-bromo-2'-deoxy-uridine (BrdU) incorporation, reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blot hybridizations and flow cytometry. A77 1726 inhibited epidermal proliferation at concentrations above 5 microM after 24 hr. However, the cells were still fully viable at a concentration of 100 microM. The drug caused a dose-dependent reduction in the mRNA level of the type A receptor for the proinflammatory cytokine interleukin-8 (IL-8-RA) and, in contrast, induced gene expression of the receptor for the anti-inflammatory cytokine IL-10 (IL-10R) at the mRNA and protein levels. In addition, the mRNA and protein levels of the p53 gene, which is a negative cell cycle regulator, were up-regulated by A77 1726. These data suggest that A77 1726 exerts its anti-inflammatory action via the modulation of epidermal gene expression.

Aniline Compounds↗
PubMed1998

Characterization of tau phosphorylation in glycogen synthase kinase-3beta and cyclin dependent kinase-5 activator (p23) transfected cells.

One of the histopathological markers in Alzheimer's disease is the accumulation of hyperphosphorylated tau in neurons called neurofibrillary tangles (NFT) composing paired helical filaments (PHF). Combined tau protein kinase II (TPK II), which consists of CDK5 and its activator (p23), and glycogen synthase kinase-3beta (GSK-3beta) phosphorylate tau to the PHF-form in vitro. To investigate tau phosphorylation by these kinases in intact cells, the phosphorylation sites were examined in detail using well-characterized phosphorylation-dependent anti-tau antibodies after overexpressing the kinases in COS-7 cells with a human tau isoform. The overexpression of tau in COS-7 cells showed extensive phosphorylation at Ser-202 and Ser-404. The p23 overexpression induced a mobility shift of tau, but most of the phosphorylation sites overlapped the endogenous phosphorylation sites. GSK-3beta transfection showed the phosphorylation at Ser-199, Thr-231, Ser-396, and Ser-413. Triplicated transfection resulted in phosphorylation of tau at 8 observed sites (Ser-199, Ser-202, Thr-205, Thr-231, Ser-235, Ser-396, Ser-404, and Ser-413).

Animals↗
PubMed1998

Laparoscopic ovarian transposition for pelvic malignancies: indications and functional outcomes.

OBJECTIVE: To assess the indications and effectiveness of laparoscopic ovarian transposition before pelvic irradiation for a gynecologic cancer. DESIGN: Prospective study. SETTING: A gynecologic oncology department in a French anti-cancer center. PATIENT(S): Twenty-four patients treated for pelvic cancer. INTERVENTION(S): Laparoscopic ovarian transposition to paracolic gutters. Uterine conservation in 18 patients. MAIN OUTCOME MEASURE(S): Clinical and laboratory follow-up tests of ovarian function. RESULT(S): Bilateral laparoscopic ovarian transposition was achieved in 22 patients (94%). Twelve patients were treated for clear cell adenocarcinoma of the cervix and/or upper vagina, 6 patients for invasive squamous cervical carcinoma, 3 patients for pelvic sarcoma, 1 patient for recurrent cervical cancer to the upper vagina, 1 patient for ependymoma of the cauda equina, and 1 patient for ovarian dysgerminoma. Ovarian preservation was achieved in 79%. Three pregnancies were obtained. CONCLUSION(S): Laparoscopic ovarian transposition is a safe and effective procedure for preserving ovarian function. Bilateral ovarian transposition should be performed. The main indications for laparoscopic ovarian transposition are a patient with a small invasive cervical carcinoma (<2 cm) in a patient <40 years of age who is treated by initial laparoscopically assisted vaginal radical hysterectomy and a patient with a clear cell adenocarcinoma of the cervix and upper vagina.

Adolescent↗
PubMed1998

Lymphatic spread in stage Ib and II cervical carcinoma: anatomy and surgical implications.

OBJECTIVE: To determine the frequency and topography of pelvic and para-aortic node involvement in cervical carcinoma and to identify the appropriate level for resection of the lymphatic chains. METHODS: Between 1985 and 1994, 421 women with stage Ib or II cervical carcinoma were treated by surgery in combination with irradiation. Each underwent a radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy. RESULTS: A median of 34 lymph nodes were removed per patient. The overall frequency of lymph node involvement was 26%, and the frequency of para-aortic metastases was 8%. The frequency of lymph node metastasis was associated significantly with stage (chi(2) = 7.8; P < .02), tumor size (chi(2) = 14.8; P < .001), and patient age (chi(2) = 5.9; P < .05). The frequency of para-aortic involvement was below 3% in patients with small tumors (under 2 cm). When pelvic nodes were involved, the obturator group was concerned in 76 cases (18%) and the external iliac group in 48 patients (11%). When para-aortic nodes were involved, the left para-aortic chain was the most frequently concerned (23 patients [5%]). In eight of these patients, nodal involvement was found only above the level of the inferior mesenteric artery. Among 106 patients with pelvic positive nodes, 28 (26%) also had para-aortic metastatic nodes. CONCLUSION: Para-aortic lymphadenectomy should remove all of the left para-aortic chain (inframesenteric and supramesenteric) and so should be performed up to the level of the left renal vein. According to the low frequency of para-aortic involvement when tumor size is below 2 cm, such a procedure could be avoided in patients with small tumors.

Adult↗
PubMed1998

Identification of a soluble interleukin-8 inhibitor in the supernatant of polymorphonuclear leukocytes.

Interleukin-8 (IL-8) plays a crucial role in the pathogenesis of inflammatory and hyperproliferative diseases in various organs. The purpose of the present investigation was to establish whether there is any naturally occurring inhibitor of IL-8. Here we demonstrate that an IL-8 inhibitor (IL-8INH) is present in the supernatant of polymorphonuclear (PMN) leukocytes. The release of IL-8INH could be increased by stimulating the PMN leukocytes by concanavalin A. IL-81NH blocks the IL-8-induced chemotaxis and Candida albicans killing activity of PMN leukocytes and epidermal cells in vitro, and IL-8-induced neutrophil infiltration in the mouse ear in vivo. The mechanism of action of IL-8INH involves blocking of 125I-IL-8 binding to the IL-8 receptor. Binding of 125I-IL-8 to neutrophils could not be displaced by the IL-8INH, however, preincubation of 125I-IL-8 with IL-8INH increased binding inhibition, suggesting an interaction between IL-8 and the inhibitor. Crosslinking of 125I-IL-8 to IL-8INH shows that IL-8INH binds specifically to 125I-IL-8, and the IL-8INH protein has an apparent molecular weight of 52 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The partial purification of the IL-8INH on DEAE-Sephadex anion-exchange chromatography column also suggests a 50-60-kDa inhibitor protein which blocks IL-8-induced effects on neutrophils by binding to IL-8.

Animals↗
PubMed1998

Activation of tau protein kinase I/glycogen synthase kinase-3beta by amyloid beta peptide (25-35) enhances phosphorylation of tau in hippocampal neurons.

According to the amyloid hypothesis for the pathogenesis of Alzheimer's disease (AD), amyloid beta peptide (Abeta) directly affects neurons, leading to neurodegeneration and tau phosphorylation, followed by the production of paired helical filaments (PHF) in neurofibrillary tangles (NFT). To analyze the relationship between the phosphorylation sites of tau and the activation of kinases in response to Abeta, we treated cultured rat hippocampal neurons with a peptide fragment of Abeta, Abeta(25-35). Abeta(25-35) treatment activated tau protein kinase I/glycogen synthase kinase-3beta (TPKI/GSK-3beta) but not glycogen synthase kinase-3alpha (GSK-3alpha) or mitogen activated protein kinase (MAP kinase) in primary culture of hippocampal neurons. Using antibodies that recognize phosphorylated sites of tau, we showed that tau phosphorylation was enhanced in at least five sites (Ser199, Ser202, Ser396, Ser404, and Ser413 numbered according to the human tau isoform containing 441 amino acid residues), to an extent that depended on the level of TPK I/GSK-3beta. Treatment with TPK I/GSK-3beta antisense oligonucleotide inhibited the enhancement of tau phosphorylation induced by Abeta(25-35) exposure. Thus, TPK I/GSK-3beta activation by Abeta(25-35) may lead to extensive tau phosphorylation.

Amyloid beta-Peptides↗
PubMed1998

Mobilisation of healthy donors with lenograstim and transplantation of HLA-genoidentical blood progenitors in 54 patients with hematological malignancies: a pilot study.

Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 microg/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA: n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 10(6)/kg CD34+ cells, 332 (33-820) x 10(6)/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 10(9)/l ANC and 25 x 10(9)/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade > or =2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation.

Adjuvants, Immunologic↗