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Biomedical subjects

G Michel

Publications and source records attributed to G Michel.

At least 109 records · Page 6Linked to original sources

Critical study of prognostic factors in childhood acute lymphoblastic leukaemia: differences in outcome are poorly explained by the most significant prognostic variables. Fralle group. French Acute Lymphoblastic Leukaemia study group.

We determined the proportion of survival variability explained by the usual prognostic factors in childhood acute lymphoblastic leukaemia (ALL) during a prognostic study of 1552 patients enrolled in three consecutive Fralle group protocols (Fralle 83, Fralle 87 and Fralle 89). The event-free survival rates at 5 years were 54.8% (SD 1.9), 43.1%) (SD 2.7) and 55.6% (SD 2.2), respectively. In the univariate analysis the following variables were predictive of poor outcome: male gender, elevated leucocytosis (> 50 x 10(9)/l), circulating blastosis. haemoglobin >12 g/dl, platelet count <100 x 10(9)/l, age under 1 year or over 9 years, enlarged mediastinum, nodes, spleen and liver, T phenotype, absence of CD10+ cells; testicular and meningeal involvement, poor response to induction therapy (CCSG M3), and LDH >400 U/l. Among the cytogenetic features, hyperdiploidy had a protective effect, whereas hypodiploidy, translocation and other structural abnormalities had a negative influence, particularly in cases of t(9;22) or t(4;11). Multivariate analysis summarized the prognostic information in terms of four variables: age, gender, leucocytosis and cytogenetic features. Missing data had little influence on the results. However, despite their significance in the multivariate analysis, these four variables each had very low predictive power (1.1% for gender, 2.0% for age, 3.5% for leucocytosis, and 1.6% for cytogenetic features). Thus, the most significant prognostic factors in childhood ALL each explain no more than 4% of the variability in prognosis. This may explain the disappointing practical value of these factors and underlines the need for prognostic tools in childhood ALL.

Age Factors↗

Total body irradiation-high-dose cytosine arabinoside and melphalan followed by allogeneic bone marrow transplantation from HLA-identical siblings in the treatment of children with acute lymphoblastic leukaemia after relapse while receiving chemotherapy: a Société Française de Greffe de Moelle study.

We investigated the use of a new conditioning regimen followed by allogeneic bone marrow transplantation (BMT) for treating children with acute lymphoblastic leukaemia (ALL) after relapse within 6 months of the completion of therapy. One hundred and sixteen children with acute lymphoblastic leukaemia in second or subsequent complete remission (CR) underwent allogeneic bone marrow transplantation from HLA-identical siblings after a preparative regimen comprising total body irradiation (TBI), high-dose cytosine arabinoside and melphalan (TAM regimen). The Kaplan-Meier product-limit estimate (mean +/- SE) of disease-free survival (DFS) at 7 years was 59.5 +/- 9% (95% confidence interval). The estimated chance of relapse was 22.5 +/- 15% with a median follow-up of 88.5 months (range 51-132). 26 patients (22.4%) died with no evidence of recurrent leukaemia, mainly from interstitial pneumonitis, veno-occlusive disease or acute graft-versus-host disease (GVHD). Three factors significantly affected DFS: acute GVHD. site of relapse and, for children in second remission after a marrow relapse, the disease status at the time of transplantation. The DFS were 59.02 +/- 12.6%, 37.5 +/- 19.8% and 774 +/- 15% among patients in CR2 after a marrow relapse, in CR3 or in untreated partial marrow relapse, and in CR2 after an isolated CNS relapse, respectively. The lowest DFS was seen in children with acute GVHD grades 3-4. Two significant factors were associated with relapse: the marrow status at the time of transplantation and chronic GVHD. The relapse rate was lower among children in CR2 or with chronic GVHD. We conclude that transplantation after the TAM regimen is an effective therapy for this population with acceptable toxicity, particularly for children in second remission after a very early marrow relapse, or those with early isolated CNS involvement.

Adolescent↗

Prognostic value of follicular dendritic cells in nodular sclerosing Hodgkin's disease.

AIMS: In nodular sclerosing Hodgkin's disease (NSHD), the prognostic relevance of the histopathological grading in two subtypes NSI (low-grade) and NSII (high-grade) remains controversial. Analysis of follicular dendritic cells (FDC) may provide new prognostic parameters. METHODS AND RESULTS: Tumours from 59 patients with NSHD were studied. Mean follow-up time was 8 years. Forty-one cases were classified as NSI and 18 as NSII. FDC were immunostained with the paraffin-resistant monoclonal antibodies CD21 and CNA.42. We distinguished three patterns in the neoplastic tissue: FDC1, the presence of well-defined follicle-like structures (n = 20); FDC2, the presence of largely destroyed FDC networks (n = 25); and FDC3, no or a few isolated FDC (n = 14). The three groups differed clearly regarding the frequency of relapse and the survival. The longest survival was seen in the FDC1 group, the shortest in the FDC3 group, the FDC2 group being intermediate (P = 0.0025). FDC status was a discriminating prognostic factor for all patients, and within various age and stage categories. Combining the FDC status and the NSI-NSII grading defined the best survival group as FDC1-NSI. CONCLUSIONS: Assessment of FDC pattern, associated with histological subtyping, brings valuable data for predicting survival and outcome in NSHD.

Adolescent↗

The secretion apparatus of Pseudomonas aeruginosa: identification of a fifth pseudopilin, XcpX (GspK family).

The xcp gene products in Pseudomonas aeruginosa are required for the secretion of proteins across the outer membrane. Four of the Xcp proteins, XcpT, U, V and W, present sequence homology to the subunits of type IV pili at their N-termini, and they were therefore designated pseudopilins. In this study, we characterized the xcpX gene product, a bitopic cytoplasmic membrane protein. Remarkably, amino acid sequence comparisons also suggested that the XcpX protein resembles the pilins and pseudopilins at the N-terminus. We show that XcpX could be processed by the prepilin peptidase, PilD/XcpA, and that the highly conserved glycine residue preceding the hydrophobic segment could not be mutated without loss of the XcpX function. We, therefore, classified XcpX (GspK) as the fifth pseudopilin of the system.

Amino Acid Sequence↗

Are psychoactive-drug-induced changes in plasma lipid and lipoprotein levels of significance for clinical remission in psychiatric disorders?

In the present pilot study, our aim was to investigate whether associations could be demonstrated in psychiatric patients between the changes in plasma lipid and lipoprotein levels expected during treatment with psychoactive drugs and the changes in the patients' depressive and hostile behavior. One hundred and fourteen patients with various psychiatric disorders (depressive episode in bipolar affective disorder, depressive episode or recurrent depressive disorder, paranoid schizophrenia, and schizoaffective disorders) were included in the study. The following examinations were carried out in each patient on admission and at discharge: (1) the plasma lipid parameters total cholesterol (TC), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), high-density lipoprotein (HDL), and triglycerides (TRI) were determined, and (2) the psychopathological features were recorded employing the AMDP system and the AMDP Syndrome Scales. Within the context of a naturalistic clinical setting with a choice of psychoactive drugs available, patients were subdivided at the end of treatment into eight treatment groups, as follows: group 1, treatment with butyrophenones; group 2, treatment with tricyclics; group 3, treatment with butyrophenones and tricyclics; group 4, treatment with butyrophenones, tricyclics and selective serotonin reuptake inhibitors; group 5, treatment with butyrophenones and lithium; group 6, treatment with tricyclics and lithium; group 7, treatment with butyrophenones, tricyclics and lithium; and group 8, treatment with butyrophenones, tricyclics, selective serotonin reuptake inhibitors and lithium. To compare the changes in the eight treatment groups, mixed general linear models including diagnosis, gender, age, body mass index changes, and baseline values were applied using proc GLM of SAS. Butyrophenones induce an increase in TC, LDL, and TC/TRI ratio, whereas tricyclics lead to an increase in TC, LDL, VLDL, and TRI. In combined medication of butyrophenones and tricyclics the effects of tricyclics predominate. Comedication of lithium inhibits the increase in TC and LDL induced by butyrophenones and/or tricyclics. Treatment groups with lipid changes of the same type (decrease, no change, or increase) were combined in "lipid change groups". Analyses of variance or covariance (with psychopathological admission value as covariate where there were significant differences in psychopathological admission mean values between the groups) of these lipid change groups with regard to the changes in the Depressive Syndrome Scale and the Hostility Syndrome Scale gave results which are interpreted as follows: an increase in TC or LDL inhibits the remission of hostility, whereas an increase in TRI with concomitant decrease in TC, or else a relatively greater increase in TRI than in TC promotes the remission of hostility. A decrease in TRI or VLDL promotes the remission of depression. Our data and findings published in the literature may suggest that systemic changes in plasma lipid parameters, at the cellular level, induce changes in the fluidity of brain cell membranes. We hypothesize that an increase in plasma TC or LDL and/or a decrease in plasma TRI or VLDL may induce a relative decrease in brain cell membrane fluidity with decreased presynaptic serotonin reuptake and increased postsynaptic serotonin function. This proposed increase in brain serotonin function would finally result in an anti-depressive, aggression-promoting effect. Conversely, a decrease in plasma TC or LDL and/or an increase in plasma TRI or VLDL may induce a relative increase in brain cell membrane fluidity with increased presynaptic serotonin reuptake and decreased postsynaptic serotonin function. This proposed decrease in brain serotonin function would result in an anti-aggressive, depression-promoting effect.

Adult↗

Fertility results after ovarian transposition for pelvic malignancies treated by external irradiation or brachytherapy.

The aim of this study was to assess the fertility outcome after ovarian transposition with uterine conservation and pelvic irradiation therapy for pelvic cancer. A total of 37 consecutive cases were reviewed. Of these, 27 patients were treated for a clear cell adenocarcinoma of the vagina and/or the cervix (group 1), nine for an ovarian pure dysgerminoma and one for a para-uterine soft tissue sarcoma (group 2). The pregnancy rate was 15% (4/27) in group 1 and 80% (8/10) in group 2 (P=0.01). A total of 18 pregnancies was observed in 12 patients. Of these, 16 pregnancies were obtained spontaneously and two after in-vitro fertilization. Of the spontaneous pregnancies, 12 (75%) were observed with ovaries still in the abdominal cavity (not repositioned). These results show that the prognosis for fertility is excellent after ovarian transposition and irradiation in patients with morphologically normal genital tracts (group 2). The prognosis is not as good for patients treated for a clear cell adenocarcinoma of the vagina and/or the cervix who may have morphological and/ or functional anomalies of the genital tract, following exposure to diethylstilboestrol and brachytherapy (group 1). Furthermore, these results show that repositioning of the ovary is not essential to achieve pregnancy.

Adenocarcinoma, Clear Cell↗

Malignant blue nevus of the vulva with late ovarian metastasis.

We report a case of malignant blue nevus (MBN) of the vulva which led to an ovarian metastasis 15 years after the initial diagnosis. To our knowledge, this is the first report of MBN of the vulva. The patient was a 28-year-old woman with a nodule of the labia majora. The patient noted the lesion when she was 12 and stated it did not change at that time. The lesion had the histopathologic features of MBN and was characterized by a low mitotic rate but substantial cytologic atypia. No abnormality was noticed over a 15 year period of follow-up. Fifteen years after the initial diagnosis, vaginal examination and ultrasonography imaging showed a 6.5 cm solid ovarian tumor. Hysterectomy and bilateral salpingo-oophorectomy was performed. Histologic evidence of metastasis was identified in the ovary. Malignant blue nevus can lead to late metastasis and needs long-term follow-up, as do other types of melanoma. Despite low mitotic activity in a melanocytic lesion resembling cellular blue nevus, a careful assessment of cytologic atypia is necessary before ruling out malignancy.

Adult↗

GSP-dependent protein secretion in gram-negative bacteria: the Xcp system of Pseudomonas aeruginosa.

Bacteria have evolved several secretory pathways to release proteins into the extracellular medium. In Gram-negative bacteria, the exoproteins cross a cell envelope composed of two successive hydrophobic barriers, the cytoplasmic and outer membranes. In some cases, the protein is translocated in a single step across the cell envelope, directly from the cytoplasm to the extracellular medium. In other cases, outer membrane translocation involves an extension of the signal peptide-dependent pathway for translocation across the cytoplasmic membrane via the Sec machinery. By analogy with the so-called general export pathway (GEP), this latter route, including two separate steps across the inner and the outer membrane, was designated as the general secretory pathway (GSP) and is widely conserved among Gram-negative bacteria. In their great majority, exoproteins use the main terminal branch (MTB) of the GSP, namely the Xcp machinery in Pseudomonas aeruginosa, to reach the extracellular medium. In this review, we will use the P. aeruginosa Xcp system as a basis to discuss multiple aspects of the GSP mechanism, including machinery assembly, exoprotein recognition, energy requirement and pore formation for driving through the outer membrane.

Amino Acid Sequence↗

Localized proton magnetic resonance spectroscopy of the brain in children infected with human immunodeficiency virus with and without encephalopathy.

Twenty children older than 2 y infected with human immunodeficiency virus (HIV) were examined by in vivo proton magnetic resonance spectroscopy (1H MRS) to study their cerebral metabolism and to identify metabolic profiles in relation with different stages of the disease. Patients were rated regarding their clinical and immunologic status according to the Centers for Disease Control classification and were divided into two groups: without encephalopathy (E-, n = 15) and with progressive encephalopathy (E+, n = 5). The acquisition was performed in the centrum semiovale using the short echo stimulated echo acquisition mode 20-ms sequence. The MRS profile was abnormal in all HIV-infected children compared with healthy age-matched controls (n = 7), even when magnetic resonance images were normal. A significant increase of the proportion of the lipid signals (ANOVA, p < 0.05) was found in all HIV-infected children. In addition, a significant decrease of the proportion of the N-acetylaspartate signal and a significant increase of the proportion of the myo-inositol signal (ANOVA, p < 0.05) characterized the E+ group. The principal component analysis performed on eight variables on 30 spectra confirms that the spectra of HIV-infected children differ from control spectra. The E+ group and the E- group are clearly separated on the map of subjects on the principal plane. The E- group lies in an intermediate position between the E+ group and the control group. The evolution of metabolic alterations in the brain of HIV-infected children can clearly be monitored by 1H MRS and associated with the occurrence of an encephalopathy.

AIDS Dementia Complex↗

[Prognostic factors of cancer of the endometrium and therapeutic implications].

Tumor differentiation, myometrial invasion and lymph node metastasis are the most important prognostic factors in endometrial carcinoma. Tumor stage, positive peritoneal cytology, obesity and race seems to be also prognostic factors. The surgical treatment of stage I and II endometrial carcinoma is hysterectomy with bilateral adnexectomy and pelvic lymphadenectomy (obturator group). This procedure can be performed by laparotomy or laparoscopy.

Age Factors↗

Demonstration and functional analysis of IL-10 receptors in human epidermal cells: decreased expression in psoriatic skin, down-modulation by IL-8, and up-regulation by an antipsoriatic glucocorticosteroid in normal cultured keratinocytes.

The chronic skin disease psoriasis is characterized by epidermal hyperproliferation and inflammation. The exact etiology of the disease is still unknown. At the molecular level, overexpression of growth factors and proinflammatory cytokines such as IL-8 and the corresponding receptor has been described in psoriatic plaques. On the other hand, the loss of inhibitory control mechanisms is involved in the pathogenesis of the disease, as exemplified by the reduced mRNA levels for the cell cycle inhibitor p53 found in lesional skin. Here we extend these findings to a cytokine with negative regulatory functions, IL-10. Only under certain conditions are human keratinocytes able to synthesize IL-10. In skin, pathological overexpression of IL-10 was described om atopic dermatitis. IL-10 exerts its effects via a specific receptor (IL-10R). We show here for the first time the presence and functionality of IL-10R in epidermal cells and its dramatically decreased expression in acute exanthematic psoriatic epidermis by in vitro and in situ binding studies. These results were substantiated using semiquantitative reverse transcriptase-PCR, demonstrating decreased expression of the IL-10R gene in psoriatic skin, its down-modulation by the proinflammatory cytokine IL-8, and its pharmacological induction in cultured cells. Biological responsiveness of epidermal cells toward IL-10 could also be demonstrated by a reduction of the growth rate and inhibition of IFN-gamma-induced HLA-DR expression. Our results provide the first evidence for a role of the IL-10R gene in the homeostasis of the epidermis and substantiate the concept of a loss of negative regulatory peptides as a step in the eruption of psoriasis.

Acute Disease↗

Different effects of Alzheimer-associated mutations of presenilin 1 on its processing.

Presenilin 1 (PS 1) shows missense mutations in most early-onset familial Alzheimer's disease (FAD). Transfection of cDNA for wild type PS 1 into rat pheochromocytoma PC12 cells generated a 47 kDa full-size PS 1 protein, which was processed into a 28 kDa N-terminal fragment and a 19 kDa C-terminal fragment. We prepared selected Alzheimer-associated mutations (Gly384Ala, Leu392Val, and Cys410Tyr) of PS 1, which localized after a possible cleavage site. By transient expression in PC12 cells and rat glioma cell line, C6, we examined their influence on the processing of PS 1. Cys410Tyr inhibited proteolytic processing of PS 1, while Gly384Ala and Leu392Val did not. Thus, the Alzheimer related mutations can be divided into two groups in terms of their effect on the proteolytic cleavage of PS 1.

Alzheimer Disease↗

Idiopathic thrombocytopenic purpura in two mothers of children with DiGeorge sequence: a new component manifestation of deletion 22q11?

The phenotypic spectrum caused by the microdeletion of chromosome 22q11 region is known to be variable. Nearly all patients with DiGeorge sequence (DGS) and approximately 60% of patients with velocardiofacial syndrome exhibit the deletion. Recent papers have reported various congenital defects in patients with 22q11 deletions. Conversely, some patients have minimal clinical expression. Ten to 25% of parents of patients with DGS exhibit the deletion and are nearly asymptomatic. Two female patients carrying a 22q11 microdeletion and presenting with idiopathic thrombocytopenic purpura are reported. Both had children with typical manifestations of DGS.

Adult↗

Cisplatin-based chemotherapy in the management of germ cell tumors of the ovary: The Institut Gustave Roussy Experience.

The past two decades have seen great improvements in the diagnosis and management of ovarian germ cell tumors. To assess the impact of cisplatin-based chemotherapy, a retrospective review based on a standardized questionnaire was conducted in 54 patients with malignant germ cell neoplasms of the ovary who received cisplatin-based chemotherapy as part of their first-line or salvage therapy at the Institut Gustave Roussy from September 1980 to December 1992. Chemotherapy was administered as primary postoperative treatment in 40 (75%) patients while 14 patients received chemotherapy as part of their salvage treatment for recurrent disease. With a median follow-up of 6 years, the overall survival is 74%. Twenty-three (96%) of the 24 patients who received chemotherapy in an adjuvant setting are alive without evidence of disease compared to 9 (56%) of 16 and 8 (57%) of 14 who were treated for advanced or recurrent disease, respectively. The long-term toxicity was minimal. Among 22 patients who underwent conservative surgery, 13 resumed normal menstrual function. Four patients delivered 5 healthy children. With male germ-cell tumors as a template, cisplatin-based chemotherapy clearly improves the prognosis for patients with ovarian germ cell tumors, especially in the adjuvant setting.

Adolescent↗

1,25-(OH)2-vitamin D3 and calcipotriol induce IL-10 receptor gene expression in human epidermal cells.

Psoriasis is a common hyperproliferative and inflammatory skin disease with a prevalence of 0.5-3%. Lesional skin is characterized by pathological overexpression of proinflammatory cytokines such as IL-8 and its receptor and the decreased presence of negative regulatory control factors like the anti-oncogene p53. The expression of these genes can be modulated in the opposite direction by antipsoriatic drugs. Another possible candidate gene is the receptor for the anti-inflammatory cytokine IL-10 (IL-10R). Recently, vitamin D3 and its analogues have attracted interest as new therapeutic agents in the treatment of psoriasis. In extension of these findings we studied here the effect of the physiologically active metabolite, 1,25-dihydroxyvitamin D3 (calcitriol) and its synthetic analogue calcipotriol (MC 903) on the expression of the IL-10R in HaCaT cells by RT-PCR. IL-10 receptor gene expression was effectively induced in the range of 10(-8)-10(-9) M. Upregulation by calcitriol was about 10-fold, by calcipotriol 12-fold. Induction of the receptor for the anti-inflammatory cytokine IL-10 may be involved in the antipsoriatic action of vitamin D derivatives.

Calcitriol↗

Significance of IgM anti-HCV core level in chronic hepatitis C.

AIM: To investigate the significance of IgM antibody to hepatitis C virus (HCV) core antigen (IgM anti-HCV core) in chronic hepatitis C. METHODS: In a group of 112 patients with histologically proven chronic hepatitis C positive for HCV RNA, IgM anti-HCV core level was studied by a sensitive semi-quantitative enzyme immunoassay. Quantitation of serum HCV RNA was done by a second generation bDNA assay and determination of HCV genotype by RT-PCR and reverse hybridization. RESULTS: IgM anti-HCV core was detected in 72 (64.3%) of the 112 patients. ALT levels were significantly higher in IgM anti-HCV core positive than negative patients. No other significant difference was observed in any of the patients' characteristics between IgM anti-HCV core positive and negative groups. On the contrary, IgM anti-HCV core level was found to be significantly higher in females than in males, in patients with moderate or severe chronic hepatitis, in patients with high HCV RNA levels and in patients infected with HCV genotype 1b. Moreover, IgM anti-HCV core level was significantly correlated with age and ALT level. Multiple regression analysis showed that IgM anti-HCV core level was significantly related only to the HCV genotype (p=0.001), histological grade (p=0.017) and ALT level (p=0.038). CONCLUSIONS: Our data support the hypothesis that IgM anti-HCV core level is associated mainly with HCV genotype and secondly with liver disease necroinflammatory activity. These associations may have implications in the pathogenesis of chronic hepatitis C.

Adult↗