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1.
Jannot AS Meziani R Bertrand G Gérard B Descamps V Archimbaud A Picard C Ollivaud L Basset-Seguin N Kerob D Lanternier G Lebbe C Saiag P Crickx B Clerget-Darpoux F Grandchamp B Soufir N Melan-Cohort 《European journal of human genetics : EJHG》2005,13(8):913-920
The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer. We wondered whether allele variations at this locus could influence susceptibility to malignant melanoma (MM). In all, 10 intragenic single-nucleotide polymorphisms (SNPs) were genotyped in 113 patients with melanomas and in 105 Caucasian control subjects with no personal or family history of skin cancer. By comparing allelic distribution between cases and controls, we show that MM and OCA2 are associated (p value=0.030 after correction for multiple testing). Then, a recently developed strategy, the 'combination test' enabled us to show that a combination formed by two SNPs was most strongly associated to MM, suggesting a possible interaction between intragenic SNPs. In addition, the role of OCA2 on MM risk was also detected using a logistic model taking into account the presence of variants of the melanocortin 1 receptor gene (MC1R, a key pigmentation gene) and all pigmentation characteristics as melanoma risk factors. Our data demonstrate that a second pigmentation gene, in addition to MC1R, is involved in genetic susceptibility to melanoma. 相似文献
2.
Jean Reignier Michael Darmon Romain Sonneville Anne-Laure Borel Maité Garrouste-Orgeas Stéphane Ruckly Bertrand Souweine Anne-Sylvie Dumenil Hakim Haouache Christophe Adrie Laurent Argaud Lilia Soufir Guillaume Marcotte Virginie Laurent Dany Goldgran-Toledano Christophe Clec’h Carole Schwebel Elie Azoulay Jean-François Timsit 《Intensive care medicine》2015,41(5):875-886
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Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations 总被引:10,自引:1,他引:9 下载免费PDF全文
Unexplained hyperferritinemia is a common clinical finding, even in asymptomatic persons. When early onset bilateral cataracts are also present, the hereditary hyperferritinemia-cataract syndrome (HHCS), because of heterozygous point mutation in the L ferritin iron-responsive element (IRE) sequence, can be suspected. We sequenced the L ferritin exon 1 in 52 DNA samples from patients referred to us for molecular diagnosis of HHCS. We identified 24 samples with a point mutation/deletion in the IRE. For the 28 samples in which no IRE mutation was present, we also genotyped HFE mutations and sequenced both H ferritin and ferroportin genes. We found an increased frequency of His63Asp heterozygotes (12 of 28) but no H ferritin mutations. We identified 3 new ferroportin mutations, producing, respectively, Asp157Gly, Gln182His, and Gly323Val amino acid replacements, suggesting that these patients have dominant type 4 hemochromatosis. This study demonstrates that both L ferritin IRE and ferroportin mutations can account for isolated hyperferritinemia. The presence of cataract does not permit the unambiguous identification of patients with HHCS, although the existence of a family history of cataract was only encountered in these patients. This raises the intriguing possibility that lens ferritin accumulation might be a factor contributing to age-related cataract in the general population. Additional causes of isolated hyperferritinemia remain to be identified. 相似文献
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Claessens YE Cariou A Monchi M Soufir L Azoulay E Rouges P Goldgran-Toledano D Branche F Dhainaut JF 《Critical care medicine》2003,31(4):1042-1047
OBJECTIVE: Our first objective was to determine a blood lactate threshold predictive of survival in human immunodeficiency virus patients experiencing lactic acidosis related to nucleoside analogs, and second, to test l-carnitine for the treatment of patients exceeding that threshold. DESIGN: a) Retrospective study using data from personal and published observations to determine the lactate threshold between survivors and nonsurvivors in human immunodeficiency virus patients being treated with nucleoside analogs. b) Prospective multicenter open trial to test l-carnitine treatment of human immunodeficiency virus patients receiving nucleoside analogs. SETTING: Medical intensive care units of four teaching hospitals and one general hospital. PATIENTS: Retrospective analysis of data from 39 human immunodeficiency virus patients (five personal cases and 34 patients from the literature) receiving nucleoside-analog treatment from which lactate values were available. An additional six patients with high lactate values were included as a pilot study testing the use of l-carnitine therapy. MEASUREMENTS AND MAIN RESULTS: An initial lactate level of 9 mmol/L, which gave good positive and negative predictive values, was determined as a threshold between survivors and nonsurvivors for the patients receiving nucleoside-analog treatment. Six patients with initial lactate levels >10 mmol/L were prospectively treated with l-carnitine; three survived beyond the end of the study. CONCLUSIONS: The blood lactate levels in human immunodeficiency virus patients receiving nucleoside-analog therapy can predict mortality in these patients. The preliminary data from this pilot study suggest that l-carnitine may be helpful for patients who have nucleoside-analog-related lactic acidosis with blood lactate levels >10 mmol/L. Further studies will be necessary to affirm the therapeutic efficacy of l-carnitine in this setting. 相似文献
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BACKGROUND: Hormonal treatments lasting 2-6 months inhibit spermatogenesis in men and have been proposed as germ cell protection against anticancer therapy. Because it is unthinkable to delay anticancer treatments, the authors investigated the protection afforded against irradiation of rats by 22 days of hormonal pretreatment. METHODS: Adult Sprague-Dawley rats were assigned to an untreated control group (C) or to one of 5 treatments: medroxyprogesterone acetate plus testosterone only (M), 3 or 5 gray of irradiation (R3 and R5), or hormonal treatment prior to 3 or 5 gray of irradiation (MR3 and MR5). Mating trials were conducted 1, 24, 45, 65, 86, and 109 days after treatment. At 122 days, genital organ weights, testis histology, and epididymal spermatozoa were evaluated. RESULTS: Irradiation reduced sperm production and had a clastogenic effect on postmeiotic germ cells. No protective effect of steroid treatment was observed. Moreover, testis weight, tubule diameter, the repopulating index, and the sperm head count decreased more in the MR5 group than in the R5 group. Mating tests showed decreases in positive vaginal smears and fertility at both 45 and 65 days, and an increase in resorption at 109 days. CONCLUSIONS: These results indicate that hormonal pretreatment potentiates irradiation damage to germ cells, especially stem cells, as regards survival and genomic alterations, probably because of increased lipoperoxidation of late spermatids. 相似文献
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C. Touvay B. Vilain P. Sirois M. Soufir P. Braquet 《The Journal of pharmacy and pharmacology》1987,39(6):454-458
Gossypol, a substance extracted from cotton plants, markedly inhibited the contractile responses of guinea-pig lung parenchyma strips stimulated with leukotriene B4 (LTB4), leukotriene D4 (LTD4) and PAF-acether but not the responses to histamine (except at high concentration). It was slightly less potent than nordihydroguaiaretic acid (NDGA) and a PAF-antagonist (BN 52021). From previously reported effects of gossypol on the cyclooxygenase and lipoxygenases, and on the similarity of the inhibition produced by NDGA and gossypol on the lung parenchyma, it is suggested that the inhibition of the myotropic activity of the lung parenchyma by gossypol is due to interactions with the formation of cyclooxygenase products within the guinea-pig lung. 相似文献
9.
Azoulay E Recher C Alberti C Soufir L Leleu G Le Gall JR Fermand JP Schlemmer B 《Intensive care medicine》1999,25(12):1395-1401
Objective: Intensivists generally view patients with hematological malignancies as poor candidates for intensive care. Nevertheless,
hematologists have recently developed more aggressive treatment protocols capable of achieving prolonged complete remissions
in many of these patients. This change mandates a reappraisal of indications for ICU admission in each type of hematological
disease. Improved knowledge of the prognosis is of assistance in making treatment decisions. Patients and methods: The records of 75 myeloma patients consecutively admitted to our ICU between 1992 and 1998 were reviewed retrospectively
and predictors of 30-day mortality were identified using stepwise logistic regression. Results: The median age was 56 years (37–84). Chronic health status (Knaus scale) was C or D in 39 cases. Fifty-five patients (73
%) had stage III disease and 17 had a complete or partial remission. Autologous bone marrow transplantation had been performed
in 28 patients (37 %). ICU admission occurred between 1992 and 1995 in 41 patients (54.7 %), and between 1996 and 1998 in
34 patients (45.3 %). The median SAPS II and LOD scores were 60 (23–107) and 7 (0–21), respectively. Reasons for ICU admission
were acute respiratory failure in 39 patients (52 %) and shock in 31 (41 %). Forty-six patients (61 %) required mechanical
ventilation. Fifty patients (66 %) received vasopressors and 24 dialysis. Thirty-day mortality was 57 %. Only five parameters
were independently associated with 30-day mortality in the multivariate model: female gender (OR = 5.12), mechanical ventilation
(OR = 16.7) and use of vasopressor agents (OR = 5.67) were associated with a higher mortality rate, whereas disease remission
(OR = 0.16) and ICU admission between 1996 and 1998 (OR = 0.09) were associated with a lower one. Conclusion: The prognosis for myeloma patients in the ICU is improving over time. This may reflect either recent therapeutic changes
in hematological departments and ICUs or changes in patient selection for ICU admission. Hematologists and intensivists should
work closely together to select hematological patients likely to benefit from ICU admission.
Received: 11 June 1999 Accepted: 22 September 1999 相似文献
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