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I Richard O Broux D Hillaire D Cherif F Fougerousse D Cohen J S Beckmann 《Human molecular genetics》1992,1(8):621-624
Limb-Girdle Muscular Dystrophy (LGMD) is a myopathy with clinical and transmission heterogeneity. The recessive form, LGMD2, has been recently mapped by linkage analysis to 15q. As an attempt to identify the gene involved in this pathology, we tested as candidate gene the LD locus, called LD for limb deformity. This gene has recently been identified and mapped to chromosome 15q13-q14. It is homologous to the murine formin gene which is localized to mouse chromosome 2. Mutations in this murine gene have been shown to cause limb deformity and kidney defect. YAC clones containing the LD gene were isolated and utilised to confirm the cytogenetic localisation. Internal DNA polymorphisms of the LD locus were analyzed in LGMD2 and CEPH families. The LD gene was mapped between the alpha cardiac actin gene and the D15S24 locus. Crossovers between the LGMD2 and the LD loci excluded the LD gene as a candidate for LGMD2. 相似文献
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In vivo induction of tolerance by an Ig peptide is not affected by the deletion of FcR or a mutated IgG Fc fragment 总被引:1,自引:0,他引:1
To induce tolerance to a variety of epitopes, we have designed a gene therapy approach in which peptides or antigens are expressed in frame on a soluble IgG fusion protein scaffold and delivered via retroviral gene therapy in B cells in vivo. Initially, tolerance to the lambda repressor cI sequence p1-102 or its immunodominant epitopes (e.g. p12-26 or p73-88) was elicited in both T cells and B cells when lipopolysaccharide (LPS) blasts are transduced and injected into naive or even primed recipients. While a role of secreted Ig fusion protein in this process is not clear, we have previously demonstrated the importance of antigen presentation on MHC class II of B cell antigen-presenting cells (APC) for tolerance induction. To further examine the role of the Ig and especially of the Fc portion of the IgG in tolerogenesis, we transduced LPS blasts from FcR gamma II(-/-), Fc gamma RI(-/-), Fc gamma RIII(-/-), FcR(-/-) or naive mice with retroviral vectors expressing IgG1-102, Delta IgG1-102 (mutated construct on position 297 of the Fc portion) or IgG12-26. When these transduced LPS blasts from FcR knockout mice were injected into normal (or knockout) syngeneic recipient mice, they induced tolerance both to the immunodominant epitopes and the full-length protein in that the antibody responses to the immunodominant epitopes were reduced. In this paper, we show that this tolerance resides at both the T and B cell level. Moreover, mutation of residue 297, which affects IgG functions including FcR binding, did not alter the tolerogenicity of the construct. These results suggest that the Fc portion of the IgG molecules is not required for humoral nor for cellular tolerance induction using the IgG-antigen tolerogens. 相似文献
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Jack Feehan Moustapha Kassem Robert J Pignolo Gustavo Duque 《Journal of bone and mineral research》2021,36(1):12-23
Circulating osteogenic progenitor (COP) cells are a population of cells in the peripheral blood with the capacity for bone formation, as well as broader differentiation into mesoderm-like cells in vitro. Although some of their biological characteristics are documented in vitro, their role in diseases of the musculoskeletal system remains yet to be fully evaluated. In this review, we provide an overview of the role of COP cells in a number of physiological and pathological conditions, as well as identify areas for future research. In addition, we suggest possible areas for clinical utilization in the management of musculoskeletal diseases. © 2020 American Society for Bone and Mineral Research (ASBMR). 相似文献
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Salam Bennouar Abdelghani Bachir Cherif Amel Kessira Djamel-Eddine Bennouar Samia Abdi 《Nutrition Clinique et Métabolisme》2021,35(2):144-151
Introduction/ObjectivesAcute kidney injury (AKI) and malnutrition are two complications commonly reported in severe forms of COVID-19, their combined effect on short-term mortality is, however, not yet investigated. The objective of this study is to determine both their individual and combined effects on short-term prognosis.Materials and methodsThis is a prospective, uni-centric study, including 247 severe COVID-19 patients, admitted between April 25th and June 20th, 2020, at the University Hospital of Blida. AKI was defined according to the KDIGO-2012 guidelines. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score. The association with in-hospital mortality was assessed using the Kaplan-Meier method and proportional Cox regression.ResultsAmong the 247 severely affected COVID-19 patients included in this study, 34.4% developed AKI, 30.4 and 1.2%, respectively, had moderate and severe CONUT scores, 17.7% worsened and progressed to a critical state and 26.7% did not survive. Both AKI and CONUT score were significantly associated with mortality in a dose-response manner (pLog-Rank < 0.0001). Their relative risks are respectively (HR = 3.25 CI 95% [1.99–5.3] and HR = 2.42 CI 95% [1.5–3.9], p < 0.0001). In multivariate analysis, the highest risk was observed for the AKI-CONUT-high combination (HR = 3.0, 95% CI [1.5–6.1], p = 0.002).ConclusionA possible synergistic interaction between AKI and CONUT score for COVID-19 short-term mortality has been highlighted. Monitoring of renal function associated with assessment of nutritional status should be performed routinely and systematically from the early stages of admission. 相似文献
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We sought to identify risk factors and neonatal outcomes associated with the failure of the INSURE method ( INtubation- SURfactant- Extubation) during nasal continuous positive airway pressure for preterm infants with respiratory distress syndrome. We used a retrospective analysis of the prenatal histories, clinical courses, and laboratory data of all inborn infants with gestational age 27 to 34 weeks and respiratory distress syndrome treated with INSURE method. Infants were categorized into two groups: INSURE failure group and INSURE success group. One hundred nine infants were eligible to the study. INSURE failure was registered in 35 infants (32.1%). After control for confounding variables, INSURE failure was significantly associated with arterial partial pressure of carbon dioxide (adjusted odds ratio [OR] = 1.82; 95% confidence interval [CI] = 1.76 to 90.56), mean arterial-to-alveolar oxygen tension ratio (adjusted OR = 1.13; 95% CI = 1.06 to 85.34) and severe radiological grade (adjusted OR = 1.31; 95% CI = 1.15 to 70.16). Positive predictive values of these variables were 70, 75, and 55%, respectively. Patent ductus arteriosus and mortality rates were significantly higher in INSURE failure group. Arterial partial pressure of carbon dioxide, arterial-to-alveolar oxygen tension ratio, and severe radiological grade are predictors of the failure of INSURE method in preterm infants with respiratory distress syndrome. However, a prospective randomized controlled trial is needed to determine whether or not infants at risk for INSURE failure are better off being treated with mechanical ventilation. 相似文献
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Oral ibuprofen in early curative closure of patent ductus arteriosus in very premature infants 总被引:1,自引:0,他引:1
Intravenous indomethacin and intravenous ibuprofen are widely used for the treatment of patent ductus arteriosus (PDA) in premature infants. Intravenous indomethacin may lead to renal impairment, enterocolitis, and intraventricular hemorrhage. Intravenous ibuprofen was shown to be as effective and to cause fewer side effects. If ibuprofen is effective intravenously, it will probably be effective orally, too. This study was conducted to test oral ibuprofen in early curative closure of PDA in very premature infants hoping for a better tolerance and the same efficacy as intravenous ibuprofen. Forty very premature infants (mean gestational age: 29.4 +/- 1 to 2 weeks [range: 26 to 31.5 weeks]; mean weight: 1237.2 +/- 198 g [range: 650-1770 g]) with PDA and respiratory distress were studied prospectively. They received, while between 48 and 96 hours old, oral ibuprofen at a dose of 10 mg/kg, followed, if needed, at 24-hour intervals by one or two additional doses of 5 mg/kg each. Color Doppler echography of the heart, brain, and abdomen were performed before treatment and after each dose administration. Ductal closure, early outcome (1 week after treatment), and late outcome were recorded. Thirty-eight patients (95%) achieved pharmacological closure. Two patients did not respond to the treatment: One required surgical ligation of the ductus, and the other patient received and well tolerated ductal shunting. Twenty-four patients were treated with one dose of oral ibuprofen, 10 were treated with two doses, and 6 were treated with three doses. Early outcome showed no case of renal impairment, no significant differences in serum creatinine levels, nine cases (22.5%) of intraventricular hemorrhage, three cases (7.5%) of necrotizing enterocolitis, and two cases (5%) of gastrointestinal bleeding. Late outcome showed 15 cases (37.5%) of nosocomial sepsis, 3 cases (7.5%) of chronic lung disease, 2 cases (5%) of periventricular leukomalacia, and 17 cases of death. In this study, oral ibuprofen was effective and well tolerated for early curative closure of PDA in very premature infants. Nevertheless, larger randomized comparative studies with pharmacokinetics measures are warranted. 相似文献
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Ahmadou Dem Mamadou Moustapha Dieng Sidy Ka Pape Macoumba Gaye Doudou Diouf Mame Coumba Gaye-Fall 《Bulletin du cancer》2013,100(2):155-160
IntroductionEpithelial ovarian cancer are the most frequent of ovarian cancer, their prognosis is very bad. The aim of this study is to describe the diagnosis, the treatment and to assess the survival rate of the patients.MethodsIt was a retrospective study realized at the Cancer Institute of Dakar from December 2000 to January 2007. We have collected 117 patients with epithelial ovarian cancer. The mean age was 49 years. Patients were comprised: 22 stage I, 32 stage II, 35 stage III and 26 stage IV. Primary surgery was performed to 34 patients and the other patients were treated with chemotherapy and surgery. The survival rate was assessed by Kaplan-Meier method and the Logrank test had allowed to compare the survival among age and optimal surgery.ResultsOptimal surgery R0 was done in 20 cases and surgical resection R2 was performed in 45 cases. Pathological exam had found 65 serous cystadenocarcinoma, 28 mucinous cystadenocarcinoma and 21 endometrioid cystadenocarcinoma, one malignant tumor of Brenner. Overall survival at five years was 13.3%. The survival among optimal surgery was 16.3 and 2.3% for suboptimal surgery. There was no significant difference of the survival among patients who were less than 40 years old (P = 0.334).ConclusionPrognosis of epithelial ovarian cancer is worse in Senegal as like as in the world. To improve the survival of our patients, we must detect the early diagnosis of these tumors and to introduce the neoadjuvant chemotherapy before optimal surgery. 相似文献
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