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991.
Benoit L Faivre L Cheynel N Ortega-Deballon P Facy O Marty M Olschwang S Fraisse J Cuisenier J 《Journal of clinical gastroenterology》2007,41(3):297-300
Desmoid tumors may occur sporadically or as part of the extraintestinal manifestations of familial adenomatous polyposis. Different phenotypes have been described and some genotype-phenotype correlations have been raised, associated with different sites of germline mutations in the adenomatous polyposis coli (APC) gene. We report on a 42-year-old woman ascertained for a large desmoid tumor of the anterior chest wall with pleural involvement, which persistently recurred despite a decade of treatment including hormone therapy, chemotherapy, and surgery. Spontaneous disappearance of the tumor was later noted after 1 year without any treatment and confirmed after 4 years of regular follow-up. Repeated colonoscopies were normal in the proband and DNA sequencing showed a frameshift mutation due to a single adenosine deletion at position 5772 (codon 1924). This mutation, located in the exon 15 at the 3' end of the APC gene, leads to an unusual and late onset phenotype. The pedigree revealed other isolated or familial adenomatous polyposis-associated cases of desmoid tumors. This family report shows that a molecular analysis of the APC gene should be performed in familial desmoid tumors for accurate genetic counseling and follow-up. 相似文献
992.
Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance 总被引:3,自引:0,他引:3
Tremblay F Brûlé S Hee Um S Li Y Masuda K Roden M Sun XJ Krebs M Polakiewicz RD Thomas G Marette A 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(35):14056-14061
S6K1 has emerged as a critical signaling component in the development of insulin resistance through phosphorylation and inhibition of IRS-1 function. This effect can be triggered directly by nutrients such as amino acids or by insulin through a homeostatic negative-feedback loop. However, the role of S6K1 in mediating IRS-1 phosphorylation in a physiological setting of nutrient overload is unresolved. Here we show that S6K1 directly phosphorylates IRS-1 Ser-1101 in vitro in the C-terminal domain of the protein and that mutation of this site largely blocks the ability of amino acids to suppress IRS-1 tyrosine and Akt phosphorylation. Consistent with this finding, phosphorylation of IRS-1 Ser-1101 is increased in the liver of obese db/db and wild-type, but not S6K1(-/-), mice maintained on a high-fat diet and is blocked by siRNA knockdown of S6K1 protein. Finally, infusion of amino acids in humans leads to the concomitant activation of S6K1, phosphorylation of IRS-1 Ser-1101, a reduction in IRS-1 function, and insulin resistance in skeletal muscle. These findings indicate that nutrient- and hormonal-dependent activation of S6K1 causes insulin resistance in mice and humans, in part, by mediating IRS-1 Ser-1101 phosphorylation. 相似文献
993.
Immunity is believed to share limited resources with other physiological functions and this may partly account for the fitness costs of reproduction. Previous studies have shown that the acquired immunity of female common eiders (Somateria mollissima) is suppressed during the incubation fast. To save energy, triiodothyronine (T(3)) is adaptively decreased during fasting in most bird species, despite T(3) levels are maintained throughout incubation in female eiders. However, the relationship between thyroid hormones and the immune system is not fully understood. The current study aimed to determine the endocrine mechanisms that underlie immunosuppression in incubating female eiders. To this end we assessed the effects of exogenous T(3) on both components of the acquired immune system in 42 free-ranging incubating birds. Half of the females were implanted with T(3) pellets, while the other half sham implanted served as control. We measured variations in the immunoglobulin index, the T-cell-mediated immune response, body mass, and plasma parameters in both groups before and after manipulation. T(3) levels in implanted females were four times higher and mass loss was 40% greater than in control females. Implanted females also showed an 18% decrease in the immunoglobulin index, while the T-cell-mediated immune response was not significantly affected by the treatment. Finally, the treatment did not induce any significant changes in corticosterone levels. Our study shows that exogenous T(3) decreased only one component of the acquired immune system. We suggest that the immunosuppressive effect of T(3) could be mediated by its effects on body fat reserves. Further experiments are required to determine: (1) the relationship between adiposity and immune function, (2) the adaptive significance of immunosuppression during incubation in eiders. 相似文献
994.
INTRODUCTION: Given the hypothesis of a common soil for atherosclerosis, type 2 diabetes and metabolic syndrome, we tested the contribution of gene polymorphisms involved in cardiovascular diseases on fasting insulin concentration (FIC). METHODS: The polymorphisms were investigated by a multiplex assay in 308 apparently healthy French middle-aged men and women, taken from the STANISLAS cohort. FIC was measured by a microparticular enzymatic immunoassay. RESULTS: After a series of regression analyses involving 34 polymorphisms, FGB -455G/A was the only polymorphism that remained significantly associated with FIC when adjusting the analyses for multiple testing. Stepwise models showed that FGB polymorphism accounted for 4.39% of FIC variability in men. Additionally, interactions between FGB and with environmental factors (alcohol and smoking in men, and BMI in women) were found. DISCUSSION: To our knowledge, this is the first study reporting an influence of FGB polymorphism on FIC in a healthy population. Our results concord with the already shown link between fibrinogen concentration and FIC, and support the hypothesis of a relationship between fibrinogen and endothelium in FIC homeostasis whose alteration may induce several metabolic disorders. The contribution of this gene, although modest, is consistent with the polygenic nature of insulin levels. 相似文献
995.
996.
Pulmonary vascular manifestations of hereditary hemorrhagic telangiectasia (rendu-osler disease) 总被引:2,自引:0,他引:2
Cottin V Dupuis-Girod S Lesca G Cordier JF 《Respiration; international review of thoracic diseases》2007,74(4):361-378
Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a genetic disorder with autosomal dominance and variable penetrance, characterized by epistaxis, telangiectasia and visceral manifestations of the disease. The estimated minimal prevalence is 1/10,000 inhabitants. The diagnosis is established on clinical criteria, and may be further confirmed by the identification of causative mutations in either the ENG or the ACVRL1 gene coding for endoglin and ALK1, respectively. Pulmonary vascular manifestations of HHT include pulmonary arteriovenous malformations (PAVMs; especially in patients with ENG mutations) and less frequently pulmonary hypertension (especially in patients with ACVRL1 mutations). In 15-33% of patients with HHT, PAVMs consist of abnormal communications between pulmonary arteries and pulmonary veins, causing right-to-left shunting, and thus, frequently hypoxemia and dyspnea on exertion, although PAVMs may remain asymptomatic and frequently undiagnosed unless complications occur. PAVMs result in severe and frequent complications often at a young age, which may reveal the diagnosis, e.g. transient ischemic attack and cerebral stroke (10-19% of patients), systemic severe infections and abscesses (including cerebral abscess in 5-19% of patients), and rarely massive hemoptysis or hemothorax. Infections in HHT are related to the right-to-left shunting that bypasses the pulmonary capillaries and facilitates the passage of septic or aseptic emboli into the systemic and especially cerebral circulation, and potentially to minor defects in innate immunity. Treatment of PAVMs based on transcatheter coil vaso-occlusion of the feeding artery significantly decreases right-to-left shunting, hypoxemia and dyspnea on exertion, and reduces the risk of systemic complications. Long-term follow-up is warranted after transcatheter vaso-occlusion of PAVMs due to frequent recanalization of treated PAVMs and development or growth of untreated PAVMs. Patients with HHT should be informed of the risk of PAVM and potentially severe complications occurring in heretofore asymptomatic subjects. All adult patients with HHT should be proposed systematic screening for PAVM, by contrast echocardiography (preceded by anteroposterior chest radiograph) or computed tomography of the chest. Pulmonary hypertension is rare in HHT, and may be due either to systemic arteriovenous shunting in the liver increasing cardiac output or be clinically and histologically indistinguishable from idiopathic pulmonary arterial hypertension. Pulmonary hypertension is detected by systematic examination of right cardiac cavities and tricuspid regurgitation flow at echocardiography, and the diagnosis is established by right heart catheterization. 相似文献
997.
Revel MP Triki R Chatellier G Couchon S Haddad N Hernigou A Danel C Frija G 《Radiology》2007,244(3):875-882
PURPOSE: To retrospectively determine sensitivity and specificity of four findings for distinguishing pulmonary infarction from other causes of peripheral pulmonary consolidations on multidetector computed tomographic (CT) images, with other CT and clinical findings as reference. MATERIALS AND METHODS: Institutional review board approved the study and waived informed consent. Three independent radiologists blindly analyzed selected multisection CT images of 50 pulmonary infarctions-not showing direct arterial signs of pulmonary embolism-and 100 peripheral consolidations of other origins. Readers analyzed four findings: triangular shape, vessel sign (defined as presence of an enlarged vessel at the apex of consolidation), central lucencies, and air bronchograms. Interobserver agreement; frequency on CT images with and without infarct; and sensitivity, specificity, and positive likelihood ratio (LR) for diagnosis of pulmonary infarction were assessed for each finding. RESULTS: One hundred fifty peripheral consolidations were analyzed in 134 (75 men, 59 women) patients (mean age, 55.9 years+/-17.4 [standard deviation] vs 54.7+/-19.9; P=.71). Interobserver agreement was good for central lucencies and air bronchograms and poor to moderate for the other two findings (kappa<0.61). Compared with CT images without infarct, CT images with infarct had a higher frequency of vessel sign (32% [16 of 50] vs 11% [11 of 100], P=.029) and central lucencies (46% [23 of 50] vs 2% [two of 100], P<.001) and a lower frequency of air bronchograms (8% [four of 50] vs 40% [40 of 100], P=.003). Frequency of triangular shape was similar in both groups (52% [26 of 50] vs 40% [40 of 100], P=.17). Positive LR was 23.0 for central lucencies, 2.9 for vessel sign, 1.3 for triangular shape, and 0.2 for air bronchograms. Presence of central lucencies had 98% specificity and 46% sensitivity for pulmonary infarction. When the vessel sign and negative air bronchogram were combined with central lucencies, specificity increased to 99% but sensitivity decreased to 14%. CONCLUSION: Central lucencies in peripheral consolidations are highly suggestive of pulmonary infarction. 相似文献
998.
Wallis GA Yeo SE Blannin AK Jeukendrup AE 《Medicine and science in sports and exercise》2007,39(1):131-138
PURPOSE: The effect of different quantities of carbohydrate (CHO) intake on CHO metabolism during prolonged exercise was examined in endurance-trained females. METHOD: On four occasions, eight females performed 2 h of cycling at approximately 60% .VO2max with ingestion of beverages containing low (LOW, 0.5 g.min(-1)), moderate (MOD, 1.0 g.min(-1)), or high (HIGH, 1.5 g.min(-1)) amounts of CHO, or water only (WAT). Test solutions contained trace amounts of [U-13C] glucose. Indirect calorimetry combined with measurement of expired 13CO2 and plasma 13C enrichment enabled calculation of exogenous CHO, liver-derived glucose, and muscle glycogen oxidation during the last 30 min of exercise. RESULTS: The highest rates of exogenous CHO oxidation were observed in MOD, with no further increases in HIGH (peak rates of 0.33 +/- 0.02, 0.50 +/- 0.03, and 0.48 +/- 0.05 g.min(-1) for LOW, MOD, and HIGH, respectively; P < 0.05 for LOW vs MOD and HIGH). Endogenous CHO oxidation was lowest in MOD (0.99 +/- 0.06, 0.82 +/- 0.08, 0.70 +/- 0.07, and 0.89 +/- 0.09 g.min(-1); P < 0.05 for MOD vs all other trials). Compared with WAT, CHO ingestion reduced liver glucose oxidation during exercise by approximately 30% (P < 0.05 for WAT vs all CHO). Differential rates of muscle glycogen oxidation were observed with different CHO doses (0.57 +/- 0.07, 0.53 +/- 0.08, 0.41 +/- 0.07, and 0.60 +/- 0.09 g.min(-1) for WAT, LOW, MOD, and HIGH respectively; P < 0.05 for MOD vs HIGH). CONCLUSION: In endurance-trained women, the highest rates of exogenous CHO oxidation and greatest endogenous CHO sparing was observed when CHO was ingested at moderate rates (1.0 g.min(-1), 60 g.h(-1)) during exercise. 相似文献
999.
Riches SF Collins DJ Charles-Edwards GD Shafford JC Cole J Keevil SF Leach MO 《Journal of magnetic resonance imaging : JMRI》2007,26(5):1346-1352
PURPOSE: To determine if magnetic field exposure close to two clinical 1.5 T magnetic resonance imaging (MRI) scanners during image acquisition and when moving in the spatially-varying static magnetic field is compliant with European Union (EU) Directive 2004/40/EC (the Directive). MATERIALS AND METHODS: Using commercially available equipment we measured the magnetic flux density around the scanners during two clinical pulse sequences. The data was compared with frequency-dependent limits that will limit occupational exposure following transposition of the Directive into national law in 2008. The static magnetic field was measured around the scanners and the exposure from movement within this field was simulated. RESULTS: The whole-body exposure experienced when standing close to the face of the magnet exceeds the limits in the Directive on the two scanners tested during clinical sequences. Simulation of movement toward the scanner shows that speeds must be restricted to 1/5 of normal walking speed to comply with the Directive. CONCLUSION: EU Directive 2004/40/EC will have a major impact on the current use and future development of MRI due to limitations on exposure to time-varying gradient fields and movement within the spatially-varying static field. This will make interventional work impossible and routine MRI use impracticable in Europe. 相似文献
1000.
Vera P Ouvrier MJ Hapdey S Thillays M Pesquet AS Diologent B Callonec F Hitzel A Edet-Sanson A Ménard JF Jardin F Tilly H 《European journal of nuclear medicine and molecular imaging》2007,34(12):1943-1952
Purpose In patients with lymphoma, we investigated the impact of contrast-enhanced CT on PET attenuation correction in lesions and
normal tissues, particularly when PET/CT was performed after chemotherapy.
Methods Fifty patients (51±18 years) with Hodgkin’s disease (n=17) or non-Hodgkin lymphomas (n=33) were studied before and after chemotherapy. PET/CT scans were performed 60 min after injection of FDG. Iopamiron 300
(iopamidol, 1.5 cc/kg) was injected immediately afterwards, followed 50 s later by a second craniocaudal CT (CT+). PET images
were successively reconstructed using the unenhanced CT (PET−) and the CT+ (PET+) for attenuation correction, using iterative
reconstruction (4 iterations, 8 subsets, 5 mm post-filtering). HUmean, SUVmax and SUVmean were measured before and after chemotherapy in ten non-tumoural ROIs [aorta, femur, kidney, lung, iliopsoas muscle, occipital
cortex, T12 vertebra, liver, spleen and inferior vena cava (IVC)] and in tumoural lymphadenopathies or malignant tissues (n=397 and 51 VOIs respectively before and after chemotherapy) using a 3D-thresholding method (identical threshold for PET−
and PET+). ROIs were defined on the PET− and automatically applied on the unenhanced CT (CT−), the CT+ and the PET+.
Results In the non-tumoural tissues, HUmean increased significantly in the CT+ compared with the CT− in the vessels and the highly vascularised organs, and slight increases
were observed in the occipital cortex (+11%), the iliopsoas muscle (+6%) and the femur (+3%). SUVmax increased significantly in the PET+ compared with the PET− in the aorta (+14%), the liver (+10%), the spleen (+10%) and the
IVC (+12%). SUVmean increased significantly in the PET+ compared with the PET− in the aorta (+15%), the kidney (+13%), the liver (+11%), the
spleen (10%) and the IVC (+12%). In the lesions, HUmean was not significantly different before and after chemotherapy, whatever the normal region considered. SUVmax increased significantly after treatment in the T12 vertebra (+12%). SUVmean increased significantly after treatment in the T12 vertebra (+13%) and in the liver (+12%). HUmean increased significantly in the CT+ compared with the CT− in the lesions (+55%) before chemotherapy. SUVmax and SUVmean increased significantly in the PET+ compared with the PET− in the lesions (+4%) only before chemotherapy. No significant
difference was seen in measurements (HUmean, SUVmax and SUVmean) after chemotherapy.
Conclusion Our study demonstrates that use of enhanced CT for attenuation correction has a negligible effect on quantification at staging
and after chemotherapy. A “single-shot” enhanced PET/CT may thus be performed in the evaluation of patients with lymphoma
at staging, during treatment and at follow-up. 相似文献