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71.
We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation. 相似文献
72.
R Rodríguez-Rodríguez P Yarova P Winter KA Dora 《British journal of pharmacology》2009,158(6):1609-1620
Background and purpose:
Extracellular nucleotides play a crucial role in the regulation of vascular tone and blood flow. Stimulation of endothelial cell P2Y1 receptors evokes concentration-dependent full dilatation of resistance arteries. However, this GPCR can desensitize upon prolonged exposure to the agonist. Our aim was to determine the extent and nature of P2Y1 desensitization in isolated and pressurized rat small mesenteric arteries.Experimental approach:
The non-hydrolyzable selective P2Y1 agonist ADPβS (3 µM) was perfused through the lumen of arteries pressurized to 70 mmHg. Changes in arterial diameter and endothelial cell [Ca2+]i were obtained in the presence and absence of inhibitors of protein kinase C (PKC).Key results:
ADPβS evoked rapid dilatation to the maximum arterial diameter but faded over time to a much-reduced plateau closer to 35% dilatation. This appeared to be due to desensitization of the P2Y1 receptor, as subsequent endothelium-dependent dilatation to acetylcholine (1 µM) remained unaffected. Luminal treatment with the PKC inhibitors BIS-I (1 µM) or BIS-VIII (1 µM) tended to augment concentration-dependent dilatation to ADPβS (0.1–3 µM) and prevented desensitization. Another PKC inhibitor, Gö 6976 (1 µM), was less effective in preventing desensitization. Measurements of endothelial cell [Ca2+]i in pressurized arteries confirmed the P2Y1 receptor but not M3 muscarinic receptor desensitization.Conclusions and implications:
These data demonstrate for the first time the involvement of PKC in the desensitization of endothelial P2Y1 receptors in pressurized rat mesenteric arteries, which may have important implications in the control of blood flow by circulating nucleotides. 相似文献73.
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75.
Objective To observe the time course of changes in synaptophysin (P38) expression in the cortex and hippocampus of rats with posttraumatic epilepsy (PTE), and explore the role of synaptic plasticity in the epileptogenesis of PTE. Methods Thirty-seven male Sprague-Dawley rats were randomized into normal control group (n=5), sham-operated group (n=12) with intracortical saline injection, and PTE model group (n=20) with stereotactic FeCl<,2> injection (0.1 mol/L, 10 μ1) into the motor cortex. The expression of P38 in the brain cortex and hippocampus of the rats was detected immunohistochemically at 1 h and 7, 14 and 30 days after the injections. Results Most of the rats with FeCl<,2> injection developed isolated epileptiform discharges soon alter the injection. Compared with the sham-operated groups, the rats in PTE group showed significantly decreased P38 expression in the right frontal cortex at all the time points of measurement (P<0.05). At 1 h after FeCl<,2> injection, P38 expression in the polymorphic layer, stratum lacunosum and stratum radiatum of the right hippocampai CA3 area and DG molecular layer underwent no significant changes (P>05), but at 7 days, the expression increased significantly in all the stratum regions of the right hippocampal CA3 area, and this high expression level was maintained till 30 days after the injection. Conclusion Synaptic plasticity alterations in relation to P38 expression changes in the cortex and hippocampus may play an important role in the epileptogenesis of PTE in this rat model. 相似文献
76.
CHI WAI CHENG SIU FOON PETER CHAN LUNG WAI CHAN CHI KWOK CHAN CHI FAI NG HO YUEN CHEUNG SHU YIN EDDIE CHAN WAI SANG WONG FERNAND MAC-MOUNE LAI KA FAI TO MIU LING LI 《International journal of urology》2005,12(5):449-455
AIM: To compare bacillus Calmette-Guerin (BCG) with epirubicin in adjuvant therapy of superficial bladder transitional cell carcinoma, with respect to recurrence, progression and survival. Prognostic factors are also evaluated. METHODS: Between October 1991 and September 1999, all patients harboring superficial bladder cancers (Ta or T1) with any of the relevant criteria (stage>a, grade>1, size>1 cm, multiple or recurrent tumors), after complete transurethral resection were randomized to receive either 81 mg Connaught strain BCG or 50 mg epirubicin. Patients with recurrences were eligible to crossover, even repeatedly, until progression. Recurrence, progression and survival were analyzed in relation to initial treatment, patient characteristics and tumor characteristics. RESULTS: There were 209 patients included in the study, 149 men and 60 women. The mean age was 69.9 years (range, 24-92). The BCG group consisted of 102 patients and the epirubicin group contained 107 patients. Final analysis was made at a median follow up of 23, 47 and 61 months for recurrence, progression and survival, respectively. The 10-year Kaplan-Meier estimates for recurrence-free, progression-free and disease-specific survival were 61%, 78% and 80%, respectively, for the BCG group. The corresponding figures were 32%, 74% and 92%, respectively, for the epirubicin group. Time to recurrence differed significantly between two treatment groups (P=0.0004). Multiplicity increased the risk of recurrence, while grading influenced recurrence, progression and disease specific survival. CONCLUSIONS: Bacillus Calmette-Guerin prolonged time to recurrence when compared with epirubicin. Grading was shown to be a universal prognostic factor for recurrence, progression and disease specific survival. 相似文献
77.
78.
CJ Keith M Griffiths B Petersen RJ Anderson KA Miles 《Journal of Medical Imaging and Radiation Oncology》2002,46(3):221-230
The development of thrombolytic and neuroprotective agents for the treatment of acute stroke has created an imperative for improved imaging techniques in the assessment of acute stroke. Five cases are presented to illustrate the value of perfusion CT in the evaluation of suspected acute stroke. To obtain the perfusion data, a rapid series of images was acquired without table movement following a bolus of contrast medium. Cerebral blood flow, cerebral blood volume and mean transit time were determined by mathematically modelling the temporal changes in contrast enhancement in the brain and vascular system. Pixel‐by‐pixel analysis allowed generation of perfusion maps. In two cases, CT‐perfusion imaging usefully excluded acute stroke, including one patient in whom a low‐density area on conventional CT was subsequently proven to be tumour. Cerebral ischaemia was confirmed in three cases, one with an old and a new infarction, one with a large conventional CT abnormality but only a small perfusion defect, and one demonstrating infarct and penumbra. Perfusion CT offers the ability to positively identify patients with non‐haemorrhagic stroke in the presence of a normal conventional CT, to select those cases where thrombolysis is appropriate, and to provide an indication for prognosis. 相似文献
79.
<正>电子结肠镜检查是诊断和筛查肠道疾病常用、有效的检查方法之一,而进行结肠镜检查的基本条件是清洁良好的肠道准备。虽然近年来肠道清洁剂的商品化和肠道准备方法的标准化不断完善,但仍有约30%的患者肠道准备不充分[1-3]。不充分的肠道准备会导致检查时间延长、操作难度增加、病变检出率降低、漏诊及检查费用增加等。肠道准备的质量多与患者的依从性有关,加强对患者肠道准备相关知识的教育,增强患者对肠道准备方法的认识和理解,可以提高检查前的肠道准备质量[4 相似文献
80.
Progressive platelet activation with storage: evidence for shortened survival of activated platelets after transfusion 总被引:14,自引:0,他引:14
HM Rinder ; M Murphy ; JG Mitchell ; J Stocks ; KA Ault ; RS Hillman 《Transfusion》1991,31(5):409-414
Platelets are known to become activated during storage, but it is unclear whether such activation affects recovery or survival after platelet concentrate (PC) transfusion. With the use of flow cytometry to determine the percentage of platelets expressing the alpha-granule membrane protein 140 (GMP-140), a known adhesive ligand appearing on the platelet surface after activation, several studies were conducted. These investigations evaluated 1) the occurrence of significant platelet activation over time in PCs (n = 46) stored under standard blood bank conditions; 2) the correlation between platelet activation and platelet recovery in normal subjects after PC storage (n = 12), as assessed by the recovery of Indium-labeled platelets; and 3) the recovery of activated and unactivated platelets in thrombocytopenic cancer patients transfused with standard PCs (n = 11). It was determined 1) that an increasing duration of storage of PC was associated with increasing platelet activation as measured by the percentage of platelets expressing GMP-140, progressing from a mean of 4 +/- 2 percent (SD) on the day of collection to a mean of 25 +/- 8 percent by 5 days of storage: 2) that, in normal subjects, posttransfusion recovery of autologous platelets stored for 2 to 4 days and then labeled with In111 was inversely correlated with the percentage of activated platelets in the transfused PC (r = -0.55, p = 0.05); and 3) that, when thrombocytopenic patients were transfused with standard PCs, the recovery of the activated platelets in the transfused PCs averaged only 38 +/- 15 percent of the number predicted by the absolute platelet increment.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献