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81.
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
82.
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83.
84.
The purpose of this study is to define family management styles (FMSs) and determine distinctive characteristics of each FMS used by families participating in the process of withdrawal of life-sustaining therapy from a family member with an unexpected, life-threatening illness or injury. A total of 56 family members of 19 families participated in interviews and observations. Data were managed and analyzed maintaining a family focus, and each family was first examined for within family patterns of management, then compared to other families to identify differing patterns. A typology of five FMSs emerged: progressing, accommodating, maintaining, struggling, and floundering. Within this typology, dimensions emerged describing the families' varying definitions of the situations, management behaviors, and consequences. FMSs were constructed through typifying how these dimensions differed across families. Understanding FMSs can aid health care providers as families are assessed and interventions are planned. 相似文献
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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
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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
90.