Fyn and Lck tyrosine kinases regulate tyrosine phosphorylation of p105CasL, a member of the p130Cas docking protein family, in T-cell receptor-mediated signalling

We have previously shown that engagement of the T-cell receptor (TCR)/CD3 complex with anti-CD3 antibody induces tyrosine phosphorylation of p105CasL (CasL), a member of the p130Cas docking protein family. In the present work, we attempted to determine which protein tyrosine kinases (PTKs) regulate TCR-mediated phosphorylation of CasL. We show here that an association between CasL and two types of Src family PTKs, Fyn and Lck, is induced by anti-CD3 cross-linking of human H9 T cells. In contrast, ZAP-70, another PTK that also plays a critical role in the TCR signalling, failed to bind CasL, even after anti-CD3 stimulation. In vitro kinase assays revealed that Fyn and Lck, but not ZAP-70, were capable of phosphorylating CasL. Moreover, we found that CasL was constitutively hyperphosphorylated in vivo in splenocytes of MRL-MP-lpr/lpr mice, in which overproduction and excessive activation of Fyn and Lck have previously been shown to occur. Constitutive in vivo binding of CasL to both kinases was also demonstrated in lpr splenocytes. These results strongly suggest that CasL is a substrate for Fyn and Lck PTKs in TCR signal transduction.     

Efficacy of Prophylactic Endoscopic Variceal Sclerotherapy in Patients with Hepatocellular Carcinoma

Abstract: A setrospective study to determine the influence of prophylactic endoscopic sclerotherapy on the survival rate of patients with hepatocellular carcinoma complicated by esophageal varices was conducted. The subjects included 132 patients without esophageal varices at the time of diagnosis (NV group), 37 patients with hepatocellular carcinoma for whom prophylactic sclerotherapy had been performed for risky esophageal varices (PS group) and 26 patients with hepatocellular carcinoma and risky varices for whom prophylaxis was not performed (NPS group). Multiple regression analysis was used to identify factors affecting the survival rate of the 132 patients without esophageal varices. A tumor embolus in the primary branch or main trunk of the portal vein adversely affected long-term survival in these patients. The patients were further divided into 2 subgroups, namely those with (Vp3) and without (Vp0-Vp2) tumor emboli in the main trunk and primary branch of the portal vein. In the Vp0– Vp2 emboli subgroup, the patients who received prophylactic sclerotherapy and the patients without varices had similar survival rates. Patients without prophylactic sclerotherapy had a significantly shorter survival rate than the group without varices and the prophylactic sclesotherapy group (p<0.01 and p<0.05). A significant bleeding rate was observed in the group without prophylaxis and not in the group with prophylaxis. However, in the Vp3 subgroup, the survival rate in each group was identical. Thus prophylactic variceal sclerotherapy is indicated for patients with hepatocellular carcinoma who do not have tumor emboli in the main trunk or primary branch of portal vein.     

Clinical outcome of conservative therapy for stage T1, grade 3 transitional cell carcinoma of the bladder

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed. RESULTS: In this series, the median follow-up period was 25 months (range, 5- 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT. CONCLUSION: These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.     

Renal Cell Carcinoma in a Solitary Kidney Treated by Partial Nephrectomy --Case Report and Review of Japanese Literature

Renal cell carcinoma in a solitary kidney is rather rare. Wepresent a case of this condition occurring in a 50-year-oldman. He was treated by partial nephrectomy and temporary hemodialysisfor postoperative acute renal failure. Perusal of the literaturereveals that in situ partial nephrectomy, if possible, seemsto be a reasonable treatment of choice for renal cell carcinomain a solitary kidney. This is the fifth case ever reported inJapan.     

Dissociation between Anterograde and Retrograde Conduction during Transvenous Cryoablation of Parahissian Accessory Pathways

Ablation of parahissian accessory pathways (APs) is a challenging procedure because of the high risk to provoke “iatrogenic” atrioventricular (AV) nodal block. The feasibility and safety of cryoablation (CA) have been already demonstrated both in patients with AV nodal reentry tachycardia and in those with anteroseptal APs. However, dissociation between anterograde and retrograde conduction after CA has not yet been described. We report two cases of CA of parahissian AP associated with transient dissociation between anterograde and retrograde conduction. (PACE 2011; 34:e98–e101)     

Primary Palliative Stenting against Obstructive Mixed-Type Total Anomalous Pulmonary Venous Connection Associated with Right Atrial Isomerism

This case report presents a low-birth-weight neonate who received primary stent implantation as a long-term palliative intervention for obstructive mixed-type total anomalous pulmonary venous connection (TAPVC) without common pulmonary venous chamber associated with right atrial isomerism, which was considered difficult to surgically repair in the neonatal period. Stent redilation with balloon catheters was repeated for in-stent stenosis from neointimal proliferation, resulting in successful TAPVC repair with cavopulmonary connection at 17 months of age.     

Stenotic bicuspid aortic valve associated with a ventricular septal defect in an adult presenting with congestive heart failure: a rare observation

This report is concerned with an adult presenting with stenoticbicuspid aortic valve associated with a ventricular septal defect(VSD). The association between aortic regurgitation (AR) andVSD has often been described, but that between a stenosed aorticvalve and VSD has been rarely observed, although bicuspid aorticvalves and ventricular septal defects are probably the two mostcommon congenital heart defects. The development of congestiveheart failure in the presented case was considered to be dueto an increase in the left to right shunt through the VSD. Thiswas attributable to a progressive elevation in left ventricularpressure as a result of the development, with age, of stenosisof the bicuspid aortic valve.     

The Influence of Morphological Changes in Amplatzer Device on the Atrial and Aortic Walls Following Transcatheter Closure of Atrial Septal Defects

Objective: This study prospectively investigated morphological changes in Amplatzer Septal Occluder (ASO) over time and the influences of these changes on the atrial and aortic walls after atrial septal defect (ASD) closure.
Methods: Between August 2005 and December 2007, 78 patients with ASD were treated with ASO devices and changes in the device shape, the device thickness, and relations of the discs to the atrial and aortic walls over time were evaluated by transesophageal echocardiography immediately and 3–12 months after deployment.
Results: The maximum unstretched ASD diameter was 16.2 ± 4.8 mm and the device diameter selected was 20.6 ± 5.5 mm. At the time of last follow-up, the device thickness decreased by 17–33%, 6 of 26 devices with a flare shape on the aortic side developed a closed shape, and the relations of the discs to the anterior atrial and aortic walls changed from touching to intermittent compression in 14 of the 78 cases. In these 14 cases, the aortic rim was significantly smaller, the number of flared device shapes on the aortic side/the number of closed shapes immediately after deployment was significantly larger, and the maximum device thickness at the middle part was significantly more decreased than those in other cases.
Conclusion: As the device becomes thinner, loses its flexibility, and often changes from a flare-to-closed shape on the aortic side over time, the edges of ASO can start to compress the atrial and aortic walls. However, erosion was not recognized in these cases.     

Successful Prevention of Recurrent Ventricular Fibrillation by Intravenous Isoproterenol in a Patient with Brugada Syndrome

TANAKA, H., et al. : Successful Prevention of Recurrent Ventricular Fibrillation by Intravenous Isoproterenol in a Patient with Brugada Syndrome. Intravenous administration of isoproterenol restored the ST-segment configuration to nearly normal in the right precordial leads and completely prevented spontaneous VF attacks in a patient with Brugada syndrome. The formation of a Brugada-type ECG has been attributed to the transmural dispersion of repolarization of the right ventricular epicardium and related to modulation of the autonomic nervous system. Our case may provide clues to the pathophysiological mechanism of this syndrome.