Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.     

Usefulness of ATP-sensitivity-assay of intravesical instillation therapy of anti-cancer agents for superficial bladder cancer

Intravesical instillation of anti-cancer drugs for superficial urinary bladder cancer is generally carried out with the aim of prophylaxis against recurrence and chemotherapy against tumor. But since sensitivity of tumor cells to each anti-cancer drug differs individually, the anti-cancer drug to be used should also be decided individually. We selected a new sensitivity test, ATP-sensitivity-assay, which measures intracellular adenosine triphosphate (ATP) volume by Luciferin-Luciferase reaction, for the decision of the anti-cancer drug. In this paper, we evaluated the direct anti-tumor activity of the drugs that were decided by ATP-sensitivity-assay of intravesical chemotherapy. Six drugs, that are Doxorubicin (ADM), Mitomycin C (MMC), Pirarubicin (THP-ADM), Cytarabine (Ara-C), Bleomycin (BLM) and Cisplatin (CDDP) were tested in this research and size of tumors of six patients reduced to 34-93% after 6 times' installation. A woman got cystitis induced by ADM after 3 times' instillation but instillation was completed. ATP-sensitivity-assay is useful for deciding the anti-cancer drugs for intravesical chemotherapy and prophylaxis for superficial bladder cancer.     

Multifactorial analysis of the pyuria after transurethral prostatectomy]

Multifactorial analysis on 395 patients revealed important factors which prolong the pyuria after transurethral prostatectomy. They were the age of the patient, anemia and leukocytosis before surgery. These are factors which relate with the defense mechanism of the patient. Local factors, such as the duration of indwelling urethral catheter, the size of the prostate or prostatic bed and preoperative infection, were not so important for prolonging the pyuria after transurethral prostatectomy. The time of the resection and weight of the prostate had an intimate relation each other, and the former was the more important factor. The use of antimicrobials probably controlled these local risk factors, thus making them unimportant in the prolongation of the pyuria after transurethral prostatectomy.     

A study of the native kidneys in patients with chronic renal failure. Report 1: Morphological changes and occurrence of acquired cysts of the native kidneys in patients with chronic renal failure

As morphological changes of the native kidneys, the presence of acquired cysts, intra-renal calcification and renal tumor was investigated mainly by ultrasonography and computed tomography in 151 patients with chronic renal failure. 1) Among 140 uremic patients caused by medical diseases. 40 patients had simple cysts, and 37 had acquired cystic disease of the kidneys (ACDK). However 4, uremic patients caused by urological diseases were not seen to be with an acquired cysts. 2) The patients with ACDK were with significantly longer durations of dialysis therapy than those with simple cysts or no cysts. Furthermore, the patients with ACDK were younger than those of the other groups. 3) Intra-renal calcification was more frequently found in patients with cystic disease (simple cyst, ACDK and polycystic disease) than in those without cystic disease with statistic significance. 4) Native kidneys became larger after the occurrence of ACDK. 5) Three cases of renal tumor were found.     

ENDOSCOPIC PANCREATIC STENTING IN CHRONIC PANCREATITIS WITH DUCTAL DILATION PROXIMAL TO A STRICTURE: A SAFE and EFFECTIVE PROTOCOL

After removal of intraductal stones, a 10‐Fr or 7‐Fr pancreatic stent was placed in 16 patients with upstream ductal dilation proximal to a stricture of the main pancreatic duct. Stents were removed after a mean duration of 52.5 days. Nine patients underwent repeated stenting. About one year after removal of the initial stent, when the remaining upstream ductal dilation was found on follow‐up pancreatograms, the next stent was replaced. Repeated stenting improved outflow of pancreatic juice more effectively than one‐time stenting. Correlation between long‐term pain relief without recurrence of intraductal stones and reduction of duct diameter was also shown. Stent occlusion was observed in 14 of 30 stents. Stent occlusion was frequently associated with recurrence of pancreatitis and intraductal stones, and was also associated with morphologic changes in the pancreatic ductal system. Although there were no significant differences between stent patency of the initial stents and that of the next stents, stent patency of 10‐Fr stents was superior to that of 7‐Fr stents. 10‐Fr stents should be removed within 8 weeks and 7‐Fr stents should be removed within 4 weeks for the prevention of stent occlusion. Repeated stenting with short‐term stenting is therefore considered a safe and effective protocol of endoscopic pancreatic stenting.