Inhibition of protein synthesis by a Vero toxin (VT2 or Shiga-like toxin II) produced by Escherichia coli O157:H7 at the level of elongation factor 1-dependent aminoacyl-tRNA binding to ribosomes

A Vero toxin (VT2 or Shiga-like toxin II) from Escherichia coli O157:H7 was shown to inhibit protein synthesis in a rabbit reticulocyte lysate, but not in wheat germ or Ercherichia coli lysates. The toxin, VT2, inactivated 60S ribosomal subunits of rabbit reticulocytes. The site of inhibition of protein synthesis by VT2 was shown to be elongation factor 1-dependent aminoacyl-tRNA binding to ribosomes. VT2 did not affect Met-tRNAf binding to ribosomes, non-enzymatic binding of aminoacyl-tRNA to ribosomes, peptide bond formation or translocation.     

Layer-specific dilation of penetrating arteries induced by stimulation of the nucleus basalis of Meynert in the mouse frontal cortex

To clarify mechanisms through which activation of the nucleus basalis of Meynert (NBM) increases cerebral cortical blood flow, we examined whether cortical parenchymal arteries dilate during NBM stimulation in anesthetized mice. We used two-photon microscopy to measure the diameter of single penetrating arteries at different depths (∼800 μm, layers I to V) of the frontal cortex, and examined changes in the diameter during focal electrical stimulation of the NBM (0.5 ms at 30 to 50 μA and 50 Hz) and hypercapnia (3% CO₂ inhalation). Stimulation of the NBM caused diameter of penetrating arteries to increase by 9% to 13% of the prestimulus diameter throughout the different layers of the cortex, except at the cortical surface and upper part of layer V, where the diameter of penetrating arteries increased only slightly during NBM stimulation. Hypercapnia caused obvious dilation of the penetrating arteries in all cortical layers, including the surface arteries. The diameters began to increase within 1 second after the onset of NBM stimulation in the upper cortical layers, and later in lower layers. Our results indicate that activation of the NBM dilates cortical penetrating arteries in a layer-specific manner in magnitude and latency, presumably related to the density of cholinergic nerve terminals from the NBM.     

Inhibitor of apoptosis protein family as diagnostic markers and therapeutic targets of colorectal cancer

The apoptosis and antiapoptotic signaling pathways are important for regulating carcinogenesis and cancer progression, and for determining prognosis. Molecules involved in apoptosis represent potential cancer diagnostic markers and therapeutic targets. The inhibitor of apoptosis protein (IAP) family includes several important molecules involved in apoptosis that might represent such targets. Increasing evidence has demonstrated that the IAP family of proteins is integral for antiapoptotic and nuclear factor-κB signal transduction, and enhanced expression of IAPs contributes to colon carcinogenesis and its poor prognosis, as well as to drug resistance of tumors. X-linked IAP, cIAP1, cIAP2, and survivin are prognostic markers of colorectal cancer, and survivin and cIAP2 are also utilized to predict the effect of anticancer treatment in colorectal cancer patients. Novel therapies such as YM155 and LY2181308 targeting survivin, AEG35156 and phenoxodiol targeting X-linked IAP, AT-406 as a Smac mimetic, and survivin peptides are currently being evaluated in clinical trials. This report reviews the involvement of the IAP family in colorectal adenocarcinoma in order to summarize the role of the IAP family members as diagnostic and therapeutic targets, and to provide an overview of the future course of research in this area.     

Pylorus-preserving pancreaticoduodenectomy with combined resection of the portal vein and gastrointestinal reconstruction by imanaga procedure for ductal cancer of the head of the pancreas

Twenty-six patients who underwent pyloruspreserving pancreaticoduodenectomy (PPPD) for ductal cancer of the head of the pancreas between 1983 and 1993 were reviewed. Gastrointestinal continuity was restored by the methods of Imanaga (n=21) and Traverso (n=5). Combined resection of the portal vein and/or superior mesenteric vein was performed in 13 patients. Surgical complications occurred in 5 patients, but there were no postoperative deaths. Delayed gastric emptying was observed in 42% of patients. The median survival time for all 26 patients was 13 months. Three patients survived for more than 3 years, and one of them is currently alive without recurrence at 10 years. Differences in survival rates were not apparent between patients who underwent PPPD with and without portal vein resection. Survival rate after PPPD was compared with that after pancreaticoduodenectomy (PD) performed between 1974 and 1992; the difference was not significant. Patients who underwent noncurative PPPD had a significantly better survival rate than those who underwent noncurative PD (P<0.05). PPPD has improved the quality of life of the resected patients, without reducing survival rate. At present, PPPD by the Imanaga procedure could be the best choice for management of cancer of the pancreatic head.     

Surgical Resection of Hilar Cholangiocarcinoma: Analysis of Survival and Postoperative Complications

Background Surgery is the only potentially curative treatment for hilar bile duct cancer. This study sought to evaluate the efficacy and feasibility of surgical management of hilar bile duct carcinoma, including radical hepatectomy, at a single institution. Methods We performed a retrospective review of 49 consecutive patients who underwent surgery at our hospital between 1990 and 2003. Results Altogether, 44 of 49 patients underwent radical hepatectomy combined with caudate lobectomy and lymphadenectomy. One and four patients underwent partial hepatectomy or bile duct resection, respectively. No patients underwent preoperative portal vein embolization. The 5-year survival rate was 39.7%, with a median survival time of 3.75 years. The postoperative morbidity and mortality rates were 46.8% and 2.0%, respectively. Cox’s proportional hazard model revealed that lymph node status and the residual tumor factor were independent prognostic factors. Multivariate analysis revealed that preoperative hyperbilirubinemia, postoperative complications, and extended surgical procedures were independently associated with postoperative hyperbilirubinemia. After potentially curative resection, 39.4% of patients suffered from disease recurrence. In 60% of the total cases, the sites of recurrence were distant metastases. Conclusion Surgery, including radical hepatectomy combined with caudate lobectomy and lymph node dissection, is a feasible, effective treatment for hilar bile duct cancer.     

Is Hepatic Resection for Large or Multinodular Hepatocellular Carcinoma Justified? Results From a Multi-Institutional Database

Background The role of surgical resection in patients with large or multinodular hepatocellular carcinoma (HCC) remains unclear. This study evaluated the long-term outcome of patients with hepatic resection for large (>5 cm in diameter) or multinodular (more than three nodules) HCC by using a multi-institutional database.Methods The perioperative and long-term outcomes of 404 patients with small HCC (<5 cm in diameter; group 1) were compared with those of 380 patients with large or multinodular HCC (group 2). The prognostic factors in the latter group were analyzed.Results The postoperative complication rate (27% vs. 23%; P = .16) and hospital mortality rate (2.4% vs. 2.7%; P = .82) were similar between groups. The overall survival rates were significantly higher in group 1 than group 2 (1 year, 88% vs. 74%; 3 years, 76% vs. 50%; 5 years, 58% vs. 39%; P < .001). Among patients in group 2, five independent prognostic factors were identified to be associated with a worse overall survival: namely, symptomatic disease, presence of cirrhosis, multinodular tumor, microvascular tumor invasion, and positive histological margin.Conclusions Hepatic resection can be safely performed in patients with large or multinodular HCC, with an overall 5-year survival rate of 39%. Symptomatic disease, the presence of cirrhosis, a multinodular tumor, microvascular invasion, and a positive histological margin are independently associated with a less favorable survival outcome.     

The relationship between clinical signs and hypercoagulable state in toxemia of pregnancy.

The hypercoagulable state in patients with toxemia of pregnancy was investigated in comparison with normal pregnant women using new coagulation parameters, mainly thrombin-antithrombin III (TAT) complexes, alpha 2-antiplasmin-plasmin complexes (PIP), and D-dimer FDP. When the patients were categorized by the classification of the WHO Study Group (1985), significant increases of TAT complexes and alpha 2-PIP complexes with decreases of the ATIII level were observed in the groups with preeclampsia and severe gestational hypertensive disease as compared to normal pregnant women. A significant increase of D-dimer FDP was observed in a group with severe gestational hypertensive disease. Additionally, the relationship between clinical signs and the hypercoagulable state in the patients was analyzed using canonical correlation analysis as a multivariate analysis. The clinical signs and coagulation parameters had a significantly high correlation of lambda 1 = 0.7219, p less than 0.01. The results showed that clinical signs were associated with simultaneous coagulation abnormalities. The indices obtained from the results of canonical correlation analysis, which were called the clinical index and the coagulation index, should be useful in evaluating the efficacy of anticoagulation therapy.     

Renal artery thrombosis — an unusual complication following removal of a neuroblastoma

A 2-month-old female infant with a retroperitoneal neuroblastoma on the left side was admitted to Niigata University Hospital. Her systolic blood pressure, as high as 220 mmHg, was attributed to renovascular hypertension because the plasma renin activity was increased up to 208 ng/ml per hour. Excision of the tumor, including the left kidney, and periaortic lymphnode dissection were performed. For safety during the lymphadenectomy, Nelaton catheters were placed around the inferior vena cava, aorta, superior mesenteric artery, and right renal artery. On the 2nd postoperative day anuria was noted, and aortography was performed revealing obstruction of the right renal artery, inferior mesenteric artery, and left common iliac artery. Thrombectomy via aortic incision was performed immediately to restore the blood flow. The patient developed chronic renal failure, however, and still requires hemodialysis or peritoneal dialysis. Pediatric surgeons should bear in mind that extensive periaortic lymphadenectomy may cause postoperative arterial thrombosis.