Inhibition of shiga toxin cytotoxicity in human renal cortical epithelial cells by nitrobenzylthioinosine

Nitrobenzylthioinosine (NBTI), a nucleoside-transport inhibitor, has been found to possess the ability to prevent the cytotoxic action of Shiga toxin (Stx) 1 in human renal cortical epithelial cells (HRCECs), thereby protecting HRCECs from cell death. Further examination revealed that NBTI does not affect either the binding or the endocytosis of Stx1 but alters the intracellular transport of Stx1. Generally, endocytosed Stx1 is thought to be transported from endosomes to the endoplasmic reticulum. In NBTI-treated cells, however, the endocytosed Stx1 is delivered to an early endosome, but no further transportation occurs. Moreover, Stx1 is rapidly excreted from NBTI-treated HRCECs, preventing the accumulation of Stx1. Investigation of the NBTI-mediated protection mechanism against Stx cytotoxicity may provide insights into the analysis of Stx-mediated cell damage and lead to improvements in therapeutic approaches for diseases caused by Stx.     

Activation of the epsilon isoform of protein kinase C in the mammalian nerve terminal

Activation of protein kinase C (PKC) by phorbol ester facilitates hormonal secretion and transmitter release, and phorbol ester-induced synaptic potentiation (PESP) is a model for presynaptic facilitation. A variety of PKC isoforms are expressed in the central nervous system, but the isoform involved in the PESP has not been identified. To address this question, we have applied immunocytochemical and electrophysiological techniques to the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) of rat auditory brainstem. Western blot analysis indicated that both the Ca(2+)-dependent "conventional" PKC and Ca(2+)-independent "novel" PKC isoforms are expressed in the MNTB. Denervation of afferent fibers followed by organotypic culture, however, selectively decreased "novel" epsilon PKC isoform expressed in this region. The afferent calyx terminal was clearly labeled with the epsilon PKC immunofluorescence. On stimulation with phorbol ester, presynaptic epsilon PKC underwent autophosphorylation and unidirectional translocation toward the synaptic side. Chelating presynaptic Ca(2+), by using membrane permeable EGTA analogue or high concentration of EGTA directly loaded into calyceal terminals, had only a minor attenuating effect on the PESP. We conclude that the Ca(2+)-independent epsilon PKC isoform mediates the PESP at this mammalian central nervous system synapse.     

Prognosis of primary central nervous system lymphoma treated with radiotherapy alone

Purpose

Standard treatment for patients with primary central nervous system (CNS) lymphoma involves combining high-dose methotrexate-based chemotherapy and radiation. However, chemotherapy is sometimes contraindicated, and radiotherapy alone becomes the only option. We retrospectively investigated the clinical outcomes of primary CNS lymphoma patients treated with radiotherapy alone.

Materials and methods

Between 1983 and 2006, 35 patients (median age 69 years, range 37–89 years) with primary CNS lymphoma were treated with radiotherapy alone. Of these, 74 % had an Eastern Cooperative Oncology Group performance status (PS) of 2–4. Most patients (91 %) received whole-brain irradiation with or without irradiation boost to the tumor site (median dose 50 Gy, range 22–50 Gy); remaining patients received partial brain irradiation.

Results

Median follow-up time was 20 (range 1–152) months, median survival time was 20 months, and the 1- and 2-year overall survival rates were 65 and 32 %, respectively. Median survival in patients aged <70 and ≥70 years was 26 and 10 months, respectively (p = 0.01).

Conclusion

Median survival with radiotherapy alone was 20 months. Patients aged <70 years have a better prognosis than those ≥70 years.     

Survival after simultaneous repair of bichamber cardiac and pulmonary vein rupture caused by blunt chest trauma

A 44-year-old woman was transferred to our institution because of blunt chest trauma. Transthoracic echocardiography revealed decompression of the right ventricle resulting from pericardial effusion. Her hemodynamic condition was worsening gradually, and the decision was made to take the patient to the operating room. After releasing a large amount of clotting blood within the pericardial cavity, catastrophic hemorrhage occurred. Under better visualization after the patient was placed on cardiopulmonary bypass, we identified a 5-cm longitudinal tear and a 2-cm tear in the right atrium (RA), a 2-mm tear in the right ventricle (RV), and a 5-mm tear in the right lower pulmonary vein (PV). Those tears were repaired successfully with 5-0 polypropylene sutures.     

Relapse of unilateral favorable histology Wilms’ tumor: Significant clinicopathological factors

Purpose

To evaluate the clinicopathological features that indicate relapse and suggest a new risk based therapeutic strategy for unilateral Favorable Histology Wilms Tumor (FH-WT).

Materials & Methods

Thirty-three patients with unilateral WT were treated in two institutions between 1986 and 2010. Twenty-eight patients with FH-WT received primary nephrectomy according to the National Wilms’ Tumor Study (NWTS) or the Japanese Wilms’ Tumor Study (JWiTS) protocol. Retrospective analyses of the non-relapsed group (n = 23) and the relapsed group (n = 5) compared age, gender, tumor laterality, tumor weight, initial tumor stage, known histological subtype, chemotherapy (2 or 3 drugs), and any irradiation delivered. Stages and histological subtypes of the tumors were re-evaluated according to the Japanese staging system.

Results

Five of the twenty-eight tumors relapsed, and one patient died. The initial staging (P = 0.029) and the histological subtype (P = 0.003) were the only factors indicating relapse. Nine of the twenty-three tumors were histologically classified as blastemal predominant subtype (BPT-WT). Five relapsed.

Conclusion

According to the basic Japanese therapeutic strategy, all patients underwent a primary nephrectomy before chemotherapy. This study suggests that the histological subtype pre-treatment “BPT-WT” should be included as a strong indicator of poor prognosis. Such patients should be treated as a high-risk group.     

Long-term outcomes after excision of choledochal cysts in a single institution: Operative procedures and late complications

Purpose

The purpose of this study was to evaluate long-term outcomes for a minimum of 3 years after cyst excision in children with choledochal cysts, focusing on the relationship between operative procedures and outcomes.

Methods

Between 1977 and 2008, 138 children underwent cyst excision. Follow-up results were obtained from 120 patients. Their mean age was 20.9 years (range 4–49). The mean interval between surgery and conducting the analysis was 16.6 years (range 3–34). These patients were divided into two groups based on their operative procedures: group A (1977–2000) comprising 76 patients who underwent cyst excision with hepaticojejunostomy below the hilum, and group B (2001–2008) comprising 44 patients who underwent excision of the extrahepatic bile duct from the confluence of the hepatic duct to near the level of the pancreatobiliary junction with wide hilar hepaticojejunostomy. When hepatic strictures were seen near the hilum, duct plasty was made. We evaluated the long-term outcomes in the two groups.

Results

Late complications were seen in a total of 18 patients (15.0%). In group A, 16 patients (21.1%) had late complications, which included cholangitis and/or hepatic stones in 9, stones in residual intrapancreatic cysts in 4, intestinal obstruction in 2, and pancreatitis in 1. Of these 16 patients, 12 patients (15.8%), including 7 with hepatic stones (6 IV-A and 1 Ic cysts), 4 with remnant intrapancreatic cysts, and 3 with intestinal obstruction underwent surgical intervention. In group B, none of the patients developed cholangitis, pancreatitis, or stone formation. However, 2 patients (4.5%) developed intestinal obstruction that required surgery.

Conclusions

Although a longer follow-up period is necessary, late complications were more frequent in group A than in group B patients and with type IV-A cysts. We believe that excision of the extrahepatic bile duct with wide hilar hepaticojejunostomy is essential for the prevention of postoperative complications.