Arsenic (V) induces a fluidization of algal cell and liposome membranes

Arsenate is one of the most poisonous elements for living cells. When cells are exposed to arsenate, their life activities are immediately affected by various biochemical reactions, such as the binding of arsenic to membranes and the substitution of arsenic for phosphate or the choline head of phospholipids in the biological membranes. The effects of arsenate on the life activities of algae Chlorella vulgaris were investigated at various concentrations and exposure times. The results demonstrated that the living activities of algal cells (10(10)cells/L) were seriously affected by arsenate at a concentration of more than 7.5mg As/L within 24h. Algal cells and the artificial membranes (liposomes) were exposed to arsenate to evaluate its effects on the membrane fluidization. In the presence of arsenate, the membranes were fluidized due to the binding and substitution of arsenate groups for phosphates or the choline head on the their membrane surface. This fluidization of the biological membranes was considered to enhance the transport of toxicants across the membrane of algal cells.     

Epithelial-cadherin Gene Is Not Mutated in Ductal Carcinomas of the Breast

We investigated mutations of the epithelial (E)-cadherin gene and loss of heterozygosity (LOH) at flanking loci using three microsatellite markers on the long arm of chromosome 16 in 25 ductal carcinomas of the breast. Expression of E-cadherin was also investigated immunohistochemically. No mutations were detected in exons 6 through 9 of the E-cadherin gene. LOH was observed more frequently (42%) at D16S402 (16q-ter) than at D16S421 (16q22.3-q23.1) (17%), which is located near the E-cadherin gene. Expression of E-cadherin was observed at the cell borders in 92% (11/12) of the tumors examined. The absence of mutations in the E-cadherin gene and its conserved expression suggest that inactivation of E-cadherin does not contribute significantly to the invasion or metastatic potential of ductal carcinomas of the breast. Furthermore, the high frequency of LOH at 16q-ter suggests the existence of another tumor suppressor gene which may play a crucial role in the genesis of ductal carcinomas of the breast.     

Endovascular treatment for poorest-grade subarachnoid hemorrhage in the acute stage: has the outcome been improved?

OBJECTIVE: Patients with poor-grade subarachnoid hemorrhage (SAH) have been considered good candidates for endovascular treatment. The results of treatment of Grade V SAH, the poorest grade, however, have not been fully elucidated. METHODS: The clinical characteristics and outcome parameters of 22 World Federation of Neurosurgical Societies Grade V SAH patients treated endovascularly in the acute stage between 1998 and 2000 are summarized and compared with those of 18 Grade V SAH patients treated conservatively between 1995 and 1997. RESULTS: Among the 22 patients treated endovascularly, 8 patients (36.4%) survived. The rate was significantly higher than that of the 18 patients treated conservatively (5.6%), only one of whom survived. The favorable outcome rate, however, was not significantly different between the two groups (4.5% versus 6.0%). Subdivision of both treatment groups according to Glasgow Coma Scale (GCS) score showed that the improved survival among those treated endovascularly was attributable to the improved survival in those with a preprocedural GCS score of 6 but not of 4 or 5. CONCLUSION: Endovascular treatment of the 22 World Federation of Neurosurgical Societies Grade V SAH patients improved their survival rate but not their favorable outcome rate in comparison with conservative treatment. Further accumulation of clinical data is essential to determine whether endovascular treatment can improve the functional outcome of those with GCS scores of 6 and whether there is no role for endovascular treatment in those with GCS scores of 4 or 5.     

Surgery of the liver and pancreas in Japan--message to the special symposium commemorating Dr. Ichio Honjo

About half a century ago, Ichio Honjo performed successful right hepatic lobectomy following ligation of the right hepatic artery and the right branch of the portal vein. That was the world's first successful case of right hepatic lobectomy with preliminary hilar ligation of the right branches of both the hepatic artery and portal vein. In the same year, Honjo carried out a total pancreatectomy for pancreatic cancer for the first time in Japan. Since then, marked progress in the surgical fields of the liver and pancreas has been made and appear to have nearly reached the pinnacle. Surgeons in the late half of the 20th century attempted to extend operative interventions and expand surgical fields while devoting themselves to treating incurable diseases. Therefore the period may be called the "challenging era." We are entering the era of evaluation and selection of the procedures most suitable to both the disease stage and each individual patient.     

Three-dimensional reconstruction of biliary tract using spiral computed tomography for laparoscopic cholecystectomy

To increase the safety of laparoscopic cholecystectomy, we have analyzed the biliary tract in a three-dimensional fashion. The union of the biliary ducts was studied in 50 patients using spiral computed tomography (CT) after intravenous infusion cholangiography. Depending on the union and course of the cystic duct to the common bile duct, cystic duct anatomy was classified into six categories: ipsilateral gallbladder side (type I) and contralateral side with anterior course (type II); contralateral side with posterior course (type III); intrahepatic side (type IV); intrapancreatic side (type V); and unclassified (type VI). The length of the cystic duct was also determined. The cystic duct was identified in 42 cases (84%); 30 cases (60%) were type I, 9 cases (18%) type III, and a single case (2%) of types II, IV and V, respectively. The length of the cystic duct was < or =2 cm in 30 cases that had a shorter operating time compared to 12 cases with a cystic duct <2 cm (p <0.01). In conclusion, three-dimensional reconstruction of the cystic duct anatomy using spiral CT provides simple classification of bile duct anatomy, and this preoperative information may increase the safety of laparoscopic cholecystectomy.     

Feasibility of Induction Chemotherapy Using Bronchial Arterial Infusion for Locally Advanced Non-Small Cell Lung Cancer: A Pilot Study

Purpose: We examined the feasibility and effectiveness of bronchial arterial infusion (BAI) as induction chemotherapy before surgery for locally advanced non-small cell lung cancer (NSCLC). Methods: Eighteen patients with locally advanced NSCLC were given BAI consisting of cis-diamminedichloroplatinum (CDDP) (50–100 mg/m²) as induction chemotherapy before surgery (induction BAI). Six patients with clinical stage IIIA cancer had bulky N2 metastatic lymph nodes, and 12 patients with clinical stage IIIB cancer had T4 disease. Results: Of the 18 patients, 12 (67%) showed a partial response to the BAI therapy. Standard pulmonary resection was performed in 5 patients, pulmonary resection with the combined resection of adjacent organs was performed in 10 patients, and pulmonary resection with carinal resection and reconstruction was performed in 3 patients. Complete resection was possible in 14 patients (78%). There were no serious BAI therapy-related complications or postoperative deaths. The 5-year survival rate of the 18 patients was 35.7% and the median survival time (MST) was 19.4 months. Survival was better when complete resection was achieved after the induction BAI, especially in patients with stage IIIB (T4) disease. Conclusion: Based on our preliminary findings, BAI with CDDP as induction chemotherapy is feasible and may be an effective therapeutic modality for locally advanced NSCLC. Received: July 26, 2001 / Accepted: March 5, 2002     

High metabolic function of primary human and porcine hepatocytes in a polyurethane foam/spheroid culture system in plasma from patients with fulminant hepatic failure

It has been demonstrated that plasma from patients with fulminant hepatic failure (FHF) interferes extensively with cellular function. We placed primary human and primary porcine hepatocytes in a polyurethane foam (PUF)/spheroid culture system and compared the metabolic functions in the plasma of patients with FHF in a 24-h stationary culture to those in a monolayer culture. The PUF/spheroid culture system using primary human and primary porcine hepatocytes significantly decreased ammonia content during 28-day culture. Fisher's ratio significantly increased at culture days 3 and 7. Tauroursodeoxycholic acid significantly increased and glycochenodeoxycholic acid and taurochenodeoxycholic acid decreased in the FHF patients' plasma at culture day 3. During at least a 24-h culture in the FHF patients' plasma, metabolic functions of primary human and primary porcine hepatocytes were almost identical. The present results indicate that the PUF/spheroid culture system using primary human or primary porcine hepatocytes demonstrated more advantageous metabolic functions in the plasma from patients with FHF than the monolayer culture.     

Pharmacokinetic interaction between TAK-044, a new endothelin antagonist,and ciclosporin in rats

The pharmacokinetic interaction between TAK-044 (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]-L-alanyl-L- alpha-aspartyl-D-2-(2-thienyl) glycyl-L-leucyl-D-tryptophyl] disodium, CAS 157380-72-8) and ciclosporin (CAS 59865-13-3) was investigated after concomitant intravenous (i.v.) administration in rats. After i.v. administration of 14C-labeled TAK-044 ([14C]TAK-044 alone at a dose of 3 mg/kg, the radioactivity concentration in the plasma was 1.65 micrograms/ml at 5 min and decreased biphasically with half-lives of 0.09 h and 0.39 h. AUC0-1 h was 0.38 microgram.h/ml. The pharmacokinetics of [14C]TAK-044 were affected dose-dependently by coadministration with ciclosporin. The AUC value for [14C]TAK-044 was increased 5- and 14-fold by the coadministration with cyclosporin at doses of 3 and 10 mg/kg, respectively. On the other hand, TAK-044 (3 and 10 mg/kg) did not change the pharmacokinetic parameters for ciclosporin (3 mg/kg). Biliary excretion is the major elimination route for both TAK-044 and cyclosporin. Ciclosporin delayed biliary excretion of [14C]TAK-044 in a dose-dependent manner, which might be due to inhibition of process(es) of hepato-biliary excretion of TAK-044. In conclusion, the AUC values for TAK-044 in rats are increased dose-dependently by coadministration with ciclosporin. Therefore, it may be necessary to adjust the dosage of the TAK-044 in combination with ciclosporin in the course of the first clinical trials.     

Helicobacter pylori may survive ampicillin treatment in the remnant stomach

Helicobacter pylori (H. pylori) is a Gram-negative curved rod-like or spiral bacterium that chronically infects the human gastric mucosa, and is a major risk factor for gastritis, gastric and duodenal ulcer and adenocarcinoma of the stomach. After partial gastrectomy, some patients may have persistent H. pylori infection for five years or more. In this study, we detected three bacteria, i.e., Klebsiella pneumoniae, Enterobacter aerogenes, and Escherichia coli, in the gastric juice of patients with a remnant stomach. Some of these bacteria produced beta-lactamase. These findings are potentially important since such bacteria could provide H. pylori with the chance to acquire drug resistance and to transfer drug resistance genes. This could be one reason why H. pylori is difficult to eradicate in the remnant stomach.