Effects of bafilomycin A1, a vacuolar type H+ ATPase inhibitor, on the thermosensitivity of a human pancreatic cancer cell line.

PURPOSE: It has been known that the thermosensitivity of tumour cells can be increased by lowering intra-cellular pH (pHi) by inhibiting pHi control mechanisms. The pHi is partially controlled by transport of H+ from cytoplasm into endocytic and secretary systems in the cells mediated by vacuolar type H+ATPase and also by transport of H+ through plasma membrane. METHODS: This study investigated the effects the bafilomycine A1, an inhibitor of the vacuolar type H+ATPase and the EIPA, an inhibitor of the Na+/H+ exchanger in plasma membrane, on thermosensitivity of AsPC-1 cells, a human pancreatic cancer cell line. It also investigated the effects of combination of bafilomycine A1 and EIPA. RESULTS: The treatment of cancer cells with bafilomycine A1 or EIPA individually slightly lowered pHi of the cells in vitro and increased the thermosensitivity of the cells. CONCLUSION: The combination of these two drugs significantly lowered pHi and increased thermosensitivity of cancer cells in vitro and enhanced the heat-induced the growth delay of AsPC-1 tumours grown s.c in the legs of BALB/cA nude mice.     

Early and late gastric cancer arising in the remnant stomach after distal gastrectomy

AIM: Following distal gastrectomy, carcinogenesis has been suggested to result from gastroduodenal reflux. In this study, surgical cases of gastric cancer arising after distal gastrectomy were analyzed clinico-pathologically and the possible link to reflux examined. PATIENTS: Thirty-two patients (24 males, 8 females; mean age, 68.7 years; age range, 33-84 years) with gastric cancer arising in the remnant stomach after gastrectomy (also known as gastric stump cancer) were included in this study. Patients were divided into two groups on the basis of the initial diagnosis (benign or malignant) prompting surgery, and distal gastrectomy reconstruction method (Billroth I or II). RESULTS: The interval between distal gastrectomy and detection of cancer in the remnant stomach of patients treated initially for a benign gastric condition vs. malignancy was 360+/-33.04 and 63+/-19.16 months (median+/-SE), respectively (p<0.0001). However, the benign and malignant groups did not differ significantly in the clinicopathological analysis of their stump cancers. All 10 patients in whom gastric cancer was diagnosed within five years of initial surgery had initially been surgically treated for malignancy. The interval between surgery and detection of gastric cancer in the Billroth I and Billroth II groups was 84+/-26.67 and 276+/-44.26 months (median+/-SE), respectively (p<0.01). In the remnant stomach, cancer tended to occur near the site of gastrojejunostomy in the Billroth II group (p=0.05). Helicobacter pylori infection was only detected histologically in four patients who had undergone Billroth I reconstructions after distal gastrectomy for malignancy. CONCLUSION: After distal gastrectomy, careful periodic endoscopic examination for microcarcinoma is required in patients, particularly in those who undergo surgery for malignancy, to maximize detection of gastric cancer.     

Spontaneous regression of bone metastasis from renal cell carcinoma; A case report

Background  

Spontaneous regression of metastatic renal cell carcinoma is rarely observed.     

Apolipoprotein E epsilon3 allele is not a risk factor of schizophrenia: a study of 314 Japanese patients

The association between apolipoprotein E (ApoE) alleles and schizophrenia has remained controversial. A recent report claiming that ApoE epsilon3 Taiwan Chinese carriers have an increased risk of schizophrenia prompted us to investigate the allele frequency in a large group of Japanese schizophrenic patients. Serum samples were obtained from 314 schizophrenic patients and 188 controls in Japan and examined using isoelectric focusing/immunoblotting. There were no significant differences in ApoE allele frequencies between schizophrenic patients and controls and in the odds ratios for schizophrenia among the epsilon2, epsilon3 and epsilon4 carriers. In contrast to the report from Taiwan, our findings and results of the majority of previous studies suggest no effects of ApoE alleles on the development of schizophrenia.     

A new approach to detect reticulated platelets stained with thiazole orange in thrombocytopenic patients

Recent studies have shown that reticulated platelets stained with Thiazole Orange (T.O.) are useful markers for thrombopoiesis. The percentage of T.O. positive platelets tends to be inconsistent using the original method, especially when the peripheral blood platelet count is very low. We measured T.O. positive platelet levels in patients with severe thrombocytopenic disorders, using concentrated platelet-rich plasma and carrying out a two-color analysis involving T.O. and an anti-glycoprotein IIb/IIIa monoclonal antibody. This method allowed us to obtain consistent T.O. positive platelet rates in patients with thrombocytopenia whose platelet counts were below 20 approximately 30×10⁹/l. By this method, the T.O. positive rates of platelets from idiopathic thrombocytopenic purpura patients were found to be significantly higher than in the control group. The T.O. positive rates of other thrombocytopenic disorders were similar to those of the control group. These results are consistent with those previously reported. We conclude that our technique of measuring of T.O. positive platelets using platelet-rich plasma is useful for analyzing severe thrombocytopenic disorders.     

Eyelid fluttering accompanying diffuse epileptic EEG induced by eye closure

A 13-year-old male exhibited the following clinical and electroencephalographic (EEG) manifestations. He exhibited marked photosensitivity on EEG from the first visit at 9 years of age until 11 years of age and had an episode of television epilepsy at 9 years of age. Generalized epileptic EEG findings followed by marked eyelid fluttering, induced by eye closure in a bright room that lasted until the eyes were opened, but not by eye closure in a dark room, were first noticed at 11 years of age. A generalized epileptiform EEG was not induced when the light was turned off if the eyes were kept open. His photosensitivity disappeared by 12 years of age, but the eyelid fluttering with epileptic EEG induced by eye closure was still present at 13 years of age. The epileptic EEG was thought to be induced by a modification of the retinal input on eye closure, not by mechanical or sensory stimulation on eye closure or fixation-off sensitivity. In addition, in this patient a change from photosensitive to eye closure-sensitive epilepsy seemed to occur, which suggests that the correlation between the epileptic EEG and retinal input are complex.     

Decreased blood flow at neuroretinal rim of optic nerve head corresponds with visual field deficit in eyes with normal tension glaucoma

PURPOSE: To determine the relationship between the blood flow parameters of the optic disc rim and the glaucomatous visual field changes. DESIGN: Observational cross-sectional study. METHODS: Tissue blood flow in the neuroretinal rim within the optic disc was determined with the Heidelberg retina flowmeter(HRF) in 54 eyes of 54 patients with normal tension glaucoma (NTG). Patients were selected whose visual field defects were confined to either the superior or inferior hemifield. Blood flow measurements were made in a 10 degrees x 2.5 degrees area of the superior and inferior neuroretinal rim within the optic disc. The mean blood flow (MBF) was calculated by the automatic full-field perfusion image analyzer program, and the ratio of the MBF in the superior to the inferior rim areas (the S/I ratio) was calculated from the same HRF image in order to minimize the variation of measurement condition. RESULTS: Inferior rim blood flow is less than superior rim blood flow in patients with superior hemifield defect, and superior rim blood flow is reduced compared to inferior in patients with inferior hemifield defect. The mean S/I ratios of the MBF in the patients with superior hemifield defect (1.46, n=37) was significantly higher than that in the patients with inferior hemifield defect (0.79, n=17; P<0.0001, Mann-Whitney U-test). CONCLUSIONS: The blood flow in the neuroretinal rim was found to correspond to the regional visual field defect in eyes with NTG. Reductions in flow were associated with reductions in function.     

Significance of K-ras mutation and CEA level in pancreatic juice in the diagnosis of pancreatic cancer

The early diagnosis of pancreatic carcinoma is essential for increasing patient survival rates. In this study, 52 patients with suspected pancreatic diseases were examined to investigate the value of K-ras codon 12 point mutation, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9), and cytology of pancreatic juice in the diagnosis of pancreatic carcinoma. Pancreatic juice was taken without secretin stimulation. K-ras mutation was detected by enriched polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). K-ras mutation in pancreatic juice was more frequent in carcinoma than in benign diseases (P = 0.0448). The positive predictive value of K-ras mutation for the diagnosis of neoplastic disease was 83%. The CEA level in pancreatic juice in carcinoma was significantly greater than that in benign disease (P < 0.0001). When the cutoff level of CEA was set at 50 ng/ml, its accuracy for the diagnosis of carcinoma was 85%. A multivariate analysis showed that K-ras mutation and CEA level in pancreatic juice, as well as serum CA19-9 level and age of the patient were independent variables for the diagnosis of carcinoma, and the accuracy of diagnosis by this analysis was increased to 90%. In conclusion, both K-ras mutation and CEA level in pancreatic juice may be valuable for the diagnosis of carcinoma. Better discrimination was possible with a multivariate analysis. Received for publication on Dec. 12, 1998; accepted on July 19, 1999     

Intrafamilial transmission of Salmonella oranienburg

BACKGROUND: There were diffuse outbreaks of Salmonella oranienburg in Japan since March 1999 which included 1505 patients. The outbreak was caused through ingestion of a dried squid snack contaminated with S. oranienburg. Such a large number of cases has not been previously recorded in Japan or other countries. METHODS: A 9-month-old boy was admitted to our hospital with enteritis and bacteremia due to S. oranienburg. His older brother had eaten the contaminated snack. We detected S. oranienburg in the stools of five out of his six family members. RESULTS: With the exception of the index case's brother, no other family members had eaten the contaminated snack. The S. oranienburg strain detected in the family was confirmed to be the same strain by pulse field gel electrophoresis. Therefore, we presumed there had been a series of household transmissions. CONCLUSION: Our observation of intrafamilial transmission suggests that S. oranienburg may be highly infectious.