Relapsed duodenal ulcer after cure of Helicobacter pylori infection

We report a patient—a 42-year-old man—who had suffered from recurrent duodenal ulcer for about 20 years. Successful curative therapy for Helicobacter pylori infection was performed for 2 weeks with new triple omeprazole, anoxicillin, clarithromycin (OAC) treatment in October 1995, and cure of the infection was repeatedly confirmed by histology, culture, and the ¹³C urea breath test. One month after the curative therapy, recurrence of a small duodenal ulcer was observed and in February another duodenal ulcer and reflux esophagitis occurred, with severe symptoms, despite the continuous administration of ranitidine. None of the examinations to reconfirm cure of the infection revealed the presence of H. pylori. As the patient experienced continual psychological stress and smoked more frequently during the recurrent episode and had not used nonsteroidal anti-inflammatory drugs, stress and smoking appeared to play important roles in the relapse of duodenal ulcer in this patient after cure of H. pylori infection. (Received Aug. 18, 1997; accepted Jan. 23, 1998)     

Japanese pharmaceutical professors of a medical university and colleges in colonial Korea (1916-1945)

This study investigates the 14 Japanese pharmaceutical professors who worked in colonial Korea from 1916 to 1945. Of these professors, four worked at Keijyo Imperial University, five worked at Keijyo Medical College, two worked at Taikyu Medical College and two worked at Heijyo Medical College. Nine were physicians and four were pharmacists. Four persons graduated from Tokyo Imperial University, one from Kyoto Imperial University, two from Kumamoto Medical College, one from Toyama Pharmaceutical College, one from Nagasaki Medical College, one from Okayama Medical College and one unknown. A medical degree was obtained by 9 of 14 professors (69.2%), a high rate compared to the same grade of medical institution in Japan at that time. Regarding the positions of the professors in Japan after the end of the Second World War in 1945, four obtained professor positions at universities, three were clinical doctors, one worked for a pharmaceutical company, one was a researcher at an institute, one died and three are unknown.     

Clinical islet transplantation in Japan

Introduction  The results of clinical islet transplantation in Japan are, here in, reported and discussed its efficacy and problems. Methods  Since the first islet transplantation was performed in 2004, 65 islet isolations and 34 islet transplantations to 18 type 1 diabetic patients have been performed in Japan. Results  Following islet transplantation, patients experienced decreased insulin requirements and lower hemoglobin A1C levels, and positive serum C-peptide levels. All patients achieved stabilized blood glucose levels and the disappearance of hypoglycemic unawareness. Although three patients achieved insulin independency for a limited period, persistent islet graft function was difficult to maintain. Overall islet graft survival was 86.5% at 6 months, 78.7% at 1 year, and 62.9% at 2 years after the first islet transplantation. In our institution, we carried out 23 islet isolations and six islet transplantations to four patients. Although insulin independency was not achieved, all patients showed a disappearance of hypoglycemic unawareness. Conclusions  Using data from the Japanese Trial of Islet Transplantation, the effectiveness of islet transplantation was shown even when using the pancreata from non-heart-beating donors. Although there are a number of problems to be solved and further improvement is needed, we can state that the introduction of clinical islet transplantation offers hope for type 1 diabetic patients.     

High postnatal oxidative stress in neonatal cystic periventricular leukomalacia

Oxidative stress plays an important role in cystic periventricular leukomalacia (PVL). We performed a case-control study of preterm infants delivered at <35 weeks of gestation between January 2003 and December 2006. Patients were stratified into three groups, according to age at which cysts were initially identified: ?10 days old (early cystic PVL; n = 10), >10 days old (late cystic PVL; n = 12); and no cystic PVL (controls; n = 22). Serum total hydroperoxide, biological antioxidant potential and oxidative stress index (calculated as total hydroperoxide/biological antioxidant potential) were measured within 3 h after birth. Frequencies of preterm rupture of membrane and chorioamnionitis were significant higher in early cystic PVL than in late cystic PVL or controls. Duration of oxygen treatment and mechanical ventilation and frequency of apnea were significantly higher in late cystic PVL than in controls or early cystic PVL. Serum total hydroperoxide levels and oxidative stress index were significantly higher in early cystic PVL than in late cystic PVL or controls (p < 0.05, respectively). Postnatal duration until cyst identification displayed a significant negative correlation with oxidative stress index and total hydroperoxide level (r = −0.497, p < 0.05; r = −0.50, p < 0.05, respectively). These findings suggest that early onset of cystic PVL might be due to either antenatal or intrapartum factors, but late onset might be due to postnatal factors. In the pathophysiology and therapy of cystic PVL, oxidative stress and onset timing appear crucial. This is the first study to reveal that neonates experiencing much more oxidative stress at birth show earlier onset of cystic PVL.     

Reliability and validity of a Japanese version of the Cambridge depersonalization scale as a screening instrument for depersonalization disorder

Aims:  The Cambridge Depersonalization Scale (CDS) is an instrument that has obtained reliability and validity in some countries for use in detecting depersonalization disorder under clinical conditions, but not yet in Japan under non-psychiatric conditions. The purposes of this study were to develop a Japanese version of the CDS (J-CDS) and to examine its reliability and validity as an instrument for screening depersonalization disorder under non-clinical conditions.
Methods:  The CDS was translated from English into Japanese and then back-translated into English by a native English-speaking American. After making the J-CDS, we examined its reliability and validity. Questionnaires that were composed of J-CDS, the Dissociative Experience Scale (DES), the Zung self-rating scale and the Maudsley Obsessional–Compulsive Inventory were administrated to 59 participants (12 patients with depersonalization disorder, 11 individuals who had recovered from depersonalization and 36 healthy controls).
Results:  Cronbach's alpha and split-half reliability were 0.94 and 0.93, respectively. The J-CDS score in the depersonalization group was significantly higher than in the healthy control group. The J-CDS score was significantly correlated with scores of total DES, and DES-depersonalization. The best compromise between the true positive and false negative rate was at a cut-off point of 60, yielding a sensitivity of 1.00 and a specificity of 0.96.
Conclusions:  In this study, J-CDS showed good reliability and validity. The best cut-off point, when we use this for distinguishing individuals with depersonalization disorder from individuals without psychiatric disorders, is 60 points.     

MEK Activation Suppresses CPT11-Induced Apoptosis in Rat Intestinal Epithelial Cells Through a COX-2-Dependent Mechanism

Resistance to chemotherapeutic agents is one of the distinct features of cancer cells. We evaluate the role of activated MEK-ERK signaling in Camptotecin/irinotecan (CPT-11)-induced cell death using constitutively activated MEK1-transfected normal rat intestinal epithelial cells (IEC-caMEK cells). A CPT-11-induced inhibitory concentration of 50% was determined by WST assay. Apoptosis was evaluated by DNA staining and fragmented DNA analysis. Protein expressions were analyzed by western blotting. We also examined the role of cyclooxygenase-2 in the cell systems. IEC-caMEK cells possessed survival advantages compared to control cells. Apoptosis was remarkably suppressed in IEC-caMEK cells. Western blot analysis revealed increased expression of Bcl-2, Bcl-xL, Mcl-1, and COX-2 and decreased expression of Bak in IEC-caMEK cells. The COX-2 selective inhibitor ameliorated the antiapoptotic nature of IEC-caMEK cells. MEK activation suppressed CPT-11-induced apoptosis in IEC-caMEK cells via a COX-2- dependent mechanism. Therefore, MEK-ERK signaling may contribute to the drug-resistant nature of cancer cells.     

Involvement of Mutation-based Inhibition of β-Catenin Phosphorylation at Ser33 in the Malignant Progression of Lung (Pre)neoplastic Lesions Induced by N-nitrosobis(2-hydroxypropyl)amine in Male Fischer 344 Rats

In this study we investigated the Ser33 phosphorylation status of beta-catenin protein in relation to genomic mutations in lung (pre)neoplastic lesions induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in male Fischer 344 rats. Six-week-old animals received 2000 ppm of BHP in the drinking water for 8 weeks and were sacrificed 12 weeks thereafter. Histopathologically, 69 of 75 rats demonstrated multiple lung (pre)neoplastic lesions, classified into 27 slight and 33 advanced hyperplasias (preneoplasms) and 61 neoplasms, including adenomas, adenocarcinomas, and adenosquamous carcinomas. Nucleotide mutation analysis of the beta-catenin gene detected a total of 33 mutations in 12 assessed lung (pre)neoplastic lesions. The mutations tended to accumulate in positions near the phosphorylation region of the gene, between codons 33 and 45. Immunohistochemical analysis showed beta-catenin protein expression to be increased and its localization changed from the cell membrane to the cytoplasm and finally the nuclei with advancing malignancy of the lung lesions. In contrast, the expression of phosphorlyated beta-catenin protein at Ser33 was weakened in lung (pre)neoplastic lesions compared to normal lung tissues. These results suggest that BHP-induced mutation of the beta-catenin gene results in amino acid conversions in its product protein, which in turn lead to inhibition of phosphorylation of the protein and escape from protein degradation. These phenomena might contribute to the malignant progression of the lung (pre)neoplastic lesions, which start from the relatively early stage in lung carcinogenesis.     

Development of multiplex real-time PCR assay for the detection of herpes simplex virus types 1 and 2

We developed a multiplex real-time PCR assay to simultaneously detect herpes simplex virus-1 (HSV-1) and HSV-2 genomes. TaqMan PCR primer pairs and fluologenic probes targeting the HSV-1 or HSV-2 gpD region were originally designed. The detection limit was 15 copies/tube, and the quantitative range was from 15 to 1.5 x 10(6) copies/tube of HSV-1 or HSV-2 DNA. The sensitivity of this assay was 10(3) times higher than the conventional PCR assay. No other herpes virus DNA-Cytomegalovirus, Epstein-Barr virus, human herpes virus 6, human herpes virus 7, or varicella-zoster virus-were detected by this assay. These results indicated that the multiplex real-time PCR assay is useful for rapidly diagnosing HSV-1 and HSV-2.