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Objectives The aim of this AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial subgroup analysis was to examine rivaroxaban monotherapy benefits and their relation to the time between stenting and enrollment among patients after coronary stenting. Background Of 2,215 patients with atrial fibrillation and stable coronary artery disease in the AFIRE trial, rivaroxaban monotherapy was noninferior to rivaroxaban plus antiplatelet therapy (combination therapy) in terms of efficacy and superior for safety endpoints. However, thrombotic risk after antiplatelet therapy cessation remained a concern among 1,444 patients who had undergone coronary stenting >1 year before enrollment. Methods The benefits of rivaroxaban monotherapy in coronary stenting subgroups were assessed for efficacy (a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death of any cause), safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria), ischemic endpoints, net adverse clinical event, and time between stenting and enrollment. Results Efficacy and safety endpoints for monotherapy were superior to combination therapy, with HRs of 0.70 for efficacy (95% CI: 0.50-0.98; P = 0.036) and 0.55 for safety (95% CI: 0.33-0.92; P = 0.019). For ischemic endpoints, the HR was 0.82 (95% CI: 0.58-1.15; P = 0.240). The HR became smaller with longer time between stenting and enrollment (efficacy, P for interaction = 0.158; safety, P = 0.097). Conclusions In patients with atrial fibrillation after coronary stenting, the benefits of rivaroxaban monotherapy for efficacy and safety endpoints were consistent with those in the whole AFIRE trial population. The benefits became apparent with longer time between stenting and enrollment. (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study [AFIRE]; UMIN000016612 , NCT02642419 )

We investigated soil organic carbon (SOC) storage and the quantitative relationship between SOC and geochemical properties in tropical surface and subsurface soils, where information on various soil geochemical properties remains limited. We used soil samples from 178 sites in Indonesia, Thailand, Cameroon, and Tanzania as tropical soils and 34 sites in Japan as a comparison. The tropical soils were acidic, formed under high precipitation. We separated the soil samples into three groups based on the degree of weathering. We applied correlation and single regression analyses between SOC and geochemical properties including oxalate extractable Al and Fe (Alo + Feo), pyrophosphate extractable Al and Fe (Alp + Fep), and clay + silt. In the subsurface soils, Alo + Feo and Alp + Fep were strongly correlated with SOC (r = 0.79–0.85 and 0.58–0.85, respectively), and the quantitative relationships of SOC with these properties were similar in all the weathering groups (4–5 and 5–8, respectively). On the other hand, no strong correlation with SOC or similar quantitative relationships among the weathering groups were found for clay + silt. In the surface soils, Alo + Feo and Alp + Fep were correlated with SOC (r = 0.48–0.56 and 0.55–0.76, respectively), but the ratio of C to active Al and Fe was higher probably because of the large C input. Our results highlight the importance of Alo + Feo and Alp + Fep in SOC storage, of which the ratios to SOC are similar in each of the surface and subsurface soils regardless of the weathering degree.

Lactobacillus-fermented milk can stimulate anabolic effects in skeletal muscle. Fermented milk containing Lactobacillus produces aqueous molecules, such as free AA and lactate. This study aimed to investigate how processing fermented milk by centrifugation and removal of supernatant affects AA absorption and postprandial skeletal muscle protein synthesis (MPS) when mice are fed fermented milk. We gavaged male Sprague-Dawley rats with skim milk (S), fermented milk (F), or processed fermented milk (P), and examined the total AA content in portal vein blood (reflecting AA absorption) and plantaris muscle MPS at 30, 60, and 90 min following administration. Relative to fasted rats, at 30 min the total AA concentration in portal vein blood from rats in the P groups was significantly higher, followed by F and S, respectively. The MPS rates were higher for the F or P groups compared with the S group. Phosphorylation levels of p70S6 kinase in the P and F groups were significantly higher than those for the S group 30 min after administration, although the level of Akt phosphorylation was similar among the groups. These results suggested that fermentation improves AA absorption that in turn enhances postprandial MPS via Akt-independent mechanisms, and that processed fermented milk retains these favorable effects on MPS.

Despite the numerous materials that have been developed, controlling the self-organisation and detailed characterisation of hierarchical nanostructures composed of various functional molecular units remains a challenging task. Herein, we report a facile approach for creating flat nanosheets and helical nanofibres for ultrathin films (ca. 12 nm) and thin films (ca. 120 nm), respectively. These films contain a member of the cyclodextrin family, trimethyl β-cyclodextrin (TMCD), and form via self-organisation with heating (thermal annealing) in the absence of both polymeric components and organic solvent. X-ray reflectivity (XRR) and grazing-incident-angle X-ray diffraction (GIXD) readily explain the characteristic molecular assembling behaviour in the thin films, such as the highly perpendicularly ordered polycrystalline structure of the nanosheet crystal films and the dewetting behaviour for the fabrication of bundled nanofibres. In addition to X-ray analysis, scanning electron microscopy (SEM) and atomic-force microscopy (AFM) imaging reveals that the obtained nanofibres are well rounded and partially double or triple-helical coiled, with highly frustrated characteristics. The surface homogeneity prior to the thermal annealing was found to be crucial to determine the creation of the helical nanofibre structure. Also, the results suggest the importance of the absence of solvent vapour for the creation of the helical nanofibres. Thus, this report proposes a facile self-organisation process for creating polymer-free cyclodextrin-based nanostructures that should have wide applications. It also shows the effectiveness of X-ray analyses combined with several surface-sensitive X-ray techniques and microscopy observations.

Background The percutaneous coronary intervention (PCI) strategy for chronic total occlusion (CTO) based on the guidewire manipulation time remains infrequent. Purpose We aimed to assess CTO-PCI strategy on the basis of guidewire manipulation time. Methods A total of 5843 patients undergoing CTO PCI between January 2014 and December 2017 and enrolled in the Japanese CTO-PCI expert registry were assessed. Their CTO-PCI strategies, procedural outcomes, and guidewire manipulation time were analysed. Results The primary retrograde approach was performed on 1562 patients (26.7%). The overall guidewire and technical success rates were 92.8% and 90.6%, respectively. Median guidewire manipulation time of guidewire success and failure were 56 (interquatile range [IQR]: 22 to 111) min and 176 (IQR: 130 to 229) min, respectively. The average Japanese CTO score of the primary antegrade approach with the antegrade alone, the primary antegrade approach with the retrograde approach, and the primary retrograde approach were 1.7±1.1, 2.1±1.2, and 2.3±1.1, respectively (p Conclusions Although successful guidewire crossing time of the primary antegrade approach with the antegrade alone is short, that of the primary retrograde approach can be shorter than that of the primary antegrade approach with the retrograde approach. Choosing an appropriate CTO-PCI strategy leads to shortening of successful guidewire crossing time.

Background TAK-438 (vonoprazan) is a potassium-competitive acid blocker that reversibly inhibits gastric H+, K+-ATPase. Aim To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of TAK-438 in healthy Japanese and non-Japanese men. Methods In two Phase I, randomised, double-blind, placebo-controlled studies, healthy men (Japan N = 60; UK N = 48) received TAK-438 10–40 mg once daily at a fixed dose level for 7 consecutive days. Assessments included safety, tolerability, pharmacokinetics and pharmacodynamics (intragastric pH). Results Plasma concentration–time profiles of TAK-438 at all dose levels showed rapid absorption (median Tmax ≤2 h). Mean elimination half-life was up to 9 h. Exposure was slightly greater than dose proportional, with no apparent time-dependent inhibition of metabolism. There was no important difference between the two studies in AUC0-tau on Day 7. TAK-438 caused dose-dependent acid suppression. On Day 7, mean 24-h intragastric pH>4 holding time ratio (HTR) with 40 mg TAK-438 was 100% (Japan) and 93.2% (UK), and mean night-time pH>4 HTR was 100% (Japan) and 90.4% (UK). TAK-438 was well tolerated. The frequency of adverse events was similar at all dose levels and there were no serious adverse events. There were no important increases in serum alanine transaminase activity. Serum gastrin and pepsinogen I and II concentrations increased with TAK-438 dose. Conclusions TAK-438 in multiple rising oral dose levels of 10–40 mg once daily for 7 days was safe and well tolerated in healthy men and caused rapid, profound and sustained suppression of gastric acid secretion throughout each 24-h dosing interval. Clinicaltrials.gov identifiers: NCT02123953 and NCT02141711.

Aliment Pharmacol Ther 2011; 33: 213–224 Summary Background The efficacy of rabeprazole 5 mg/day for patients with non-erosive reflux disease (NERD) has not been reported in the literature. Aim To evaluate the efficacy of rabeprazole 5 mg and 10 mg/day in Japanese NERD patients. The influence of baseline characteristics as well as genetic background on efficacy was also analysed. Methods Subjects were grade M (minimal changes) NERD patients. Two hundred and eighty-eight of these subjects, who were nonresponders to open label antacid therapy, entered in a 4-week, double-blind treatment (placebo, rabeprazole 5 mg or 10 mg/day). Results Complete heartburn relief rates were 21% in placebo, 34% in rabeprazole 5 mg and 44% in rabeprazole 10 mg (5 mg vs. placebo P = 0.074, 10 mg vs. placebo P = 0.001). Rabeprazole 5 mg was significantly more effective than placebo in elderly patients and in patients with low heartburn frequency or without hiatal hernia. The efficacy of rabeprazole 10 mg was not influenced by age, BMI, hiatal hernia, Helicobacter pylori infection, frequency and severity of heartburn or CYP2C19 genotypes. Conclusions Rabeprazole 5 mg was effective in a subgroup of Japanese NERD patients. Rabeprazole 10 mg provided more potent heartburn relief than 5 mg and was less fragile to baseline characteristics.

Despite an intriguing understanding of trabecular bone dynamics, little is known about corticosteroid-induced cortical bone loss and fractures. Recently, we verified a steroid-induced decrease in cortical bone volume and density using peripheral quantitative computed tomography (pQCT) in adult asthmatic patients given oral corticosteroids. Subsequently, the pQCT parameters and presence of vertebral fractures were investigated to further clarify the role of cortical bone quality in fractures in 86 postmenopausal (>5 years after menopause) asthmatic patients on high-dose oral steroid (>10 g cumulative oral prednisolone) (steroid group) and 194 age-matched controls (control group). Cortical and trabecular bone was subjected to measurement of various parameters using pQCT (Stratec XCT960). Relative Cortical Volume (RCV) was calculated by dividing the cortical area by the total bone area. Strength Strain Index (SSI) was determined in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. Patients treated with high doses of oral steroid (>10 g cumulative oral prednisolone) were found to have an increased risk of fracture compared with control women receiving no steroid medication (odds ratio, 8.85; 95% CI, 4.21-18.60) after adjustment was made for years since menopause, body mass index and RCV. In both groups, the diagnostic and predictive ability of the pQCT parameters for vertebral fracture was assessed by the areas under their receiver operating characteristic (ROC) curves. All parameters were found to be significant predictors ( p

Plastic deformation behaviour and microstructure in Ti-62.5at.%Al single crystals with [201] loading axis were examined at high temperatures between 800°C and 1200°C. Two types of Al 2 Ti superstructures which were based on the L1 0 -type ordered structure were formed in the L1 0 matrix depending on the temperature: a plate-like r-Al 2 Ti-type phase was formed below 1200°C, while fine h-Al 2 Ti-type precipitates in several ten nanometre size were visible at and above 1200°C. The yield stress decreased with increasing temperature, while elongation and stress sensitivity index m showed an opposite temperature dependence accompanied by a rapid increase at 1200°C. The large elongation and uniform deformation at 1200°C may be related to the balance between the softening by the frequent climb motion of dislocations and the hardening by dragging due to fine coherent h-Al 2 Ti precipitates in the γ matrix during deformation at the steady state region.

Arterial rings were prepared from the branchial artery, coeliac artery and ventral aorta of the Japanese dogfish Triakis scyllia and used to determine arterial contraction in a myograph. Noradrenaline caused a dose-dependent contraction (10 -9 -3× 10 -6 M) that was completely inhibited by pre-treatment with 10 -7 M phentolamine. Homologous dogfish angiotensin II (ANG II) ([Asn 1 , Pro 3 ,Ile 5 ]-ANG II) also caused dose-dependent contraction (10 - 9 -3 × 10 -6 M), but phentolamine had no effect on this response. Administration of dogfish angiotensin I (ANG-I) ([Asn 1 ,Pro 3 ,Ile 5 ,Gln 9 ]-ANG I) resulted in a contraction similar to that produced by ANG II and the effect could be blocked with 10 -7 M captopril. The mammalian ANG II receptor antagonists [Sar 1 ,Ile 8 ]-ANG II and [Sar 1 ,Ala 8 ]-ANG II caused dose-dependent contractions of coeliac artery rings, but were less potent than homologous ANG I and ANG II. These results show that the contractile effect of [Asn 1 ,Pro 3 ,Ile 5 ]-ANG II is not mediated by the α-adrenergic system and contractions of arterial rings by noradrenaline and elasmobranch ANG II are mediated by separate vascular receptors. The elasmobranch ANG II vascular receptor may have co-evolved with the unusual structure of this peptide.

The interaction between homologous dogfish angiotensin II ([Asn1, Pro3, Ile5]-AngII) and catecholamines was examined using blood pressure bioassay. Both noradrenaline and [Asn1, Pro3, Ile5]-Ang II elicited a pressor response. Pre-treatment with phentolamine (1 mg kg-1) completely abolished the noradrenaline pressor response but did not alter the magnitude of the [Asn1, Pro3, Ile5]-Ang II pressor response although there was an initial delay in the response to [Asn1, Pro3, Ile5]-Ang II. These results indicate that the Ang II-induced pressor response is a direct Ang II-mediated vascular response in elasmobranchs.

Diurnal variation in intragastric pH in children with peptic ulcers has not been previously reported. Therefore, we monitored intragastric pH during a 24-h period in 82 subjects (10 children with gastric ulcers, 9 children with duodenal ulcers, 58 non-ulcer (comparison group) children, and 5 healthy adults) using a monopolar glass pH electrode. The percent of readings below pH 2, 3, 4, and 5 for each subject was calculated and compared between the comparison group and the two ulcer groups using means and slopes (i.e. changes in percent with age for each group) of percent readings for each pH analysis. In the comparison group children, gastric acidity increased with age and reached adult levels by 14 y. Mean readings for all pH analyses in gastric ulcer children were lower than those in age-adjusted comparison children (p < 0.05). The slopes of the relationships between age and the percent time below any pH for the gastric ulcer group were different from those in the comparison group (p < 0.05) and were negative for all pH analyses. The mean time below pH 2 in children with duodenal ulcers was greater than that in age-adjusted comparison children (p = 0.002). The slope of the relationship between age and the percent time below pH 2 in the duodenal ulcer group was different from that in the comparison group (p < 0.05). Gastric acidity in children with primary gastric ulcers was reduced during childhood, but in children with primary duodenal ulcer, gastric acidity was at or above adult levels.

Three types of models, i. e. one fluid model, two fluid model and particlefluid model, are generally applied to investigate the characteristics of two phase flows. In each model, the careful consideration on the structures of governing equations and the constitutive relations employed should be needed. Essential point to be discussed in this paper is how the effects of interactions between two phases are taken into account in these basic equations.

This study demonstrates the potent vasopressor activity of homologous dogfish angiotensin (A) I and II. The AII competitive binding inhibitors [Sar1-Val5-Ala8]-AII and [Sar1-IIe8]-AII did not inhibit the pressor action of dogfish AII but the converting enzyme inhibitor captopril effectively blocked conversion of AI to AII.

Proton pump inhibitors (PPIs) are less effective in non-erosive reflux disease (NERD) patients than in reflux oesophagitis patients. Whether the addition of prokinetics to PPIs improves NERD patients' symptoms remains unknown.To evaluate the efficacy of mosapride in NERD patients when used with PPI.A total of 200 NERD patients were randomised to one of two arms: omeprazole (10 mg once daily) plus mosapride citrate (5 mg three times a day) (treatment arm) and omeprazole plus placebo (placebo arm). The primary endpoint was the rate of responders [visual analogue scale (VAS) was zero or1 cm] after 4 weeks of treatment. The secondary endpoints were changes in the VAS score and the safety profile.There was no significant difference between the rates of responders in both arms in intent-to-treat (ITT) and per-protocol (PP) analysis. The change in the VAS score in treatment arm was significantly better than placebo arm in PP analysis (-4.0 ± 0.2 and -3.3 ± 0.2, mean ± S.E.M.) (N.S. in ITT analysis). The rate of adverse events was similar in both groups.The addition of mosapride to omeprazole was not more effective than omeprazole alone.

The efficacy of rabeprazole 5 mg/day for patients with non-erosive reflux disease (NERD) has not been reported in the literature.To evaluate the efficacy of rabeprazole 5 mg and 10 mg/day in Japanese NERD patients. The influence of baseline characteristics as well as genetic background on efficacy was also analysed.Subjects were grade M (minimal changes) NERD patients. Two hundred and eighty-eight of these subjects, who were nonresponders to open label antacid therapy, entered in a 4-week, double-blind treatment (placebo, rabeprazole 5 mg or 10 mg/day).Complete heartburn relief rates were 21% in placebo, 34% in rabeprazole 5 mg and 44% in rabeprazole 10 mg (5 mg vs. placebo P = 0.074, 10 mg vs. placebo P = 0.001). Rabeprazole 5 mg was significantly more effective than placebo in elderly patients and in patients with low heartburn frequency or without hiatal hernia. The efficacy of rabeprazole 10 mg was not influenced by age, BMI, hiatal hernia, Helicobacter pylori infection, frequency and severity of heartburn or CYP2C19 genotypes.Rabeprazole 5 mg was effective in a subgroup of Japanese NERD patients. Rabeprazole 10 mg provided more potent heartburn relief than 5 mg and was less fragile to baseline characteristics.

Micro mechanical fabrication is one of practical manufacturing technologies for small and precise products and devices. It mainly covers mesoscopic region between 10 microns and 1 mm. Near the lower limit of the region, it is believed silicon-based technologies are the most efficient processes and mechanical fabrication can be applied only to one-off production. The authors proposed a concept of a miniature factory called ldquoMicrofactoryrdquo and showed that the concept could be rather efficient when the system configuration is designed properly. We insisted the ldquoMicrofactoryrdquo is a hopeful system not only for one-off production, but also for diverse-types-and-small-quantity production. In addition, since manufacturing technologies should be also environmentally conscious, downsizing the manufacturing system can be an option to reduce environmental impact of manufacturing. However, whether the system is really ldquoeco-efficientrdquo has not been examined quantitatively. An appropriate index to evaluate manufacturing systems by considering environmental impacts, costs and system throughput, simultaneously, will help the concept to become more practical. In this report the authors propose an efficiency index named ldquototal performance indicator (TPI).rdquo Using the microfactory as an example, the paper tries to show that the proposed efficiency index is useful in designing configurations of manufacturing systems. Later, the paper also introduces the next generation microfactory which is called ldquoon-demand factoryrdquo to prove that the concept is really practical. Comparison with a conventional system indicates that the on-demand factory is an efficient manufacturing system in environmental and economical aspects.

This paper shows the performance evaluation of the mathematical formula recognition system applied to a large scale of printed formula images, which has been developed in our laboratory. Our laboratory has collaborated with Michler of University of Essen, Germany, on project of "Retro-digitalization of mathematical journals, and their integration searchable digital libraries". In this project, two kinds of mathematical journals were scanned for digitalization. In this process, we cut out formulas manually from many pages, and created the answer database, "Ground-Truth." We report the results of performance evaluation with respect to the recognition of symbols, various types of sub-expressions and whole expressions of mathematical formulas.

The injection system for the new 8-GeV storage ring is described. The system is composed of a 1.5-GeV linac and a 8-GeV synchrotron which are able to accelerate electrons and positrons. In order to fill the storage ring with positrons in a short time, the synchrotron is operated as an accumulation ring to store the particles at 1.5 GeV for 8 s. The acceleration and deceleration in the synchrotron are each realized in 0.9 s. The linac and the synchrotron are described, and the operation scenario is presented. >

The valence-band structure of Yb-filled CoSb/sub 3/ skutterudites has been investigated by X-ray photoelectron spectroscopy for an understanding of the effect of Yb filling on the electronic and thermoelectric properties of CoSb/sub 3/. The valence-band and core-level spectra clearly indicated the intermediate valence states of Yb between divalent and trivalent in Yb-filled CoSb/sub 3/, in good agreement with the results of band calculations made by the full-potential linearized augmented-plane-wave method. The effect of Yb filling on the electronic properties (carrier mobility, effective mass, lattice thermal conductivity, etc.) is discussed in terms of an electronic model obtained from band calculations. The electronic properties of CoSb/sub 3/ are substantially affected by Yb filling, resulting in the large thermoelectric figure of merit for Yb filling as compared to other rare-earth filling. It is suggested that the mixed valence states of Yb play an important role in the improvement of thermoelectric properties.

The presence of serum anti-p53 antibody has been reported to be associated with survival of patients with breast cancer, ovarian cancer, and hepatocellular carcinoma. To clarify prognostic significance of p53 antibody in colorectal cancer, serum p53 antibody was measured in patients with colorectal cancer. The 89 patients included 71 with colorectal cancer and 18 with colon polyp. An enzyme-linked immunosorbent assay was used to detect p53 antibodies in serum. Clinicopathological parameters such as age, sex, degree of differentiation of cancer, location of tumor, liver metastasis, stage classification, Dukes classification, CEA, CA19-9, and immunostaining of p53 and anti-p53 antibody were evaluated as prognostic factors of colorectal cancer. p53 antibody was positive in 18 of 71 (25%) with colorectal cancer, whereas it was positive in only 1 of 18 (6%) with colon polyp. The patients with p53 antibody had higher CEA and CA19-9 levels, higher positive rates of p53 protein expression in cancer cells, and higher liver metastasis rates. The p53 antibody positivity at stage classification I-IIIb/ Dukes classification A-C was significantly lower than that at stage classification IV/Dukes classification D. Overall survival in colorectal cancer patients with p53 antibody was significantly shorter than in those without p53 antibody. A Cox regression analysis showed that liver metastasis, stage classification, Dukes classification, CA19-9, and p53 antibody were significant prognostic factors in colorectal cancer. Serum anti-p53 antibody could serve as one of the prognostic factors in patients with colorectal cancer.

The c-erbB-2 proto-oncogene encodes a transmembrane protein which is highly homologous to epidermal growth factor receptor. Overexpression of this c-erbB-2 protein has been reported in many human carcinomas, including breast carcinoma. However, there have been few studies of the expression of c-erbB-2 in cholangiocarcinoma and hepatolithiasis, a condition occasionally associated with cholangiocarcinoma.In this study, we evaluated immunoreactivity for the c-erbB-2 protein in human cholangiocarcinomas (n = 47), hepatolithiasis (n = 20), fetal livers (n = 36) and normal adult livers (n = 6). In normal adult livers and fetal livers, expression of c-erbB-2 protein could not be detected in hepatocytes or intrahepatic biliary cells. In hepatolithiasis, there was overexpression of c-erbB-2 in 15/20 (75%). The expression was found with a membranous pattern on the proliferated intrahepatic bile ducts and proliferated intrahepatic peribiliary glands around the bile ducts containing stones. Hepatocytes were negative for c-erbB-2 protein. Moreover, the biliary cell expression of the c-erbB-2 protein correlated significantly with Ki67 labelling index. On the other hand, aberrant expression of c-erbB-2 was found in 33/47 (70%) cholangiocarcinomas. The c-erbB-2 expression in cholangiocarcinomas did not correlate with Ki67 labelling index or p53 expression.These results indicate that aberrant expression of c-erbB-2 protein is found in cholangiocarcinoma and also in noncancerous biliary proliferative lesions such as hepatolithiasis. These findings also suggest that c-erbB-2 oncogene participates not only in cholangiocarcinogenesis but also in biliary cell proliferation in non-neoplastic conditions.

An examination was made of the postoperative long-term effects of limited gastrectomy (LG) on nutritional status, as one of the factors that influence quality of life.Nutritional status in 33 patients who underwent LG for early gastric cancer, was compared with that of 36 patients who underwent standard gastrectomy (SG). Nutritional conditions were assessed preoperatively, and then 1 and 2 weeks, 1 and 6 months, and 1, 2 and 3 years after surgery.Postoperative recovery of both body weight and body fat mass was greater in LG than SG, and there were significant differences between the two groups of patients from six months after surgery until three years had elapsed.LG minimized the extent of nutritional impairment during long-term recovery from surgery, as compared with SG. LG would seem to be a suitable operative procedure for some patients with mucosal gastric cancer, without reducing radicality for cancer.

The presence of serum p53 antibody has been reported to have prognostic significance in patients with breast and ovarian cancers. In order to clarify clinical and prognostic significance of p53 antibody in serum, we measured p53 antibody in patients with gastric cancer. Twenty-five patients with gastric cancer were examined as well as 9 patients with gastric polyp as controls. Eight of 25 patients (32%) with gastric cancer were positive for p53 antibody, while no patients with gastric polyp were positive in gastric polyp group (p0.05). The presence of p53 antibody was significantly associated with histology, liver metastasis and stage classification in gastric cancer (p0.05, respectively). Presence of liver metastasis, type of histology and presence of p53 antibody are independent prognostic factors (p0.05, respectively). The overall survival in patients with p53 antibody was significantly shorter survival than for those without antibody (p0.05%). These data suggest that p53 antibody serves as one of the prognostic factors in gastric cancer.

To evaluate cell proliferative activity and expression of cytokeratins (CKs) and epithelial membrane antigen (EMA) in intraductal papillary-mucinous neoplasm of the pancreas (IPNP).We examined cell proliferative activity in normal pancreatic ducts, IPNP, and invasive ductal adenocarcinoma of the pancreas by immunohistochemistry for proliferating cell nuclear antigen (PCNA) and Ki67 antigen. Expression of CKs and EMA was also examined immunohistochemically.In normal pancreas (n = 5), PCNA- or Ki67-positive ductal epithelia were not found. Cytokeratins (polyclonal, CAM5.2, CK-7, CK-8, CK-18, and CK-19) were expressed in the ducts and ductules but not in the acinus, and EMA expression was noted in the acinus but rarely in the ducts. In IPNP (n = 9) and invasive ductal adenocarcinoma (n = 6) of the pancreas, the overall PCNA-labeling index (PCNA-LI) was 3.2 +/- 4.1 and 16.0 +/- 7.2, respectively, and overall Ki67-LI was 2.2 +/- 2.6 and 14.5 +/- 6.3, respectively. In IPNP, the PCNA-LI and Ki67-LI were low in adenoma areas (PCNA-LI = 0.9 +/- 0.7), intermediate in dysplastic areas (PCNA-LI = 3.7 +/- 2.4), and rather high in carcinoma in situ areas (PCNA-LI = 11.5 +/- 8.4). Both CKs and EMA were noted in tumor cells.The data suggest that cell proliferative activity is low in IPNP compared to invasive ductal adenocarcinoma, that cell proliferative activity increases with the grade of cell atypia in IPNP, and that CK expression is not changed during the neoplastic change, but EMA is newly expressed or overexpressed during the neoplastic change.

The endocrine cells in intraductal papillary-mucinous neoplasms (IPN) of the pancreas have rarely been investigated. In the normal pancreatic ducts of normal pancreases (n = 5) there were a few endocrine cells: argyrophil in 5 (100%), chromogranin A in (100%), pancreatic polypeptide (PP) in 3 (60%), and insulin in 7 (20%). These endocrine cells were scattered, and located in the basal portions of pancreatic ducts. In IPN of the pancreas (n = 9), there were many endocrine cells: argyrophil in 7 (78%), argentaffin in 8 (89%), chromogranin A in 8 (89%), PP in 7 (78%), serotonin in 7 (78%), insulin in 4 (44%), and gastrin in 5 (56%). In invasive ductal adenocarcinoma of the pancreas (n = 6), many endocrine cells were also detected: argyrophil cells in (67%), chromogranin A in 3 (50%), insulin in 3 (50%), glucagon in 4 (67%), and somatostatin in 3 (50%). In positive cases, endocrine cells were situated under or among the neoplastic cells and the proportion of endocrine cells in IPN was less than 5% of the total neoplastic cell population. These data show that normal pancreatic ducts contain endocrine cells and that IPN frequently contain argyrophil, argentaffin, chromogranin A, and hormone-containing endocrine cells. These data also suggest that endocrine differentiation occurs during neoplastic transformation and progression of IPN of the pancreas.

To evaluate the effects of complex spa therapy (swimming training in a hot spring pool + fango therapy + inhalation of iodine salt solution) on psychological factors, three psychological examinations; CMI (Cornell Medical Index), SDS (Self-Rating Depression Scale) and CAI (Comprehensive Asthma Inventory); were given 25 patients with bronchial asthma (10 male, 15 female, mean age 60 years), and the results of these examinations were compared before and after spa therapy. 1. Physical symptoms, respiratory system and CIJ symptoms by CMI were significantly improved after spa therapy, however the improvement of psychical symptoms was not significant. 2. In SDS, 11 of 25 patients showed more than 40 points, indicating depressive state. The number of such patients decreased from 11 to 2 and the mean SDS score significantly improved from 38.7 to 34.2 after spa therapy. 3. Conditioning, suggestion, fear of expectation, frustration, flight into illness, negative attitudes towards prognosis, and decreased motivation towards therapy by CAI were significantly reduced after spa therapy, with the reduction in negative attitudes towards prognosis and decreased motivation towards therapy being relatively large. Furthermore, CAI score, which is the average of the categories in CAI, was also significantly decreased from 37.9 to 28.4 after spa therapy. These results suggested that complex spa therapy improves psychological factors in patients with bronchial asthma.

We quantified regional cerebral blood flow using 99mTc-bicisate ethyl cysteinate dimer (ECD) radionuclide (RN) angiography, one-point arterial sampling and static SPECT in 12 patients. The tracer was injected as a bolus into the right antecubital vein, and time-activity curves over the cerebrum and the aortic arch were sequentially recorded for 300 s with 3 s intervals in a 128 x 128 format with a large-field of view gamma camera equipped with a low-energy collimator. Blood was obtained from the femoral artery immediately after stopping the RN angiography and the arterial concentration of 99mTc-ECD was calculated. Thereafter, the SPECT data acquisition was started with the subject's head immobilized. We applied a three-compartment kinetic model: The influx constant of 99mTc-ECD from blood to brain (K1) and the transfer of ECD from diffusible compartment to nondiffusible one in the blood (k5). The K1 value was compared with the global cerebral blood flow value (Fa) measured by the 133Xe clearance technique. From the kinetic analysis, the following parameter values could be calculated: K1 = 0.21 +/- 0.05 (ml/ml/min), k5 = 0.66 +/- 0.15 (/min), Fa = 0.32 +/- 0.09 (ml/ml/min) and the extraction fraction E = K1/Fa = 0.65 +/- 0.05. There was a strong correlation between K1 and Fa (Y = 0.53X + 3.7; rs = 0.91). By combining the K1 and E values in the whole-brain, we can obtain the absolute global flow value and regional 99mTc-ECD CBF maps if the average concentration of the tracer in the whole-brain is used as a reference. Our method is less invasive and suitable for quantitation of cerebral blood flow in patients with brain disorders.

A 57-year-old man was admitted because of headache, nausea, and fever up (38 degrees C). He showed nuchal rigidity slightly. CSF analysis showed 833 white blood cells (WBC) (80% monocyte), protein value of 68 mg/dl, glucose level of 36 mg/dl and ADA level of 11.8 IU/l. Brain pre-contrast CT indicated high density area in right parietal lobe, and it showed slightly homogeneously enhancement with contrast medium. MRI on T2 WI demonstrated hypointense lesion with bright central core in right parietal lobe. The lesion showed isointense on T1WI, and indicated homogeneous enhancement with Gd-DTPA. He was sent to our hospital after one week. With only antibiotics the symptoms were relieved and the CSF findings improved during the previous hospital. However, Mycobacterium tuberculosis (M. tuberculosis) DNA was detected in CSF by PCR amplification, and he recovered completely with anti-tuberculous treatment. This case was interesting to reveal atypical features of spontaneous recovery. Since Shankar's study using polymerase chain reaction (PCR) for detection of M. tuberculosis in cerebrospinal fluid (CSF), the PCR assay have been recognized to be a rapid method for diagnosis of tuberculous meningitis (TBM). But there are problems of PCR sensitivity when dealing with CSF samples containing small amount of M. tuberculosis DNA. Comparing direct PCR with nested PCR, we studied on the evaluation of PCR for diagnosis of TBM. In this study the nested PCR was positive in all CSF specimens from 4 patients with TBM, but we could not detect M. tuberculosis DNA by only the direct PCR. Nested PCR amplification improved the sensitivity and specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Endoscopic mucosal resection (EMR) enables one to examine resected specimens histologically and judge the curability by the histological findings. A mucosa and a part of submucosa can be resected by EMR. Therefore, mucosal cancers are indications for EMR. The present study showed that better indications for EMR were as follows: lesions less than 10 mm in size, lesions without ulceration, and lesions in the antrum or at the greater curvature. However, it is difficult to judge correctly before EMR whether the lesions are completely resected or not. The lesions with better indications are not always resected completely, and, conversely, the lesions more than 11 mm in size are completely resected at times. Therefore, it is most important to know how to deal with resected specimens. Specimens must be dealt with in strict conformity with the regulations. At present, when EMR may be regarded as the least invasive modality of curative sugeries, a new systematic treatment combining surgical laparotomic treatment and EMR is desirable for curative treatment of early gastric cancer.

A simple, noninvasive method of measuring cerebral blood flow (CBF) that uses single-photon emission computed tomography (SPECT) of CBF-tracer and whole brain CBF obtained by xenon-133 (133Xe) clearance technique was developed. In nine healthy volunteers, SPECT data were normalized to the count density of 123I-IMP or 99mTc-HMPAO uptake in the whole-brain, and then converted to the absolute units of CBF by multiplying average 133Xe-CBF in the whole brain. The CBF values measured by 99mTc-HMPAO CBF-SPECT was significantly lower in the high flow regions of cortical gray matter (bilateral frontal lobe; p0.05 and right occipital lobe; p0.05), and was significantly higher in the bilateral white matter (p0.05 or 0.01) and the cerebellum (p0.005) compared with the flow values measured by 123I-IMP CBF-SPECT. Whereas, the IMP-CBF values were significantly lower in the bilateral striatum (p0.02 or 0.05) compared with the HMPAO-CBF values. Good correlations were found between IMP-CBF and the HMPAO-CBF values in the cortical gray matter (rs = 0.761; p0.001, n = 108), the white matter (rs = 0.739; p0.001, n = 18) and the cerebellum (rs = 0.731; p0.001, n = 18). In the striatum (rs = 0.58; p0.05, n = 18) and the thalamus (rs = 0.628; p0.05, n = 18), the correlations between IMP-CBF and HMPAO-CBF values were inferior to those of the other three regions.(ABSTRACT TRUNCATED AT 250 WORDS)

The cerebral blood flow (CBF) of a patient suffering from locked-in syndrome (LiS) was examined before and after the onset using 99mTc-hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) and the intravenous 133Xe injection method. The mean CBF during the locked-in state was 32.2 ml/100 g/min, a 42% reduction from the asymptomatic stage. SPECT showed profound reductions of perfusion in the bilateral cerebral cortices, subcortical regions and in the cerebellum, with a less marked reduction in the frontal cortices. On Day 49, the patient showed some minimal voluntary return with a moderate increase in mean CBF of 40.2 ml/100 g/min. The relative CBF values in the cerebral cortices and subcortical regions were restored, but the bilateral cerebellar hypoperfusion remained unchanged. SPECT and CBF are useful for a better characterization of the brain pathophysiology in LiS.

We converted an absolute value of 133Xe-CBF (initial slope index, ISI) to the three dimensional CBF-SPECT using the intravenous 133Xe injection technique and 99mTc-HMPAO SPECT according to the microsphere model (method A), and the three compartment model described by Lassen et al. (method B): [formula: see text] [formula: see text] where f = flow in the region of interest (ROI), fr = flow in the reference region, C = count density of 99mTc-HMPAO SPECT in the ROI, Cr = count density of 99mTc-HMPAO SPECT in the reference region, and alpha = conversion to clearance ratio of HMPAO. We used alpha value of 1.5, and the whole cerebrum as a reference region. Four asymptomatic subjects and 15 patients with ischemic cerebrovascular disease were entered the study. In method A, excellent correlation was seen between ISI and SPECT-CBF in both of the cerebral hemisphere (r = 0.993; p0.001, n = 38) and the cerebellar hemisphere (r = 0.901; p0.001, n = 38). When back diffusion of HMPAO was corrected by method B, correlation coefficient of SPECT-CBF with ISI was equivalent to that in method A in the cerebrum (r = 0.978; p0.001, n = 38), while the correlation coefficient ih the cerebellum was lowered (r = 0.726; p0.001, n = 38) although high flow to low flow ratio was increased. Reproducibility of rCBF assessed 1 week apart from the first CBF-SPECT was highly reproducible in all of the brain regions; correlation coefficient ranged from 0.757 to 0.910 with a mean correlation coefficient of 0.834 (n = 11). The slope and intercept of the linear regression line between 2nd rCBF versus 1st CBF were 0.889 (range, 0.791-1.141) and 5.5 (range, -9.1-13.4), respectively. Regional CBF measured by method B was approximately 20% increase from that measured by method A. However, there was no significant difference in the reproducibility of rCBF between the two methods. Our results indicate that rCBF can be simply and noninvasively quantified using 99mTc-HMPAO SPECT and absolute unit of CBF measured by 133Xe injection technique. SPECT-CBF offers high resolution images and may be applicable for various cerebrovascular disorders in routine clinical use.

In order to assess the vulnerability of the inner ear, auditory function and morphology of the inner ear were compared between adult budgerigars and adult guinea pigs. Budgerigars have been considered to have an excellent auditory-vocal system. Two experimental conditions were produced in each species; one by acoustic hyperstimulation (1500 Hz, 120 dBSPL) for 96 hours, the other by administration of kanamycin (200 mg/kg) for 7 weeks. Measurement of auditory evoked potentials (AEP) and observation of hair cells by electron microscopy were performed both immediately and 14 days after exposure. In the acoustic hyperstimulation experiment, AEPs of budgerigars showed less damage and better recovery than those of guinea pigs, probably because of morphological differences between the two species in hair and supporting cells. Electron microscopic observation on the budgerigars showed that a small part of the hair cell area was damaged and that regeneration of hair cells had occurred in this area 14 days after exposure. Such observations in guinea pigs revealed that outer hair cells had been damaged and replaced by supporting cells 14 days after exposure. In the kanamycin administration experiment, AEPs showed the same degree of damage and recovery in both species. This suggests that blood supply and drug transport to the inner ear are almost the same although the structure of the inner ear differs markedly between the two species. Electron microscopic observation did not show an apparent regeneration of hair cells 14 days after administration in the budgerigars. Guinea pigs had a tendency to show progressive damage of both auditory function and inner ear morphology even after the cessation of administration. Regeneration of hair cells in the budgerigar differed under both experimental conditions, suggesting that there is a difference in the mode of auditory disturbance between acoustic hyperstimulation and administration of kanamycin. In conclusion, resistance to acoustic hyperstimulation is higher in the avian inner ear than in the mammalian inner ear, while resistance to administration of kanamycin does not differ significantly between the two species.

Even during the symptom-free stages, patients with transient ischemic attacks (TIA) often show cerebral blood flow (CBF) disturbances. For evaluating the factors which cause these abnormalities, we studied CBF and CBF reactivity to acetazolamide (Diamox) using a 99mTc-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT). The results from CBF-SPECT were compared with X-ray computed tomography (CT), cerebral arteriogram, clinical characteristics of TIA and cerebrovascular risk factors. The overall sensitivity rates in detecting the lesion were 68% in CBF-SPECT and 9% in CT. The size of the hypoperfused area tended to be wide in patients who had intracranial, severe stenotic or multiple arterial lesions on the ipsilateral side. No such relations were found between CBF and other examinations. Brain hypoperfusion was located in the subcortical region in eight patients; two patients showed a small hypodense lesion on CT which corresponded to the hypoperfusion on SPECT, and three patients showed no arteriographic abnormality. Hypoperfusion in the cortex was seen in seven patients; all patients showed arteriographic abnormality, but no CT abnormality. The severity rating of the vascular stenosis and hypoperfusion, and the incidence of the intracranial lesions were higher in this group than the group with subcotical hypoperfusion. Seven patients showed fixed normoperfusion before and after diamox injection. Two patients with a subcortical small infarction showed fixed hypoperfusion even after diamox injection. Twelve patients showed focal hypoperfusion before diamox with a new filling-in after diamox. Only one patient showed resting hypoperfusion and decreased CBF reactivity to diamox.(ABSTRACT TRUNCATED AT 250 WORDS)

We report the relationship between cerebral blood flow (CBF) and neuropsychologic tests in a patient with a chronic subdural hematoma suffering from severe dementia and left hemiparesis. Regional CBF was quantified using 99mTc-HMPAO SPECT and 133Xe-CBF. CBF-SPECT could detect the hematoma which was isodense by CT scan and the neuropsychological test improved remarkably with the increase in CBF after surgery. We conclude that if there is a strong clinical suspicion of subdural hematoma and CT scan is not diagnostic then CBF-SPECT may be valuable in localizing the hematoma and monitoring the effect of operation.

An expression for the relation between stress and strain rate, which has been developed in terms of a energy dissipation function in the flow of the mixture of water and sand particles [1], is introduced briefly. The consititutive equation is applied to discuss the distributions of velocity and particle concentration in uniform debris flows as well as sediment discharge rates in the regimes from debris flows to general flows with bed-loads. A bed-load equation, thus, has been formulated.