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IntroductionGiven an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methodsWe registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.ResultsOf the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.ConclusionsAlogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Cyclopolymerization of a divinyl monomer, where two different vinyl groups, that is, acrylate and vinyl ether, are connected via an ester bond, was performed under diluted condition with nitroxide-meditated radical polymerization (NMP). Both vinyl groups were consumed at almost same rate under suitable condition, although the inherent cross-propagation ability between the two vinyl groups are pretty low in radical copolymerization. Furthermore, the polymerization was controlled to some extent to give polymers of unimodal molecular weight distributions. The results obviously differed from copolymerization and homopolymerization with vinyl monomers that constitutes the divinyl monomer, 2-methoxyethyl acrylate and 2-acetoxyethyl vinyl ether. Structural analyses indicated formation of the cyclopolymer but the cyclo-efficiency was imperfect indicating that some units of olefinic dangling were incorporated. Eventually, the ester bonds of the cyclo units were cleaved to convert into the copolymer consisting of acrylic acid and 2-hydroxy ethyl vinyl ether and the composition ratio (DP

In this study, it is discussed how the cutting conditions for drilling deep holes in austenite stainless steel affect the machining accuracy of the hole straightness and the cutting temperature rise. As a result, it is possible to reduce the thrust force and make the machining time short by the combination of the step-feed amount and the feed rate. By changing the drill in incremental step from short drill length to long drill length, the straightness was improved. It was also found that the temperature rise of the drill was around 10 K regardless of the cutting speed when the small step-feed amount of 10 μm was given.

This paper describes influence of the cutting conditions on the hole shape accuracy in deep-hole machining of stainless steel with small-diameter drill. The drilling tests were carried out by changing the step feed, the rotational speed and the feed rate in order to investigate the relationship between the straightness of the hole and the cutting conditions. As a result, it was found that the thrust force decreased with a decrease in the step feed amount and accordingly the straightness was improved. By changing the drill in incremental step from short drill length to long drill length, the straightness was improved.

Aim: Pitavastatin significantly improved lipid profiles and reduced serum high-sensitivity C-reactive protein (hs-CRP) levels in a multi-center and prospective study. The aim of this study was to explore the effect of pitavastatin on serum levels of another inflammatory biomarker, interleukin-18 (IL-18), in a sub-analysis of the previous multi-center prospective study.Methods: The subjects were 83 patients derived from the KISHIMEN study. Pitavastatin (1-2 mg/day) was administered for 12 months. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), remnant-like particle cholesterol (RLP-C), triglycerides (TG), IL-18, and high sensitivity C-reactive protein (hs-CRP) levels were measured.Results: TC, LDL-C, and RLP-C levels were significantly reduced by 18.3%, 30.1%, and 21.0% (mean values) at 12 months after pitavastatin administration. TG levels were decreased by 9.8% in subjects whose basal TG levels were above 150 mg/dL. HDL-C levels were significantly increased at 6 months (11.9%). Pitavastatin did not significantly alter IL-18 levels in overall subjects, but reduced IL-18 levels in the highest quartile by 24.5% (median value) at 12 months. Pitavastatin significantly reduced hs-CRP levels by 28.6% in overall subjects and by 62.4% in the highest quartile at 12 months. There was a significant correlation between IL-18 and hs-CRP at baseline after both values were transformed into logarithms (Pearson's correlation coefficient, r=0.259, p=0.0181); however, percent changes in these levels were not significantly correlated.Conclusion: Pitavastatin significantly improves lipid profiles, and reduces enhanced inflammation monitored by IL-18, as well as by hs-CRP, in hypercholesterolemic subjects.

〔目的〕経口摂取に際し嚥下リハビリテーションなどを含めた専門的な対応が必要と思われる症例を判別する摂食・嚥下フローチャートを作成する。〔対象〕嚥下造影 (videofluorography: 以下VF) を施行した嚥下障害患者28例 (平均年齢78.7±11.3歳)。〔方法〕反復唾液テスト，改訂水飲みテスト，食物テストの代表的テストを評価し，VF所見，藤島の摂食・嚥下能力のグレードとの関連を調査した。〔結果〕反復唾液テスト (感度0.83，特異度0.22)，改訂水飲みテスト (感度0.56，特異度0.72)，食物テスト (感度0.33，特異度0.75)，嚥下造影，藤島の摂食・嚥下能力のグレードを検討した結果，改訂水飲みテスト，食物テストを採用した。しかし改訂水飲みテスト，食物テストがカットオフ値以上であった4例は誤嚥していた。この4例はいずれも脳卒中後遺症のある症例であったことも考慮して，フローチャートを作成した。

脳卒中や骨折の病態が落ち着いたとしても障害を伴った高齢の患者は，転院という環境の変化によって日常生活活動能力が低下する可能性がある。代表的なADL評価であり，信頼性が実証されているBarthel Indexを用いて，環境の変化の影響を評価した。対象は脳卒中と大腿骨頸部骨折を伴う患者で，急性期病院の転院時に療法士が評価した得点と，転院後1週間以内に連携病院にて看護師が評価した得点を検討した。脳卒中の総合得点は58%が低く評価され，差の平均は-5.9±16.0点であった。大腿骨頸部骨折の総合得点は68%が低く評価され，差の平均は-7.3±14.1点であった。脳卒中の順位相関係数は0.91 (p

Akutagawa Bridge is a continuous rigid frame bridge located between Takatsuki junction and Kobe junction on the New Meishin Expressway. This is where the new concrete precast "Butterfly Web Bridge" was applied, which uses butterfly shaped panels fabricated in a factory. Compared to a conventional concrete box-girder structure, this unique structure enables the reduction in dead load of the superstructure by approximately 10%. And, a decrease in construction costs is expected through the reduction of both prestressing steel weight and size of bridge substructure.

A transcription factor NF kappa B, which regulates expression of various cellular genes involved in immune responses and viral genes including HIV, is sequestered in the cytoplasm as a complex with an inhibitory protein I kappa B. Various extracellular signals induce phosphorylation and rapid degradation of I kappa B alpha to release NF kappa B. Cu2+ was found to inhibit the activation of NF kappa B induced by TNF-alpha, TPA, or H2O2. Deoxycholate treatment of the cytoplasmic extract prepared from cells stimulated by TNF-alpha in the presence of Cu2+ resulted in the release of NF kappa B from I kappa B alpha, indicating that Cu2+ interferes with the dissociation of the NF kappa B-I kappa B complex. Neither phosphorylation nor degradation of I kappa B alpha was observed upon TNF-alpha stimulation in the presence of Cu2+. These results indicate that Cu2+ inhibits the release of NF kappa B by blockade of a signal leading to the phosphorylation of I kappa B alpha.

In order to investigate the pathophysiology of the diabetic osteopenia observed in non-insulin-dependent diabetes mellitus, the circulating levels and the bone contents of bone γ-carboxyglutamic acid-containing protein (osteocalcin) were determined in rat models of non-insulin-dependent diabetes mellitus, neonatally streptozotocin-induced rats and in genetic Wistar fatty rats. In Wistar fatty rats the plasma level of osteocalcin was 8.1±0.8 nmol/l, significantly lower than the value of 1 7.3±0.9 nmol/l in their lean littermates (p

The complementary DNA for the human brain type glucose transporter (GLUT3) was used to determine its tissue specific expression in human, monkey, rabbit, rat, and mouse. Under high stringent conditions, 4.1 and 3.2 kilobase (kb) GLUT3 transcripts in monkey and a single 4.1 kb GLUT3 mRNA in rabbit, rat, and mouse were detected by RNA blot analysis. Although the GLUT3 transcripts were widely distributed, as are the erythrocyte type glucose transporter (GLUT1) transcripts, this mRNA is most abundant in the brain. However, the relative abundance of GLUT3 mRNA in the various regions of the monkey brain shows a different pattern from that of GLUT1 mRNA: GLUT3 is most highly expressed in the frontal lobe of the cerebrum, whereas GLUT1 is most abundant in the basal ganglia and the thalamus. Moderately higher GLUT3 mRNA levels were detected in the parietal lobe of the cerebrum, hippocampus, and cerebellum than the levels of GLUT1 transcripts. We also detected GLUT3 mRNA in adult human psoas major muscle, although it has been reported that the GLUT3 gene is scarcely expressed in adult human skeletal muscle of the thigh. In addition, in the rat and the mouse, no transcripts of the GLUT3 gene were detected in liver, kidney, small intestine, skeletal muscle, or fat besides in brain. Thus, the expression of the GLUT3 gene seems to be restricted to the brain in rodents. These results suggest that the expression of GLUT1 and GLUT3 genes might be regulated by different mechanisms.

To investigate the role of the β-cell in the occurrence of diabetes in obesity, longitudinal changes of insulingene expression and pancreatic insulin content were compared among genetically obese diabetic (Wistar fatty) rats, genetically obese nondiabetic (Zucker fatty) rats, and ventromedial hypothalamus (VMH)-lesioned obese rats. Plasma glucose levels were significantly elevated with age in Wistar fatty rats, whereas they were virtually unchanged in VMH-lesioned and Zucker fatty rats. Obesity and hyperinsulinemia were evident in VMH-lesioned rats 1 wk after the operation and in Zucker and Wistar fatty rats at 5 wk of age. In VMHlesioned rats, the pancreatic preproinsulin I mRNA (pplmRNA) level and pancreatic insulin content markedly increased approximately two- to threefold (P < 0.001) with the development of hyperinsulinemia, whereas sham-operated rats showed no significant change. In Zucker and Wistar lean rats, the pplmRNA level and pancreatic insulin content increased with age, corresponding to increases in body weight. In Zucker fatty rats, the pplmRNA level and pancreatic insulin content at 5 and 14 wk of age were significantly higher than those of lean littermates. The pplmRNA level in Zucker fatty rats at 14 wk of age reached 290% of that of their lean littermates (P < 0.001). On the other hand, the pplmRNA level and pancreatic insulin content in Wistar fatty rats at 5 and 14 wk of age did not increase more than those of their lean littermates at the corresponding ages and were therefore significantly lower than in Zucker fatty rats, which had a higher grade of hyperinsulinemia at 14 wk of age. The pplmRNA level in Wistar fatty rats at 14 wk of age was found to be 41% of that of Zucker fatty rats at corresponding age (P < 0.001). Increased pplmRNA level in association with hyperinsulinemia in VMHlesioned and Zucker fatty rats suggests that the activation of insulin-gene expression for adaptation to a large demand for insulin is common to obesity without diabetes (both experimental and genetic). Furthermore, the inability to augment pplmRNA level to meet a large demand for insulin in Wistar fatty rats is associated with the occurrence of diabetes. These findings suggest that obesity induces diabetes only when a primary defect exists in the β-cell.

The expression of five facilitative glucose transporter genes, GLUT1 (erythrocyte type), GLUT2 (liver type), GLUT3 (brain type), GLUT4 (muscle/fat type), and GLUT5 (small intestine type), was examined in human cancer tissues of the digestive system by RNA blotting analysis. The amounts of the GLUT1, GLUT2, and GLUT3 transcripts were elevated in most cancer tissues studied, although the expression of the GLUT2 gene is primarily restricted to the liver. On the other hand, mRNA levels of GLUT4 and GLUT5 were below sensitivity in all cancer tissues examined. These results suggest that over-expression of GLUT1 and GLUT3 might be closely related with tissue development and that the acceleration of glucose uptake by transformed cells may result, at least in part, from the increase in the expression of these two glucose transporters.

A polarizing microscope is used to investigate the ferroelectric phase transition of hexagonal type BaTi03. Extinction positions of thin crystal c-plates change rather steeply with temperature in the ferroelectric phase near the Curie point of Tc ∼ 70K. suggesting that a cooperative phenomenon is taking place. Orthorhombic crystal symmetry above Tc changes to a lower one, probably monoclinic P21 in the ferroelectric phase.

The effects of four different diets, a balanced (BD), a high protein (HP), a high fat (HF), and a high carbohydrate (HC) diet on glucose tolerance and pancreatic hormone secretion were compared during the ten-week period immediately after weaning in rats having glucose intolerance induced by streptozocin in the neonatal period (NSZ). Feeding HF or HC produced a decrease in calorie intake and a delay in body weight increase. All NSZ rats showed glucose intolerance as adults; the HF rats showed a further deterioration of glucose tolerance and a decreased insulinogenic index after oral glucose loading. Plasma insulin levels of HC rats were lowest. The glucose-induced insulin and somatostatin secretion from the isolated perfused pancreas was almost identical in all four groups. The arginine-induced insulin and glucagon secretion was decreased in HF and HC rats, compared to both HP and BD rats, but somatostatin secretion was not. These results indicate that a high fat or high carbohydrate dietary environment is an important factor in the development of glucose intolerance and in the impairment of pancreatic hormone responsiveness to stimulation.

We propose the Multiple Character-Agents Interface (MCI) as an information integration platform where multiple animated life-like characters interact with each other and with the user to retrieve and integrate information from the Internet. The MCI makes the process open to the user and allows him/her to collaborate with the character-agents. We implemented the MCI as a multi-agent system in which information agents distributed over the Internet are integrated, then we developed a prototype called Venus and Mars, which is a cooperative cooking recipe search engine consisting of three character-agents that collaborate with the user to locate cooking recipe pages.

Our previous studies have shown that increased expression of GLUT1/erythrocyte and GLUT3/brain type glucose transporter genes in human tumors is associated with cellular transformation. We have now determined the levels of messenger RNAs (mRNAs) encoding these two glucose transporter isoforms as well as that of GLUT2/liver isoform in insulin-, glucagon-, and gastrin-secreting islet cell tumors. Northern blot analysis and reverse transcriptase-polymerase chain reaction revealed the presence of GLUT1 and GLUT3 mRNA in all human islet cell tumors and normal islets examined. In contrast, GLUT2 mRNA, which is present at high levels in normal islets, was not detected in insulinomas or other types of islet cell tumors. These results imply that GLUT1 and GLUT3 are primarily responsible for glucose uptake by these tumors.

In order to determine the role of insulin and glucose transporter gene expression in the development of diabetes in obesity, we examined insulin and GLUT2-liver type and GLUT4-muscle-fat type glucose transporter mRNA levels in obese and diabetic rats. Ventromedial hypothalamus-lesioned (VMH), Zucker fatty (ZF), and Wistar fatty (WF) rats were used as models. VMH and ZF rats are most frequently used as models for simple obesity. In contrast, WF rats, which have been established by transferring the fa gene of ZF rats to Wistar Kyoto rats, develop both obesity and diabetes. Pancreatic insulin content of VMH rats at 10 weeks after the operation and of ZF rats at 5 and 14 weeks of age was significantly higher than that of controls. On the other hand, insulin content of WF rats at 5 and 14 weeks of age was not significantly different from that of lean littermates. The insulin mRNA levels of VMH rats were increased progressively and were significantly higher than those in sham-operated animals at 4 and 10 weeks after the operation. In ZF rats, the insulin mRNA levels at 5 and 14 weeks of age were significantly higher than those of their lean littermates. In WF rats, by contrast, the insulin mRNA levels were similar to those of lean littermates at 5 and 14 weeks of age. The insulin mRNA levels of WF rats were about 40% of that of ZF rats at 14 weeks of age. On the other hand, at 14 weeks of age, the GLUT2 mRNA levels of liver were significantly higher in ZF and WF rats than those in their respective littermates, but not at 5 weeks of age. The GLUT4 mRNA levels of skeletal muscle in both ZF and WF rats were not significantly different from those of controls. It is suggested that the inability of WF rats to augment insulin gene expression in response to a large demand for insulin is associated with the occurrence of diabetes, and that the activation of GLUT2 mRNA without the activation of GLUT4 mRNA is common to obesity with and without diabetes.

In order to investigate the regulation of glucose transporter gene expression in the altered metabolic conditions of obesity and diabetes, we have measured mRNA levels encoding GLUT2 in the liver and GLUT4 in the gastrocnemius muscle from various insulin resistant animal models, including Zucker fatty, Wistar fatty, and streptozocin(STZ)-treated diabetic rats. Northern blot analysis revealed that GLUT2 mRNA levels were significantly (P less than 0.001) elevated in 14 wk Zucker fatty and Wistar fatty rats relative to lean littermates but were similar in these two groups at 5 wk of age. Furthermore, there was significant increase (P less than 0.01) in GLUT2 mRNA levels in STZ diabetic rats at 3 wk after treatment. GLUT4 mRNA levels were not significantly different between control and insulin resistant rats in all animal models. These results indicate that neither hyperinsulinemia nor hyperglycemia affects GLUT4 mRNA levels in the muscle. However, GLUT2 mRNA levels in the liver were elevated in obesity and diabetes, although this regulatory event occurred independently from circulating insulin or glucose concentrations.

A review is given on the structural phase transition of hexagonal type BaTiO3 at 222 K and on the ferroelectric · ferroelastic phase transition at ∼ 70 K. X-ray studies and Raman studies have disclosed that an E2u phonon mode condenses below 222 K where crystal changes from hexagonal P63/mmc to orthorhombic C2221-D5 2. As for the ferroelectric transition at ∼70 K, dielectric and elastic behaviors strongly suggest that the transition is primarily of a ferroelastic nature associated with softening of the elastic stiffness c66. A probable space group below 70 K is monoclinic P21.

Six kinds of twins appear in the intermediate phase of hexagonal BaTiO3 (74K < T< 222K). The six can be classified into three pairs, each consisting of enantiomorphic twins which are indistinguishable by conventional means with a polarizing microscope. The six kinds of twins can be transformed into one another by applying both a suitable uniaxial stress and a dc electric field. The transformations are explained as a compound effect of piezoelectric strain and of uniaxial stress.

Die Saurespaltung des Addukts A aus endo-Dicyclopentadien und Phenylazid bzw. seines Hydrierungsproduktes B liefert jeweils drei Verbindungen. Je zwei Verbindungen. II und III bzw. V. und VI sind durch WAGNER-MEERWEIN-Umlagerung entstanden und besitzen exo-Struktur. Die Konstitution und Stereochemie der restlichen Reaktionsprodukte I und IV ist noch ungeklart.

For determining the space group of the intermediate phase (74 K< T

Aim The effect of pitavastatin on high-sensitivity C-reactive protein (hs-CRP) has not been reported, yet, in humans. We, therefore, investigated the effects of pitavastatin on lipid profiles and hs-CRP in Japanese subjects with hypercholesterolemia. Methods The subjects were 178 Japanese with hypercholesterolemia, including 103 (58%) with type 2 diabetes. Pitavastatin (12 mg/day) was administered for 12 months. Serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), remnant-like particle cholesterol (RLP-C), triglycerides (TG) and hs-CRP levels were measured for 12 months. Results Serum LDL-C and RLP-C levels were significantly decreased by 30.3% and 22.8%, respectively. Serum TG levels were decreased by 15.9% in subjects with basal TG levels above 150 mg/dl. Serum HDL-C levels were significantly increased. The administration of pitavastatin reduced serum hs-CRP levels by 34.8%. No serious adverse events were observed, including changes in glycosylated hemoglobin levels of diabetic patients. Conclusion These results suggest that pitavastatin significantly improves lipid profiles and reduces proinflammatory responses, without adverse effects, in Japanese subjects with hypercholesterolemia, including those with diabetes mellitus.

World Wide Web contains a vast amount of different information stored in a huge number of distributed Web sites. Search engines and information agents have been developed to facilitate efficient information retrieval tasks from the Web. By integrating multiple search engines and information agents as an interoperable system, we increase the value of each of them. In conventional collaborative systems, the integration process is designed by system designers and is concealed from the end users. This paper proposes an interactive multiagent-based interface called Multiple Character-agent Interface (MCI) where animated character-agents interact with each other and with the user for assisting in information retrieval. By using the MCI, even a novice user can create a team of information agents and can self-customize the agents through the interactions with them. We here report the architecture of MCI and two prototype systems based on MCI, Venus and Mars, which is a cooperative multiagent system for information retrieval, and Recommendation Battlers, which is a competitive multiagent system for information recommendation.