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Dementia and diabetes are highly prevalent among the older society in Japan. People living with dementia (PLWD) often face hurdles in managing diabetes. This study explored the perspectives of healthcare providers in Japan regarding diabetes management in PLWD.We conducted a qualitative study using in-depth interviews as a data collection method. A total of 15 physicians and nurses were interviewed. A qualitative content analysis of the codes was performed to generate the themes.The major themes focused on the management of medications/therapeutic regimen, difficulties of continuing health care, emotional aspects of PLWD for adherence to lifestyle modification, and varying direction and degree of family support for diabetes care.PLWD in Japan face challenges in medication management, food restriction, and lifestyle modification. Policies to engage home visit care workers in medication management, consideration of the emotional aspect of PLWD, and utilisation of social support might help in the proper management of diabetes in PLWD.

Objectives One of the characteristics of colorectal cancer complicating Crohn's disease (CD) in the Japanese population is that it frequently occurs in the lower anorectal site. This study aimed to examine CD patients biopsied in the lower anorectal sites to investigate the significance and problems associated with this method of cancer surveillance. Methods Among 116 patients with CD duration of ≥10 years, we examined patients diagnosed with cancer using histological examination of the lower anorectal site (287 times). We also evaluated the detection rates of cancer and atypical cells using this method. Results Of the 116 patients, neoplastic lesions were detected through biopsy in 22 (19.0%), of which 18 had carcinomas and 4 had atypical cells. The clinicopathological traits of the cancer patients were early-age onset and chronic disease duration of CD before cancer diagnosis. Histologic findings were characterized by a high frequency of poorly differentiated adenocarcinoma and mucinous carcinoma. The 18 patients with cancer were assigned to groups A and B depending on the presence or absence of cancer-related symptoms, and their characteristics were compared. Of these, 5 patients whose cancer was detected without symptoms (group A) had better prognosis than those detected with symptoms (group B) based on survival curves. We next examined 103 patients for surveillance after excluding 13 patients who were diagnosed with cancer-related symptoms from the 116 patients and found a 5.8% (6 patients) detection rate of cancer and atypical cells. Conclusions Our results suggest the effectiveness of transanal histological testing for the surveillance of anorectal cancer with CD.

Summary: Background/Objective: Mixed-type early gastric cancer (differentiated and undifferentiated components) incurs a higher risk of lymph node metastasis than pure-type early gastric cancer (only differentiated or only undifferentiated components). Therefore, we investigated the expansion of lymph node metastasis in mixed-type submucosal invasive gastric cancer in order to establish the most appropriate treatment for mixed-type cancer. Methods: We retrospectively analyzed 279 consecutive patients with submucosal invasive gastric cancer who underwent curative gastrectomy for gastric cancer between 1996 and 2015. We classified the patients into the mixed-type and pure-type groups according to histologic examination and evaluated the expansion of lymph node metastasis. Results: The rate of lymph node metastasis was 23.7% (66/279) in the total patients, 36.4% (36/99) in the mixed-type group, and 16.6% (30/180) in the pure-type group. The significant independent risk factors for lymph node metastasis were tumor size ≥2.0 cm (P = 0.014), mixed-type gastric cancer (P

We have developed highly reliable oxide TFT arrays by allprinted maskless process from gate to passivation layers with 100 ppi RGB resolution. The threshold voltage shifts under positive and negative bias-temperature-stress at 50 °C after 105 seconds were less than 0.8 and 0.3 V, respectively.

We have demonstrated all-printed oxide TFT arrays for 100 ppi RGB active matrix fabricated by inkjet printing and spin coating without photolithography and mask process. The average mobility of TFTs was 7.49 ± 1.67 cm2/Vs on a thermally oxidized SiO2 /Si substrate. Moreover, in the case of using of a printed oxide high-k gate insulator and an n-type doped active layer on a glass substrate, the average mobility of all-printed oxide TFTs was 2.54 ± 0.32 cm2/Vs.

Perianal lesions are a frequent complication of Crohn's disease (CD) and include fistula, abscess, anal ulcer, skin tag, anal stricture, and carcinoma. Perianal fistula is the most commonly observed condition and exhibits multiple incidence and intractable characteristics. The starting point for the management of perianal fistula is an accurate diagnosis, which requires careful exploration during an EUA. The condition is treated with medications such as antibiotics, immunosuppressants, or anti-tumor necrosis factor agents. However, it is difficult to maintain long-term remission. Surgical therapy is selected according to the type of fistula and can include conventional fistulotomy, seton drainage, diverting stoma, and anorectal amputation. After fistulotomy, recurrence is frequent and there is an increased risk of incontinence. Seton drainage is the preferred treatment to improve symptoms and preserve anal function. Stoma is useful to relieve symptoms but difficult to indicate for young patients. The optimum treatment for perianal fistula associated with CD remains controversial. Currently, the goal of therapy for these patients has shifted from complete fistula closure to reducing drainage from the fistula to improve their quality of life. Ongoing careful management is important to control anal symptoms and maintain long-term anal function in the treatment of patients with CD, while monitoring them to detect possible progression to anorectal carcinoma.

Background Guillain-Barre syndrome (GBS) is an acute acquired demyelinating polyneuropathy, presumed to be immune-mediated. Intravenous immunoglobulin (IVIg) has been used to treat GBS and was found to be effective. However, a well-controlled study of pediatric GBS has not been conducted in Japan. Therefore, to evaluate the efficacy of IVIg in the treatment of GBS, an open-labeled study was performed in pediatric patients. Methods Participants in the study were required to be younger than 15 years old, and diagnosed as having moderate or severe GBS. IVIg (400 mg/kg per day) was administered to patients for five consecutive days. Predefined outcome measures were defined on a seven-point scale of motor function (Hughes' functional grade [FG]). Results Eleven patients were treated with IVIg. The median time taken to improve by one grade on the FG scale was 10.0 days after initial treatment. Two weeks after initial treatment, 72.7% of patients treated with IVIg improved by one or more grades, and 36.4% improved by two or more grades, measured on the FG scale. After 4 weeks an improvement by one or more grades was observed in 81.8% of patients, and two or more grades in 63.6% of patients. These improvement rates were markedly greater than would occur with the natural course of GBS1. Adverse events (subjective symptoms or abnormal laboratory findings) were observed in four patients, although all were temporary and mild. Conclusions The authors conclude that IVIg is a safe and effective treatment for childhood GBS, which shortens the time to recovery.

大腸ポリープはポリープ癌化説の支持を基に微小ポリープに対しても数多くの内視鏡切除が行われている。その中で, 通常内視鏡観察では腺腫と過形成性ポリープとの鑑別を困難とする病変も存在し, 不要な切除や生検が行われていることも事実である。本研究の目的は, 大腸がん検診における内視鏡検査において, 腫瘍・非腫瘍性病変に対する拡大内視鏡観察の有用性を検討することである。拡大内視鏡導入前の2001年1月から6月の6ヵ月間 (通常内視鏡観察のみ, 術者は通常内視鏡診断の熟練者2人) と導入後の2001年7月から12月の6ヵ月間 (拡大内視鏡と通常内視鏡を無作為に使用, 術者は拡大内視鏡診断を習得した1人) に当センターで大腸内視鏡検査を受けた全症例376人538病変を対象とした。検討1として, 拡大内視鏡導入前と導入後において内視鏡切除 (ホットバイオプシー) した病変における過形成性ポリープと腺腫の比率を比較検討した。次に, 上記の検討では, 内視鏡術者が比較群間で異なるため, 診断能に関して拡大内視鏡の診断能以外に, 術者間の診断能のバイアスが関与している可能性が考えれる。そこで, 検討2として拡大内視鏡導入後, 同一術者が通常内視鏡と拡大内視鏡を無作為に使用した成績において, 同様にホットバイオプシーした病変における過形成性ポリープと腺腫の比率を比較検討した。検討1において, ホットバイオプシーをした病変に占める過形成性ポリープの割合は通常群 (21%) と拡大群 (7%) を比較すると有意に拡大群で低い値をとった (p=0.0075) 。検討2においても同様にホットバイオプシーをした病変に占める過形成性ポリープの割合は通常群 (19%) と拡大群 (7%) を比較すると有意な傾向をもって拡大群で低い値をとった (p=0.08) 。拡大内視鏡観察は, 人間ドックにおける大腸内視鏡検査において, 腫瘍・非腫瘍性病変の鑑別に有用であることがわかった。

5-Fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX) therapy and 5-FU, leucovorin, and irinotecan (FOLFIRI) therapy are standard chemotherapies to treat advanced/recurrent colorectal cancer. However, these chemotherapies require continuous infusion of 5-FU for a prolonged time of 40 h or more, every two weeks. Accordingly, these chemotherapies require hospitalization and placement of a central venous catheter. Because of frequent catheterization, long-term use of these therapies potentially risks complications such as infection and thrombosis. In contrast, S-1 (tegaful, gimeracil, oteracil) combined with irinotecan (IRIS) therapy involves giving one drug orally and infusing the other for about two hours every two weeks, so placement of a central venous catheter is not necessary. The current study examined the efficacy and safety of IRIS therapy in 90 patients at this Hospital who underwent such therapy to treat advanced/recurrent colorectal cancer.The study comprised 90 patients who underwent IRIS therapy to treat advanced/recurrent colorectal cancer from December 2004 to December 2011.The ratio of male-to-female patients was 64:26. The mean age at the start of IRIS therapy was 64.5 years, and patients underwent an average of 11 courses of therapy. The response rate to IRIS therapy was 14.8%, the disease control rate was 60.5%, and the overall survival time was 26.7 months. The incidence of adverse events was 70.0%, and the incidence of grade 3 or more severe adverse reactions was 17.8%.In comparison to the standard therapies of FOLFOX and FOLFIRI, IRIS therapy had a lower response rate but led to an equivalent overall survival time. IRIS therapy had a low incidence of serious adverse events and allowed patients to continue therapy on an out-patient basis. These findings indicate that IRIS therapy may be a useful form of chemotherapy to treat advanced/recurrent colorectal cancer.

To investigate the clinical features of paroxysmal dyskinesias and carry out a pedigree analysis, we conducted a multicenter survey in Japan. A questionnaire was mailed to 229 medical institutions. A total of 150 patients with paroxysmal kinesigenic choreoathetosis (PKC), including 53 sporadic cases and 97 affected individuals from 32 pedigrees, were identified. The mean age of onset of PKC was 8.8 years, and 80% of the cases were men. Of the 32 pedigrees with familial occurrence, 18 (56%) were compatible with an autosomal-dominant inheritance (AD) with complete penetrance, and seven (22%) had AD with incomplete penetrance; the remaining seven were sibling recurrence cases with apparently healthy parents. In six of seven familial cases with incomplete penetrance, the disease gene was thought to be transmitted by clinically unaffected females. Paroxysmal dystonic choreoathetosis (PDC) was found in five cases, including two sporadic cases and three affected individuals from two pedigrees; the mean age of onset was 0.6 years, and a male predominance was noted (male:female = 4:1). There was one case of paroxysmal hypnogenic dyskinesia and one case of paroxysmal exertion-induced dyskinesia. There is an unexplained male predominance for paroxysmal dyskinesias. When the genetic defect of patients with paroxysmal dyskinesias is identified, the pathophysiology of the disease will become more clear.

We report on three Japanese patients (two families) with familial Mediterranean fever (FMF), a rare disease in the Far East. Two of the patients (siblings with definite FMF) were heterozygous for both E148Q and M694I, and the remaining patient (with probable FMF and no family history of the disease) was heterozygous for both P369S and R408Q. Although the M694I mutation is less common among Mediterranean populations, it was present in 22 (76%) of 29 Japanese patients with FMF (previously reported cases). We therefore investigated the allele frequency of M694I in the healthy Japanese population, as well as other FMF-causing mutations in exon 10 (M680I, M694V, and V726A) and polymorphisms (E148Q, P369S, and R408Q) of the Mediterranean fever gene (MEFV). The allele frequencies of disease-causing mutations, even M694I, were

本研究では再石灰化反応における歯質に含まれるフッ素の役割を明らかにする目的で, 哺乳類 (ヒト, サル, ブタ, イヌ) の歯とサメの歯を材料に選び, in vitroにおいて乳酸を含む酸性ゼラチン溶液を用いてpH4.5とpH3.5の条件下で酸脱灰を行った。また, これら哺乳類エナメル質およびサメエナメロイドの化学組成と溶解度を測定した。本研究で得られた結果として, 1) 哺乳類エナメル質においては, いずれのpH条件においても表層部に高石灰化層を伴う表層下脱灰病巣が形成されたが, サメエナメロイドにおいてはいずれのpH条件においても脱灰病巣の表層部と脱灰前線部において石灰化の高まりを示す層は形成されなかった。2) ヒトエナメル質での脱灰病巣部では顕著な元素組成の変化 (F量は増加し, Mg量は減少) が認められたが, サメエナメロイドの脱灰病巣ではF量の増加を検知することはできなかった。3) エナメル質結晶は炭酸アパタイト (CA) と類似した溶解度をもち, その溶解度はハイドロキシアパタイト (HA) や合成アパタイト (FCA, FA) の溶解度より高いこと, またサメのエナメロイド結晶はFCAに類似した溶解度をもつことがわかった。以上のことから, 歯質に含まれているフッ素は歯質の溶解性を低下させ, う蝕病変の進行を遅らせるが, 他方, 高濃度のFを含む歯質表面では脱灰に併って溶出される格子イオン濃度が低く抑えられるため, 再石灰化反応の駆動力が小さくなり, 必ずしも表層下脱灰病変の成立に結びつかないことが明らかにされた。

We have analysed bony defects of the hard palate in patients with submucous cleft palate to find out whether velopharyngeal insufficiency (VPI) is dependent on the extent of these defects. We evaluated the maxillofacial structures associated with cleft palate by 3-dimensional computed tomography (CT) in 23 children diagnosed with submucous cleft palate. Bony defects of the hard palate were divided into Type I, defined as absent posterior nasal spine (n=12), Type II, V-shaped bony notch (moderate, n=7), and Type III, as bony defect extending into the incisive foramen (severe, n=4) defects, respectively. VPI was found in 10, 3, and 4 patients, respectively. Neither VPI nor the degree of bifid uvula was significantly associated with the types of bony defects.

To reveal the frequency and the clinical characteristics of dystrophic calcification that occurs in children with juvenile dermatomyositis, multi-center analysis was constructed.Fifty children with JDM were enrolled, and 14 of them (28.0%) were complicated with calcinosis. Clinical symptoms and laboratory tests at onset, initial therapy and disease course were compared in children with and without calcinosis.The mean age of the onset of calcinosis was 4.78 +/- 3.33 years, and it was younger than those of children without calcinosis (8.66 +/- 3.85 years) (P = 0.0017). No differences of clinical manifestation except Gower's sign were observed. The frequency of positive anti-nuclear antibody was 7.1% in children with calcinosis and 52.9% without calcinosis (P = 0.0112). The initial therapy of methylprednisolon pulses gave no effects on prognosis of calcium deposition. The calcinosis appeared in 1.56 +/- 1.91 year after the onset of the disease. The various types of calcium deposition including large tumorous clumps, subcutaneous plaques or nodules, sheet-type calcification were deserved. They appeared over knee joints (64.3%), elbow joint (64.3%), and hip processes (50.0%). Calcinosis affecting the subcutaneous tissues frequently resulted in painful superficial ulceration of the overlying skin (42.9%), local infection (50.0%), and limitation of joint movement (14.3%). Although aluminum phosphate was effective in 2 children among 7, no other effective treatment was recommended. In 5 cases, surgical removal of tumorous clumps was operated. Thus, juvenile dermatomyositis is frequently complicated with calcinosis. This type of calcinosis was found to be unlikely to resolve completely, and resulted in severe disability in children.

A boy had infantile-onset systemic inflammation, growth failure, hepatosplenomegaly, anemia, leukocytopenia, progressive muscular dystrophy, and hypercalprotectinemia, resulting in marked hyperzincemia. His mother had a history of chronic arthritis since childhood and also showed hypercalprotectinemia/hyperzincemia. We postulate an inherent defect in calprotectin metabolism.

We studied the early-onset variant of benign childhood epilepsy with occipital paroxysms (EVBCEOP) proposed by Panayiotopoulos, to confirm whether his five criteria are sufficient to delineate EVBCEOP as a new epileptic syndrome, as well as to predict a good outcome prospectively at the time of the first examination.The subjects were 649 children with localization-related epilepsies (LREs) observed in our hospital for4 years.We applied the International Classification of Epilepsies and Epileptic Syndromes to the 649 patients and identified patients who had EVBCEOP from among those with nonspecific idiopathic LRE. The inclusion criteria were to satisfy all five criteria and all but one criterion (i.e., either ictal vomiting or occipital EEG paroxysms). We were blind as to the outcomes and selected patients who satisfied the following three of the five criteria at the time of the first examination, (a) normal development before the onset, (b) epilepsy onset age between 2 and 8 years, and (c) occipital EEG foci. We attempted to determine whether the outcome can be predicted prospectively, and whether the presence or absence of ictal vomiting affects the prognosis.We identified 19 patients who satisfied all five criteria, 22 who exhibited all but occipital EEG foci, and 21 who exhibited all but ictal vomiting. The incidence of status convulsivus was higher in those with ictal vomiting than in those without ictal vomiting (p0.05). Interictal EEG performed every 6 months showed shifting and multiplication of EEG foci in 42 and 52% of all subjects, respectively. We identified 57 patients, 42 (74%) of whom were in remission by age 12 years. The number of patients who experienced remission did not differ significantly between those with (76%, n = 25) and without (72%, n = 32) ictal vomiting (p0.05).Nosologically, EVBCEOP appears to constitute the earliest form of idiopathic epileptic syndrome different from classic BCEOP. However, its clinical spectrum, ranging from the absence of ictal vomiting to a combination of extraoccipital and multifocal EEG foci, is broad, such that further prospective study is expected to reveal the exact prerequisite criteria for determining the border of this epileptic syndrome and for clarifying the clinical spectrum within this syndrome.

Mice and rats homozygous for mutations at the nude {nu) locus exhibit the pleiotroplc phenotypes of halriessness and athymia. A recent positional cloning study Identified, as a nude gene, a novel fork head transcription factor, Hfh11 (also called whn), that is expressed in skin and thymus, and is mutated In nude rodents. To obtain the direct biological proof that this gene is responsible for the nude phenotype, we mlcroinjected a cosmid clone containing the wild-type Hfh11 genomic locus into fertilized nude eggs. Two Independent founder lines of transgenic mice were generated that corrected the hairless phenotype, but not the thymic defect. This partial rescue demonstrates that Hfh11 is the gene responsible for the hairless defect in the nude mouse. Taken together with previous genetic studies, this complementation result Indicates that Hfh11 Is Indeed the nude gene and the Hfh11 locus is likely to be subject to complicated regulation.

Exposure of various neural cells to ATP increased intracellular Ca2+ and the production of inositol trisphosphate. The Ca2+ responses were also observed in the absence of extracellular Ca2+, suggesting that a part of Ca2+ mobilization took place from cytosolic storage. Since adenosine had no effect on intracellular Ca2+ increment, ATP appears to act through a P2-purinergic receptor. Islet-activating protein or pertussis toxin pretreatment hardly influenced the increase in intracellular Ca2+ and inositol trisphosphate production induced by ATP, suggesting that IAP-sensitive GTP-binding proteins do not play a practical role in this reaction.

Seven children with acute disseminated encephalomyelitis (ADEM) after treatment with Japanese B encephalitis vaccine (JBEV) (Nakayama-Yoken strain 1968-88 and Beijing strain 1989-93) were identified by mailed questionnaires and by compilation of previously published case reports. It was considered that encephalomyelitis might have been related to vaccine treatment as the vaccine is derived from mouse brain tissue infected with Japanese B encephalitis virus, a potentially cross reactive antigen. The incidence of severe neurological complications associated with the newer Japanese B encephalitis Beijing strain vaccine seemed to be less than one case per 1,000,000, which is similar to the incidence of neurological complications associated with the older Nakayama-Yoken strain vaccine.

It has been demonstrated that ACh receptors in Xenopus nerve-muscle cultures migrate in the membrane to the nerve contact area during junction formation (Anderson et al., 1977) and that “diffusion trapping” is the major mechanism for nerve-induced receptor accumulation (Kidokoro and Brass, 1985; Kuromi et al., 1985; Kidokoro et al., 1986). A crucial remaining question is how the nerve induces the trap for randomly diffusing ACh receptors. In this study we examined the effect of various glycosaminoglycans in the culture medium on the nerve-induced receptor accumulation and found that heparin and heparan sulfate partially inhibited nerve-induced receptor accumulation, but similar molecules, chondroitin sulfate type A and type C, did not. By chemical modification of heparin we also showed that N-sulfate residues and a large-molecular-weight molecule are essential for this inhibitory effect. Heparin did not affect ACh receptor clustering (hot-spot formation) in myocytes cultured without nerve. By changing the time and duration of heparin application, we found that heparin was effective in inhibiting nerve-induced receptor accumulation only when it was present in the culture medium during the period that neurites are actively forming contact with muscle membrane.

The In(Lu) phenotype is inherited as an autosomal dominant trait and is characterized by suppression of the Lutheran, P1, i, and Aua erythrocyte blood group antigens. We have developed a monoclonal antibody (L21) that strongly agglutinates all erythrocytes except In(Lu), and we have identified eight In(Lu) individuals among 42,000 blood donors tested. Studies of two families confirmed the dominant mode of inheritance and revealed several new features of this phenotype. The erythrocytes of all five affected individuals from the two families exhibited diminished hemagglutination by the lectin concanavalin A, although they reacted normally with several other lectins. The erythrocytes of two affected individuals in one family exhibited marked acanthocytosis. The erythrocytes of the proposita of the other family exhibited a mild degree of poikilocytosis, but the cells of the other two affected individuals in this family had normal morphology. The osmotic fragility of fresh In(Lu) erythrocytes was normal, but after incubation for 24 hours at 37 degrees C in plasma the In(Lu) cells exhibited a marked increase in resistance to osmotic lysis. During the incubation period the erythrocytes lost K+ and their total cation content was diminished. These data indicate that in addition to the suppression of blood group antigens noted previously, the In(Lu) phenotype includes a variety of morphological abnormalities and a defect in electrolyte metabolism. The use of L21 and similar monoclonal antibodies provides a more sensitive means of detecting In(Lu) erythrocytes than typing with human anti-Lub antisera.

The effect of Platonin on human peripheral blood lymphocytes (PBL) was studied in vitro. Platonin showed proliferative effect on PBL. When PBL was stimulated with T cell mitogen Phytohemagglutinin (PHA) and B cell mitogen Staphylococcus aureus Cowan I (Cowan I), it showed enhancing effect on the former and suppressive effect on the latter. In Pokeweed mitogen (PWM) induced immunoglobulin (Ig) productive system, both of the T.B cells, T cells only, or B cells only were pretreated with Platonin and then co-cultured. The Ig secreting cells were demonstrately decreased than that of the absent Platonin pretreated in any groups. However, the 3H-thymidine incorporation failed to give a significant variation in any groups. In the experiment of T cell subsets detected with monoclonal antibodies and by Fluorescent Activaed Cell Sortor (FACS), the OKT8+ T cells showed a high proportion in the Platonin treated groups. In summary, B cells were directly suppressed by Platonin and concerning T cells, the T cell subsets showed a high proportion of suppressor/killer T cells. So it is suggested that Platonin suppressed Ig prodution through suppressing B cells and enhancing suppressor/killer T cells.

A new model useful for studying capillary growth in vitro is described. When the microvessel fragments and accompanying single cells (myofibroblastic cells) from rat epididymal fat pads were co-cultivated, the myofibroblastic cells initially began to grow and reached confluence. A few days later, endothelial cells started to sprout from the vessel fragments, forming cellular cord networks on and in the multilayered myofibroblastic cells. Ultrastructurally, the lumina, surrounded by the endothelial cells having intercellular junctions, were observed at cross-sectioned cellular cords. The growth of cellular cords from the fragments always occurred after the myofibroblastic cells had reached confluence. The medium conditioned to isolated rat myofibroblastic cells stimulated not only the proliferation of the endothelial cells from the bovine capillary and human vein but also the migration of bovine capillary endothelial cells in vitro. Moreover, the extracellular matrix produced by rat myofibroblastic cells modulated the morphology of bovine capillary endothelial cells to a cordlike shape. These observations strongly suggest that the formation of the capillary in vitro is induced by myofibroblastic cells.