Search

The purpose of this study was to clarify the current status of collaboration between nurses and community pharmacists as well as the requests and expectations that community pharmacists have of nurses in community-based comprehensive care systems. Questionnaires requiring open-ended responses were sent to 867 pharmacies throughout Fukushima prefecture (excluding four suspended pharmacies). We asked one pharmacist at each facility to answer the questions. We then analyzed the collected questionnaires using descriptive statistics, including the current status of nurse cooperation and the basic information about the pharmacies. Additionally, the open-ended descriptions of nurses' requests and expectations were analyzed quantitatively and qualitatively. The questionnaire collection rate was 32% (278 cases), and the breakdown of pharmacies that responded was 68.0% for facilities with 1 or 2 full-time pharmacists and 27.0% for facilities with 3 to 5 pharmacists. About 30% of respondents reported contact with the nursing profession at least once a week, while about 50% reported no contact at all or several times a year. The types of nurses collaborating with the pharmacies were clinic nurses (54.6%) and visiting nurses (43.4%). Some pharmacists had expected nurses to work cooperatively and rely on pharmacists. These results indicate that only about half of the pharmacists had opportunities to cooperate with nurses. For trust to be established between nurses and pharmacists, it is necessary for nurses to ask the pharmacists about medication and consult with them about patient medication management.

In this paper, we aim to investigate how researchers in Japan and Sweden perceive and approach the term "sharing economy" in research publications. Systematic literature reviews were used to explore academic discussions in both countries. The main finding of this research is that although researchers in both contexts use similar definitions and concepts, the meanings and connotations of the sharing economy differ among the two contexts. In summary, Japanese researchers tend to focus first and foremost on the economic effects of the sharing economy, as it serves the purpose of economic revitalisation. In contrast, Swedish researchers focus on its environmental effects. The differences reflect country-specific socio-cultural, technological, and economic contexts. Finally, we suggest future directions for research and policy development.

Various types of pre-learning-including pre-learning for practical training-provide pharmacy students with practical training and sufficient knowledge, skills, and attitudes for practical work. Opportunities in the medical field, including for pharmacists, have been greatly expanded for students with a hearing disability, and we have responded with appropriate training for such students. In this study, we report on the results of an evaluation of a survey on the preparatory training conducted by the students and the changes in their consciousness, such as in their level of understanding, knowledge, and self-confidence. Before the training, the participants' anxiety concerning items related to dispensing and communication were quite high; after the training, however, these anxiety levels were reduced. In addition, we were able to encourage the participant's concern for people and to face the difficulty of expressing words in letters, as well as to drive enthusiasm for the Objective Structured Clinical Examination (OSCE) and practical training. These results suggest that having a teacher as an assistant is useful for helping students with hearing disability in practical training.

Summary Background Mizagliflozin is a novel oral sodium-glucose cotransporter 1 (SGLT1) inhibitor that increases luminal glucose and water. This study assessed the efficacy and safety of mizagliflozin in patients with functional constipation. Methods In this multicentre, randomised, double-blind phase 2 trial at 32 hospitals and community outpatient clinics in Japan, we enrolled patients with functional constipation or constipation-predominant irritable bowel syndrome, aged 20 years or older. Patients were randomly assigned (1:1:1), by use of an independent centralised registration system and dynamic allocation method, to receive mizagliflozin 5 mg, mizagliflozin 10 mg, or placebo, orally once daily for 4 weeks. Patients, investigators, staff, and the sponsor were blinded to the group assignments. The primary outcome was the change from baseline in the number of spontaneous bowel movements per week after 1 week. Efficacy analysis was done in all patients except those who deviated from good clinical practice, did not receive at least one dose of the study drug, withdrew before starting treatment, were ineligible, or for whom the primary outcome could not be assessed, and safety was assessed in all patients except those who deviated from good clinical practice, who did not receive the study drug, or who withdrew before receiving treatment. This trial is registered with ClinicalTrials.gov , number NCT02281630 , and is completed. Findings Between Oct 15, 2014, and March 7, 2015, 258 patients with functional constipation were randomly assigned: 86 patients per group. Two patients from the placebo group and three from the 10 mg mizagliflozin group were excluded because the primary outcome could not be assessed, and one patient from the 5 mg mizagliflozin group was excluded for not receiving the study drug; therefore 84 patients in the placebo group, 85 in the 5 mg mizagliflozin group, and 83 in the 10 mg mizagliflozin group were included in the full analysis population. Mean change from baseline in the number of spontaneous bowel movements per week after 1 week with mizagliflozin 5 mg (3·85 [SD 3·96]) and mizagliflozin 10 mg (5·85 [6·01]) was significantly greater than those in the placebo group (1·80 [1·80]; p Interpretation The SGLT1 inhibitor mizagliflozin showed favourable efficacy and tolerability at 5 mg and 10 mg doses in patients with functional constipation, providing a potential alternative therapy to available drugs. Funding Kissei Pharmaceutical.

Ebola virus disease (EVD) is a life-threatening viral disease with a fatality rate ranging from around 30% to 90%. The first EVD outbreak was reported in the 1970s in Zaire (now the Democratic Republic of the Congo). Until 2013, most outbreaks occurred in the Central Africa region, including Zaire, Sudan and Uganda. However, between March and October 2014, over 10 000 cases of EVD have been recorded in West Africa, such as in Guinea, Liberia, Sierra Leone, and Nigeria, and a few hospital or secondary infections of EVD have occurred in Spain and the United States of America. EVD is presently one of the world's most feared diseases. In this literature review, we describe the epidemiology, clinical features, diagnosis, and treatment of EVD.

The scope of pharmaceutical education in Japan has been expanding, and with it an awareness of the importance of team medical care. However, pharmaceutical education still gives little attention to the psychosocial aspects of care, instead focusing on the structures and functions of drugs. In contrast, nursing education emphasizes the fact that medical care involves patients' family and significant others as much as the patients themselves, and thus nursing students are taught the basic needs and developmental stages of those people requiring care alongside their practical nursing skills. In this study, we examined the effect of incorporating certain aspects of introductory nursing education into pharmaceutical education on the self-efficacy of pharmaceutical students. We thus ran an introduction to nursing education course for fourth-year pharmaceutical students (n=86). After the course had finished, we surveyed students about the course. Approximately 94.2% of the students became more interested in team medical care and nearly all (98.8%) thought that what they had learned in the course would be useful in their career. The results indicated that the introduction to nursing education course offered students an opportunity to acquire different viewpoints on clinical situations because the lectures were given by a pharmacist with a nurse license and they were based on his clinical experiences. We therefore propose that more facets of introductory nursing education be incorporated into pharmaceutical education to help students develop their ability to consider patients' psychosocial backgrounds.

A 64-year-old male fell from an altitude of 10 m while paragliding after stalling due to the wind. The purpose of this case report is to describe the outcomes after multiple injuries sustained during a paragliding accident, including a potentially life-threating injury to the thoracic aorta. The subject sustained a bite wound on his tongue, injuries to his chest (left side) and back, and a right forearm deformity. Enhanced whole body computed tomography (CT) revealed fractures of the bilateral laminae of the second and third cervical bones, right first rib, the tenth thoracic vertebral body (compression type), second lumbar vertebral body (burst type) and the right radius, Other injuries included an injury to the thoracic aortic arch and the presence of intraabdominal fluid collection without perforation of the digestive tract. Endovascular treatment was selected for the aortic injury because of multiple injuries. Immediate management included hypotensive rate control therapy using calcium and a beta blocker. On the fourth hospital day, the subject underwent deployment of a stent-graft to the aorta and subsequent surgical immobilization for the lumbar burst fracture. He also underwent surgical immobilization of the radial fracture and was discharged on the 28th hospital day. First responders or physicians should consider the possibility of aortic injury when treating patients who suffer falls while paragliding and provide appropriate management. Failure to provide appropriate management of an aortic injury could result in death.4.

Rationale : Angiogenesis contributes to physiological and pathological conditions, including atherosclerosis. The Rap1 small G protein regulates vascular integrity and angiogenesis. However, little is known about the effectors of Rap1 involved in angiogenesis. It is not known whether afadin, an adherens junction protein that connects immunoglobulin-like adhesion molecule nectins to the actin cytoskeleton and binds activated Rap1, plays a role in angiogenesis. Objective : We investigated the role of endothelial afadin in angiogenesis and attempted to clarify the underlying molecular mechanism. Methods and Results : Treatment of human umbilical vein endothelial cells (HUVECs) with vascular endothelial growth factor (VEGF) and sphingosine 1-phosphate (S1P) induced the activation of Rap1. Activated Rap1 regulated intracellular localization of afadin. Knockdown of Rap1 or afadin by small interfering RNA inhibited the VEGF- and S1P-induced capillary-like network formation, migration, and proliferation, and increased the serum deprivation-induced apoptosis of HUVECs. Knockdown of Rap1 or afadin decreased the accumulation of adherens and tight junction proteins to the cell–cell contact sites. Rap1 regulated the interaction between afadin and phosphatidylinositol 3-kinase (PI3K), recruitment of the afadin–PI3K complex to the leading edge, and the activation of Akt, indicating the involvement of Rap1 and afadin in the PI3K–Akt signaling pathway. Binding of afadin to Rap1 regulated the activity of Rap1 in a positive-feedback manner. In vivo, conditional deletion of afadin in mouse vascular endothelium using a Cre-loxP system impaired the VEGF- and S1P-induced angiogenesis. Conclusions : These results demonstrate a novel molecular mechanism by which Rap1 and afadin regulate the VEGF- and S1P-induced angiogenesis.

While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome.

In the hippocampus, synapses are formed between mossy fiber terminals and CA3 pyramidal cell dendrites and comprise highly developed synaptic junctions (SJs) and puncta adherentia junctions (PAJs). Dynamic remodeling of synapses in the hippocampus is implicated in learning and memory. Components of both the nectin–afadin and cadherin–catenin cell adhesion systems exclusively accumulate at PAJs. We investigated the role of afadin at synapses in mice in which the afadin gene was conditionally inactivated in hippocampal neurons. In these mutant mice, the signals for not only nectins, but also N-cadherin and β-catenin, were hardly detected in the CA3 area, in addition to loss of the signal for afadin, resulting in disruption of PAJs. Ultrastructural analysis revealed an increase in the number of perforated synapses, suggesting the instability of SJs. These results indicate that afadin is involved not only in the assembly of nectins and cadherins at synapses, but also in synaptic remodeling.

Purpose: Helicobacter pylori is reportedly involved in the development of gastric cancer. We investigated the mechanisms by which H. pylori affects gastric cancer growth and antitumor immunities in the host, focusing on H. pylori–derived lipopolysaccharide (LPS).Experimental Design: H. pylori and four gastric cancer cell lines (MKN28, MKN45, NUGC3, and KATOIII) were used. We examined the effect of H. pylori or its LPS stimulation on cancer growth and the involvement of the H. pylori LPS-toll-like receptor 4 (TLR4) pathway. We also examined the cytotoxicities of H. pylori/LPS–stimulated human mononuclear cells (MNC) against gastric cancer cells and the effect of H. pylori LPS stimulation on cytokine production by MNC.Results: H. pylori, as well as its LPS, augmented the growth of gastric cancers, all of which expressed TLR4. Neutralization of TLR4 almost completely abrogated the H. pylori–induced proliferative activity of cancer cells. Escherichia coli LPS also augmented cancer growth via the LPS-TLR4 pathway. However, only H. pylori–derived LPS attenuated the cytotoxicity of MNC against gastric cancer cells. Stimulation with H. pylori/LPS also down-regulated perforin production in cancer cell–cocultured CD56+ natural killer cells. H. pylori LPS induced neither interleukin-12 nor IFN-γ production by MNC, although E. coli LPS did induce production of both significantly. Nevertheless, interleukin-12 stimulation restored the IFN-γ–producing capacity of H. pylori LPS–stimulated MNC.Conclusion: H. pylori augmented the growth of gastric cancers via the LPS-TLR4 pathway, whereas it attenuated the antitumor activity and IFN-γ–mediated cellular immunity of MNC. H. pylori infection might thereby promote proliferation and progression of gastric cancers.

In our pre-clinical training program,students acquire expertise in reviewing prescriptions and measurement of powder and liquid form drugs in four stages with the objective of preventing dispensing errors.Through experiencing the preparation of drugs,students learned how to prevent potential errors in their clinical training.The effectiveness of the pre-clinical training program was determined through an evaluation by students and having them think about the causes of errors in drug preparation and measures to prevent them in groups.Our findings showed that the program achieved a significant improvement in risk management awareness.Further,the pre-clinical training increased the motivation of many students and after completing it,some of them said,“It was beneficial to learn the risks in drug preparation prior to practical training”and others,“I want to start working as a pharmacist as soon as possible”.These findings showed that a pre-clinical training program focusing on risk management was effective in helping students to learn about the knowledge and skills required of the pharmacist and increased their motivation prior to taking clinical training.

Underwater pulsed streamer discharges using a wire-to-cylinder electrode contained in a 42-mm-diameter glass tube were investigated with respect to its spatial spread associated with voltage waveforms. A discharge reactor with a continuous flow system was employed to sterilize E. coli suspended in saline water (10 mS/m). The discharge electrode consisted of a 0.1-mm-diameter metal wire for the high voltage and a mesh cylinder for the ground electrode. Tens of disk-shaped discharges emerged from the wire electrode and propagated toward the cylinder as long as the voltage lasted. The spatial expanse of the discharge was proportional to the cube of the pulse duration and to the amplitude of the voltage. The sterilization experiment showed that the survival ratio of bacteria over discharges was proportional to the average number of the exposures to the discharges while in the reactor. The minimum ratio of surviving bacteria was only 15% under 130 exposures, which corresponds to an energy expenditure of 35 J/ml. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 164(1): 1–7, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20554

Background/Aims Although mouse liver contains a large population of B cells, little is known about how hepatic B cells respond to bacterial lipopolysaccharide (LPS). Methods The cytokine and IgM productions of hepatic B cells were compared with those of splenic B cells. The effect of LPS-treated hepatic B cells on IFN-γ production from co-cultured NK1.1 + cells was also examined by irradiation and transwell experiments. Results Hepatic B cells stimulated with LPS produced substantial amounts of IFN-γ and IL-12 but a small amount of IgM, while splenic B cells did not produce any of these cytokines but produced a large amount of IgM. The hepatic B cells expressed surface markers similar to those on spleen B cells but expressed more C–X–C chemokine receptor 3 than spleen B cells. Notably, depletion of B220 + cells from liver MNCs (but not from spleen MNCs) greatly decreased LPS-induced IFN-γ production. Furthermore, LPS-treated hepatic B cells stimulated liver NK1.1 + cells to produce a remarkable amount of IFN-γ, not only through their soluble factors but also through direct cell–cell contact. Conclusions Liver B cells may play an important role in the defense against gram-negative bacterial infections by inducing IFN-γ production from liver NK cells.

Pulsed streamer discharges in water using a wire to cylinder electrode contained in 42 mm inner glass tube were investigated with respect to its spatial expanse associated with voltage waveforms. The discharge reactor with a continuous flow system was employed to sterilize E. coli suspended in saline water (10 mS/m). The discharge electrode consisted of a 0.1 mm diameter metal wire for the high voltage and a mesh cylinder for the ground electrode. Tens of disk-shape discharges emerged from the wire electrode and propagated toward the cylinder as long as the voltage lasts. The spatial expanse of the discharge was proportional to the cube of pulse duration and to the amplitude of the voltage. The sterilization experiment showed that the survival ratio of bacteria over discharges was proportional to the average number of the exposure to the discharges while in the reactor. The minimum ratio of survival bacteria was only 15% under 130 exposures, which corresponds to the energy expenditure of 35 J/ml.

症例は75歳の女性で, 近医整形外科手術翌日より腹痛・下痢出現. 腹部症状の増悪と意識障害が出現したため, 当科に転院となった. 腹部CTでは腸間膜・後腹膜の肥厚, および腹水を認めた. 大腸内視鏡検査で黄白色の偽膜の形成を認め, 偽膜よりClostridium difficile毒素Aが検出された. 直ちに集中治療およびvancomycin (VCM)やmetronidazoleによる治療を開始したが, septic shockに陥ったため大腸亜全摘術を施行. 術後, 血圧の上昇および意識障害の改善が見られたものの, 多臓器不全が進行し, 大腸亜全摘術より第49病日に永眠された. 抗生剤投与後に下痢や腹痛などの消化器症状を呈した場合には本症を念頭においた診断・治療が重要であり, さらにsepsisや臓器障害が進行する症例では早期から積極的な外科治療を考慮すべきであると考えられた.

Highly activated neutrophils play a critical role in mediating organ injury in sepsis by releasing neutrophil elastase (NE). Toll-like receptors (TLRs) play an important role in the host defense against invading microbes, and their signaling pathway is critical to the activation of the proinflammatory response. However, the relationship between TLR expression and the host defense mechanism during sepsis has not been fully elucidated. In this paper, we investigated the relationships among chemokine (MIP-2), TLR-4, and NE expression in human sepsis and murine peritonitis (CLP). TLR-4 expression on monocytes/macrophages was examined in patients with sepsis and in murine peritonitis and was markedly increased in both populations. LPS-induced MIP-2 production by bronchoalveolar cells and liver mononuclear cells in mice with peritonitis was also significantly increased compared with sham-operated mice. Pretreatment of the macrophage cell line, RAW 264.7 cells, with a NE inhibitor before their exposure to LPS resulted in a significant dose-dependent decrease in MIP-2 production, which was comparable to that seen following pretreatment with TLR-4 antibody. Furthermore, NE and LPS both up-regulated TLR-4 expression on human peripheral blood monocytes. Thus, chemokine-induced recruitment of neutrophils in sepsis may result in further increased chemokine production and increased expression of TLR-4. Neutrophil-derived NE may be associated with increased expression of monocyte/macrophage TLR-4, thereby serving as a positive feedback loop for the inflammatory response among the different cell populations.

Background: CD16+CD14+monocytes dramatically increase in number in patients with severe infection. Hemoperfusion with PMX-F (direct hemoperfusion with polymyxin B immobilized fibers) has been reported to be a safe and effective treatment for patients with septic shock, although the molecular mechanism that accounts for its effectiveness is still unclear. The purpose of this study was to quantify the number of CD16+CD14+monocytes in patients with an intra-abdominal infection and to evaluate the effects of PMX-F treatment on clinical parameters and leukocyte surface antigen expression in these patients.Materials and Methods : Seventeen septic patients who had an intra-abdominal infection were enrolled in this study; 7 of these patients received PMX-F treatment. Peripheral blood samples were obtained immediately after admission, and were also collected from the above 7 patients before, during, and immediately after their PMX-F treatment. The expression of CD14, CD16, and Toll-like receptor (TLR)-4 on these patients' monocytes was evaluated using flow cytometry. In addition, lipopolysaccharide (LPS)-induced production of TNF-α and IL-1β by these cells was measured by ELISA.Results: Monocytic expression of CD16 and TLR-4 was significantly greater in septic patients than in healthy controls, and their proportion of CD16+CD14+monocytes was similarly elevated. LPSinduced production of TNF-α and IL-1β by peripheral blood mononuclear cells (PBMCs) of septic patients was significantly reduced compared to controls. Furthermore, there was a reduction in the proportion of CD 16+CD 14+monocytes during PMX-F treatment, and in the expression of TLR-4 on monocytes after PMX-F treatment.Conclusions: These results showed that the number of peripheral blood CD16+CD14+monocytes and monocytic TLR-4 expression were markedly increased, and the production of pro-inflammatory cytokines in response to LPS significantly reduced in patients with sepsis. PMX-F treatment was found to be effective in reducing the number of CD 16+CD 14+monocytes and in decreasing the monocytic expression of TLR-4 in patients with septic shock.

Background: CD16 +CD14+ monocytes dramatically increase in number in patients with severe infection. Hemoperfusion with PMX-F (direct hemoperfusion with polymyxin B immobilized fibers) has been rep...

Background. The Japanese Gastric Cancer Association’s (JGCA’s) Gastric cancer treatment guidelines for doctors’ reference and the guidelines (GLs) for popular use were both published in 2001. The purpose of this study was to know whether or not it is useful for patients to read the GLs for popular use. Methods. We lent the GLs for popular use to patients with gastric cancer for several days and had them read the GLs before they were informed about their condition and the recommended treatment. Then they received questionnaires concerning the GLs. Results. Most of the patients, even the elderly, had read and understood the GLs. Nearly 70% of the patients answered that it was very useful for them to read the GLs. On the other hand, 34% of the patients suggested negative aspects, such that reading the GLs increased their anxiety about the disease or treatment. Only 9% of the patients expected treatment that followed the GLs, whereas 54% of the patients expected treatment based on the doctor’s own experience without adherence to the GLs. If the doctor were to suggest treatment that did not follow the GLs, 87% of the patients answered that they would follow the doctor’s suggestion, and it was only 8% who answered that they would seek a second opinion. These results did not differ when patients were requested to fill out questionnaires anonymously. Conclusion. Although the GLs for popular use are useful to provide patients with information concerning the disease and the treatment modalities, they may not have a great impact on patients’ decisions about their treatment.

症例1: 58歳の男性.内視鏡検査で胃体上部後壁に3型腫瘍を, 胃前庭部にIIc病変を認め, 生検の結果おのおの低分化腺癌, 高分化腺癌であった.入院待機期間を利用してTS-1 100mg日を1クール投与したところ, 胃体上部の腫瘍は, 浅い陥凹のみとなり, 前庭部の病変は消失した.胃全摘, D2郭清術を施行.手術標本においても腫瘍細胞は検出されず, 組織学的にCRと診断した.症例2: 87歳の男性.内視鏡検査において胃噴門部の2型腫瘍を認め, 生検にて乳頭腺癌の診断をえた.高齢であること, 併存症が多いこと, 本人が手術を希望しなかったことから, TS-1 100mg/日を開始.投与開始後19日目の内視鏡検査では, 原発巣の周堤は明らかに縮小し, 潰瘍も軽快傾向であり, 140日目には, 原発巣は潰瘍廏痕となり, 組織診でも腫瘍細胞は検出されなかった.胃癌に対するTS-1投与は, CRがえられた報告も散見され, 外科手術の危険性が高い症例などでは, 侵襲の少ない治療として選択肢の1 つとなりえると考えられた.

2B4 is expressed on all NK and a subset of memory/effector CD8+ T cells. 2B4 binds to CD48 and activates NK cytotoxicity, but its function on CD8+ T cells is not clear. Furthermore, two isoforms of 2B4 (2B4S and 2B4L) exist in mice but the role of individual isoforms is not known. To address these questions, we generated primary T cell cultures from Ld-specific 2C/Rag2−/− TCR transgenic mice and transduced them with 2B4S or 2B4L. 2B4S- or 2B4L-transduced T cells showed greater cytotoxicity over control cells against CD48+ and CD48− targets, suggesting that ligation of 2B4 by CD48 on target cells was not necessary for 2B4 function. Rather, 2B4/CD48 interaction on adjacent T cells appeared to be critical for cytotoxicity. Therefore, 2B4 functions as a costimulator of CD8+ T cells in MHC-restricted cytotoxicity. We conclude that 2B4/CD48 interactions among T cells themselves can augment CTL lysis of their specific targets.

Background. Acute lung injury is a frequent extraabdominal complication of bacterial peritonitis, and neutrophil plays an important role in this lung damage. Macrophage inflammatory protein 2 (MIP-2) serves the same chemotactic function as IL-8 which is a potent neutrophil chemotactic factor in humans, and we investigated the role of MIP-2 associated with neutrophil recruitment in the lung of murine peritonitis. Methods. Cecal ligation and puncture (CLP) were performed on mice. MIP-2 levels in blood and lung tissue, MIP-2 mRNA expression in lung tissue and bronchoalveolar lavage fluid (BALF), and CD11b expression on peripheral blood neutrophil and BALF cells were determined after CLP. In addition, we investigated the effect of anti-MIP-2 antibody on the lung injury associated with peritonitis. Results. MIP-2 mRNA expression was observed in lung tissue after CLP and numerous neutrophils were accumulated in the lung under those conditions. Anti-MIP-2 antibody contributed to the inhibition of the CD11b expression and chemotaxis of pulmonary neutrophils, lung edema, and thus the reduction in peritonitis-related mortality. Conclusions. MIP-2 plays a pivotal role in neutrophil recruitment in the lung following peritonitis, and control of neutrophil accumulation in the lung by neutralizing MIP-2 is recommended as a new therapeutic approach to the lung damage associated with peritonitis.

A water-filled Blumlein generator was operated at different repetition rates of up to 15 Hz, and its temporal performance was investigated. The Blumlein generator having an impedance of 10 Ω provides a rectangular voltage pulse with an amplitude of 200 kV and a duration of 75 ns into a matched load. The resistance of the water in the line decreases quickly at >10 Hz during a continuous operation for an hour and results in a decrease in the output voltage of the Blumlein line. The generator works with a repetition rate of up to 6 Hz without serious degradation in the voltage, while the averaged power density dissipated in the water is approximately 40 mW/cm3. The increase in the water temperature during operation is only a few degrees. This implies that the resistive heating of the water is not the dominant cause of the decrease in the water resistance.

NC/Nga (NC) mice raised under conventional conditions (Conv. NC mice) spontaneously develop dermatitis similar to human atopic dermatitis, whereas NC mice raised under the specific pathogen-free conditions do not develop dermatitis. In the present study, we show that the representative Th1 cytokine, IFN-γ levels in the sera of NC mice, injected with either staphylococcal enterotoxin B or endotoxin (LPS), to be severalfold lower than those of normal mice. The low IFN-γ response to staphylococcal enterotoxin B was correlated to the lack of regular Vβ8+ T cells and Vβ8+ NK T cells, and the low IFN-γ response to LPS was correlated to an impaired IL-18 production of macrophages. The CD3-stimulated IL-4 production from liver and spleen T cells from Conv. NC mice in vitro was greatly augmented. The serum IL-4 levels of untreated Conv. NC mice also were higher than those of normal mice and specific pathogen-free NC mice. Treatment of Conv. NC mice either with IFN-γ, IL-12, or IL-18 twice a week from 4 wk of age substantially inhibited the elevation of the serum IgE levels, serum IL-4 levels, and dermatitis, and IL-12 or IL-18 treatment also reduced the in vitro IL-4 production from CD3-stimulated liver T cells. The systemic deficiency in the Th1 response to bacterial stimulation thus leads to a Th2-dominant state and may induce an abnormal cellular immune response in the skin accompanied with an overproduction of IgE and a susceptibility to dermatitis in NC mice.

Afadin is an actin-filament-binding protein that binds to nectin, an immunoglobulin-like cell-cell adhesion molecule, and plays an important role in the formation of adherens junctions. Here, we show that afadin, which did not bind to nectin and was localized at the leading edge of moving cells, has another role: enhancement of the directional, but not random, cell movement. When NIH3T3 cells were stimulated with platelet-derived growth factor (PDGF), afadin colocalized with PDGF receptor, αvβ3 integrin and nectin-like molecule-5 at the leading edge and facilitated the formation of leading-edge structures and directional cell movement in the direction of PDGF stimulation. However, these phenotypes were markedly perturbed by knockdown of afadin, and were dependent on the binding of afadin to active Rap1. Binding of Rap1 to afadin was necessary for the recruitment of afadin and the tyrosine phosphatase SHP-2 to the leading edge. SHP-2 was previously reported to tightly regulate the activation of PDGF receptor and its downstream signaling pathway for the formation of the leading edge. These results indicate that afadin has a novel role in PDGF-induced directional cell movement, presumably in cooperation with active Rap1 and SHP-2.

We propose a novel system level power estimation method for wireless communication devices. The method estimates the power consumption of a processor and external devices by only using OS level profile information (i.e., the system call information), and is applicable to both off-line and online power optimizations. Evaluations on a commercial wireless communication device showed that the method achieves an estimation error of less than 10 %.

The nectin-afadin complex is involved in the formation of cell-cell junctions, such as adherens junctions (AJs) and tight junctions (TJs). Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules, whereas afadin is an intracellular nectin-binding protein that connects nectins to the cadherin-catenin system at AJs and to the claudin–zona-occludens (ZO) protein system at TJs. Afadin–/– mice show embryonic lethality, resulting from impaired migration and improper differentiation of cells due to disorganization of cell-cell junctions during gastrulation. However, it remains to be elucidated whether disruption of afadin affects apoptosis. In the present study, we first found that embryoid bodies derived from afadin-knockout embryonic stem (ES) cells contained many more apoptotic cells than those derived from wild-type ES cells. We also revealed that apoptosis induced by serum starvation or Fas-ligand stimulation was increased in cultured NIH3T3 cells when afadin or nectin-3 was knocked down. The nectin-afadin complex was involved in the platelet-derived growth factor (PDGF)-induced activation of phosphatidylinositol 3-kinase (PI3K)-Akt signaling for cell survival. This complex was associated with PDGF receptor on the plasma membrane at cell-cell adhesion sites. Thus, the nectin-afadin complex is involved in PDGF-induced cell survival, at least through the PI3K-Akt signaling pathway.

The level of serum CCL5, a C-C chemokine, is reportedly correlated with tumor progression in several cancers. We herein investigated the mechanisms by which CCL5 might contribute to tumor progression in gastric cancer. Serum CCL5 levels significantly correlated with tumor progression and prognosis in patients with gastric cancer. Immunohistochemistry showed that tumor-infiltrating lymphocytes expressed CCL5, while the tumor cells expressed the CCL5 receptors. Fluorescent double staining showed that tumor-infiltrating CD4+ cells rather than CD8+ cells preferentially expressed CCL5. Using gastric cancer cell lines (MKN45, KATO III), we examined CCL5 production by coculturing whole peripheral blood mononuclear cells (PBMCs), CD4+ cells, or CD8+ cells, with tumor cells. CD4+ cells cocultured with tumor cells remarkably enhanced CCL5 production in a direct cell-cell contact manner over other cocultured PBMCs, including CD8+ cells. Gastric cancer cell lines expressed CCL5 receptors and augmented their proliferation in response to CCL5 stimulation. Furthermore, we examined the effect of CCL5-treated cancer cells on the cocultured PBMCs, focusing on the CD4+/CD8+ proportion and apoptosis. Coculture of CCL5-treated gastric cancer cells with PBMCs resulted in a significant decrease in the proportion of CD8+ cells but not CD4+ cells, suggesting Fas-FasL-mediated apoptosis in CD8+ cells. In immunodeficient mice coinjected with KATO III and PBMCs, neutralization of CCL5 significantly suppressed tumor progression, resulting in a favorable outcome. In conclusion, gastric cancer cells might thus induce CD4+ T cells to secrete CCL5 and exploit it for their progression, as well as to aid in the prevention of CD8+ T cell-involved tumor elimination.

Despite advances in surgical reconstruction, total gastrectomy still is accompanied by various complications, especially chronic ones, such as pernicious anemia, resulting in refractory malnutrition. As an alternative approach, we have proposed a tissue-engineered stomach as a replacement of the native stomach. This study aimed to assess the secretory functions of a tissue-engineered stomach in a rat model and the nutritional status of the recipients over an extended time period. Stomach epithelial organoid units were isolated from neonatal rats and seeded onto biodegradable polymers. These constructs were implanted into the omenta of adult recipient rats. After 3 weeks, cyst-like structures had formed, henceforth referred to as tissue-engineered stomachs. The recipient stomachs were resected and replaced by their tissue-engineered counterparts. At 24 weeks after implantation, the secretory function of the tissue-engineered stomach was evaluated using immunohistochemical staining. The hemoglobin levels and nutritional status of the recipients were compared with a control group that had undergone a simple Roux-en-Y reconstruction following total gastrectomy. Recipient rats tolerated the tissue-engineered stomachs well. X-ray examination using barium as contrast showed no bowel stenosis. Staining for proton pump alpha-subunit and gastrin demonstrated the existence of parietal cells and G-cells in the neogastric mucosa, respectively, suggesting secretory functions. The treatment group showed significantly higher hemoglobin levels than the control group, although no differences in the body weight change, total protein, or cholesterol levels were observed between the two groups. A tissue-engineered stomach has the potential to function as a food reservoir following total gastrectomy. It is conjectured that replacement with a tissue-engineered stomach might restore the proton pump parietal cells and G-cells, and thereby improve anemia after a total gastrectomy in a rat model.

Background: Granulysin is a cytolytic molecule present in human cytotoxic T cells and natural killer cell granules, and plays a key role in the cell-mediated immunity against tumor and infection. However, few studies have estimated serum granulysin concentrations in patients with solid or hematological malignancies. Methods: Peripheral blood samples were taken from patients with gastric carcinoma preoperatively and from healthy volunteers. Serum and tumor tissue granulysin concentrations were measured using a granulysin-specific ELISA kit in order to assess its prognostic value. Results: Both serum and tumor tissue granulysin concentrations were higher in patients with stage II or III gastric cancer and lower in patients with stage IV disease as compared to healthy controls. The low preoperative granulysin levels were associated with more frequent hepatic and peritoneal metastases, and with a poor outcome of the curative gastrectomy. Conclusions: Preoperative serum granulysin levels reflect the status of cell-mediated immunity in patients with gastric carcinoma. It has significance as a prognostic determinant following a curative resection.

Molecular dynamics (MD) studies are carried out to investigate the electron irradiation damages in carbon nanomaterials. The interaction between an incident electron and a carbon atom is modeled based on the Monte Carlo method using the elastic scattering cross section. The electron irradiation damages in graphen, graphite, single-walled carbon nanotube (SWNT) and carbon nanopeapod are demonstrated. The cross-links among the nanostructures caused by the knock-on effect are observed as typical damages. The dependence of the damages on the electron primary energy is also shown for the SWNT.

Backgrounds Toll-like receptor (TLR)-9 plays a critical role in the recognition of the CpG motifs, which is frequently observed in bacterial DNA. To date, there have not been any reports regarding the role of bacterial DNA in the systemic circulation on the development of sepsis. Methods We examined the expression of TLR-9 in the liver and spleen in a murine peritonitis model (CLP mice). We also measured the cytokine response of mononuclear cells (MNCs) from normal and CLP mice to CpG oligodeoxynucleotides (ODN) in vitro and in vivo . Results TLR-9 expression on F4/80 + and NK1.1 + CD3e + cells in the liver of CLP mice was elevated compared to sham-operated mice. With regard to cytokine production, we found that CpG ODN markedly stimulated the production of inflammatory cytokines by murine macrophages and liver MNCs. The intravenous injection of CpG ODN in mice that underwent CLP 12h earlier led to their increased cytokine production and their increased mortality. In addition, the depletion of NK/NKT cells contributed to improve their survival rate. Conclusions Our results suggest that, in patients with overwhelming bacterial infection, bacterial DNA may induce liver toxicity that is mediated by liver NKT cells and macrophages that express high levels of TLR-9.

Interleukin-18 (IL-18) is a pleiotropic cytokine that enhances Th1 or Th2 immune response. We show a novel mechanism of gastric cancer cells that allows their immune escape utilizing IL-18. All 4 gastric cancer cell lines, but not colon lines, constitutively expressed IL-18 receptors and IL-18 dose-dependently enhanced their in vitro proliferation accompanied by nuclear factor kappaB activation. When IL-18-pretreated gastric cancer cells were cultured with cytokine-activated peripheral blood killer lymphocytes, the antitumor machineries, perforin or interferon-gamma production of killer lymphocytes decreased, resulting in a decreased susceptibility of cancer cells to killer lymphocytes. Furthermore, gastric cancer cells cultured with IL-18 showed an increased expression of a granzyme B inhibitor, protease inhibitor 9. IL-18 injections into severe combined immuno-deficient mice intraperitoneally inoculated with gastric cancer cells consistently decreased the mouse survival time. Our results indicate that gastric cancers exploit IL-18 to grow/invade and evade immunosurveillance in the hosts.

In addition to natural killer (NK) cells, T cells expressing natural killer cell markers, CD56 or CD57 (NK type T cells), have been considered to play an important role in antitumor immunity. We examined the proportion of NK cell and NK type T cell subsets in the peripheral blood from patients with gastric cancer. The IFN-gamma production capacity and population of cytoplasmic perforin positive cells in peripheral blood mononuclear cells (PBMC) were evaluated. Peripheral blood samples were obtained from 56 patients with gastric cancer and 21 healthy volunteers. The proportion of CD56- CD57+ T cells (CD57+ T cells) was significantly higher in advanced gastric cancer patients than those in healthy volunteers and patients with early stage gastric cancer, whereas no correlation was observed between the proportion of CD56+ T cells or NK cells and tumor progression. Furthermore, a significant decrease of CD8+ CD57+ T cells was found in patients with advanced gastric cancer. The proportion of CD57+ T cells did not correlate with interferon-gamma (IFN-gamma) production from PBMC in gastric cancer patients, although a significant correlation was found between them in healthy volunteers. The proportion of perforin positive CD57+ T cells, especially CD8+ CD57+ T cells, in patients with gastric cancer was markedly lower than that in healthy volunteers. Collectively, although the proportion of CD57+ T cells in PBMC was found to increase with tumor progression, their function in antitumor immunity is impaired in patients with gastric cancer.

We investigated the individual CD8+ populations with natural killer (NK) cell markers (NK-type T cell); CD56 single positive (CD56)-T cells, CD56/CD57 double positive (DP)-T cells and CD57 single positive (CD57)-T cells in the peripheral blood. All NK-type T-cell populations expressed CD122 and intermediate levels of T-cell receptor (TCR; regular CD8+ T cells are CD122- and express high levels of TCR). The number of both DP-T cells and CD57-T cells, but not CD56-T cells, gradually increased with age. All NK-type T-cell populations produced larger amounts of interferon-gamma than did regular CD8+ T cells after stimulation with interleukin (IL)-2, IL-12 and IL-15. However, CD56-T cells and CD57-T cells but not DP-T cells showed a potent antitumour cytotoxity to NK-sensitive K562 cells, whereas only CD56-T cells showed a potent cytotoxity to NK-resistant Raji cells. Furthermore, although NK-type T cells produced large amounts of soluble Fas-ligands, their cytotoxic activities appeared to be mediated by the perforin/granzyme pathway. The oligoclonal or pauciclonal expansions of certain VbetaT cells were found in each NK-type T-cell population. The non-variant CDR3 region(s) for the TCRbeta chain(s) showed CD57-T cells and CD56-T cells to be derived from distinct origins, while the DP-T cell population consisted of a mixture of the clones seen in both CD56-T cells and CD57-T cells. Our results suggest that CD57-T cells and CD56-T cells are functionally and ontogenically different populations while DP-T cells appear to originate from both CD56-T cells and CD57-T cells.

Summary form only given, as follows. A water-filled Blumlein generator was operated at different repetition rates of up to 15 Hz, and its temporal performance was investigated. The Blumlein generator having an impedance of 10 ohms provides a rectangular voltage pulse with an amplitude of 200 kV and a duration of 75 ns into a matched load. The resistance of the water in the line decreases quickly at >10 Hz during a continuous operation for an hour and results in a decrease in the output voltage of the Blumlein line. The generator works with a repetition rate of up to 6 Hz without serious degradation in the voltage, while the averaged power density dissipated in the water is approximately 40 mW/cm/sup 3/. The increase in the water temperature during operation is only a few degrees. This implies that the resistive heating of the water is not the dominant cause of the decrease in the water resistance.

Although the peritoneal cavity (PC) is the most common site of metastasis in gastric carcinoma, its immune status in patients with advanced cancer remains largely unknown. We investigated the relationship between clinical parameters and cytokine levels in the PC and also evaluated IFN-y production by peritoneal exudate cells (PEC), obtained during surgery from patients with stage III-IV gastric carcinoma. Although the IFN-gamma and IL-12 levels in the PC did not differ between stage III and stage IV cancer patients, the latter had higher levels of IL-10 and IL-18. Those patients with higher IFN-gamma levels experienced a significantly better survival-rate than those with lower IFN-gamma levels, whereas IL-18 (but not IL-10) levels were inversely-correlated with survivaL IFN-gamma levels increased in parallel with IL-18 levels in patients who survived more than two years, but this correlation did not apply to patients who died of disease within two years. In addition, anti-CD3-Ab or cytokine- stimulated PEC from patients with low IL-10 levels in their PC produced a significantly greater amount of IFN-gamma than PEC from patients with high PC IL-10 levels. In conclusion, a high level of IFN-y in the PC is an indicator of favorable outcome. Both IL-10 and IL-18 levels in the PC increased with tumor progression. Although the number of PEC capable of producing IFN-gamma increases with tumor progression, their ability to secrete IFN-gamma in response to IL-18 may be influenced by local IL-10 levels in the PC.

The aim of this study was to determine whether the cytologic features of cancer cells in the peritoneal lavage fluid from patients undergoing surgery for gastric cancer affect prognosis. A total of 141 patients with stage III-IV gastric cancer were enrolled in this study. Among 111 patients without peritoneal metastasis (P0), 43 were noted to have positive peritoneal cytology (P0/CY1). These patients were subclassified into two groups according to the cluster formation of cancer cells in the cytology specimen, namely, 17 with cluster formation and 26 without cluster formation. The clinicopathologic parameters and survival rates were compared between these two groups. Among the P0/CY1 patients, no significant difference in clinicopathologic features existed between patients with or without the cluster formation of cancer cells. However, the survival rate of patients without cluster formation was significantly higher than that of those with cluster formation. Furthermore, the survival curves of patients without cluster formation was similar to that of the P0/ CY0 patients with stage IV cancer. Subclassification according to the presence or absence of the cluster formation of cancer cells may be useful for predicting the outcome of patients with positive cytology after surgery for advanced gastric cancer.

To assess the applicability of the sentinel node concept to gastric carcinoma. The location of metastatic lymph nodes was analyzed retrospectively in 119 patients with gastric carcinoma in whom metastasis was limited to one or two nodes. Intraoperative lymphatic mapping was attempted in 62 patients using indocyanine green injected endoscopically into the gastric submucosa adjacent to the tumor. Metastatic lymph nodes were distributed beyond the perigastric area in 4% of patients with a single node involved. The positive node was located along the greater curvature in 21% of the patients with a tumor on the lesser curvature. Two patients had a metastatic node totally occupied by cancer tissue. In 16% of patients with two nodes involved, a positive node was located on both the lesser and greater curvatures. Lymphatic mapping was successful in all subjects. A larger number and wider distribution of green-stained nodes were observed in patients injected with 8 ml of indocyanine green solution than in those injected with 4 ml. No metastasis was observed in any nodes in 47 (96%) of the 49 patients who had no metastasis in green nodes. In one patient showing metastasis in non-green nodes without metastasis in green nodes, the positive nodes were totally occupied by cancer tissue. Our results showed the complexity of lymphatic streams within and from the stomach. Lymphatic mapping using indocyanine green can be a tool for identifying sentinel nodes in gastric carcinoma although lymph nodes occupied by cancer tissue may not be detected by this technique.