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The number of hospitalizations of older patients with dementia who require medical treatment has increased and delirium or physical restriction have become problems in the acute care setting. Dementia nursing intervention ability developing program by e-learning assumed the quality improvement of dementia medical care and the nursing of older patients with dementia based on person-centered aimed at reduction of body restriction. The purpose of this study was to validate the effectiveness of the developed e-learning programs for nurses in the acute care setting of seven to one nursing standards.This study was conducted between April and December 2020. This study was introduced to the floor nurse of the hospital for suitable application. Interested nurses were asked to attend "Developing programs for Dementia nursing intervention ability (4 weeks)" at four different time points (1) before attendance (baseline), post-attendance (1 month later), (3) practiced 3 months post-attendance, and (4) practiced 6 months post-attendance. A questionnaire to evaluate program effectiveness asked about consciousness of the dementia nursing with four items on "Interest in nursing of people with dementia and so on (four items)".In the evaluation on the person-centered dementia care, using the Self-assessment Scale of Nursing Practice for Elderly Patients with Cognitive Impairment, the Approach to Dementia Questionnaire - Japanese Edition (19 items). In the evaluation of ethics, ethical sensitivity scale for clinical nurses (19 items), self-efficacy on reduction of the physical restriction (six items). A statistical analysis was conducted using the Bonferroni test as the multiple test method to compare baseline values with the values obtained 1, 3, and 6 months later.A total of 70 subjects were analyzed in this study. They belonged to different wards including the surgical and internal wards from where 60 subjects (85.7%) were recruited. The average clinical experience of the nurses was 13.5±9.5 years. The degree of self-efficacy was assessed in terms of attaching mitten type gloves as a physical restraint to avoid the pulling of tubes used for intravenous feeding, central veins, normal feeding, etc. by the patients and so on. Most patients had cognitive functional disorder, including dementia [n = 30 (42.9%)]. The self-assessed scale of nursing practice for elderly people with cognitive impairment, which aimed to promote person-centered care in an acute care hospital, revealed that the total score of each of the Approaches to Dementia Questionnaire - Japanese Edition significantly increased just after intervention (1 month) in comparison to baseline, and 3 months and 6 months after intervention.This study indicated that the program developed to improve dementia nursing intervention ability significantly increased the above-mentioned evolution and consciousness of nurses after the intervention program (1 month), followed by 3 months and 6 months later. Along with ethical sensitivity, practice aimed at person-centered care was also found to improve. It was suggested that the intervention program of this study was effective and that nurses could easily learn using their respective free time and practice.

The aim of this study was to create a model and verify its fitness for focusing on unlearning of senior clinical nurses who transferred from acute to rehabilitation wards.The processes by which nurses with experience in acute wards acquire expertise in rehabilitation wards, the 'process of unlearning', have not yet been clarified.This research used a cross-sectional study.Content analysis of interview data of 23 senior clinical nurses was used to reveal factors constituting nurses' unlearning and a base model was created. Data were collected between May - September 2016. For its verification, categories extracted through content analysis were used as latent variables and subcategories as observation variables. The model's fit was confirmed through a survey of 5,435 senior clinical nurses from July to September 2017.We extracted six categories-'awareness', 'conflict', 'discard', 'acquisition', 'acceptance' and 'establishment'-and 22 subcategories of the factors constituting unlearning and created a base model. The effective response rate in the survey for verifying the fitness of the base model was 20.2%. The base model generally fulfilled the fitness, but we further studied the model fit with the data and modified it to comprise five categories, excluding 'acceptance', with 16 subcategories. The fitness of the modified model further improved. Through revalidation, we confirmed that the modified model satisfies the goodness of fit.Our findings add to the development of rehabilitation nursing skills of nurses transferred from acute to rehabilitation wards in a Japanese community-based integrated care system.This study revealed the unlearning process of senior clinical nurses. The unlearning process identified in this study contributes to knowledge and skills acquisition specific to nurses specializing in rehabilitation. It will be used for developing a re-education programme for rehabilitation nurses in the future.目的: 本研究的目的是建立一个模型,并验证其在专注于从急症病房转向康复病房的高级临床护士的忘却过程的适用性。 背景: 有急症病房经验的护士在康复病房获取专业知识的过程,即“忘却过程”,尚未得到阐释。 设计: 该调查使用横断面研究。 方法: 通过对23名高级临床护士访谈资料的内容分析,揭示了护士忘却过程的构成因素,建立了护士忘却过程的基本模型。 数据收集与2016年五月至九月之间。为了验证它,内容分析中选取的类别被用作潜在变量,子类别被用作观察变量。2017年七月至九月,通过对5435名高级临床护士的调查,证实了模型的适用性。 结果: 我们选取了构成忘却过程因素的六个类别--“意识”、“冲突”、“抛弃”、“获得”、“接受”和“建立”,以及22个子类别,并建立了一个基本模型。验证基本模型适用性的调查有效应答率为20.2%。基本模型基本上满足了适用性,但我们进一步研究了模型与数据的拟合,并将其修改为包含5个类别(不包括“接受”类别)和16个子类别。改进模型的拟合度进一步提高。通过重新验证,证明了修正后的模型满足拟合优度。 结论: 我们的发现为日本社区综合护理系统中从急症病房转到康复病房的护士的康复护理技能的发展提供了补充。 影响: 本研究揭示了高级临床护士的忘却过程。本研究中发现的忘却过程有助于专业康复护理人员获得知识和技能。它将用于制定针对康复护士的再教育计划。.

Utilizing automatic daily body weight (BW) measurements may be helpful for assessing nutritional status and detecting underlying diseases particularly in older people who require nursing care. This preliminary study aimed to verify effectiveness of eating assistance for maintaining BW in older people using a contact-free load cells under the bed (Bed Sensor System: BSS). BW was measured every night for 3 months in eight nursing home older people with severe cognitive and physical dysfunctions. Body composition of the subject's trunk and each limb was measured using a segmented multi-frequency bioelectrical impedance analyzer (BIA). A monthly BW loss was estimated as a slope of linear regression of the daily BW plot. BSS successfully measured daily BW for the study period in all participants. The 4 residents with eating assistance gained slightly more weight, while the 4 residents without eating assistance lost weight. There was a significant difference between the two groups in the monthly BW change (− 0.79 ± 0.51 kg/month versus 0.20 ± 0.49 kg/month, P = 0.030). None of the BIA-derived parameters was associated with the monthly BW change. BSS revealed effectiveness of eating assistance to maintain BW in nursing home residents with severe cognitive and physical dysfunctions.

Aims This review aimed to determine the characteristics of a nurse-led intervention for people with dementia including mild cognitive impairment and their family in an ambulatory care setting. Background Enhancing the role of nurses in a multidisciplinary team of ambulatory care follow-up after a diagnosis of dementia is thought to lead to successful dementia care. Design This is a scoping review. Data sources MEDLINE, CINAHL, EMBASE, Cochrane, JBI, Japan Medical Abstracts Society, PsycINFO and Web of Science were searched on 14 March 2019. Review methods This scoping review was conducted using the Joanna Briggs Institute methodology, followed the PRISMA-ScR checklist and considered studies that included interventions conducted by nurses and included outcomes regarding dementia symptoms or family care burden. Results Eleven studies were included. Of these, all interventions were multifactorial and reported effective results. Educational interventions were most common, and the content of education included the characteristics of dementia and how to interact with patients with dementia. The roles of nurses included caregiver education, assessment, care plan creation for continuous monitoring and team building. Conclusion This scoping review suggested that effective nurse-led interventions in the ambulatory care of people with dementia are continuous patient and family supports, primarily caregiver education within multidisciplinary teams.

In the 1990s, interprofessional education (IPE) was introduced to health professionals in higher education; it has come to be regarded as a standard learning method. However, major barriers remain regarding its introduction and smooth operation. This study conducted a questionnaire survey at educational facilities for health professionals in Japan; it developed scales to measure the recognition of barriers to and benefits of IPE implementation. We surveyed chairpersons responsible for 2,690 courses in Japanese health education facilities. We used for analysis the responses related to 767 courses (valid response rate, 28.5%). In all, 216 courses (28.7%) implemented IPE. We conducted exploratory factor analysis and developed scales for measuring the recognition of barriers to IPE implementation (15 items) and its benefits (11 items). We observed a significant relationship between the state of IPE implementation and recognition of barriers to and benefits of IPE. Using information and communication technology and faculty development for faculty members would be effective in removing the barriers to IPE implementation.

Although many screening tools for delirium are available, delirium is still occasionally overlooked or misdiagnosed. One of the reasons for this is the lack of brief screening tools that do not require specialized training to use. The 4 'A's test (the 4AT) is a validated screening tool for delirium that can be administered in a very short time without specialized training. Herein, we evaluated the reliability and validity of the Japanese version of the 4AT (the 4AT-J). A total of 150 patients aged ≥ 65 years were enrolled. Their demographics and clinical characteristics were obtained within 24 hr of their hospitalization. On each patient's high-risk day of developing delirium, the 4AT-J was administered by a nurse, and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-Ⅴ) and the Japanese version of Delirium Rating Scale-Revised-98 (DRS-98-J) were administered by a psychiatrist. Our analyses revealed that when a cut-off score of 4, the 4AT-J showed high sensitivity and specificity. The Cronbach's α-coefficient was similar to that of the original version. A receiver operating curve analysis showed sufficient power of the 4AT-J to discriminate delirium. The 4AT-J showed adequate reliability and validity for delirium screening in elderly patients.

Objective: The number of older patients with dementia hospitalised in acute care hospitals increased and these patients underwent physical restrictions leading to a degeneration of essential mental and physical function. The dementia nursing competence e-learning program with audio-visual materials has been developed in acute care hospitals. Methods: An application form that explained the research was distributed to 1,944 registered nurses from seven hospitals, and 110 people applied. Nurses used an e-learning program for a month in May and practiced applying the knowledge learned from programs June through November 2020. The nurses completed a questionnaire survey at four periods: first (before program/baseline), second (after program), third (three months later), and fourth (six months later). In the second, third, and fourth periods, ‘Technical knowledge of the dementia nursing’ and ‘dementia nursing intervention’ were significantly improved as compared with the first. In the fourth period, ‘confidence of reduce of physical restriction’ showed significant improvement compared to the first. In ‘Ethical sensitivity scale of nurses’, the first of the four sub-scales significantly increased as compared with the first period. In ‘Self-assessment Scale of Nursing Practice for Elderly Patients with Cognitive Impairment with the Aim of Person-centred Care in Acute Care Hospitals’, the fourth sub-scale showed significant improvement compared to the first. In the ‘Personhood’ sub- scale of the Japanese version of Approaches to Dementia Questionnaire, the fourth period showed a significant increase compared to the first. Conclusion: The results suggest that this program was effective and led to reduced physical restrictions in nursing practice.

On January 1, 2015, the Interprofessional Education Research Center (IPERC) was opened at the Graduate School of Nursing at Chiba University, while being positioned as one of the Inohana Campus High Functionality Initiatives by the university. As the result of the establishment of an education research center in the nursing graduate school, various changes are coming into view. In particular, the active participation of young instructors of the medical, nursing, and pharmacology departments and university hospital in interprofessional education (IPE) efforts deserve special mention. In addition, IPE training with treatment participation, which had been a pending matter for many years, is being implemented on a trial basis in the university hospital ICU and pediatric departments starting this year. During this training, treatment plan proposals will be conducted in cooperation with university hospital specialists. IPE is also having a great influence on the formation of curriculums in each department. A factor behind this is the awareness of issues by young instructors such as whether practical training fully utilizes the team building, conference management, and joint learning ability being nurtured at IPE. IPE is unable to perform fundamental education without influencing professional education, and professional education also cannot help but change into "training of specialists with the ability to make contributions considered necessary as a specialist under any circumstances", The degree to which instructors in these three departments can together support curbing of resistance to this change and promoting transformation of values is considered key.

Background: Role-play (RP) and peer review (PR) are occasionally used in training and evaluating communication skills in clinical clerkship (CC). Thus, we evaluated the effect of combining RP and PR during student-oriented CC rounds. Methods: Clerkship students conducted medical interviews with and performed physical examinations on their patients, which were reviewed by five peer students who observed their performance while role-playing as senior physicians or patients’ families. The peer reviewers then provided feedback to the students. The performance of the students was evaluated based on a mini-clinical evaluation exercise (Mini-CEX) and a professionalism mini-evaluation exercise (P-MEX) before and after the rounds by two attending physicians. After the CC, the students responded to questionnaires about the rounds. Results: Seventy-five students completed the rounds, and the duration of each round was 41.7 ± 7.1 min. Their communication skills and professionalism abilities on Mini-CEX and P-MEX showed significant improvement after the rounds. Improvements in medical interviewing and physical examinations were also noted. Additionally, the students recognized the importance of multiple viewpoints in patient care through experiences of the rounds. Conclusions: Combining RP and PR with CC rounds improves the students’ clinical performance and professionalism and promotes their awareness of the importance of multiple viewpoints in patient care.

Background We report the changes in the health condition after using a service dog of a person with a complete C5 spinal cord injury (SCI). Case A 48-year-old married man began using a service dog after suffering a complete C5 SCI. We conducted a semi-structured interview based on the International Classification of Functioning, Disability, and Health (ICF) rehabilitation sets to describe the change in the participant's experience after using a service dog. The interview was converted into written form, and information regarding the changes in the participant's health condition was extracted. These data were categorized by similarity and then classified by the ICF conceptual framework. Discussion The participant experienced multiple changes in his health condition after using a service dog. These included the following factors from the ICF - "Body Function" category: "increased vitality and motivation," "emergence of self-affirmation," and "physical improvement." Health changes form the "Activities and Participation" category included: "emergence of new roles," "increased resilience," "expansion of moving area," "acquisition of activities incorporated with a service dog assist," "emergence of autonomous health management," "expansion of relation with other people," and "expansion of social activity." The participant experienced "reduction of psychological barriers," categorized under "Personal Factor," and "expansion of support environment," categorized under "Environmental Factor."

Aim This study aimed to clarify the association between nurses' job satisfaction, interprofessional collaborative competency and other related factors in university hospitals in Japan. Background Enhancing a team's function in the university hospital setting requires strengthening each professional's competency: high-level professional competency leads to high job satisfaction. Methods In 2014, self-administered questionnaires were sent to all nurses working at two university hospitals in Japan. A multivariate analysis of variance was conducted to evaluate the relationship between job satisfaction as the response variable and interprofessional collaborative competency and other variables as the independent variables. Results Data from 913 nurses were used in the present analysis (response rate: 60.4%). Two factors from the Chiba Interprofessional Competency Scale 29 (factor 1: attitudes and beliefs as a professional; factor 5: attitudes and behaviours that improve team cohesion) and opportunities for information exchange with other professionals outside the hospital had significant relationships with job satisfaction. Conclusion Strengthening interprofessional collaborative competency and increasing opportunities for information exchange with professionals outside the hospital would improve nurses' job satisfaction in university hospitals. Implications for nursing management Interprofessional collaborative competency and opportunities for information exchange with other professionals are worth the attention of nursing administrators.

Aim This study aimed to explore sociodemographic factors related to evidence-based practice (EBP) competency in Japanese nurses in university hospitals. Methods In March 2016, a survey was distributed to 843 clinical nurses who directly provide nursing care at two university hospitals in Japan. Multiple regression analyses were conducted on data received from 472 nurses using the Evidence-Based Practice Questionnaire (Japanese version). Results Sociodemographic factors related to EBP competency were experience with conducting nursing research as a part of continuing education, education about EBP, advanced practice certification (certified nurse specialists/certified nurses), and years of experience in clinical nursing. These factors differed across the four subscales of the questionnaire: Practice, Attitude, Knowledge of Research and Practice, and Skills of Research and Practice. Specifically, experience with two or more nursing research activities was significantly positively associated with Attitude and Knowledge/Skills Concerning Research and Practice of EBP, but not related to the implementation of EBP itself. Advanced practice certification was significantly positively associated with Practice and Attitude of EBP. Conclusions Our study quantitatively identified sociodemographic factors including experience with conducting nursing research and advanced practice certification status that were found to be related to EBP competency and these factors were differently associated with the four subscales of the Evidence-Based Practice Questionnaire (Japanese version). EBP education should depend on nurses' levels of EBP competency, and nursing educators and managers need to be cognizant of their nurses' sociodemographic factors when providing EBP education.

Bioluminescence microscopy has revealed that gene expression in individual cells can respond differently to the same stimulus. To understand this phenomenon, it is important to sequentially observe the series of events from cellular signal transduction to gene expression regulated by specific transcription factors derived from signaling cascades in individual cells. However, these processes have been separately analyzed with fluorescence and bioluminescence microscopy. Furthermore, in culture medium, the background fluorescence of luciferin—a substrate of luciferase in promoter assays of gene expression in cultured cells—confounds the simultaneous observation of fluorescence and bioluminescence. Therefore, we optimized conditions for optical filter sets based on spectral properties and the luciferin concentration based on cell permeability for fluorescence observation combined with bioluminescence microscopy. An excitation and emission filter set (492–506 nm and 524–578 nm) was suitable for green fluorescent protein and yellow fluorescent protein imaging of cells, and >100 μM luciferin was acceptable in culture medium based on kinetic constants and the estimated intracellular concentration. Using these parameters, we present an example of sequential fluorescence and bioluminescence microscopic observation of signal transduction (translocation of protein kinase C alpha from the cytoplasm to the plasma membrane) coupled with activation of gene expression by nuclear factor of kappa light polypeptide B in individual cells and show that the gene expression response is not completely concordant with upstream signaling following stimulation with phorbol‐12‐myristate‐13‐acetate. Our technique is a powerful imaging tool for analysis of heterogeneous gene expression together with upstream signaling in live single cells. Microsc. Res. Tech. 78:715–722, 2015. © 2015 Wiley Periodicals, Inc.

Aim To develop and test the validity and reliability of a Japanese version of the Evidence-Based Practice Questionnaire. Methods The Evidence-Based Practice Questionnaire was translated into Japanese, and a back-translation was performed. In March 2016, the survey was conducted among 843 nurses in 2 university hospitals in Japan. After 2 weeks, the same questionnaire for test-retest reliability was distributed to 197 nurses. We evaluated construct validity by factor analysis: convergent, discriminant, criterion-based and known-group validity, and reliability (internal consistency via Cronbach' alpha and test-retest reliability). Results A total of 533 (66%) of nurses who agreed to our study returned the completed questionnaire, and 108 nurses (55%) agreed to the test-retest. Factor analysis confirmed that the original model of the Evidence-Based Practices Questionnaire was not statistically appropriate for Japanese nurses. Therefore, the final version of the Japanese version adopted 18 items and 4 subscales including practice, attitudes, and knowledge/skills related to research and practice. In the final version, the validity and reliability were moderate (Cronbach alpha = .90). Conclusion The Japanese version of the Evidence-Based Practices Questionnaire is a reliable and valid tool and can be used to assess evidence-based practice, attitudes, and research knowledge/skills in Japan.

The objective of this study was to develop and test a competency scale, which measures the competency of interprofessional collaborative practice of health professionals. A total of 32 health professionals were interviewed, and then an item pool of 255 items was created to measure the competency of interprofessional collaboration. A questionnaire study was conducted with 1552 health professionals from four different hospitals located in the Kanto region of Japan. The questionnaires were distributed and collected by gatekeepers in each section. The valid response rate was 62.6%. There were a total of 65 questionnaire items measuring the competency of interprofessional collaboration. Each item was assessed by the number of valid responses, distribution of scores, item-total correlation analysis and good-poor analysis. Construct validity was assessed using factor analysis and the relationships among the total scores of each factor with interprofessional education experience during education before and after graduating. Moreover, Cronbach's alpha coefficient was calculated to assess reliability. Finally, 30 items were excluded, and a scale for interprofessional collaborative competency comprising 35 items and 6 factors was developed. From the perspective of construct validity and internal consistency, the scale in its pilot form shows some promising aspects.

The purpose of this study was to refine the items on a scale measuring interprofessional collaborative competency that was developed by the authors in an earlier pilot study. A questionnaire-based study was conducted with a sample of 2133 health professionals using the reformulated questionnaire. Construct validity was tested by comparing the survey results with a covariance structure analysis and the domains of interprofessional collaboration competencies presented in previous studies. A second survey was conducted 2 weeks later with a sample of 571 nursing professionals, using the same survey form to test its reliability. We constructed a model comprising 29 observed variables and six latent variables (the Chiba Interprofessional Competency Scale: CICS29), and obtained the following values for the model's goodness of fit: GFI = 0.925, AGFI = 0.908, CFI = 0.950, RMSEA = 0.049. With regard to reliability, we obtained scores ranging from 0.65 to 0.77 for the intraclass correlation coefficients of the six domains. Compared with the interprofessional collaboration scales indicated in previous studies, the CICS29 was found to have subsumed the key concepts that should be configured as interprofessional collaboration competencies. The CICS29 appeared to have satisfactory levels of reliability and validity and is recommended as a scale for measuring competencies of interprofessional practice.

This article presents a project that aimed to identify a set of competencies (domains and statements) to prepare Japanese students and healthcare practitioners for collaborative practice. The Japan Association for Interprofessional Education (JAIPE) has started a government-funded project to formulate its interprofessional competency framework, in cooperation with professional organisations (e.g. Japan Society for Medical Education) in healthcare and social sciences. This three-year project is underway as part of the Initiative to Build up the Core Healthcare Personnel programme of Mie University. This project consists of five stages: literature review, data collection, prototype development, consensus formation, and finalisation. Our efforts will culminate in Japan's first interprofessional competency framework, with consensus from relevant academic societies and other stakeholders. We hope that the involvement of stakeholder participation will improve the usability of the final interprofessional competency framework.

D-dimer, a specific fragment resulting from degradation of cross-linked fibrin, is an essential marker for the diagnosis of disseminated intravascular coagulation (DIC). Rapid assay for D-dimer using monoclonal antibody coated-latex particles might be useful for discriminating between postmortem and antemortem blood in bloodstains. We tried to detect D-dimer in nine postmortem blood samples by the rapid latex agglutination assay and to quantify them automatically using the latex photometric immunoassay system. The results showed that all samples were positive and that their amounts of D-dimer were 335-2,800 microg/ml (the normal blood level

A genotype of JC virus (JCV) DNA extracted from human urine can serve not only as a means of elucidating human migration patterns, but also of tracing the origin of unidentified cadavers. If a JCV genotype is determined using a small amount of urine or urine stain from a given person, it may be useful in identifying the geographic area in which that person was born. In the present study, we amplified a 610-bp intergenic region (IG region) of JCV DNA extracted from 200 μl of each of 82 urine samples collected in Japan. JCV DNA was detected in 45 of 82 urine samples (54.9%) and genotypes were also determined by restriction fragment length polymorphism analysis (MY genotype: 13; X (CY) genotype: 25; unclear: 7). Additionally, 16 urine stains which had been prepared 3 months earlier using 100 μl of JCV-positive urine were examined. JCV DNA was detected in 11 of 16 urine stains (68.8%), and in this case also, it was possible to determine the genotype by the phylogenetic analysis after DNA sequencing. The present study indicates that JCV genotyping can be successfully conducted using only 100 μl urine stain and even 3 months after the urine stain was made. Thus, JCV genotyping shows promise as a new analytical method for narrowing down the native place of unidentified persons or cadavers from urine stains left at the scene.

BCG vaccination using the multiple puncture device (the Heaf gun) has been used in Japan and in the United Kingdom. The appearance of the BCG scars therefore differs from that caused by the conventional intradermal BCG vaccination, which is used throughout the world. The aim of this study was to investigate the usefulness of examining BCG scars to identify the nationalities of unidentified cadavers. We investigated the BCG vaccination program not only in Japan, but also in other countries, along with the relation between the BCG scar and nationality. The results showed that the countries which domestically make and use the Heaf gun are Japan (where it is the only method that has been in use since 1968), the United Kingdom (where it has been used, in part, since 1982), and South Africa (where it has been used, in part, since 1972). In addition, for the past 10 years, the Japanese Heaf gun method has been partially applied in the Republic of Korea and in Brazil. The Heaf gun scar can be clearly distinguished from the intradermal scar, and is visible throughout a person's life when good technique is used to administer the vaccination. If the Heaf gun scar is found on the left upper arm of an unidentified Asian cadaver, it is sure to be that of a Japanese. The findings of this present study indicate that the Heaf gun scar can be examined to identify the nationalities of unidentified cadavers.

The in vivo rat brain microdialysis technique with HPLC/UV was used to determine the blood-brain barrier (BBB) penetration of pralidoxime iodide (2-PAM), which is a component of the current nerve agent antidote therapy. After intravenous dosage of 2-PAM (10, 50, 100 mg/kg), 2-PAM appeared dose-dependently in the dialysate; the striatal extracellular/blood concentration ratio at 1 h after 50 mg/kg dosage was 0.093 ± 0.053 (mean ± SEM). This finding offered conclusive evidence of the BBB penetration of 2-PAM. We also examined whether the BBB penetration of 2-PAM was mediated by a certain specific transporter, such as a neutral or basic amino acid transport system. Although it was unclear, the neural uptake of 2-PAM was Na+ dependent. The mean BBB penetration by 2-PAM was approximately 10%, indicating the intravenous administration of 2-PAM might be to a degree effective to reactivation of the blocked cholinesterase in the brain.

Crystallographic studies have elucidated the binding mechanism of forskolin and P-site inhibitors to adenylyl cyclase. Accordingly, computer-assisted drug design has enabled us to identify isoform-selective regulators of adenylyl cyclase. After examining more than 200 newly synthesized derivatives of forskolin, we found that the modification at the positions of C6 and C7, in general, enhances isoform selectivity. The 6-(3-dimethylaminopropionyl) modification led to an enhanced selectivity for type V, whereas 6-[N-(2-isothiocyanatoethyl) aminocarbonyl] and 6-(4-acrylbutyryl) modification led to an enhanced selectivity for type II. In contrast, 2′-deoxyadenosine 3′-monophosphate, a classical and 3′-phosphate-substituted P-site inhibitor, demonstrated a 27-fold selectivity for inhibiting type V relative to type II, whereas 9-(tetrahydro-2-furyl) adenine, a ribose-substituted P-site ligand, showed a markedly increased, 130-fold selectivity for inhibiting type V. Consequently, on the basis of the pharmacophore analysis of 9-(tetrahydro-2-furyl) adenine and adenylyl cyclase, a novel non-nucleoside inhibitor, 2-amino-7-(2-furanyl)-7,8-dihydro-5(6H)-quinazolinone (NKY80), was identified after virtual screening of more than 850,000 compounds. NKY80 demonstrated a 210-fold selectivity for inhibiting type V relative to type II. More importantly, the combination of a type III-selective forskolin derivative and 9-(tetrahydro-2-furyl) adenine or NKY80 demonstrated a further enhanced selectivity for type III stimulation over other isoforms. Our data suggest the feasibility of adenylyl cyclase isoform-targeted regulation of cyclic AMP signaling by pharmacological reagents, either alone or in combination.

Activation of the type-1 metabotropic glutamate receptor (mGluR1) signaling pathway in the cerebellum involves activation of phospholipase C (PLC) and protein kinase C (PKC) for the induction of cerebellar long term depression (LTD). The PLC and PKC isoforms that are involved in LTD remain unclear, however. One previous study found no change in LTD in PKCgamma-deficient mice, thus, in the present study, we examined cerebellar LTD in PLCbeta4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLCbeta1 was expressed weakly and uniformly, PLCbeta2 was not detected, PLCbeta3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLCbeta4 was expressed uniformly throughout. In PLCbeta4-deficient mice, expression of total PLCbeta, the mGluR1-mediated Ca(2+) response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKCalpha, -betaI, -betaII, and -gamma in mouse cerebellar Purkinje cells during LTD induction. Both PKCalpha and PKCbetaI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mGluR1-mediated activation of PLCbeta4 in rostral cerebellar Purkinje cells induced LTD via PKCalpha and/or PKCbetaI.

Nucleotide sequences of 2 hypervariable regions (HV1, HV2) within the control region of human mitochondrial DNA (mtDNA) were analyzed from 55 unrelated Japanese. About 700 nucleotides were sequenced by using the nested PCR and the solid-phase direct sequencing methods. Comparison of these sequences with Anderson's reference sequence revealed 97 mutation types within 93 positions, and 11 positions of them were novel. Fifty five samples analyzed were classified into 52 different sequences, while 3 pairs have shown the same sequences. Comparison of the Japanese sequences to those reported from other populations indicated many differences in such a point that the substitutions at 16,223 and 73 in Japanese were more frequent than those in Caucasian, while the substitutions at 16,126 and 16,311 in Japanese were less frequent than those in Caucasian. Twenty one of 55 samples analyzed showed a T-to-C transition at the position 16,189 of the C-stretch region in the HV1 region. This replacement caused the blurred bands on the sequence image, which resulted in the ambiguity of exact number of cytosine in the C-stretch region of HV1. For this ambiguity, the number of cytosine in the C-stretch region should not be currently taken into account in forensic practices of individualization of evidence samples. Regardless of such problem, the polymorphisms of HV1 and HV2 regions are highly useful for individual identification.

Sensitivity and specificity of commercially available ABO blood grouping monoclonal antibodies for medical use were examined for applying them to forensic blood typing. We have applied some monoclonal antibodies to hemagglutination test, enzyme-linked immunosorbent assay (ELISA) and absorption-elution test. Hemagglutination titer of these antibodies distributed ranging from ×4 to ×512. All antibodies examined could be used for detecting ABO blood type from secretor's saliva by ELISA method and using five anti-A antibodies blood group substances could be detected from non-secretor's saliva. Using anti-A and anti-B antibodies blood type could be detected from secretor's semen but using any antibody blood type could not be detected from non-secretor's semen. We could not get a correlation between hemagglutination titer and sensitivity on ELISA detected from saliva and semen. At absorption-elution test, using most of the anti-A and anti-B antibodies blood type could be detected of bloodstains and secretor's body fluid stains. Using several antibodies blood type could not be detected of non-secretor's samples. Using all of anti-A antibodies and some of anti-B antibodies it was failed to detect blood type of hair samples. Using all of the anti-H antibodies blood group substances could not be detected of stain or hair samples. This result suggested that we have to select suitable monoclonal antibodies of ABO blood grouping for each evidential sample and each blood typing method.

Medical care is an organized service made possible by the cooperation of numerous professionals. With the bachelor’s degree as a basis of career education, education which students can gain not only technical knowledge but also enable them to show their professionalism based on the concept “patient (user)-centered care” as a member of a medical organization is vital. Above all, it is essential fostering students’ abilities to work inter-professionally which might become a driving force of a team medical care. The present project covers all students in all grades from the Departments of Nursing, Medicine, and Pharmacy; and it provides multistage and comprehensive interprofessional education through lectures, drills, and practical training. The core of the program is the fostering of communication skills, ethical sensitivity, and problem-solving skills. This program is designed to train autonomous health care professionals with healthy occupational views, a strong sense of social responsibility, a sound work ethic, well-balanced views, and a willingness to commit to lifelong learning.

低温保存したブタの臓器からミトコンドリアDNA(mtDNA)を精製し,その精製mtDNAを用いたRFLP分析を行なった.ブタの肝臓,精巣,胎盤の各臓器を各種温度条件下で保存し,これらの臓器からmtDNAを定法に従って精製したところ,採取後21日目まで-20°Cないし-80°C下で保存された各臓器からは,いずれもRFLP分析に十分な純度のmtDNAが精製され,その電気泳動像は,ocDNAとcccDNA領域を示す2本のバンドが検出された.低温保存下の物理的な切断によるRFLP分析への影響は認められなかった.肝臓10g当たりからのmtDNAの収量は約300μgであり,RFLP分析に必要な電気泳動用試料として十分な収量であった.また,各臓器におけるmtDNAの収量は,肝臓>精巣>胎盤の順に多かったが,血液からの收量は極めて少なく,RFLPの検出には不適当と思われた.なお,低温保存臓器から精製されたmtDNAの電気泳動像は,4°Cにて21日間保存された各臓器についてはバンドが検出されなかった.以上の結果にもとづき,保存した肝臓を対象として各ブタ品種が有するmtDNA型を調査したところ,ランドレース種,ハンプシャー種においていずれも同一型が検出された.また,mtDNAのRFLPは,大ヨークシャー種,中ヨークシャー種に検出されたA型およびB型に見られるように.ブタの複雑な品種成立の過程をよく反映する指標となることが示された.さらに,三元交雑種LWDの持つmtDNA型の調査によって,ブタのmtDNAが母性遺伝を示すことが確認された.

The brain obtains energy by keeping the cerebral blood flow constant against unexpected changes in systemic blood pressure. Although this homeostatic mechanism is widely known as cerebrovascular autoregulation, it is not understood how widely and how robustly it works in the brain. Using a needle-like objective lens designed for deep-tissue imaging, we quantified the degree of autoregulation in the mouse hippocampus with single-capillary resolution. On average, hippocampal blood flow exhibited autoregulation over a comparatively broad range of arterial blood pressure and did not significantly respond to pressure changes induced by the pharmacological activation of autonomic nervous system receptors, whereas peripheral tissues showed linear blood flow changes. At the level of individual capillaries, however, about 40% of hippocampal capillaries did not undergo rapid autoregulation. This heterogeneity suggests the presence of a local baroreflex system to implement cerebral autoregulation.

The in vivo rat brain microdialysis technique with HPLC/UV was used to determine the blood-brain barrier (BBB) penetration of pralidoxime iodide (2-PAM), which is a component of the current nerve agent antidote therapy. After intravenous dosage of 2-PAM (10, 50, 100 mg/kg), 2-PAM appeared dose-dependently in the dialysate; the striatal extracellular/blood concentration ratio at 1 h after 50 mg/kg dosage was 0.093 +/- 0.053 (mean +/- SEM). This finding offered conclusive evidence of the BBB penetration of 2-PAM. We also examined whether the BBB penetration of 2-PAM was mediated by a certain specific transporter, such as a neutral or basic amino acid transport system. Although it was unclear, the neural uptake of 2-PAM was Na+ dependent. The mean BBB penetration by 2-PAM was approximately 10%, indicating the intravenous administration of 2-PAM might be to a degree effective to reactivation of the blocked cholinesterase in the brain.

Various neurotransmitters, such as dopamine, stimulate adenylyl cyclase to produce cAMP, which regulates neuronal functions. Genetic disruption of the type 5 adenylyl cyclase isoform led to a major loss of adenylyl cyclase activity in a striatum-specific manner with a small increase in the expression of a few other adenylyl cyclase isoforms. D1 dopaminergic agonist-stimulated adenylyl cyclase activity was attenuated, and this was accompanied by a decrease in the expression of the D1 dopaminergic receptor and G(s)alpha. D2 dopaminergic agonist-mediated inhibition of adenylyl cyclase activity was also blunted. Type 5 adenylyl cyclase-null mice exhibited Parkinsonian-like motor dysfunction, i.e. abnormal coordination and bradykinesia detected by Rotarod and pole test, respectively, and to a lesser extent locomotor impairment was detected by open field tests. Selective D1 or D2 dopaminergic stimulation improved some of these disorders in this mouse model, suggesting the partial compensation of each dopaminergic receptor signal through the stimulation of remnant adenylyl cyclase isoforms. These findings extend our knowledge of the role of an effector enzyme isoform in regulating receptor signaling and neuronal functions and imply that this isoform provides a site of convergence of both D1 and D2 dopaminergic signals and balances various motor functions.

The signals that prompt the axons to send out processes in peripheral nerves after axotomy are not well understood. Here, we report that galectin-1 can play an important role in this initial stage. We developed anin vitronerve regeneration model that allows us to monitor the initial axon and support cell outgrowth from the proximal nerve stump, which is comparable to the initial stages of nerve repair. We isolated a factor secreted from COS1 cells that enhanced axonal regeneration, and we identified the factor as galectin-1. Recombinant human galectin-1 (rhGAL-1) showed the same activity at low concentrations (50 pg/ml) that are two orders of magnitude lower than those of lectin activity. A similarly low concentration was also effective inin vivoexperiments of axonal regeneration with migrating reactive Schwann cells to a grafted silicone tube after transection of adult rat peripheral nerve. Moreover, the application of functional anti-rhGAL-1 antibody strongly inhibited the regenerationin vivoas well asin vitro.The same effect of rhGAL-1 was confirmed in crush/freeze experiments of the adult mouse sciatic nerve. Because galectin-1 is expressed in the regenerating sciatic nerves as well as in both sensory neurons and motor neurons, we suggest that galectin-1 may regulate initial repair after axotomy. This high activity of the factor applied under nonreducing conditions suggests that galectin-1 may work as a cytokine, not as a lectin.

We clarified the roles of IL-1 beta in peripheral neural regeneration after axotomy in a three-dimensional collagen gel culture system ranging from a single neurone to a dorsal root ganglion (DRG) explant with its associated nerve bundles. Application of 30 U/ml IL-1 beta to the culture systems clearly enhanced neural regeneration. This regeneration was evident in transected nerve terminals of DRG explants with or without associated nerve bundles, but not in dissociated single neurones. Neural survival was not affected by IL-1 beta in any of these culture systems. These results suggest that IL-1 beta stimulates surrounding non-neuronal cells to secrete neurotrophic factors, thus enhancing neurite regeneration from transected nerve terminals in cultured adult DRG explants.

MCT118 (D1S80) locus is widely used for forensic DNA typing. Many population studies have been reported by using allelic ladder marker. However, the whole DNA sequences of each allele of MCT118 locus have not been reported. In this report the whole DNA sequence of MCT118 locus including both flanking regions and repeat regions has been revealed and the difference between different alleles has been analyzed.

This investigation was undertaken as an efficient method for isolating sperm DNA from a mixed fluid sample which contains vaginal epithelial cells in a greater amount. The modified method of the two-step differential extraction procedure was found to be suitable for separating sperm DNA and vaginal epithelial cell DNA from the mixed stains. As the first step of digestion, vaginal epithelial cells in the mixed stains were lysed with Proteinase K and SDS, and sperm heads remaining in the lysed solution were collected by centrifugation. As the second step digestion, the sperm heads were lysed with the buffer containing Proteinase K, SDS and DTT as reducing agent. DNA fractions extracted from the two lysed solutions were enriched, one with sperm DNA and the other with vaginal epithelial cell DNA. MCT118(D1S80), ApoB VNTR and HLADQ alpha types of sperm DNA were detected and were confirmed by matching with corresponding male blood DNA. In the case of vaginal secretion mixed with semen of two males, the mixture of MCT118 types of the two males was detected in sperm DNA fraction.