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Background: Report writing in class provides basic training for academic writing. However, report writing education in medical schools in Japan has rarely been reported and no teaching strategy has been established for it., Methods: This study developed a report writing program using peer review for first-year medical students consisting of two 120-minute classes. The goal of being able to write reports appropriately was established and presented to students at the beginning of the program. In session 1, students decided on a topic, gathered information, and structured their report. In session 2, students' written reports were peer reviewed. The reports were improved based on the peer reviews. The responses of the pre- and post-program questionnaires were evaluated to determine the program's effectiveness. The other reports that were assigned one month after the program were used as comparison with the reports of students who did not participate. Furthermore, the long-term effects of the program were also evaluated by comparing the results of students from the previous year who did not participate in the program with those of program participants six months after the program., Results: A total of 106 students completed the questionnaire evaluation. The program was rated as being acceptable for the students. Self-assessment of report writing significantly improved after the program. The report scores of program participants (n = 99) were significantly higher overall and in all domains than were those of non-participants (n = 99). The self-assessment of students who participated (n = 96) was significantly higher than that of non-participants (n = 109). No difference was observed for students' sense of burden in report writing., Conclusions: The report writing skills of medical students can be improved by clearly establishing the goals of report writing and practicing the basic skills of report writing step-by-step. Moreover, the use of peer review may enhance the effectiveness of learning opportunities for report writing., (© 2024. The Author(s).)

Background and Objectives: The global shift towards competency-based medical education (CBME) has led to the development of national guidelines for CBME implementation (CBME Guides). The characteristics of CBME Guides from CBME-developed countries were analysed to inform the revision process for the CBME Guide in Japan, a CBME-developing country., Methods: Document analysis of CBME Guides from Canada, Singapore, the Netherlands, the United Kingdom, and the United States was conducted by six Japanese medical education experts. The process of analysing the CBME Guides was also reviewed., Results: While the CBME Guides contain many commonalities in structure and content, there is variation in terminology and forms of expression. The characteristics vary according to national systems, culture, and customs. The content of the Guides may have changed depending on the publication date, in line with changes in medical technology, medical needs, and advances in the understanding of CBME., Conclusions: Analysing CBME Guides from CBME-developed countries may lead to more meaningful revisions to a CBME-developing country's guide, enabling it to be better aligned with the local, social, cultural, and historical context of the country now and in the future.

In clinical clerkship (CC), medical students can practice evidence-based medicine (EBM) with their assigned patients. Although CC can be a valuable opportunity for EBM education, the impact of EBM training, including long-term behavioral changes, remains unclear. One hundred and nine fourth- and fifth-year medical students undergoing CC at a medical school in Japan attended a workplace-based learning program for EBM during CC (WB-EBM), which included the practice of the five steps of EBM. The program's effect on the students' attitudes toward EBM in CC was assessed through questionnaires. A total of 88 medical students participated in the program. Responses to the questionnaire indicated high satisfaction with the WB-EBM program. The most common theme in students' clinical problems with their assigned patients was the choice of treatment, followed by its effect. Based on the responses in the post-survey for the long-term effects of the program, the frequency of problem formulation and article reading tended to increase in the 'within six months' group comprising 18 students who participated in the WB-EBM program, compared with the control group comprising 34 students who did not. Additionally, the ability to self-assess problem formulation was significantly higher, compared with the control group. However, among 52 students who participated in the WB-EBM program more than six months later, EBM-related behavioral habits in CC and self-assessments of the five steps of EBM were not significantly different from those in the control group. The WB-EBM program was acceptable for medical students in CC. It motivated them to formulate clinical questions and enhanced their critical thinking. Moreover, the WB-EBM program can improve habits and self-evaluations about EBM. However, as its effects may not last more than six months, it may need to be repeated across departments throughout CC to change behavior in EBM practice.

Objective This study evaluated the implementation status of morbidity and mortality conferences in internal medicine specialty training programs in Japan. Methods This cross-sectional study surveyed hospitals in Japan with certified internal medicine specialty training programs. Program directors or equivalently responsible physicians managing certified internal medicine training programs were invited to participate in this study (n=619). Materials Data were collected using an online questionnaire that included questions about the number of morbidity and mortality conferences, types of cases covered, collaboration of the patient safety section and other health professions, and whether or not the conferences were conducted by a subspecialty department-led or program-based. Results Responses were received from 123 hospitals (19.8% response rate), of which 59 (48%) had some form of internal medicine morbidity and mortality conference in place. The average number per year was 9.63 (standard deviation: 18.12). Hospitals with morbidity and mortality conferences in subspecialty departments held significantly more conferences. Furthermore, the involvement of the patient safety department tended to be associated with holding more conferences. Autopsy rates were significantly higher in hospitals with program-based internal medicine morbidity and mortality conferences than subspecialty-led. Conclusion Internal medicine specialty training hospitals had more morbidity and mortality conferences than previously reported. Program-based morbidity and mortality conferences in internal medicine are associated with higher autopsy rates and may lead to an organizational reporting culture and lifelong learning attitudes that support patient safety. Collaboration with organizational management sections, such as patient safety, would be effective in implementing these conferences in internal medicine training programs.

Background and Objectives: The goal of this study was to determine whether changes in life-space mobility and quality of life (QoL) recovered in patients with cardiovascular disease (CVD) during the first two waves of the pandemic of Coronavirus disease 2019 (COVID-19) in Japan., Methods: We performed a follow-up survey in 20 CVD patients using the Life-Space Assessment (LSA) scale and the five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L), Japanese version, at three time points: January-March 2020 (before the first wave of the COVID-19 pandemic), July 2020 (following the first wave of the pandemic), and November 2020 (following the second wave of the pandemic)., Results: The LSA score in November 2020 (median [interquartile range], 90 [83.5-100] points) did not recover from the July 2020 score (83 [76.5-93] points). However, the EQ-5D-5L QoL score in November 2020 (0.89 [0.82-1]) had improved from that in July 2020 (0.80 [0.71-0.87])., Conclusion: The QoL of CVD patients might have been more affected by psychological factors rather than physical factors during the first two waves of the COVID-19 pandemic in Japan., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objective: We aimed to examine the differences in life-space mobility and quality of life (QoL) of patients with cardiovascular disease (CVD) between the pre- and postnationwide state of emergency initiated by the Coronavirus disease 2019 (COVID-19) pandemic in Japan and to show the factors associated with the decrease in life-space mobility and QoL in these patients., Methods: We undertook a longitudinal study of 20 out of 51 consecutive CVD patients with coronary artery disease (CAD) who met the study criteria. We used the Life-Space Assessment (LSA) tool to evaluate Life-space mobility and assessed QoL with the five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L) in Japanese., Results: The LSA scores and EQ-5D-5L QoL score decreased significantly from the pre- to postnationwide state of emergency in Japan (p < 0.01). ΔLSA was significantly positively associated with body mass index and significantly negatively associated with knee extensor muscle strength and pre-LSA score (p < 0.05). There were no significant relationships between ΔLSA and ΔEQ- 5D-5L QoL scores and between ΔEQ-5D-5L QoL scores and patient characteristics., Conclusion: The policies promoted to address the state of emergency in Japan might affect life-space mobility and QoL of CAD patients. Moreover, CAD patients in Japan who were not obese and maintained their physical function and activity tended to refrain from activity during the period between the pre- and post-nationwide state of emergency. Clarification of the effects of the COVID-19 pandemic on the relationship between living space motility and QoL in CAD patients will require further study., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Asian educators have struggled to implement problem-based learning (PBL) because students rarely discuss their work actively and are not sufficiently engaged in self-directed learning. Supplementing PBL with additional e-learning, i.e. 'blended' PBL (bPBL), could stimulate students' learning process., Methods: We investigated the effects of bPBL on tutorial group functioning (discussion, self-efficacy, self-directed learning, active participation, and tutor's perceived authority) and students' level of acceptance of the e-learning elements. We compared PBL and bPBL in a medical university in Japan. In the bPBL condition, the tutor's instructions were replaced with online materials and short quizzes. After the course, a 13-item questionnaire using a 5-point Likert scale was distributed regarding the tutorial group functioning of the tutorial group (influence of discussion, self-efficacy, self-directed learning, active participation, and tutors' authority). The mean scores of subscales were compared with analysis of covariance. Knowledge levels were measured using a pre-test post-test design. A multiple regression analysis was performed to explore the association between e-learning acceptance and the subscales related to PBL., Results: Ninety-six students participated in the study (PBL: n = 24, bPBL: n = 72). Self-efficacy and motivation for learning triggered by group discussions was significantly higher for students in bPBL (p = 0.032 and 0.007, respectively). Knowledge gain in test scores was also significantly better in the bPBL condition (p = 0.026), and self-directed learning related positively to the acceptance of blended learning (p = 0.044)., Conclusions: bPBL seemed more effective in promoting active learning and improving knowledge, without affecting tutors' authority. Implementing e-learning into PBL is suggested to be an effective strategy in the Asian context.

Introduction: Medical and healthcare professionals' empathy for patients is crucially important for patient care. Some studies have suggested that a significant decline in empathy occurs during clinical training years in medical school as documented by self-assessed empathy scales. Moreover, a recent study provided qualitative evidence that communication skills training in an examination context, such as in an objective structured clinical examination, might stimulate perspective taking but inhibit the development of compassionate care. Therefore, the current study examined how perspective taking and compassionate care relate to medical students' willingness to show empathic behaviour and how these relations may change with communication skills training., Methods: A total of 295 fourth-year Japanese medical students from three universities completed the Jefferson Empathy Scale and a newly developed set of items on willingness to show empathic behaviour twice after communication skills training, pertaining to post-training and retrospectively for pre-training., Results: The findings indicate that students' willingness to show empathic behaviour is much more correlated with perspective taking than with compassionate care. Qualitative descriptive analysis of open-ended question responses revealed a difficulty of feeling compassion despite showing empathic behaviour., Discussion: These findings shed light on the conceptual structure of empathy among medical students and generate a number of hypotheses for future intervention and longitudinal studies on the relation between communication skills training and empathy.

Aim: Glucagon is recommended to treat severe hypoglycemia in nonhospital environments, when a patient with type 1 diabetes mellitus (T1DM) is unconscious and unable to eat or drink. However, the actual possession rate of glucagon in Japan has not been investigated., Subjects and Methods: We recruited 208 T1DM patients older than 15 years of age. The patients were treated at 16 hospitals and clinics in different regions of Japan. Answers were obtained using a self-administered questionnaire about the possession, the experience of usage, and the preference to possess glucagon after reading what is glucagon and when it is used. A stepwise logistic regression analysis was performed to assess the influence of various factors on the possession of glucagon., Results: The possession rate of glucagon was 15.9%, and the rate of those who had experience of using glucagon to treat severe hypoglycemia was 6.0%. The rate of preference to possess glucagon at home after reading the description of glucagon was 39.0%. The possession of glucagon was significantly associated with results of the Glucagon Knowledge Test (odds ratio=24.1; 95% confidence interval, 3.2-183.3; P=0.002) and the history of severe hypoglycemia within 1 year (odds ratio=4.8; 95% confidence interval, 2.0-12.0; P=0.001)., Conclusions: Glucagon as a measure to treat severe hypoglycemia was underutilized among T1DM patients in Japan.

Objective: Adiponectin has anti-atherogenic properties and reduced serum adiponectin levels are associated with cardiovascular disease (CVD). In this study, we examined the relationship between CVD and adiponectin (ADIPOQ) gene G276T polymorphism that is associated with serum adiponectin level in a large cohort of type 2 diabetic patients., Research Design and Methods: We enrolled 2637 Japanese type 2 diabetic subjects (males, 61.1%; age, 54.9±7.9 years old), determined their genotypes regarding ADIPOQ G276T polymorphisms, and evaluated the association between this polymorphism and the prevalence of CVD (myocardial infarction and/or cerebral infarction)., Results: The prevalence of CVD tended to be higher as the number of G alleles increased [GG (9.5%), GT (6.8%), TT (5.6%), p value for trend=0.0059] and was significantly higher in the subjects with GG genotype compared to those with GT or TT genotype (9.5% vs. 6.6%, p=0.0060). Multiple logistic regression analyses revealed that the number of G alleles (Odds ratio (OR)=1.49 with 95%CI 1.09-2.05, p=0.0125) and GG genotype (OR=1.66 with 95%CI 1.13-2.43, p=0.0098) were significantly associated with CVD even after adjustment for conventional risk factors. Interestingly, the presence of obesity further and significantly increased the risk of CVD in the subjects with GG genotype (OR=1.67 with 95%CI 1.14-2.44, p=0.0090) but not in the subjects with TT or GT genotype (OR=1.17 with 95%CI 0.73-1.89, NS)., Conclusions: It is likely that the G allele of the ADIPOQ G276T polymorphism is a susceptibility allele for CVD in Japanese type 2 diabetic patients, especially when they accompany obesity., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Glycemic control is an important issue in gestational diabetes mellitus (GDM) and in diabetic pregnant women. We determined the reference intervals of glycated albumin (GA) and hemoglobin A1c (HbA1c) as glycemic control markers in healthy Japanese pregnant women and analyzed their time courses and factors that influence these variables during pregnancy. 676 women were screened for the present study. After the exclusion of non-pregnant and puerperal women, 574 women were studied to determine the reference intervals. HbA1c, GA, casual plasma glucose, urinary glucose, urinary protein, and body mass index (BMI) (non-pregnancy) were measured. HbA1c levels significantly decreased in the second trimester of pregnancy and increased in the third trimester, while GA levels significantly decreased towards the third trimester. Casual plasma glucose levels decreased in the first trimester and subsequently remained constant. The reference intervals of GA and HbA1c in the healthy pregnant women were 11.5-15.7% and 4.5-5.7%, respectively. GA levels were lower (p<0.01) and HbA1c levels were higher (p<0.05) in pregnant women with proteinuria. In the obese group, GA levels were lower (p<0.01) than those of the control group (18.5≤ BMI <25kg/m²), and HbA1c levels were higher (p<0.01) than those of the control group. On the basis of the results of this multicenter study, the reference intervals of GA and HbA1c in healthy Japanese pregnant women were determined. Strict glycemic control is essential to reduce perinatal complications. GA appears to be a useful marker for pregnant women, since it can be measured easily and changes rapidly and markedly.

Recent genomewide association studies have successfully identified several genotypes susceptible to type 2 diabetes mellitus (T2DM). However, only a few studies have investigated whether these variations confer a risk of the future development of T2DM. We conducted a longitudinal genetic epidemiological study to clarify the prognostic significance of the T2DM-associated variants. The sample population consisted of 2037 middle-aged to elderly community residents. Personal health records were obtained from a clinical database administered by the local government. Genotype risk score was calculated by the following variants, namely, KCNQ1, TCF7L2, CDKAL1, HHEX, IGF2BP2, CDKN2AB, SLC30A8, KCNJ11, PPARG, and GCKR. Susceptibility of these variants in Japanese has been confirmed by association analysis. Among the 1824 subjects who did not have T2DM at baseline, 95 cases of T2DM were newly diagnosed during the 9.4-year follow-up period. Mean genotype risk score in these subjects was significantly higher than that in the subjects who remained nondiabetic (9.5 ± 1.8 vs 9.1 ± 2.0, P = .042). Although the initial mean body mass index (24.7 ± 3.2 vs 23.0 ± 2.8, P < .001) and initial glucose (106 ± 18 vs 90 ± 13, P < .001) were also significantly higher in those subjects who developed T2DM, the genotype risk score remained an independent determinant of the development of T2DM even after adjustment for these parameters and possible confounding factors. Per-allele odds ratio for the development of T2DM was 1.12 (95% confidence interval, 1.00-1.25; P = .049). Type 2 diabetes mellitus-susceptible genetic variants identified by a cross-sectional genomewide association study were significantly associated with the future development of T2DM in a general population sample., (Copyright © 2011 Elsevier Inc. All rights reserved.)

It was recently reported that GCKR rs780094 was associated with fasting plasma glucose (FPG) and triglyceride (TG) levels in various ethnic populations (A allele for low FPG and high TG). An association between GCKR rs780094 and type 2 diabetes mellitus (T2DM) (A allele for low risk) has also been reported. We examined the association between GCKR rs780094 and T2DM in Japanese subjects by analyzing 488 cases and 398 controls. A meta-analysis was performed involving two previous association studies. We also analyzed the association between the single-nucleotide polymorphism and clinical parameters in the general Japanese population (n=1854). In the case-control study, the A allele of GCKR rs780094 was associated with a reduced risk of T2DM (odds ratio=0.711 (95% confidence interval=0.589-0.859), P=4.2 × 10(-4)). A meta-analysis confirmed the association of GCKR rs780094 with T2DM susceptibility. In the general Japanese population, subjects with the A/A genotype had lower levels of FPG, fasting plasma insulin and homeostasis model assessment of insulin resistance than those with the G/G genotype. Conversely, subjects with the A/A genotype had higher levels of TG than those with the G/G genotype. We replicated GCKR rs780094 as a marker of T2DM susceptibility in Japanese subjects. This suggests that GCKR rs780094 is a common variant for T2DM susceptibility in various ethnic groups.

Objective: Susceptibility of fat mass and obesity-associated (FTO) gene polymorphisms to obesity has been reported in various populations. Polymorphisms in the melanocortin 4 receptor (MC4R) gene were recently explored as another susceptible locus. However, prognostic significance of these genetic variations has not been fully elucidated. Here, we investigated the involvement of FTO rs9939609 and MC4R rs17782313 polymorphisms in the development of obesity. Association with type 2 diabetes mellitus (T2DM) was also investigated., Subjects: We analyzed 2806 community-dwelling middle-aged to elderly subjects (61+/-14 years). Clinical parameters were obtained from the subjects' personal health records, evaluated at their annual medical check-up., Results: FTO genotype was significantly associated with current body mass index (BMI; TT 23.2+/-3.2, TA 23.7+/-3.2, AA 24.4+/-3.2 kg m(-2), P=2.5 x 10(-6)) and frequency of obesity (26.6, 32.0, 43.0% respectively, P=2.0 x 10(-4)). Age- and sex-adjusted odds ratio for obesity was 1.30 (P=0.004) in TA and 2.07 (P=0.002) in AA genotype. During the 9.4 years comprising the follow-up period, 214 new cases of obesity were diagnosed among 1718 subjects whose retrospective data were available. A allele frequency of the FTO genotype was significantly higher in subjects who developed obesity (22.2, 15.8%, P=0.001), Age-, sex- and initial BMI-adjusted odds ratio for the development of obesity was 1.46 (95% confidence interval, 1.04-2.04) (P=0.031). However, association studies and meta-analysis of T2DM did not actively support the involvement of FTO genotype. No significant differences were observed between the MC4R genotype and BMI (P=0.015), and the frequency of obesity (P=0.284)., Conclusion: FTO genotype is an independent risk factor for future development of obesity.

To clarify the detailed clinical features and HLA subtype in the patients with fulminant type 1 diabetes, we investigated consecutive 250 case records registered to the committee of the Japan Diabetes Society between 2000/7/15 and 2006/6/30. After the classification with age at onset or gender, clinical data and HLA DR were evaluated. As a result, the prevalence of male patients, BMI, HbA(1c) and ALT levels at the onset increased significantly according to the elder quartile, but no other data showed any significant difference. Only age at onset and blood glucose level were significantly higher in male patients than in female patients without pregnancy by multivariate analysis. The distribution of HLA DR was not different in any subtype by gender or age at onset. Our present study revealed common feature in clinical and HLA-DR status regardless of age and gender within fulminant type 1 diabetes except pregnant women.

Background Aims: A mild increase in liver enzyme levels is sometimes observed in patients with diabetic ketosis or ketoacidosis. The aim of the present study was to assess the cause and prevalence of the elevation of liver transaminase levels in fulminant and acute-onset type 1 diabetic patients experiencing diabetic ketosis or ketoacidosis., Methods: We analyzed data on the liver transaminase levels of 108 patients over 18 years of age with newly diagnosed type 1 diabetes complicated by ketosis or ketoacidosis. The data were collated from a nationwide survey on fulminant type 1 diabetes and retrospective medical records., Results: Thirty-two (60.4%) out of the 53 patients suffering from fulminant type 1 diabetes were detected with transient elevation of liver transaminase (TELT) levels during the first month after initiation of insulin therapy; in the case of acute-onset type 1 diabetes, such an observation was noted in 16 (29.1%) out of 55 patients. Fatty liver was diagnosed in 20% of the patients, and 65% of these patients exhibited TELT. The dosage of insulin injected in these patients was significantly high., Conclusions: High blood glucose and fatty liver may influence the elevation of liver transaminase levels during the treatment of new-onset type 1 diabetes.

Aims/hypothesis: The aim of the present study was to assess the development of microangiopathy in patients with fulminant type 1 diabetes, a novel subtype of type 1B diabetes., Materials and Methods: In a nationwide survey, we followed 41 patients with fulminant type 1 diabetes and 76 age- and sex-matched patients with type 1A diabetes for 5 years. The following data were recorded every 12 months after the onset of diabetes: seven-point blood glucose concentrations, HbA1c level, urinary albumin excretion, serum C-peptide level, blood pressure, daily dosages of insulin, frequency of severe hypoglycaemic episodes, and neurological and fundoscopic examination., Results: The 5-year cumulative incidence of microangiopathy was 24.4% in fulminant type 1 diabetes and 2.6% in type 1A diabetes. In longitudinal studies using the Kaplan-Meier method, the cumulative incidence of each form of microangiopathy was significantly higher in fulminant type 1 diabetes than in type 1A diabetes; retinopathy was 9.8% vs 0% (p=0.014), nephropathy 12.2% vs 2.6% (p=0.015) and neuropathy 12.2% vs 1.3% (p=0.010), respectively. Mean HbA1c levels were similar in the fulminant and type 1A diabetes groups during the follow-up periods. However, the mean M-value, mean insulin dosages and the frequency of severe hypoglycaemic episodes were significantly higher, and the mean postprandial C-peptide level was significantly lower in the fulminant type 1 diabetes group., Conclusions/interpretation: These data suggest that patients with fulminant type 1 diabetes are a high-risk subgroup for diabetic microangiopathy associated with the lack of endogenous insulin secretion from the onset of diabetes.

To clarify heterogeneity in Japanese adult-onset type 1 diabetes, we analyzed the HLA-DR and -DQ haplotypes, depending on the clinical phenotype, and compared them with those in childhood-onset type 1 diabetes (CO). The patients in a previously reported Ehime Study were divided into subgroups by the mode of onset of diabetes: 68 acute-onset type 1 diabetic patients (AO) and 28 slowly progressive type 1 diabetic patients (SO). HLA haplotypes were compared with those of 80 CO patients and 190 control subjects. Two major susceptible HLA haplotypes in the Japanese, DRB1*0405-DQB1*0401 (DR4) and DRB1*0901-DQB1*0303 (DR9), were significantly increased in the AO and CO groups, but only DR9 was increased in the SO group. AO subjects had a higher frequency of DR9 than CO subjects. Accordingly, the DR9:DR4 frequency increased with increasing age of onset. Another susceptible haplotype, DRB1*0802-DQB1*0302 (DR8), was involved only in the CO group. Analysis of haplotype combinations revealed that DR4 and DR9 had significant dosage effects on the AO and CO groups (P < 0.0001), but only DR9 had such an effect in the SO group (P < 0.03). These results suggest differences in the contribution of HLA class II haplotypes to susceptibility of type 1 diabetes depending on the clinical phenotype and also indicate that HLA class II haplotypes may be associated with the onset age of type 1 diabetes.

Insulin resistance is a major cause of type 2 diabetes mellitus (T2DM). Resistin, an adipocyte-secreted hormone, antagonizes insulin. Transgenic mice that overexpress the resistin gene (Retn) in adipose tissue are insulin-resistant, whereas Retn (-/-) mice show lower fasting blood glucose, suggesting that the altered Retn promoter function could cause diabetes. To determine the role of RETN in human T2DM, we analyzed polymorphisms in its 5' flanking region. We found that the -420G/G genotype was associated with T2DM (397 cases and 406 controls) (P=.008; adjusted odds ratio = 1.97 [by logistic regression analysis]) and could accelerate the onset of disease by 4.9 years (P=.006 [by multiple regression analysis]). Meta-analysis of 1,888 cases and 1,648 controls confirmed this association (P=.013). Linkage disequilibrium analysis revealed that the -420G/G genotype itself was a primary variant determining T2DM susceptibility. Functionally, Sp1 and Sp3 transcription factors bound specifically to the susceptible DNA element that included -420G. Overexpression of Sp1 or Sp3 enhanced RETN promoter activity with -420G in Drosophila Schneider line 2 cells that lacked endogenous Sp family members. Consistent with these findings, fasting serum resistin levels were higher in subjects with T2DM who carried the -420G/G genotype. Therefore, the specific recognition of -420G by Sp1/3 increases RETN promoter activity, leading to enhanced serum resistin levels, thereby inducing human T2DM.

Resistin, specifically secreted from adipocytes, antagonizes insulin and represents a promising candidate gene for type 2 diabetes. We reported that a frequent single nucleotide polymorphism (SNP) +299G>A in this gene is not associated with type 2 diabetes. To determine whether this SNP affects insulin resistance syndrome associated with type 2 diabetes, we examined its effects on susceptibility to obesity, hyperlipidemia and hypertension in type 2 diabetic subjects and on susceptibility to type 2 diabetes by interaction with other frequent genes involved in lipid metabolism, namely, beta3-adrenergic receptor (b3AR) Trp64Arg, phosphodiesterase 3B (PDE3B) c.1389G>A or lysosomal acid lipase (LAL) Thr-6Pro. The 99 type 2 diabetic and 99 control subjects were typed by PCR direct sequencing or PCR-RFLP. No differences in frequencies of obesity, hyperlipidemia and hypertension were found between the type 2 diabetic subjects with G/G and those with G/A or A/A genotypes of the resistin SNP. When the combination of the resistin SNP with each of b3AR, PDE3B and LAL SNPs was assessed, no association with type 2 diabetes was evident. Therefore, the frequent SNP +299G>A in the resistin gene is unlikely to have major effects on susceptibility to insulin resistance syndrome associated with type 2 diabetes in Japanese subjects.

Objective: To describe the clinical and immunologic characteristics of fulminant type 1 diabetes, a novel subtype of type 1 diabetes, we conducted a nationwide survey., Research Design and Methods: History and laboratory data, including islet-related autoantibodies, were examined in 222 patients with fulminant and nonfulminant type 1 diabetes in our hospitals in addition to another 118 patients with fulminant type 1 diabetes located outside our hospitals in Japan., Results: In our hospitals, of the 222 patients studied, 43 (19.4%) were diagnosed with fulminant type 1 diabetes, 137 (61.7%) were classified as having autoimmune type 1 diabetes, and 42 were type 1 diabetic subjects who were not fulminant and did not have anti-islet antibodies. An additional 118 fulminant patients outside our hospitals were enrolled, making a total of 161 fulminant type 1 diabetic subjects (83 male and 78 female subjects; 14 children/adolescents and 147 adults) identified from all over Japan. (In 2000, the average incidence was three cases per month.) Flu-like symptoms and pregnancy were more frequently observed in the fulminant than in the autoimmune group (P < 0.001). In the fulminant patients, 4.8% were positive for anti-GAD antibodies and none were positive for anti-islet antigen 2 antibodies., Conclusions: Fulminant type 1 diabetes is a distinct subtype and accounts for approximately 20% of the ketosis-onset type 1 diabetes cases in Japan. Flu-like symptoms are characteristic of disease onset. Metabolic derangement is more severe in this subtype than in autoimmune type 1 diabetes.

The activation of phosphodiesterase 3B (PDE3B) reduces free fatty acid output from adipocytes. A reduced PDE3B gene expression could lead to insulin resistance. To determine whether there are polymorphisms associated with type 2 diabetes in PDE3B gene promoter, this 5(') flanking region was isolated. The transcription initiation site was located 206bp upstream from the translation start site. Sequences of 2kb of the 5(') flanking region for 24 type 2 diabetic Japanese subjects were initially analyzed using PCR direct sequencing, and the regions including the identified polymorphisms were then examined. In 98 controls and 98 type 2 diabetic subjects, -1947T>C, -567G>A, -465G>T, -458T>C, and -1727&#95;-1726insTCAATT were found. Only -465G>T and this insertion had more than 5% frequencies. Since a complete linkage disequilibrium existed between them, -465G>T was further analyzed, along with a previously identified +1389G>A in the coding region, in a total of 200 controls and 207 type 2 diabetic subjects. These allele frequencies were not significantly different between these two groups (controls vs. cases; -465G>T, 12.0% vs. 10.1%, P=0.435; +1389G>A, 30.3% vs. 33.3%, P=0.408). These genotype distributions were not significantly different between these two groups. The T/T genotype at -465 was rare although this frequency could be higher in type 2 diabetes (4/207 subjects) than controls (0/200 subjects). The linkage disequilibrium existed between -465G>T and +1389G>A, and the estimated haplotype frequencies defined by these SNPs were not significantly different between the cases and controls. Thus, the identified polymorphisms are unlikely to have major effects on susceptibility to Japanese type 2 diabetes.

FOXC2, a forkhead/winged helix transcription factor, represents a promising candidate gene for type 2 diabetes since transgenic mice that specifically overexpress this gene in adipocytes are lean and insulin sensitive. To determine whether there are single nucleotide polymorphisms (SNPs) in this gene that are associated with type 2 diabetes, sequences of the coding and approximately 1 kb of 5' flanking regions in 24 Japanese type 2 diabetic subjects were initially analyzed using PCR direct sequencing, and the regions containing the identified polymorphisms were then examined. In 200 control subjects, three frequent SNPs were found (g. -512C>T [32.3%] and -350G>T [13.0%] in the 5' flanking region and +1548C>T [10.0%] in the 3' flanking region). Linkage disequilibria were found between all three pairs of these SNPs. Of the eight possible haplotypes defined by these SNPs, only four were found. When the frequencies of these SNPs and the four common haplotypes between 195 type 2 diabetic and 200 control subjects were compared, no association was evident. The +898C>T (Pro300Ser), +907C>A (Leu303Met), 1167&#95;1169delCCA (389delHis), and +1251C>A (Ala417Ala) identified in the coding region were rare, although +907C>A could be higher in type 2 diabetic subjects (1.5%) than in control subjects (0.3%). Thus, the SNPs identified in the FOXC2 gene are unlikely to have major effects on susceptibility to Japanese type 2 diabetes.

The study examines the clinical significance of guanase (GU) measurement in patients with hepatitis C. 688 patients in whom either ALT was abnormal, or in whom HBsAg or HCVAb was detected in the serum, were enrolled into this study. The percentage of cases in which normal ALT while elevated GU was compared among the different disease groups. Then, the percentage of cases with normal ALT but elevated GU was compared between HBV and HCV groups. For the entire population, a significant correlation was observed between ALT and GU (r=0.872). The overall percentage of cases with normal ALT but elevated GU activity was 11.4%. In HCV group, 449 cases had normal ALT. Of these cases, 20.3% had elevated GU, while ALT was normal. Before 1989, no test to check donated blood for HCV antibody was available. However, screening of donated blood for high GU was associated with a reduced incidence of post-transfusion hepatitis. This is probably because following the screening, blood donated by patients with hepatitis C who had normal ALT but elevated GU was rejected. After the introduction of HCV antibody measurement, GU measurement is still useful to reveal the pathophysiological condition in-patients with chronic hepatitis type C.

Mortality rates from chronic liver diseases (CLD) such as liver cirrhosis and hepatocellular carcinoma have been reported to be higher in Tokushima prefecture, although its causes remain unclear. To clarify the causes of CLD in Tokushima prefecture, we evaluated the positive rates of HBs antigen and anti-HCV antibody and the mortality rates from CLD in patients with liver diseases and blood donors after dividing the entire Tokushima prefecture into 8 district boundaries of health centers. In addition, to evaluate the causes of the higher frequency of CLD and the relationship between the development of CLD and viruses, medical examinations were performed in 2 mountain villages in Tokushima prefecture where the drift of population was limited and the mortality rates from CLD differed from each other. As a result, it was found that HCV infection was the major cause of the higher mortality rates from CLD in Tokushima prefecture. Although there were marked regional differences in the mortality rates from CLD, they were mainly due to different rates of HCV infection.

Resistin is a novel polypeptide specifically secreted from adipocytes, and its serum levels are increased in obese diabetic mice. Resistin antagonizes insulin and could account for insulin resistance. To determine whether there are single nucleotide polymorphisms (SNPs) in the resistin gene associated with type 2 diabetes, sequences for 24 Japanese type 2 diabetic patients were initially analyzed using PCR direct sequencing. Three SNPs were found in the introns, but none were present in the coding regions. The allele frequencies of genomic -167C>T, +157C>T, and +299G>A in 99 Japanese control subjects were determined to be 3.5, 6.6, and 39.4%, respectively. In each pair of these SNPs, linkage disequilibria were found between either -167C>T and +299G>A or +157C>T and +299G>A. A linkage disequilibrium was also detected among -167C>T, +157C>T, and +299G>A, and only four of the eight possible haplotypes defined by these SNPs were found. A comparison of the frequencies of these SNPs and haplotypes between 99 type 2 diabetes and 99 control subjects revealed no evidence for any association. These identified SNPs, which were in linkage disequilibrium, represent potentially useful tools for searching for their association with specific phenotypes of diabetes.

Background and Study Aims: Bleeding due to esophageal variceal rupture is associated with an extremely high mortality rate. Variceal bleeding is frequent in patients who have a red color sign on endoscopy. However, the red color sign is subjectively evaluated on the basis of color tone and the shape of the varices. To allow standardization and facilitate consensus, an objective method of assessing the red color sign is needed. In this study, a system was established for quantifying the red color sign during endoscopic evaluation., Patients and Methods: Between July 1995 and February 1997, 55 untreated patients with portal hypertension and esophageal varices identified on upper gastrointestinal endoscopy were enrolled in the study. Images obtained about 5 cm oral to the esophagogastric junction during endoscopy were stored on magnetic optical disks using an endoscopic image processor. The still images were transmitted to a computer and analyzed using computer software. The RGB components (R, red; G, green; B, blue) were measured at points showing flare consistent with the red color sign. The endoscopic assessment was based on the Japanese Research Society for Portal Hypertension's general rules for recording endoscopic findings in esophagogastric varices., Results: The ratio of the red color area to the variceal area increased with increasing red color grade. There were significant positive correlations between the R and G, and G and B components. This suggests that comparing the R components alone would allow assessment of the color differences in the red color area and in the varices. The R value was significantly higher in the red color area (115 +/- 20) than in the varices (57 +/- 19). An R value of 90 was found at the boundary between the two parts (P < 0.001)., Conclusions: The red color area can be automatically calculated and quantified using the analysis program. Improvements in data storage methods may allow real-time evaluation during endoscopy in the future.

It has recently been shown that the A/A genotype at g.-23 of the insulin gene correlates with impaired insulin secretion in response to body weight gain in subjects of European descent. To examine whether there are single nucleotide polymorphisms (SNPs) in the insulin gene associated with type 2 diabetes, all exons with their flanking sequences for 113 Japanese type 2 diabetic patients and 99 nondiabetic control subjects were analyzed using PCR direct sequencing. We have only found g.-23T --> A, 806G --> C, 1128T --> C, and 1141A --> C, which have previously been reported in alpha (A-C-C-C) and beta (T-G-T-A) alleles. The allele frequency of -23T --> A in control Japanese subjects was 97.4%, whereas that in Europeans is about 30%. The A/A genotype was found in 94 of 99 Japanese subjects (94.9%) and the allele frequencies of 806G --> C, 1128T --> C, and 1141A --> C were all 96.5%. The estimated haplotype frequencies were (A-C-C-C) (96.0%), (T-G-T-A) (2.0%), (A-G-T-A) (1.5%), and (T-C-C-C) (0.5%). No association of these SNPs or haplotypes with type 2 diabetes was evident. Thus, the A/A genotype at the g.-23 of insulin gene was generally high in Japanese subjects, which could account for the fact that they typically secrete lower levels of insulin.

We encountered a patient whose blood was sucked by Haemaphysalis longicornis in the suburb of a business city in Tokushima prefecture in Japan. The tick, which had been attached to the lower limb of the patient for one week, measured 10 mm in length. There were no notable objective or subjective findings after the complete extirpation of the tick. The area had not been known in recent history to be a habitat of ticks, and, thus, this case is of importance in terms of predicting future trends of tick-borne diseases in Japan.

The incidence of C100-3 among the blood specimens qualified for transfusion according to the conventional criteria was 1.1%. The incidence of C100-3 in donor blood in Tokushima Prefecture is not significantly different from that reported for all Japan. Of the donors positive for the conventional screening test and C100-3, 73.6% showed high ALT levels. For all antibodies, the incidence of HCV-RNA was very low in the donors positive for a single antibody, but was high in those positive for multiple antibodies. All of the donors showing the 3 antibodies were positive for HCV-RNA. While a test for multiple antibodies is thought to be effective for the screening of HCV, more blood needs to be discarded, having a serious cost-performance problem. The O.D. value for C100-3 and the 2nd antibody seem to be useful reference value for antibody titers.