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Idiopathic pure red cell aplasia (PRCA) and secondary PRCA associated with thymoma and large granular lymphocyte leukemia are generally considered to be immune-mediated. The PRCA2004/2006 study showed that poor responses to immunosuppression and anemia relapse were associated with death. PRCA may represent the prodrome to MDS. Thus, clonal hematopoiesis may be responsible for treatment failure. We investigated gene mutations in myeloid neoplasm-associated genes in acquired PRCA. We identified 21 mutations affecting amino acid sequences in 11 of the 38 adult PRCA patients (28.9%) using stringent filtering of the error-prone sequences and SNPs. Four PRCA patients showed 7 driver mutations in TET2, DNMT3A and KDM6A, and 2 PRCA patients carried multiple mutations in TET2. Five PRCA patients had mutations with high VAFs exceeding 0.3. These results suggest that clonal hematopoiesis by stem/progenitor cells might be related to the pathophysiology of chronic PRCA in certain adult patients.

We would like to thank Luu et al 1 for their comments on our recent publication in the Annals of the Rheumatic Diseases , entitled ‘First external validation of sensitivity and specificity of the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for idiopathic inflammatory myopathies with a Japanese cohort’.2 We are pleased to know similar validation studies of the new criteria3–7 have been carried out to strengthen our contention. Although Luu et al 1 argue that earlier studies have been published before ours, they were …

The diagnosis of myelodysplastic syndromes (MDS) is based on morphology and cytogenetics. However, limited information is currently available on the interobserver concordance of the assessment of dysplastic lineages (10% or ≥10% in bone marrow (BM)). The revised International Prognostic Scoring System (IPSS-R) described a new threshold (2%) for BM blasts. However, the interobserver concordance of the categories (0-≤2% and2-5%) has limited data. The purpose of the present study was to investigate the assessment of dysplastic lineages and IPSS-R reproducibility. Our study was divided into two Steps. In each Step, the microscopic examinations were performed separately by two morphologists. Regarding the category of BM blasts ≤2% and2-5%, interobserver agreement was more than 'moderate' in all pairs (kappa test: 0.43-0.90). Regarding dysgranulopoiesis (dysG) and dyserythropoiesis (dysE) in BM, interobserver agreement was more than 'moderate' in all pairs (kappa test, dysG: 0.45-0.96, dysE: 0.45-0.81). Regarding the category of dysmegakaryopoiesis (dysMgk) in BM, interobserver agreement was more than moderate in 4 out of 5 pairs (kappa test: 0.58-1.00), and was fair for one pair (kappa test: 0.37). We consider that high interobserver concordance may be possible for the BM blast cell count (≤2% or2-5%) and dysplasia (10% or ≥10%) of each lineage.

Objectives To assess the performance of the EULAR/ACR idiopathic inflammatory myopathies (IIMs) classification criteria to classify juvenile IIMs (JIIMs) in an Asian paediatric population. Methods Sixty-eight JIIM patients and 49 non-JIIM patients diagnosed at seven major paediatric rheumatology centres in Japan between 2008 and 2015 were enrolled. Retrospective data were collected, and each patient’s data form was submitted. The expert group reviewed the forms and re-examined the diagnoses. The EULAR/ACR criteria were then applied and the probability of having JIIM was determined for each case. The sensitivity and specificity of the EULAR/ACR criteria were compared with those of other existing criteria. Results The sensitivity/specificity of the EULAR/ACR classification criteria were 92.1/100% with muscle biopsy data (n = 38); 86.7/100% without muscle biopsy data (n = 30) and 89.7/100% in our total cohort (n = 68). The sensitivity of Bohan and Peter’s criteria and Tanimoto’s criteria were 80.9 and 64.7% in our total cohort, respectively. Among 68 physician-diagnosed JIIM patients, seven cases (three JDM and four overlap myositis) were not classified as JIIM because the probability did not reach the cut-off point (55%). The three JDM patients all presented with only one of the three skin manifestations that are listed in the criteria: Gottron’s sign. Conclusion Our validation study with Japanese JIIM cases indicates that the EULAR/ACR classification criteria for IIM generally perform better than existing diagnostic criteria for myositis.

Introduction: Sentinel surveillance in Japan is used to estimate national influenza incidence under the assumption that Sentinel Medical Institutions (SMIs) are randomly selected. The current method might lead to overestimation when SMIs are recruited on a voluntary basis. Aims & Objectives: We aimed to improve influenza incidence estimation using auxiliary information without this assumption. Materials and Method: We used reports of influenza from SMIs in 2015, together with the number of all disease outpatients in September 2014 at all medical institutions from the Survey of Medical Institutions of Japan, as auxiliary information. The influenza incidence was estimated by the method using auxiliary information and the current method (without auxiliary information). Result and Conclusion: Influenza incidence rate per 1,000 population in 2015 estimated by using auxiliary information and by the current method was 63.7 (95% Confidence Interval (CI), 61.0-66.3) and 96.5 (95% CI, 93.0-100.0), respectively. The ratio of these estimates was 0.66. Our findings suggest that influenza incidence estimated by using the number of all disease outpatients as auxiliary information is more accurate than estimates by the current method.

The objective of this study is to develop clinical practice guideline (CPG) for Sjögren's syndrome (SS) based on recently available clinical and therapeutic evidences.The CPG committee for SS was organized by the Research Team for Autoimmune Diseases, Research Program for Intractable Disease of the Ministry of Health, Labor and Welfare (MHLW), Japan. The committee completed a systematic review of evidences for several clinical questions and developed CPG for SS 2017 according to the procedure proposed by the Medical Information Network Distribution Service (Minds). The recommendations and their strength were checked by the modified Delphi method. The CPG for SS 2017 has been officially approved by both Japan College of Rheumatology and the Japanese Society for SS.The CPG committee set 38 clinical questions for clinical symptoms, signs, treatment, and management of SS in pediatric, adult and pregnant patients, using the PICO (P: patients, problem, population, I: interventions, C: comparisons, controls, comparators, O: outcomes) format. A summary of evidence, development of recommendation, recommendation, and strength for these 38 clinical questions are presented in the CPG.The CPG for SS 2017 should contribute to improvement and standardization of diagnosis and treatment of SS.

The Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes has been conducting prospective registration, central review, and follow-up study for patients with aplastic anemia and myelodysplastic syndrome (MDS) since 2006. Using this database, we retrospectively analyzed the prognosis of patients with MDS. As of May 2016, 351 cases were registered in this database, 186 of which were eligible for the present study. Kaplan–Meier analysis showed that overall survival (OS) curves of the five risk categories stipulated by the revised international prognostic scoring system (IPSS-R) were reasonably separated. 2-year OS rates for the very low-, low-, intermediate-, high-, and very high-risk categories were 95, 89, 79, 35, and 12%, respectively. In the same categories, incidence of leukemic transformation at 2 years was 0, 10, 8, 56, and 40%, respectively. Multivariate analysis revealed that male sex, low platelet counts, increased blast percentage (>2%), and high-risk karyotype abnormalities were independent risk factors for poor OS. Based on these data, we classified Japanese MDS patients who were classified as intermediate-risk in IPSS-R, into the lower risk MDS category, highlighting the need for careful assessment of treatments within low- and high-risk treatment protocols.

Purpose To evaluate the risk factors and prevalence of hyponatremia among epilepsy patients in relation to use of antiepileptic drugs (AEDs). Methods We retrospectively reviewed 14,620 adult patients (aged 18–103 years) and classified them into the following 3 groups: patients without AED treatment (n = 2165, Group I), patients receiving antiepileptic drugs other than carbamazepine (n = 7442, Group II), and patients treated with carbamazepine (n = 5013, Group III). This study did not include the patients receiving oxcarbazepine or eslicarbazepine acetate because these AEDs are not marketed in Japan. Severe hyponatremia was defined as a serum sodium level Results In Groups I, II, and III, the mean sodium level was 140, 139, and 137 mEq/L, respectively. The highest frequency of severe hyponatremia was observed in Group III (7%), and it was much higher than in Group I (0.8%) or Group II (1.2%). In Groups II and III, old age, low body weight, and concomitant use of phenobarbital, benzodiazepines, or antipsychotics were risk factors for hyponatremia. In Group III, the sodium level decreased as the carbamazepine dose increased. At a carbamazepine dose exceeding 600 mg/day, there was 10.9-fold higher prevalence of hyponatremia, and the risk was potentiated by concomitant use of valproate. Conclusion The serum sodium level should be monitored carefully when patients are receiving AED polypharmacy combined with antipsychotics. In particular, concomitant administration of valproate enhances the risk of hyperammonemia in patients receiving carbamazepine. These findings may help clinicians to avoid hyponatremia in patients with epilepsy.

ObjectiveTo externally validate the performance of the new European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria set for idiopathic inflammatory myopathies (IIM) with a Japanese cohort.MethodsThis study included 420 IIM and 402 non-IIM cases. Probability of having IIM in each patient was calculated using the collected data set. The cut-off probability was set at 55%, as recommended by EULAR/ACR. Patients classified as IIM by the criteria were further subclassified with classification trees.ResultsWhen the probability cut-off was set at 55%, the sensitivity/specificity of the new criteria to diagnose IIM were 89.3%/91.0% in the total cohort, 88.1%/95.1% without muscle biopsy data and 90.4%/65.5% with biopsy data. The cohort included 12 overlap syndrome patients with biopsy data, who were included as non-IIM cases in accordance with traditional Japanese methods. When they were included in the IIM cases, the specificity in patients with biopsy increased to 74.4%. The sensitivity/specificity of the new criteria to diagnose polymyositis/dermatomyositis (PM/DM) plus juvenile and amyopathic DM in the Japanese cohort was 87.4%/92.4%, which were greater than those of the Tanimoto’s criteria revised to enable classification of amyopathic DM (ADM) (71.2%/87.8%) and were comparable with those of Bohan & Peter’s criteria to diagnose those diseases except for ADM (88.4%/88.3%).ConclusionsOur study externally validated high specificity of the new criteria for the first time, although with several limitations, including low percentage of child patients. The new criteria have higher sensitivity and/or specificity in classification of PM/DM than the previously reported criteria, demonstrating its usefulness for interethnic patients.

Although rheumatologists, neurologists and dermatologists see patients with polymyositis (PM) and dermatomyositis (DM), their management appears to vary depending on the physician's specialty. The aim of the present study was to establish the treatment consensus among specialists of the three fields to standardize the patient care. We formed a research team supported by a grant from the Ministry of Health, Labor and Welfare, Japan. Clinical questions (CQ) on the management of PM and DM were raised. A published work search on CQ was performed primarily using PubMed. Using the nominal group technique, qualified studies and results in the published work were evaluated and discussed to reach consensus recommendations. They were sent out to the Japan College of Rheumatology, Japanese Society of Neurology and Japanese Dermatological Association for their approval. We reached a consensus in 23 CQ and made recommendations and a decision tree for management was proposed. They were officially approved by the three scientific societies. In conclusion, a multidisciplinary treatment consensus for the management of PM and DM was established for the first time.

Background: The sentinel surveillance system in Japan provides estimates of nationwide influenza incidence. Although prefectural influenza incidences can be estimated using data from the current surveillance system, such estimates may be imprecise. Methods: We calculated the numbers of sentinel medical institutions (SMIs) needed in the surveillance system to estimate influenza incidences in prefectures, under the assumption that the standard error rates in 75% of influenza epidemic cases are less than 10%. Epidemic cases observed in 47 prefectures during the 2007/2008, 2008/2009, and 2009/2010 seasons, respectively, were used. Results: The present total number of SMIs was 6669. With respect to current standards, the increases required in prefectures ranged from 0 to 59, and the total increase required in the number of SMIs was 1668. Conclusions: We used sentinel surveillance data for Japan to calculate the number of SMIs required to estimate influenza incidence in each prefecture.

Infectious disease surveillance systems provide information crucial for protecting populations from influenza epidemics. However, few have reported the nationwide number of patients with influenza-like illness (ILI), detailing virological type. Using data from the infectious disease surveillance system in Japan, we estimated the weekly number of ILI cases by virological type, including pandemic influenza (A(H1)pdm09) and seasonal-type influenza (A(H3) and B) over a four-year period (week 36 of 2010 to week 18 of 2014). We used the reported number of influenza cases from nationwide sentinel surveillance and the proportions of virological types from infectious agents surveillance and estimated the number of cases and their 95% confidence intervals. For the 2010/11 season, influenza type A(H1)pdm09 was dominant: 6.48 million (6.33-6.63), followed by types A(H3): 4.05 million (3.90-4.21) and B: 2.84 million (2.71-2.97). In the 2011/12 season, seasonal influenza type A(H3) was dominant: 10.89 million (10.64-11.14), followed by type B: 5.54 million (5.32-5.75). In conclusion, close monitoring of the estimated number of ILI cases by virological type not only highlights the huge impact of previous influenza epidemics in Japan, it may also aid the prediction of future outbreaks, allowing for implementation of control and prevention measures.

The aim of this study was to describe age, gender distribution, and age at onset of systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), and systemic sclerosis (SSc) in Japan. We used epidemiological information on 21,405, 6,327, and 10,058 patients with SLE, PM/DM, and SSc, respectively, in a Japanese nationwide registration database of patients with intractable diseases. All three diseases occur predominantly in women, with the female-to-male ratio being 8.2:1, 2.6:1, and 7.7:1 for SLE, PM/DM, and SSc, respectively. The most susceptible age for SLE is 15–44 and 20–39 years for males and females, respectively. For PM/DM it is 45–64 and 40–64 years and for SSc, 50–69 and 40–59 for men and women, respectively. The basic descriptive epidemiological characteristics of SLE, PM/DM, and SSc in Japan, such as gender distribution, present age, and age at onset, were surveyed nationwide for fiscal 2007. It was found that these characteristics were similar to those in Western populations. Our finding provides new information on the natural history of disease development.

Differences in Lifestyle and Perceived Health in Different Occupations in a Community: Akiko OHTA, et al. Department of Public Health, Gunma University School of Medicine—It has been reported that morbidity and mortality vary according to occupation. To clarify factors which account for these differences, lifestyle, social network, job satisfaction and perceived health were measured in 1,165 men 40- 59 years old residing in a rural village in Gunma, Japan. Comparisons were made of four occupational groups: agricultural and forestry workers, the self-employed, blue-collar workers, and white-collar workers. Agricultural and forestry workers had less obesity, good social networks with relatives and local community, lower job satisfaction, and less subjective physical symptoms and psychological complaints. The self-employed had higher job satisfaction but felt their jobs were hard. Blue- collar workers had lower job satisfaction, felt that their job was hard, and had the most subjective physical symptoms and psychological complaints. White-collar workers were the most obese, ate more Western-style foods, had more physical exercise, higher job satisfaction, did not feel the job was hard, had stronger marriage ties, and had fewer subjective physical symptoms and psychological complaints. These differences may account for differences in morbidity and mortality by occupation, and will provide useful information for health care planning in the respective occupational group. For example, improved health care will be needed for blue-collar workers who had the poorest perceived health in the community. (J Occup Health 1998; 40: 325-333)

BACKGROUND: Drug-resistant bacteria have been increasing together with advancement of antimicrobial chemotherapy in recent years. In Japan, the target diseases in the National Epidemiological Surveillance of Infectious Diseases (NESID) include some drug-resistant bacterial infections.METHODS: We used the data in the NESID in Japan, 2001-2005. Target diseases were methicillinresistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP) and multi-drug-resistant Pseudomonas aeruginosa (MDRPA) infections. The numbers of patients reported by sentinel hospitals (about 500) on a monthly basis were observed.RESULTS: The numbers of patients per month per sentinel hospital of 2001-2005 were 3.37-3.98 in MRSA, 0.96-1.19 in PRSP, and 0.11-0.13 in MDRPA infections. The sex ratios (male / female) of patients were 1.69-1.82, 1.34-1.43, and 1.71-2.52, respectively. More than 50% of all patients were adults aged 70 years or older in MRSA and MDRPA infections, but more than 60% were children under 10 years in PRSP infections. The number of patients per sentinel hospital in MRSA infections showed little variation between months, but evidenced a large variation in PRSP and MDRPA infections. The annual trend in the number of patients per sentinel hospital was increasing significantly for the 5-year period in MRSA and PRSP infections, but not in MDRPA infections.CONCLUSIONS: We revealed sex-age distributions of the patients reported to NESID in Japan, 2001- 2005. An increasing incidence of MRSA and PRSP infections and monthly variation in PRSP and MDRPA infections were observed for the 5-year period. Extended observation would be necessary to confirm these trends and variations.J Epidemiol 2007; 17: S42-S47.

BACKGROUND: The method for estimating incidence of infectious diseases from sentinel surveillance data has been proposed. In Japan, although the annual incidence rates of influenza and pediatric diseases estimated using the method were reported, their weekly incidence rates have not.METHODS: The weekly sex- and age-specific numbers of cases in the sentinel medical institutions in the National Epidemiological Surveillance of Infectious Diseases in Japan in 2002-2005 were used. Annual and weekly incidence rates of influenza and 12 pediatric diseases were estimated by the above-mentioned method, under the assumption that sentinels are randomly selected from all medical institutions.RESULTS: The annual incidence rate of influenza in 2002-2005 was 57.7-142.6 per 1,000 population. The highest weekly incidence rate was 7.4 at week 8 in 2002, 14.9 at week 4 in 2003, 14.1 at week 5 in 2004, and 21.2 at week 9 in 2005. The annual incidence rate per 1,000 population of 0-14 years old in 2002-2005 was less than 5.0 for pertussis, rubella and measles, 293.2-320.8 for infectious gastroenteritis, and 5.3-89.6 for 8 other diseases. The highest weekly incidence rate was less than 1.0 for exanthem subitum, and was more than 5.0 for infectious gastroenteritis, hand-foot-mouth disease and herpangina.CONCLUSION: We estimated annual and weekly incidence rates of influenza and pediatric diseases in Japan in 2002-2005, and described their temporal variation.J Epidemiol 2007; 17: S32-S41.

BACKGROUND: A method for determining epidemics in small areas from the sentinel surveillance data has been proposed and applied in the National Epidemiological Surveillance of Infectious Diseases (NESID) in Japan. We observed epidemics of influenza and 11 pediatric diseases by the method in the NESID in Japan during 1999-2005.METHODS: We assumed that an epidemic in a public health center area began in a week when the number of cases reported to the NESID per sentinel clinic and hospital in the area in the week exceeded a given value, and that the epidemic ended when the number was lower than another given value. The proportion of public health center areas with epidemics (epidemic area proportion) by week in fiscal 1999-2005 was calculated. Total public health center area-weeks observed were about 30,000 each year.RESULTS: The mean epidemic area proportion in the 7 years was 6.0% for influenza and 0.2-7.4% for pediatric diseases. The proportion increased in pharyngoconjunctival fever and group A streptococcal pharyngitis, decreased in measles and was less than 1.0% in pertussis and rubella. In influenza, the height of the peak in the weekly epidemic area proportion varied between 6 and 90% in the 7 years and the week of the peak varied widely. In some pediatric diseases, the height of the peak varied, while the week of the peak was relatively constant.CONCLUSION: The frequency and temporal change were described in the epidemics of influenza and pediatric diseases in public health center areas from the NESID data in Japan, 1999-2005.J Epidemiol 2007; 17: S14-S22.

BACKGROUND: In 1999 the Communicable Disease Prevention Law of Japan was completely revised into the "New" Infectious Disease Control Law, which reiterated the importance of surveillance and information dissemination and re-organized the surveillance system. This paper is an attempt to illustrate the potential impact of the new surveillance system through a description of the existing surveillance system and data before and after the revision.METHODS: After a historical review of surveillance system in Japan, the current surveillance system is described. Data sets of actual case numbers reported and incidence rate per 1,000,000 population are compared before and after the revision.RESULTS: Comparison of the data between the 2 periods revealed that most of the diseases have had declining trends after the new law was enacted with several exceptions. However, although no major break in continuity is observed in seriously perceived disease, in milder diseases there are striking gaps between the numbers reported in the mandatory and sentinel reporting framework. Sentinel reporting framework maintained the continuity of data without major gaps.CONCLUSIONS: From this perspective, the new surveillance system with two different frameworks of mandatory reporting for severe diseases and sentinel reporting for milder diseases seems to be working well. But continuous efforts should be made for evaluation and improvement of surveillance system and risk communication through the research on data analysis and effective communication method.J Epidemiol 2007; 17: S3-S13.

BACKGROUND: Observing the epidemics of vector-borne diseases is important. One or more cases of 6 vector-borne diseases were reported to the National Epidemiological Surveillance of Infectious Diseases in Japan in 2000-2005.METHODS: The reports of those cases were available. The incidence was observed by region of acquired infection, prefecture reporting, and week and year of diagnosis.RESULTS: The incidence rate per year per 1,000,000 population was 0.36 for dengue fever, 0.04 for Japanese encephalitis, 0.38 for Japanese spotted fever, 0.08 for Lyme disease, 0.74 for malaria, and 3.50 for scrub typhus. There were no cases of dengue fever or malaria derived from domestic infections. The yearly incidence rate increased for dengue fever and Japanese spotted fever, and declined for malaria and scrub typhus. The proportion of cases reported in Tokyo was 44% for dengue fever and 37% for malaria. The number of prefectures reporting one or more cases of Japanese spotted fever increased in western Japan. The cases of scrub typhus increased in autumn-winter in prefectures of eastern Japan, and increased both in autumn-winter and spring in western prefectures.CONCLUSIONS: The study reveals the epidemiologic features of both temporal and geographic distributions of cases of 6 vector-borne diseases in Japan, 2000-2005.J Epidemiol 2007; 17: S48-S55.

A cross-sectional study with a self-administered questionnaire was conducted in order to examine the association between low back pain and smoking. The subjects analyzed were 6,891 adults aged 40-69 yr, who lived in a downtown district in Isesaki City, Gunma, Japan. There was a positive association between cigarette smoking and low back pain in men. The age-adjusted odds ratios of low back pain were 1.32 (95% confidence interval (Cl) 1.10, 1.57) for 1-20 cigarettes smoked per day and 1.40 (95% Cl 1.11, 1.76) for 21 or more. The association had similar strength after adjustment for alcohol consumption, physical exercise, body mass index, non-musculoskeletal disease, education, occupation, and whether living with parents, living with a child or children, or living alone. The multivariate odds ratios for low back pain were 1.29 (95% Cl 1.03, 1.62) for 1-20 cigarettes smoked per day and 1.36 (95% Cl 1.03, 1.80) for 21 or more. In conclusion, smoking was significantly related to low back pain, even if adjusted for other potential risk factors.

It is thought that prominent production of inflammatory cytokines and expression of adhesion molecules on the endothelial cells activated by unkown pathogens induce the formation of the vasculitis in Kawasaki disease (KD) . To study the anti-inflammatory effect of salicylazosulfapyridine (SASP) on the cardiovasculitis of KD, we examined the effect of SASP on IL-6 production by human coronary artery endothelial cells (HCAEC) . We used HCAEC because IL-6 production by HCAEC was greater than by human umbilical vein endothelial cells. SASP at less than 0.5 mM suppressed IL-6 production by LPS-induced HCAEC, and higher concentrations of SASP affected cell viability. On the other hand, SASP did not suppress IL-6 production by the cells stimulated with cytokines such as TNFα, IL-1 β and IL-4. Sulfapyridine and 5-aminosalicylic acid, which are degradation products of SASP, did not suppress IL-6 production.These results show that SASP may have a direct inhibitoy effect on HCAEC activated by external substances such as LPS, which may be an effective agent in the cardiovasculitis of KD.

The A2A adenosine receptor (A2AR)-mediated immunosuppression is firmly implicated in the life-saving down-regulation of collateral tissue damage during the anti-pathogen immune response and in highly undesirable protection of cancerous tissues during anti-tumor immune response. Therefore, depending on specific clinical situation there is a need to either weaken or strengthen the intensity of A2AR signal. While the A2AR-mediated immunosuppression was shown to be T cell autonomous in studies of effector T cells, it was not clear how A2AR stimulation affects regulatory T cells (Treg). Here we show in parallel assays that while A2AR stimulation on T cells directly inhibits their activation, there is also indirect and longer-lasting T cell inhibitory effect through modulation of Treg. A2AR stimulation expanded CD4(+) CD25(hi) FoxP3(+) cells, which also express CD39, CD73, and CTLA-4. Treg cultured with A2AR agonist showed increased expression of CTLA-4 and stronger immunosuppressive activity. There was a significant increase of Treg cell number after A2AR stimulation. The CD4(+) FoxP3(+) population contained those induced from CD4(+) CD25(-) cells, but CD4(+) FoxP3(+) cells predominantly derived from CD4(+) CD25(+) natural Treg. Thus, A2AR stimulation numerically and functionally enhanced Treg-mediated immunosuppressive mechanism. These data suggest that the A2AR-mediated stimulation of lymphocytes using A2AR agonists should be considered in protocols for ex vivo expansion of Treg before the transfer to patients in different medical applications.

BACKGROUND: Epidemics of infectious diseases usually start in small areas and subsequently become widespread widely. Although a method for detecting epidemics in public health center (PHC) areas has been proposed and used in the National Epidemiological Surveillance of Infectious Diseases in Japan, wide-area epidemics have not been fully investigated.METHODS: Using the abovementioned method, we defined an epidemic as that occurring for a week in at least one PHC area in a prefecture and a wide-area epidemic as that when the number of people living in epidemic PHC areas exceeds 30% of the prefectural population. The number of weeks of an epidemic or wide-area epidemic for influenza and 11 pediatric diseases was observed in 47 prefectures in Japan from 1999 through 2005.RESULTS: Epidemics and wide-area epidemics of influenza occurred for an average of 7.0 and 4.3 weeks in a year in a prefecture, respectively. The proportion of wide-area epidemics in epidemic weeks was 62%. The average number of wide-area epidemic weeks for pediatric diseases varied among diseases; it was more than 4 weeks for infectious gastroenteritis and herpangina and less than 1 week for pertussis, rubella, and measles. The proportion of wide-area epidemics in epidemic weeks was 28-41% for infectious gastroenteritis, hand-foot-mouth disease, and herpangina and less than 20% for other diseases.CONCLUSIONS: The frequency of wide-area epidemics of influenza and pediatric diseases in various prefectures was observed. Epidemics of infectious diseases such as influenza and herpangina occurring in small areas were likely to spread to wide areas.J Epidemiol 2007; 17: S23-S31.

Background: We report a patient who was diagnosed as having steroid-induced glaucoma after radial keratotomy (RK) and who suffered from severe visual field defect. Case: A 29-year-old man underwent RK for both eyes. After the operation, he was treated for six months with topical medication including 0.1% and 0.01% betamethasone without an intraocular pressure (IOP) measurement. When he consulted an ophthalmologist, his IOP was 43 mmHg in the right eye and 51 mmHg in the left eye. At our initial examination, his IOP was 8 mmHg in the right eye and 10 mmHg in the left eye. He was taking 750 mg acetazolamide peroral, 0.5% timolol maleate, and latanoprost eyedrops. There were 16 RK incisions on the cornea and we found severe glaucomatous visual field loss. Finally we performed trabeculotomy in both eyes for IOP control with conservative therapy. Conclusion: As keratorefractive surgery becomes popular, we must be alert for problems, such as steroid-induced glaucoma, and the change in refraction following the change in IOP. Nippon Ganka Gakkai Zasshi

To examine rural-urban differences in the relationships of sociodemographic, social network, and lifestyle factors to mortality in middle-aged men, we used the data from a community based prospective cohort study, the Komo-Ise study. The subjects were all men aged 40-69 years living in Komochi Village, the rural group (n=2,295), or the downtown district of Isesaki City, the urban group (n=3,334), as of 1993. They completed a self-administered questionnaire in 1993 and were followed for all-cause deaths until 2000. The Cox proportional hazards model was used to compute relative risks (RRs) with 95% confidence intervals (CIs). Low educated men and men without a spouse in the rural group had an increased risk of mortality (RR=4.4; 95%CI: 1.1-18.2, RR=2.4; 95%CI: 1.2-4.5). Men who did not enjoy good fellowship with their neighbors in the rural group had a decreased risk of mortality (RR=0.58; 95%CI: 0.35-0.97). Mortality risks were significantly higher in urban men not participating in hobbies, club activities or community groups (RR=1.6; 95%CI: 1.1-2.4). These variables remained significant risk factors, even after controlling for all sociodemographic, social network, lifestyle, and health status variables. Educational level, marital status and relation to neighborhoods showed significant rural-urban differences.

Background We report a patient with persistent hyperplastic primary vitreous(PHPV) who presented with acute angle-closure glaucoma in his adult life. Case A 30-year-old man had an attack of acute angle-closure glaucoma associated with retrolenticular fibrous tissue, atrophic retina, and elongated cilliary process in his right eye. Result Ultrasound biomicroscopy(UBM) study showed iris bowing, shallow anterior chamber, and elongated cilliary body which were being pulled by the retrolenticular mass. The posterior chamber was normal. Conclusion Although the mechanisms of secondary angle-closure glaucoma in PHPV are complicated, we suspected pupillary block resulting from constriction by the retrolenticular mass in this case.

To examine the relationship between lifestyle and sociodemographic risk factors and mortality, a population-based prospective cohort study was conducted in two areas of Gunma Prefecture, Japan, and a cohort consisting of 11,565 subjects aged 40-69 at baseline in 1993 was followed. During the five-year follow-up period, 201 men and 103 women died. The relative risks (RRs) of risk factors were estimated by the Cox proportional-hazards model. Significant RRs with multivariate adjustment for all-cause mortality was observed for body mass index (BMI). The curve for the relationship between BMI and all-cause mortality was L-shaped in men and U-shaped in women, with the lowest RRs at a BMI of 22-25 in both men and women. Other significant RRs for all-cause mortality were observed for obesity in the subjects' 30's in both men and women (RR: 2.42 and RR: 2.75), poor perceived health status in men (RR: 4.55), and having had a health examination in the past three years in both men and women (RR: 0.49 and RR: 0.46). These results suggested that increased risk of death was independently associated with a lower BMI, obesity in the subjects' 30's, and not undergoing health examinations, among both men and women, and poor perceived health status among men.

PURPOSES We studied the control of intraocular pressure(IOP) by various types of blebs after non-penetrating trabeculectomy(NPT) and the difference between bleb formation after penetrating trabeculectomy(PT) and that after NPT. METHODS The filtering blebs of 45 yeys from 40 patients after NPT were studied using ultrasound biomicroscopy. They were grouped into four types, and the space under the scleral flap was classified into three types. The filtering blebs and the space under the scleral flap were correlated with IOP level. RESULTS Overall, 40% of the blebs were L(low-reflective) type, 16% H(high-reflective) type, 16% E (encapsulated) type, and 29% F(flattened) type, but in good IOP control cases 59% of the blebs were L type, 14% H type, 14% E type, and 14% F type. L type blebs were found in 94% of eyes with good IOP control. CONCLUSION Though filtering blebs of the L type could produce sufficient IOP reduction, blebs after NPT showed a greater tendency to become flattened than after PT. Additional systematic therapy must be designed to maintain the L type of filtering blebs after NPT.

Introduction Systemic lupus erythematosus (SLE) is one of the most frequent autoimmune diseases. As SLE is unknown cause and difficult to treat, and the patients are forced to have difficult life, SLE is designated as one of the intractable diseases by Ministry of Health, Labour and Welfare of Japan, same as polymyositis and dermatomyositis (PM/DM) we report in another paper, the government provides those patients a financial aid for the treatment as a specific disease treatment research program. Simultaneously most of the patients are registered to a database, which includes basic information of patients9 characteristics. Using this database, we can clarify in detail the characteristics of the SLE patients. Methods In Japan, 21 405 SLE patients were registered in 2007. They are about 39% of the patients receiving financial aid by the government. We analysed the age, sex, age at onset, activity in daily life and clinical features. Results In the registered patients, the number of male is 2336 and the female is 19 069, sex ratio is 0.12. Though an age distribution of male patients shows almost constant frequency from age 50s to 60s, that of female shows two peaks at age 30s and 50s. The age at onset of female SLE increases from teenage and shows one large peak at age 25–29. That of male does not show any significant peak. Conclusion The characteristics observed here by the analysis of twenty thousand registered patients provided fundamental features of the disease.

Introduction Polymyositis and Dermatomyositis (PM/DM) are both rare rheumatic and autoimmune diseases manifesting muscle inflammation and progressive weakness, DM includes skin inflammation, and are unknown cause and difficult to treat. PM/DM is designated as one of the intractable diseases by Ministry of Health, Labour and Welfare of Japan. And the government provides those patients a financial aid for the treatment as a specific disease treatment research program. Simultaneously most of the patients are registered to a database, which includes basic information of patients9 characteristics. Using this database, we can clarify in detail the characteristics of the PM/DM patients. Methods In Japan, 6327 PM/DM patients were registered in 2007. They are about 43% of the patients receiving financial aid by the government. We analysed the age, sex, age at onset, activity in daily life and clinical features. Results In the registered patients, the number of male is 1735 and the female is 4592, sex ratio is 0.38. Age distribution by sex shows the mode age is 65–69 and 55–59 for male and female respectively. The age at onset of the disease distributes to wide range from 0–4 to 85−, the frequency goes up from the age 20s to the peak at age 50s, followed by descending trend. The onset age of female is a little younger than that of male. Conclusion The registered large number of rare disease (PM/DM) patients9 information provided fundamental features of the disease.