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Background: To evaluate the seasonal variability of urinary albumin to creatinine ratio (UACR) and eGFR and these effects on three-year eGFR slope in persons with type 2 diabetes (T2D)., Methods: A total of 1135 persons with T2D were analyzed in this single-center, retrospective cohort study in Japan. The standard deviation (SD) of UACR (SD [UACR]) and SD of eGFR (SD [eGFR]) were calculated for each person's 10-point data during the three years, and a multiple linear regression analysis was performed to evaluate associations with eGFR slope. A sensitivity analysis was performed in a group with no medication changes (n = 801)., Results: UACR exhibited seasonal variability, being higher in winter and lower in spring, early summer, and autumn especially in the UACR ≥ 30 mg/g subgroup, while eGFR showed no seasonal variability. The eGFR slope was significantly associated with SD (eGFR) (regression coefficient -0.170 [95% CI -0.189--0.151]) and SD (UACR) (0.000 [-0.001-0.000]). SGLT-2 inhibitors, baseline eGFR, and baseline systolic blood pressure (SBP) were also significantly associated. These associated factors, except baseline SBP, were still significant in the sensitivity analysis., Conclusions: The UACR showed clear seasonal variability. Moreover, SD (UACR) and SD (eGFR) were independently associated with a three-year eGFR slope in persons with T2D., Trial Registration: This study was not registered for clinical trial registration because it was a retrospective observational study., (© 2024. The Author(s).)

Purpose: This study aimed to evaluate the incidence of bloodstream infection (BSI) among patients undergoing hematopoietic stem cell transplantation (HSCT) for teeth indicated for extraction., Methods: Patients who underwent HSCT at Toranomon Hospital (Tokyo, Japan) between January 2017 and December 2019 were retrospectively evaluated. The incidence of BSI among patients with teeth indicated for extraction who did not undergo extraction (oral high-risk group) and patients who did not have this risk (oral low-risk group) was compared., Results: Among the 191 consecutive patients included in this study, 119 patients were classified as undergoing high-risk transplantation. BSI after HSCT was observed in 32 out of 60 (53.3%) patients and 56 out of 131 (42.7%) patients in the oral low-risk and oral high-risk groups, respectively (p = 0.173). Multivariable analyses revealed that the presence of > 3 teeth as intraoral sources of infection and age over 50 years were determinants of BSI originating from the oral cavity after engraftment (odds ratio [OR], 9.11; 95% confidential interval [CI] 2.27-36.61]; p = 0.002; OR, 3.22; CI [1.47-7.08], p = 0.004, respectively)., Conclusion: In patients undergoing HSCT, the presence of less than three intraoral sources of infection did not affect the incidence of BSI after HSCT., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although more than half of the habitual smokers recognize that they want to quit smoking cigarettes, approximately half have failed to quit and experienced distress relapse; therefore, there is an urgent need to focus on these populations. When chronic behavior occurs, it is necessary to view the behavior in the context of the entire life of the person involved, considering the history of the person. In this study, we aimed to describe experiences with smoking from the onset to the present and the need for smoking cessation among habitual smokers in Japan and to explore efforts to address them., Methods: Semi-structured interviews that lasted for 55-90 min were conducted with the cooperation of 16 habitual smokers who smoked cigarettes daily. The content of the interviews included demographic characteristics, experiences with smoking from the onset to the present, whether they have attempted to quit and related experiences, and their thoughts on smoking. Interviews were transcribed verbatim and analyzed qualitatively. The Medical Research Ethics Review Committee of Jikei University approved this study (approval number: 33-384(11008))., Results: The participants were aged 26-59 years (mean ± SD: 40.8 ± 8.9 years) and included 10 men and 6 women. The participants started smoking between age 13 and 24 years. The highest number of cigarettes smoked in the participants' lives ranged from 10 to 80 daily, and 12 participants had attempted to quit smoking so far without success. Regarding experiences with smoking from the onset to the present, four themes of "expand one's world," "unconscious attachment," "attempts and failures," and "losing oneself" were extracted. Regarding the need for smoking cessation, four themes of "empowerment from experts," "peer interaction," "social commitment," and "recovery of confidence" were extracted., Conclusion: To support smoking cessation from the perspective of habitual smokers, in addition to improvements through the existing approaches, it is important to recover their confidence using ongoing activities in peer groups according to the target background and support from experts incorporating visual assessments of lung function, along with multiple short-term goals. It is also necessary to raise awareness in communities through activities., (© 2023. The Author(s).)

Background: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items., Methods: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood., Results: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort., Conclusions: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome., (© 2022. The Author(s).)

Background: Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse., Methods: This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors., Results: Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively)., Conclusion: The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Physical activity is reported to prevent metabolic syndrome. However, it is unclear whether exercise or daily physical activity is more beneficial for residents of semi-mountainous areas. This study aimed to identify whether daily physical activity is more beneficial than exercise for the prevention of metabolic syndrome among middle-aged and older residents in semi-mountainous areas., Methods: We analyzed secondary data of 636 people who underwent a specific health checkup in a semi-mountainous area of Japan. Physical activity was classified into four types: inactivity (I-type; without exercise and without daily physical activity), only exercise (E-type; with exercise and without daily physical activity), only daily physical activity (D-type; without exercise and with daily physical activity), and full physical activity type (F-type; with exercise and with daily physical activity). We compared the means of risk factors for metabolic syndrome by these four types, followed by logistic regression analysis, to identify whether and to what extent the D-type was less likely to have metabolic syndrome than the E-type., Results: The prevalence of metabolic syndrome was 28.5% (men 45.7%, women 15.8%). The proportions of men with exercise and daily physical activity were 38.7% and 52.8%, respectively. For women, the proportions were 33.0% and 47.1%, respectively. In women, the D-type had the significantly lowest BMI, smallest waist circumference, highest HDL-C, and lowest prevalence of metabolic syndrome of the four types; the same was not observed in men. Additionally, D-type activity was more strongly associated with a reduced risk of metabolic syndrome than E-type activity in women (adjusted odds ratio 0.24; 95% confidence interval 0.06-0.85, P = 0.028)., Conclusions: Compared to middle-aged and older women residents with exercise in a semi-mountainous area of Japan, those with daily physical activity may effectively prevent metabolic syndrome.

Background: The aim of the present study was to clarify the prevalence of immunosuppressive drug use and outcomes in elderly and non-elderly patients with primary membranous nephropathy (MN) in nationwide real-world practice in Japan., Patients and Methods: Between 2009 and 2010, 374 patients with primary nephrotic syndrome were enrolled in the cohort study (The Japan Nephrotic Syndrome Cohort Study, JNSCS), including 126 adult patients with MN. Their clinical characteristics were compared with those of nephrotic patients with primary MN registered in a large nationwide registry (The Japan Renal Biopsy Registry, J-RBR). Outcomes and predictors in the elderly (≥ 65 years) and non-elderly groups were identified., Results: Similar clinical characteristics were observed in JNSCS patients and J-RBR patients (n = 1808). At the early stage of 1 month, 84.1% of patients were treated with immunosuppressive therapies. No significant differences were observed in therapies between age groups. However, elderly patients achieved complete remission (CR) more frequently than non-elderly patients, particularly those treated with therapies that included corticosteroids. No significant differences were noted in serum creatinine (sCr) elevations at 50 or 100%, end-stage kidney disease, or all-cause mortality between age groups. Corticosteroids were identified as an independent predictor of CR (HR 2.749, 95%CI 1.593-4.745, p = 0.000) in the multivariate Cox's model. sCr levels, hemoglobin levels, immunosuppressants, clinical remission, and relapse after CR were independent predictors of sCr × 1.5 or × 2.0., Conclusion: Early immunosuppressive therapy including corticosteroids for primary MN showed better remission rates in elderly patients in a nationwide cohort study.

Background: Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan., Methods: A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model., Results: Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN., Conclusions: Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.

Background: Early childhood caries (ECC) affects children across Japan and throughout the world. Thus, it is important to identify dietary and dental care habits that either promote oral health or cause ECC. The objective of this study was to identify protective and risk factors associated with ECC in Japan., Methods: In a typical rural Japanese community, we selected children born between 2004 and 2008 who had received checkups at their community health center including oral examinations conducted by dentists. We obtained data from children's records and from a questionnaire filled out by parents. We enrolled only children who at their checkup for 18-month-olds had no caries, and we obtained data about them at their checkup for 3-year-olds. We classified children as either having caries (treated or untreated) or being caries-free. We conducted bivariate analyses using data on child/family demographic characteristics, child's dietary habits, and child/parental oral health habits. We also conducted logistic regression analysis to control for variables and identify predictors of the presence/absence of caries., Results: Five hundred sixty six children (278 boys, 288 girls) were enrolled and followed. After 2 years, 173 children (30.6%) presented with caries. Logistic regression analysis predicting caries at follow-up identified the interaction term "bottlefed overnight and brushed irregularly" at 18 months of age as a highly significant predictor of developing caries-adjusted odds ratio (AOR) of 14.27, 95% confidence interval (CI) 1.02-199.71. Two variables measured at follow-up were also significant predictors: having low levels of dental plaque (AOR 2.41, 95% CI 1.34-4.35) and having a mother who had untreated caries (AOR 1.84, 95% CI 1.09-3.12)., Conclusion: Public health efforts should encourage parents to eliminate bottle feeding overnight and promote brushing twice daily as children's teeth begin to erupt. Greater efforts should be made to teach parents and daytime caregivers how to brush effectively to remove all plaque. Health professionals should pay close attention to mothers' oral health status. Mothers with caries should receive prompt treatment and be assisted in developing better dietary and oral health habits that will benefit themselves and their children. Policies and programs should focus more on family oral health rather than just child oral health.

Background: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are the leading causes of acute respiratory illness in children. Clinical burden of each infection on the respiratory distress in asthmatic patients remains unclear. The purpose of the study was to clarify the effect of these infections on the severity of asthmatic children in the seasonal outbreaks., Methods: A total of 1,217 pediatric inpatients with hMPV (n = 114) or RSV (n = 1,103) infection in Yamaguchi prefecture, Japan, between 2011 and 2014 were enrolled. Bronchial asthma was defined as having more than 3 episodes of wheezing illness over 1 year of age. Infection was determined by the positive antigen test for each virus in the nasal specimens., Results: The number of patients peaked at age 12-15 months in hMPV infection and at age 0-3 months in RSV infection. The proportion of hypoxic patients (40-50%) did not differ at any age between hMPV-infected and RSV-infected children. In the analysis of date from > 1 year old patients with hypoxia, hMPV-infection group was older (P = 0.036), and more frequently had history of asthma (P = 0.015) or abnormal chest roentgenogram (P < 0.001) than RSV-infection group. Multivariate analysis indicated that the hypoxia-associated factors were history of asthma in both hMPV (odds ratio [OR]: 15.8; P < 0.001) and RSV infections (OR, 2.2; P = 0.005), higher body temperature in hMPV infection (OR, 2.2; P = 0.009), and younger age in RSV infection (OR, 1.4; P = 0.004)., Conclusions: Outbreaks of hMPV, rather than, RSV infection may have a greater impact on the development of hypoxic respiratory illness in asthmatic children.

Background In patients with chronic kidney disease (CKD), prevalence of sleep apnoea syndrome (SAS) is reported to be markedly high. However, the factors associated with severity of SAS in such patients rarely have been reported. Methods This was a cross-sectional study of 100 stable non-dialysis patients with CKD who attended a CKD educational programme from April 2014 to August 2015. Diagnosis of SAS and its severity were assessed using a type-3 portable monitor. Results Eighty-six men and 14 women with a mean age of 71.6 ± 9.7 years were included. Mean apnoea-hypopnoea index (AHI) was 26.0 ± 13.8. Severe SAS was seen in 39 patients. Significant differences in brain natriuretic peptide (BNP) level (213.6 ± 329.6 pg/mL vs 107.8 ± 141.3 pg/mL, P < 0.05) and cardiothoracic ratio (CTR, 52.4% ± 6.3% vs 49.6% ± 5.7%, P < 0.05) were seen between patients with and without severe SAS. After adjusting for various parameters, BNP level, CTR, and diameter of the inferior vena cava at the end of inhalation were found to correlate with AHI. Conclusions In patients with CKD, prevalence of severe SAS is extremely high. In these patients, fluid retention, rather than systolic or diastolic function, correlates with severity of SAS.

Thrombocytopenia, anasarca, myelofibrosis, renal dysfunction and organomegaly (TAFRO) syndrome is a variant of Castleman's disease recently identified in Japan. A 73-year-old man was diagnosed with TAFRO syndrome according to clinical findings, and his symptoms improved after corticosteroid therapy. Ten months later, lymphadenopathy worsened during tapering of corticosteroids. Histological findings of abdominal lymph nodes showed diffuse large B-cell lymphoma. After 6 cycles of R-CHOP therapy, he has remained in sustained complete remission. This is a rare case of the development of malignant lymphoma during the treatment of TAFRO syndrome, which suggests an association between diffuse large B-cell lymphoma and TAFRO syndrome.

Leptospira spp. are the causative agents of a worldwide zoonosis, leptospirosis, maintained by various mammals. Each Leptospira serovar is frequently associated with a particular maintenance host, and recently, Leptospira genotype-host association has also been suggested to limit serovars to restricted areas. We investigated the molecular characteristics of L. interrogans and L. borgpetersenii which were isolated from small feral and wild animals in four East Asian states using multiple-locus variable-number tandem repeat analysis (MLVA). MLVA using 11 loci was performed on 110 L. interrogans serogroups from Japan (79 strains of 5 serogroups from 3 animal species), Philippines (21; 3; 2), Taiwan (7; 2; 3), and Vietnam (3; 1; 1). A MLVA method using 4 loci for L. borgpetersenii was established and performed on 52 isolates from Japan (26; 3; 7), Philippines (13; 1; 2), and Taiwan (13; 1; 3). In L. interrogans, serogroups Autumnalis and Hebdomadis appeared more genetically diverse than serogroups Bataviae, Grippotyphosa, Icterohaemorrhagiae, Pomona, or Pyrogenes. The former serogroup strains with the exception of one Hebdomadis strain were isolated from Apodemus speciosus while all the latter serogroup strains with the exception of Grippotyphosa were isolated from Rattus norvegicus. L. borgpetersenii was isolated from at least 11 animal species while L. interrogans was isolated from five species, which might suggest a wider host range for L. borgpetersenii. Broad host preference in a single genotype was also observed, which colonized not only different species of the same genera but also multiple animal genera. This study demonstrates that there may be variability in the range of genetic diversity among different Leptospira serogroups, which may be attributed to maintenance host animals and environmental factors., (Copyright © 2015. Published by Elsevier B.V.)

Aim: To reveal the prevalence of nursing students with special educational needs in Japan., Method: A mail survey of 833 nursing programs was conducted. Nurse educators were asked to report on their program's profiles and the number of extremely difficult students who belonged to the March 2011 class of graduates. They were also asked to fill a modified questionnaire developed by the Ministry of Education, Culture, Sports, Science and Technology about each extremely difficult student., Results: Among the 14,325 students enrolled the class of 2011, 146 students (1.02%) were identified as having one or more special educational needs for "listening," "speaking," "reading," "writing," "math," "reasoning," "inattentiveness," "hyperactivity/impulsivity," or "social interaction/restricted interests." The most prevalent need was "social interaction/restricted interests," followed by "listening" and "inattentiveness." These students had the most difficulty participating in "nursing care for patients during clinical practicum.", Conclusion: The proportion of nursing students with special educational needs is small but may have a large impact on the clinical practicum. Evaluation and support systems at multiple levels, including entrance examinations, course placement, and special educational programs, are warranted., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Triple-negative breast cancer (TNBC) is negative for all three markers, namely the hormone sensitivity receptors: estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). TNBC accounts for approximately 15% of all primary breast cancer cases. In general, patients with this disease have a higher risk of recurrence and a poorer prognosis compared with those with other subtypes of breast cancer. Patients with TNBC are defined as those for whom endocrine or anti-HER2 therapy are not indicated due to poor response. It is a heterogeneous disease group that shows various characteristics. There is a group that achieves a complete response to chemotherapy and has an excellent prognosis, a group that does not respond to chemotherapy and has a poor prognosis, and a group that has an excellent inherent prognosis and does not need chemotherapy. The subdivision of TNBC cases based on the prognosis and response to therapy is an issue for the future. In addition to classifying TNBC into basal and non-basal types by testing cytokeratin 5/6 (CK5/6) and epidemic growth factor receptors (EGFR) by the immunohistochemical staining method, Ki-67 may predict sensitivity to anticancer agents and a change in Ki-67 before and after therapy may potentially predict prognosis. Patients with a non-pathologic complete response (non-pCR) to preoperative chemotherapy have a high risk of early recurrence, and measures to deal with it are therefore needed. At present, the most commonly used perioperative chemotherapy is sequential combination therapy of an anthracycline drug and a taxane drug; however, it is limited because the pathologic complete response(pCR)rates following preoperative chemotherapy range from 30 to 40%. There is also an urgent need to develop a regimen that will overcome this problem. In association with BRCA gene mutations, sensitivity to DNA-damaging anticancer agents may lead to promising therapies. However, unfortunately, the use of DNA-damaging agents such as cisplatin and carboplatin is not covered by health insurance in Japan. Various new molecular targeted drugs aimed at blocking cell proliferation factors are expected to be developed in the future. Here we have summarized the current status and issues based on the clinical experience with the diagnosis and treatment of TNBC.

Background: Mucins are high-molecular-weight glycoproteins that play important roles in carcinogenesis or tumor invasion. The authors investigated the expression of mucins in ampullary cancer., Methods: MUC1 and MUC2 expressions were examined using immunohistochemistry. Tissue samples were obtained from 32 patients with ampullary cancer who underwent resection at Yamagata University Hospital, Japan. The authors classified the cases with ampullary cancer into 2 subtypes--pancreatobiliary type (PB type) and intestinal type (I type)--using H&E, MUC1, and MUC2 staining. Then, the authors made a comparison of the clinicopathologic data of the 2 subtypes., Results: Fourteen patients (44%) were classified as PB type and 18 patients (56%) as I type. The PB-type group had significantly worse histopathologic characteristics than the I-type group in nodal involvement (PB type 57% vs I type 22%; P = .04), perineural invasion (PB type 50% vs I type 17%; P = .04), duodenal invasion (PB type 100% vs I type 33%; P = .01), and pancreatic invasion (PB type 71% vs I type 33%; P = .03). The PB-type group had significantly worse outcome than the I-type group (5-year survival: PB type 40% vs I type 72%; P = .03)., Conclusion: PB-type ampullary cancers were more aggressive than I-type carcinomas. MUC1 and MUC2 expression was useful for classification as PB or I type.

A wide diversity of domesticated chicken breeds exist due to artificial selection on the basis of human interests. Miniature variants (bantams) are eminently illustrative of the large changes from ancestral junglefowls. In this report, the genetic characterization of seven Japanese miniature chicken breeds and varieties, together with institute-kept Red Junglefowl, was conducted by means of typing 40 microsatellites located on 21 autosomes. We drew focus to genetic differentiation between the miniature chicken breeds and Red Junglefowl in particular. A total of 305 alleles were identified: 27 of these alleles (8.9%) were unique to the Red Junglefowl with high frequencies (>20%). Significantly high genetic differences (F(ST)) were obtained between Red Junglefowl and all other breeds with a range of 0.3901-0.5128. Individual clustering (constructed from combinations of the proportion of shared alleles and the neighbour-joining method) indicated high genetic divergence among breeds including Red Junglefowl. There were also individual assignments on the basis of the Bayesian and distance-based approaches. The microsatellite differences in the miniature chicken breeds compared to the presumed wild ancestor reflected the phenotypic diversity among them, indicating that each of these miniature chicken breeds is a unique gene pool.

We have analyzed 105 autosomal polymorphic short tandem repeat (STR) loci for nine East and South-eastern Asian populations (two Japanese, five Han Chinese, Thai, and Burmese populations) and a Caucasian population using a multiplex PCR typing system. All the STR loci are genomewide tetranucleotide repeat markers of which the total number of observed alleles and the observed heterozygosity were 756 and 0.743, respectively, for Japanese populations. Phylogenetic analysis for these allele frequency data suggested that the Japanese populations are more closely related with southern Chinese populations than central and/or northern ones. STRUCTURE program analysis revealed the almost clearly divided and accountable population structure at K=2-6, that the two Japanese populations always formed one group separated from the other populations and never belong to different groups at K> or =3. Furthermore, our new allele frequency data for 91 loci were analyzed with those for 52 worldwide populations published by previous studies. Phylogenetic and multidimensional scaling (MDS) analyses indicated that Asian populations with large population size (six Han Chinese, three Japanese, two Southeast Asia) formed one distinct cluster and are closer to each other than other ethnic minorities in east and Southeast Asia. This pattern may be the caviar of comparing populations with greatly differing population sizes when STR loci were analyzed.

Chylous fistulas in cases treated surgically for breast cancer only, are rare. We encountered four chylous fistula cases after breast cancer operations out of a total of 851 cases, all of which involved the left breast. Chylous fistulas were confirmed by axillary white fluid and were unrelated to obesity, surgical method or the area of axillary lymph node dissection. All four cases of chylous fistulas were successfully treated conservatively, with no special dietary control and no surgical treatment.

In line with the Gifu University's initiative to map the Japanese quail genome, a total of 100 Japanese quail microsatellite markers isolated in our laboratory were evaluated in a population of 20 unrelated quails randomly sampled from a colony of wild quail origin. Ninety-eight markers were polymorphic with an average of 3.7 alleles per locus and a mean heterozygosity of 0.423. To determine the utility of these markers for comparative genome mapping in Phasianidae, cross-species amplification of all the markers was tested with chicken and guinea fowl DNA. Amplification products similar in size to the orthologous loci in quail were observed in 42 loci in chicken and 20 loci in guinea fowl. Of the cross-reactive markers, 57.1% in chicken and 55.0% in guinea fowl were polymorphic when tested in 20 birds from their respective populations. Five of 15 markers that could cross-amplify Japanese quail, chicken, and guinea fowl DNA were polymorphic in all three species. Amplification of orthologous loci was confirmed by sequencing 10 loci each from chicken and guinea fowl and comparing with them the corresponding quail sequence. The microsatellite markers reported would serve as a useful resource base for genetic mapping in quail and comparative mapping in Phasianidae.

Experimental studies suggest various features of anticancer activity of green tea including inhibitory effect of tumor invasion and metastasis. This study was conducted to examine the association between regular green tea consumption prior to diagnosis and subsequent risk of breast cancer recurrence. The Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) was started in 1988, in which information on lifestyle has routinely been collected from all first-visit outpatients by questionnaire. A total of 1160 new surgical cases of female invasive breast cancers with HERPACC information diagnosed between June 1990 and August 1998 were followed up through December 1999, and the risk (hazard ratio: HR) of recurrence was assessed with reference to daily green tea consumption using a Cox proportional hazard model. During 5264 person-years of follow-up, 133 subjects (12%) were documented to suffer recurrence of breast cancer. A decreased HR for recurrence adjusted for stage was observed with consumption of three or more daily cups of green tea (HR=0.69, 95% confidence interval (95%CI)=0.47-1.00). Particularly in stage I, the HR was decreased statistically significantly (HR=0.43, 95%CI=0.22-0.84). A similar tendency was observed for stage II subjects, but was not present among more advanced stages. Although careful interpretation is needed, these results suggest the possibility that regular green tea consumption may be preventive against recurrence of breast cancer in early stage cases.

Background: Catechol-O-methyltransferase (COMT) inactivates the estradiol metabolites, 2-hydroxy estradiol and 4-hydroxy estradiol. To date, three studies in Caucasians and one study in Chinese have been conducted to determine the association with breast cancer risk of a functional polymorphism (G-to-A, Val158Met) of this enzyme, but the results were inconsistent. In order to examine the impact of this polymorphism on breast cancer risk in Japan, a case-control study was conducted, at Aichi Cancer Center Hospital., Methods: The cases were 150 patients with histologically confirmed breast cancer who had been diagnosed within 4 years before enrollment at this hospital. The controls were 165 non-cancer patients, mainly from the gastroenterology and breast surgery clinics at the hospital. COMT-H (Val) is the wild-type allele, with high enzyme activity, while the COMT-L (Met) allele has low activity. Genotyping was conducted by a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method., Results: The allele frequency of COMT-L was 36.0% for cases and 33.0% for controls. Age-adjusted odds ratios relative to the COMT-HH genotype were 1.46 (95% confidence interval [CI], 0.90-2.36) for COMT-HL, and 0.99 (95% CI, 0.49-2.02) for the COMT-LL genotype. Significant odds ratios were not observed for any subgroup stratified by menopausal status, age at menarche, age at birth of first child, body mass index, and breast cancer history of mother and/or sister(s)., Conclusion: The present study suggested that any association of the COMT polymorphism with breast cancer risk is limited in Japanese.

We devised a multiplex polymerase chain reaction (PCR) amplification and loading system for the convenient typing of 168 short tandem repeat (STR) polymorphic markers in a commercially available screening primer set for human linkage analysis. We genotyped all these 168 STR loci with 32 healthy unrelated Japanese, calculated allele frequencies at each STR locus, and performed three kinds of tests for Hardy-Weinberg equilibrium (HWE). Significant deviations from HWE in all three tests were observed at only three loci, and the average heterozygosity in the Japanese (0.733) was slightly lower than that in Caucasians (0.773). We also examined 32 Caucasians at some selected loci, to be compared with Japanese. Some markers showed greatly different heterozygosities or allelic distributions in Japanese and Caucasian populations. In two groups of STRs, those with and without irregular alleles (or interalleles), the former had a higher proportion of bimodal allelic distribution and possessed more alleles per locus than the latter. However, no significant differences in the observed and expected heterozygosities, or in the powers of discrimination, were found between the two groups. The present basic study of allele frequency databases of these STRs will contribute to further applications in forensic science and human genetics.

In population genetics, the absence of the departure from Hardy-Weinberg equilibrium (HWE) is usually tested when a population study of a certain DNA marker is performed to show the observed allele frequencies represent those of the whole population. The goodness-of-fit test (chi 2 test) assuming chi 2 approximation has frequently been used with classical blood type markers having a few alleles. However, new tests suitable for DNA markers having many alleles, such as homozygosity test, likelihood ratio test and Guo-Thompson's (G-T') exact test, have recently been devised. In the present study, appropriate tests for HWE was studied using population data of 206 Japanese individuals with 9 different short tandem repeat loci. Firstly, we found that the recommendation of NRC II for the treatment of rare allele frequencies (If a bin in the database contains fewer than five entries, it is pooled with adjacent bins so that no bin has fewer than five) is quite reasonable for personal identification in forensic sciences. Secondly, we proposed that homozygosity test, likelihood ratio test and G-T's exact test should be applied altogether and HWE of the sample population should be valid only when all of the three tests were cleared.

A genetic polymorphism was identified in the 5'-flanking region of human CYP1A2 gene, and its effect on the transcriptional activation of the CYP1A2 gene was investigated. Nucleotide sequence analysis revealed the existence of a point mutation from guanine (wild type) to adenine (mutated type) at position -2964 in the gene. This point mutation was detected by a polymerase chain reaction-restriction fragment length polymorphism method using DdeI or BslI restriction enzyme, and was proven to be genetically inherited. Allele frequency in 116 Japanese subjects showed 0.77 and 0.23 for the wild and mutated types of allele, respectively. The point mutation caused a significant decrease of CYP1A2 activity measured by the rate of caffeine 3-demethylation in Japanese smokers (p<0.05). Gel retardation analysis showed the existence of protein bound to the polymorphic locus. These results suggest that this polymorphism is a causal factor of decreased CYP1A2 inducibility.

Nine tetranucleotide short tandem repeat (STR) loci, D3S1358, vWA, FGA TH01, TPOX, CSF1PO, D5S818, D13S317 and D7S820, were analyzed in the Japanese population with a newly released kit for personal identification using multiplex PCR with fluorescent-labeled primers following capillary electrophoresis. The observed heterozygosities were 0.67, 0.77, 0.82, 0.61, 0.62, 0.73, 0.78, 0.81 and 0.74, respectively, and the combined discrimination power of the nineplex was 0.9999999991. None of the nine loci deviated from Hardy-Weinberg equilibrium expectations using the chi-square test, homozygosity test, likelihood ratio test and exact test after the grouping of the alleles. The nine STR loci allele frequencies were significantly different from those of other ethnic populations.

Morphological effects of acrylamide (AC) on the peripheral nerves in normal and neurofilament (NF)-deficient (Quv) Japanese quails were investigated. AC (100 mg/kg) was injected intraperitoneally every other day. After the birds manifested neurological signs, they were necropsied (after 10 approximately 21 AC injections) and the sciatic and tibial nerves were examined. In both normal and Quv qualis, AC produced axonopathy with a distal-proximal progression. In AC-intoxicated normal quails, the nerve fiber pathology was characterized by typical Wallerian-like degeneration, consisting of axonal degeneration, myelin breakdown, macrophage migration. Schwann cell proliferation and regeneration of nerve fibers. Ultrastructurally, AC-induced NF accumulation was detected in the axon of myelinated nerve fibers. In AC-intoxicated Quv qualis, axonal degeneration with accumulation of membranous organelles occurred; however, sequential events of Wallerian-like degeneration were not as prominent as in AC-intoxicated normal qualis. These results demonstrated that NF-deficient Quv quails are sensitive to neurotoxic effects of AC. On the other hand, the different pathology of AC-intoxicated normal and Quv qualis indicates the presence or absence of NFs influences the appearance and extent of AC axonopathy.

Caffeine has been used as a metabolic probe to determine the relative levels of CYP1A2 activity in different individuals, since this compound is specifically 3-demethylated by CYP1A2. Urine specimen obtained at a 4-5-h interval after caffeine ingestion from 205 Japanese were analyzed using the [1,7-dimethyluric acid + 1,7-dimethylxanthine]/caffeine (1,3,7-trimethylxanthine) ratio, which better correlated with the rate constant for caffeine 3-demethylation than other ratios. The probit analyses of nonsmokers (n = 147) and smokers (n = 58) suggested that the CYP1A2 activity was not normally distributed and appeared bimodal. The breakpoints were at 5.0 and 6.0 of (1,7-dimethyluric acid + 1,7-dimethylxanthine)/1,3,7-trimethylxanthine ratio in nonsmokers and smokers, respectively. The bimodal probit plot suggested the existence of poor and extensive phenotypes. The percentage of individuals with the poor phenotype in Japanese was 14.1%. Induction of CYP1A2 by cigarette smoking was confirmed by the higher molar ratio observed in smokers (P < 0.0001). The CYP1A2 ratio was also higher in males than in females (P = 0.04). A reproducibility study of 12 subjects in an 11 month interval period showed that intraindividual variability did not alter this CYP1A2 phenotypic classification. Family study in eight pedigrees suggested that the poor phenotype of CYP1A2 inherited as an autosomal recessive trait. The sequences of CYP1A2 gene from poor and extensive metabolizers were analyzed. Although no differences of nucleotide sequence were observed in exons, exon-intron junctions and 5'-flanking regions (up to -2.6 kilobases) of CYP1A2 gene between each phenotype, there were some sequences which differed from the previous reported data. This is the first report in which the CYP1A2 phenotype and a genetic polymorphism in the CYP1A2 gene were comparably investigated.

In the present study, the hard palate of Japanese and Indian children was investigated. These children lived in different geographical areas and have different cranial characteristics, pronunciation and eating habits. Fifty-one Japanese children (26 boys and 25 girls, 3 years of age) and 66 Indian school children (31 boys and 35 girls, 5-7 years of age). The maxillary negative cast models were observed and three-dimensional measurements were taken of the hard palate with moiré Topography. The following results were obtained. 1. The palatal width and length in Japanese children was larger than the Indian children, but not in palatal height. The palatal height was significantly larger in the Indian children than in the Japanese children. 2. Observation of the moiré fringes on the deepest palate by moiré Topography shows that the Japanese children and Indian girls have a higher incidence of Crosswise type than Lengthwise type. The Indian boys have a slightly higher incidence of Lengthwise type than Crosswise type. The girls have a higher incidence of the Butterfly and Separate types than the boys. 3. The anteroposterior location on the deepest palate by moiré Topography: the Japanese children have significantly higher incidences of anterior location than the Indian children. Changes of anteroposterior location between the ages of 5 and 7 in the Indian children: the prevalence of posterior location appears to increase with age. 4. The hard palate shapes of the Japanese children appear to be broad and shallow, but those of the Indian children appear to be narrow and deep. This difference appears to be more remarkable in the boys. The shape and size of the hard palate appears to be due to genetic differences, in addition to the weather conditions, pronunciation and eating habits.

We report the first case in Japan, i.e., the first case among oriental subject of Farber's disease. This is a rare disorder of lipid metabolism in infancy subsequent to a genetically-determined defect in ceramide degradation. Main features are characterized clinically by hoarseness, joint swelling, subcutaneous nodules and retarded psychomotor development. Lipid analysis and pathological investigation on the material obtained from a subcutaneous nodule confirmed clearly the presence of ceramide and intracytoplasmic inclusion bodies characteristic for Farber's disease. In this case, we experienced also corneal opacity and striking abnormalities in electroencephalogram, which have apparently not been noticed in the 17 cases hitherto reported.