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OBJECTIVE: To determine the critical value for the standard deviation score (SDS) of waist–hip ratio (WHR)/height (Ht), as an age-adjusted measure of body fat distribution, in relation to occurrence of biochemical complications in obese girls. DESIGN: Cross-sectional, clinical study. The (WHR/Ht)-SDS was calculated as described previously. Obese girls were classified into two groups according to the occurrence of abnormal values in either serum triglyceride, alanine aminotransferase or insulin level. The criteria for obesity were subjected to the receiver operating characteristic (ROC) analysis. SUBJECTS: One-hundred and twenty-four outpatient Japanese obese girls, ranging in age from 9 to 15 y. MEASUREMENTS: Height, body weight, waist girth and hip girth as anthropometric measures. Percentage overweight, waist girth, WHR and (WHR/Ht)-SDS as criteria for obesity. Clinical laboratory analysis for fasting blood samples of obese children. RESULTS: Fifty-nine girls were classified into the no complication group, and 65 girls into the complication group. Those with complications were older, more obese, and their waist girth and WHR were larger, than the girls without complications. The (WHR/Ht)-SDS was >2-fold higher and lipoprotein profile was more atherogenic in the complication group than in the no complication group. Among the four criteria of obesity, (WHR/Ht)-SDS gave the ROC curve skewed furthest into the top left corner of the diagram. Both sensitivity and specificity for (WHR/Ht)-SDS were >80% at the critical value of 2.00. The sensitivity for waist girth was as high as that for specificity for the rest of the criteria were <80%. CONCLUSION: Only (WHR/Ht)-SDS showed high enough sensitivity and specificity to predict metabolic derangement in the present obese girls. (WHR/Ht)-SDS can serve as the diagnostic criterion that classifies obesity in Japanese adolescent girls into two types. [ABSTRACT FROM AUTHOR]

Assesses migraine therapies in Japan. Increase in the knowledge about migraine in Japan; Opportunities for studies for the use of triptan therapies in migraineurs; Improvement of the trial methodology and regulatory procedures to ensure results for the study of the therapies.

Transitional medicine refers to the seamless continuity of medical care for patients with childhood-onset diseases as they grow into adulthood. The transition of care must be seamless in medical treatment as the patients grow and in other medical aids such as subsidies for medical expenses in the health care system. Inappropriate transitional care, either medical or social, directly causes poorer prognosis for many early-onset diseases, including primary dyslipidemia caused by genetic abnormalities. Many primary dyslipidemias are designated as intractable diseases in the Japanese health care system for specific medical aids, as having no curative treatment and requiring enormous treatment costs for lipid management and prevention of complications. However, there are problems in transitional medicine for primary dyslipidemia in Japan. As for the medical treatment system, the diagnosis rate remains low due to the shortage of specialists, their insufficient link with generalists and other field specialists, and poor linkage between pediatricians and physicians for adults. In the medical care system, there is a mismatch of diagnostic criteria of primary dyslipidemias between children and adults for medical care expense subsidization, as between The Program for the Specific Pediatric Chronic Diseases and the Program for Designated Adult Intractable Diseases. This could lead some patients subsidized in their childhood to no longer be under the coverage of the aids after transition. This review intends to describe these issues in transitional medicine of primary dyslipidemia in Japan as a part of the efforts to resolve the problems by the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labour and Welfare of Japan.

Aim: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan., Method: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals., Results: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL., Conclusion: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.

Aim: This study aimed to elucidate the gene and lipid profiles of children clinically diagnosed with familial hypercholesterolemia (FH)., Methods: A total of 21 dyslipidemia-related Mendelian genes, including FH causative genes (LDLR, APOB, and PCSK9) and LDL-altering genes (APOE, LDLRAP1, and ABCG5/8), were sequenced in 33 Japanese children (mean age, 9.7±4.2 years) with FH from 29 families., Results: Fifteen children (45.5%) with pathogenic variants in LDLR (eight different heterozygous variants) and one child (3.0%) with the PCSK9 variant were found. Among 17 patients without FH causative gene variants, 3 children had variants in LDL-altering genes, an APOE variant and two ABCG8 variants. The mean serum total cholesterol (280 vs 246 mg/dL), LDL-cholesterol (LDL-C, 217 vs 177 mg/dL), and non-HDL cholesterol (228 vs 188 mg/dL) levels were significantly higher in the pathogenic variant-positive group than in the variant-negative group. In the variant-positive group, 81.3% of patients had LDL-C levels ≥ 180 mg/dL but 35.3% in the variant-negative group. The mean LDL-C level was significantly lower in children with missense variants, especially with the p.Leu568Val variant, than in children with other variants in LDLR, whereas the LDL-altering variants had similar effects on the increase in serum LDL-C to LDLR p.Leu568Val., Conclusion: Approximately half of the children clinically diagnosed with FH had pathogenic variants in FH causative genes. The serum LDL-C levels tend to be high in FH children with pathogenic variations, and the levels are by the types of variants. Genetic analysis is useful; however, further study on FH without any variants is required.

Sitosterolemia is an inherited metabolic disorder characterized by increased levels of plant sterols, such as sitosterol. This disease is caused by loss-of-function genetic mutations in ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively), both of which play important roles in selective excretion of plant sterols from the liver and intestine, leading to failure to prevent absorption of food plant sterols. This disorder has been considered to be extremely rare. However, accumulated clinical data as well as genetics suggest the possibility of a much higher prevalence. Its clinical manifestations resemble those observed in patients with familial hypercholesterolemia (FH), including tendon xanthomas, hyper LDL-cholesterolemia, and premature coronary atherosclerosis. We provide an overview of this recessive genetic disease, diagnostic as well as therapeutic tips, and the latest diagnostic criteria in Japan.

Familial hypercholesterolemia (FH) is an inherited disorder with retarded clearance of plasma LDL caused by mutations of the genes involved in the LDL receptor-mediated pathway and most of them exhibit autosomal dominant inheritance. Homozygotes of FH (HoFH) may have plasma LDL-C levels, which are at least twice as high as those of heterozygous FH (HeFH) and therefore four times higher than normal levels. Prevalence of HoFH had been estimated as 1 in 1,000,000 before but more recent genetic analysis surveys predict 1 in 170,000 to 300,000. Since LDL receptor activity is severely impaired, HoFH patients do not or very poorly respond to medications to enhance activity, such as statins, and have a poorer prognosis compared to HeFH. HoFH should therefore be clinically distinguished from HeFH. Thorough family studies and genetic analysis are recommended for their accurate diagnosis.Fatal cardiovascular complications could develop even in the first decade of life for HoFH, so aggressive lipid-lowering therapy should be initiated as early as possible. Direct removal of plasma LDL by lipoprotein apheresis has been the principal measure for these patients. However, this treatment alone may not achieve stable LDL-C target levels and combination with drugs should be considered. The lipid-lowering effects of statins and PCSK9 inhibitors substantially vary depending on the remaining LDL receptor activity of individual patients. On the other hand, the action an MTP inhibitor is independent of LDL receptor activity, and it is effective in most HoFH cases.This review summarizes the key clinical issues of HoFH as well as insurance coverage available under the Japanese public healthcare system.

Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative allergens. These are socioeconomically important diseases that can lead to work interruptions for patients and potentially job loss. We published the first guideline for managing occupational allergic diseases in Japan. The original document was published in Japanese in 2013, and the following year (2014) it was published in English. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis, occupational anaphylaxis shock, and the legal aspects of these diseases. Providing general doctors with the knowledge to make evidence-based diagnoses and to understand the occupational allergic disease treatment policies, was a breakthrough in allergic disease treatment. Due to the discovery of new occupational allergens and the accumulation of additional evidence, we published a revised version of our original article in 2016, and it was published in English in 2017. In addition to including new knowledge of allergens and evidence, the 2016 revision contains a "Flowchart to Diagnosis" for the convenience of general doctors. We report the essence of the revised guidelines in this paper., (Copyright © 2020 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Unlabelled: Equine hepacivirus (EHcV) has been identified as a closely related homologue of hepatitis C virus (HCV) in the United States, the United Kingdom, and Germany, but not in Asian countries. In this study, we genetically and serologically screened 31 serum samples obtained from Japanese-born domestic horses for EHcV infection and subsequently identified 11 PCR-positive and 7 seropositive serum samples. We determined the full sequence of the EHcV genome, including the 3' untranslated region (UTR), which had previously not been completely revealed. The polyprotein of a Japanese EHcV strain showed approximately 95% homology to those of the reported strains. HCV-like cis-acting RNA elements, including the stem-loop structures of the 3' UTR and kissing-loop interaction were deduced from regions around both UTRs of the EHcV genome. A comparison of the EHcV and HCV core proteins revealed that Ile(190) and Phe(191) of the EHcV core protein could be important for cleavage of the core protein by signal peptide peptidase (SPP) and were replaced with Ala and Leu, respectively, which inhibited intramembrane cleavage of the EHcV core protein. The loss-of-function mutant of SPP abrogated intramembrane cleavage of the EHcV core protein and bound EHcV core protein, suggesting that the EHcV core protein may be cleaved by SPP to become a mature form. The wild-type EHcV core protein, but not the SPP-resistant mutant, was localized on lipid droplets and partially on the lipid raft-like membrane in a manner similar to that of the HCV core protein. These results suggest that EHcV may conserve the genetic and biological properties of HCV., Importance: EHcV, which shows the highest amino acid or nucleotide homology to HCV among hepaciviruses, was previously reported to infect horses from Western, but not Asian, countries. We herein report EHcV infection in Japanese-born horses. In this study, HCV-like RNA secondary structures around both UTRs were predicted by determining the whole-genome sequence of EHcV. Our results also suggest that the EHcV core protein is cleaved by SPP to become a mature form and then is localized on lipid droplets and partially on lipid raft-like membranes in a manner similar to that of the HCV core protein. Hence, EHcV was identified as a closely related homologue of HCV based on its genetic structure as well as its biological properties. A clearer understanding of the epidemiology, genetic structure, and infection mechanism of EHcV will assist in elucidating the evolution of hepaciviruses as well as the development of surrogate models for the study of HCV., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

Objective: Disaster relief workers are potentially exposed to severe stressors on the job, resulting in a variety of psychological responses. This study aims to clarify the psychological effects of disaster relief activities on Japan Ground Self-Defense Force (JGSDF) personnel following the 2011 Great East Japan Earthquake., Method: A self-report questionnaire was administered to 606 JGSDF personnel one month after completing the disaster relief mission. Posttraumatic stress responses and general psychological distress were assessed using the Impact of Event Scale-Revised (IES-R) and the K10 scales. Associations between outcome variables and independent variables (age, gender, military rank, length of deployment, and exposure to dead bodies) were measured with univariate analyses and subsequent multiple logistic regression analyses., Results: The mean (± SD) IES-R score was 6.2 (± 8.1), and the mean K10 score was 12.8 (± 4.4). In the univariate analyses, exposure to dead bodies and age were identified as significant factors for IES-R and K10 scores, (p < 0.01). However, the multiple logistic regression analyses did not reveal any significant factors although body handlers' exposure approached significance for IES-R., Conclusions: The subjects reported very low psychological responses despite the severe nature of their disaster relief activities. Several factors may account for the low levels of psychological distress and posttraumatic symptoms observed in this study.

Background: The "zero death from asthma strategy" in the medical treatment for bronchial asthma has been promoted by the Ministry of Health, Labour, and Welfare from 2006, and it indicates that medical and non-medical specialists, as well as pharmacists, should cooperate, and strives to build cooperation which is suited the actual conditions of an area. It is also important for COPD. Although hospitals in some areas cooperate with clinics and pharmacies, the overall concept of cooperation appears to be absent in most Japanese hospitals., Method: A questionnaire was administered in early March, 2012 to 477 allergology institutions, and was authorized by an educational establishment., Result: Among 246 replies from the institutions, cooperation between hospitals and clinics was carried out by 98 institutions (39.8%) specializing in bronchial asthma, and in 64 institutions (37.2%) specializing in COPD. However, cooperation tools were used in only 37 of these institutions (15.0%). The ability to fill prescriptions outside the hospital was available in 209 institutions (85.0%). One-hundred and seventeen institutions (47.6%) replied that they have no tools for hospital-pharmacy cooperation. Direct indications were written in prescriptions by 82 institutions (33.3)., Conclusion: In order to build inter-regional association and to equalize medical treatment, we suggest that developing tools and organization for cooperation between health professionals who treat patients with bronchial asthma and COPD is necessary.

In Japan, hypertriglyceridemia in children is defined as the fasting serum triglyceride of more than 140mg/dL, which is the 95th percentile value of the Japanese school-aged children. The obesity-induced hypertriglyceridemia commonly appear. As the primary hypertriglyceridemia, lipoprotein lipase deficiency and familial combined hyperlipidemia (FCHL) are important. As the secondary one, diabetic dyslipidemia is of importance. Basically, children with hypertriglyceridemia are treated just by diet and exercise therapy. Only the case who is a patient with high risk of pancreatitis or with poor control of diabetes mellitus may need drug therapy. Drug therapy should be actually started with the pediatric specialist.

Background: Appropriate nutrition during childhood is important for preventing future development of lifestyle-related diseases. The effect of feeding choice on infant growth in Japan is not known., Methods: Data from 204 healthy schoolchildren (age, 6-9 years) were obtained retrospectively from their parents by questionnaires. Breast-fed (BF) and formula-fed (FF) groups were defined as those fed only breast milk or formula milk at 4 months of age, respectively. There were 71 children (M/F, 31/40) in BF and 30 (M/F, 19/11) in FF. Anthropometric data at birth, and at 1, 4, 7, 10, 18, and 36 months of age in male and female infants were compared between the groups., Results: In male infants, height was significantly lower at 4 months, bodyweight was lower from 4 to 18 months, and body mass index (BMI) was lower from 10 to 36 months in BF than in FF. The standard deviation scores (SDS) for height, weight and BMI had a similar pattern. No significant differences were observed for these variables for female infants in BF compared with FF. Multiple regression analysis showed that birthweight, mother's pre-pregnancy weight, and infant feeding choice were significant factors associated with weight-SDS at 18 and 36 months. Feeding choice was the only factor associated with BMI-SDS at 18 months., Conclusions: Infant feeding choice had a gender-associated effect on growth during infancy. When evaluating infant growth, not only birthweight and mother's pre-pregnancy weight, but also infant feeding choice and gender should be considered., (© 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.)

An 81-year-old Japanese man had organizing pneumonia (OP), and he had worked as a painter and had a history of exposure of various paints over 20 years. The major features on computed tomography (CT) in patients were cryptogenic organizing pneumonia (COP) showing airspace consolidation, and air bronchograms were consistent finding in consolidation in right lung of S¹⁰. Such parenchymal abnormalities were clinically and pathologically diagnosed COP and the lesion was improved by corticosteroid therapy. About 1.5 years later, similar shadows emerged in new locations of right S⁴ and left S⁸, and these were bronchioloalveolar carcinoma (BAC) classified as adenocarcinoma. BAC causes similar X-ray changes to COP and inflammation accompanying BAC can also respond to corticosteroids, which may lead to delay in the diagnosis of BAC associated with COP. These radiological features lead to difficulty in making a diagnosis of new parenchymal diseases. The present patient had been painter, and metals of carcinogens were proven in both tissue of COP and BAC. Here, we reported a painter with COP and new-onset BAC who had been exposed to particles proven by elemental analysis. The combination of COP with BAC is considered uncommon, but the risk of BAC may increase when there is a history of particle inhalation.

Objective: This study was designed to elucidate whether the plasma visfatin level reflects visceral or subcutaneous fat accumulation and metabolic derangement in obese children., Methods and Procedures: Fifty-six obese Japanese children, including 37 boys and 19 girls were enrolled in the study. The age of the subjects ranged from 5 to 15 (10.2 +/- 0.3; mean +/- s.e.m.) years. The age-matched control group for measuring visfatin consisted of 20 non-obese children. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured by computed tomography. The plasma concentrations for visfatin and leptin were assayed by enzyme-linked immunosorbent assay kits., Results: The plasma visfatin level was higher in the obese (14.7 +/- 0.9 ng/ml) than in the control children (8.6 +/- 0.6 ng/ml). In a univariate analysis, the visfatin correlated significantly with age, height, body weight, waist circumference, VAT and SAT area, triglyceride (TG), insulin, and the homeostasis model assessment for insulin resistance (HOMA-R). After being adjusted for age and sex, only the VAT area retained significant partial correlation with visfatin, and in contrast the body weight, BMI-s.d., and SAT area with leptin. The plasma visfatin concentration was not correlated with leptin. The plasma visfatin levels in the control, non-metabolic syndrome (MS) (n = 49), and MS groups (n = 7) were significantly different from each other., Discussion: These results suggest that plasma visfatin level is a specific marker for visceral fat accumulation in obese children. As a good surrogate marker, plasma visfatin level can predict the VAT area in obese children.

Information about the impacts of disasters on health is useful for establishing hazard prediction maps and action plans of disaster management. This study aims at learning effective asthma management from the volcano disaster of Mount Asama eruption in Japan on September 1, 2004. We conducted a cross-sectional study to assess the acute impact of volcanic ash on asthma symptoms and their treatment changes by using a questionnaire completed by 236 adult asthmatic patients and their physicians. In the ashfall over 100g/m2 area, 42.9 percent of asthma patients suffered exacerbations, PEF decreased, asthma treatments increased, and inhalation of beta2 stimulants was used most for exacerbated asthma. Compared to severe asthma patients, mild and moderate asthma patients were most at risk. Severe asthma patients were not affected since most of them knew their asthma status was severe, and did not go outside and kept windows closed. Deteriorated asthma symptoms of wheezing, chest tightness and cough appeared in the ashfall over 100g/m2 area. Ash contained inhalable 10microm diameter particles, and included high concentrations of airway toxic substrates of silica. These data suggest that ashfall over 100 g/m2 is harmful, access to these areas by asthma patients needs to be restricted, and these areas need to improve asthma treatment. In addition, the increase in the proportion of asthma patients with wheeze and cough are diagnostic clues for ash-induced asthma in affected areas, and can be used by doctors to tell whether patients are receiving sufficient asthma treatment.

The antituberculous drug isoniazid (INH) is acetylated by N-acetyltransferase 2 (NAT2), and the frequency of INH-induced hepatotoxicity is determined by the NAT2 genotype. NAT2 genotyping is not done routinely in hospital laboratories because of its difficulty. Use of microarrays for research is becoming common and its expectations of clinical application are increasing. In this study, we attempted to develop an easier method of NAT2 genotyping for clinical use. We devised a novel oligonucleotide-based DNA microarray for NAT2 genotyping using a recently developed technique for attaching oligonucleotide probes to poly carbodiimide-coated glass slides, which achieves a stronger hybridization signal and better specificity than the more widely used aminosilane-coated slides. To assess the validity of this microarray, four clones with NAT2 mutations and DNA from 42 tuberculosis patients were investigated by the microarray method and by restriction fragment length polymorphism analysis. The results of genotyping by these two methods were in agreement. Analysis of the relationship between the NAT2 phenotype determined by the DNA microarray and the risk of INH-induced hepatotoxicity revealed that slow acetylators had a significantly higher risk. These findings suggest that our microarray may be clinically useful for predicting drug reactions to INH.

Objective: To determine whether the direct measure of visceral adipose tissue (VAT) by computed tomography (CT) is a superior diagnostic criterion to the anthropometric surrogates and more classical criteria of obesity., Design: Cross-sectional, clinical study. Obese boys were classified according to the occurrence of abnormal values in either serum triglyceride, alanine aminotransferase or insulin level. A threshold value of each criterion for such metabolic derangement was calculated, using the analysis of receiver operating characteristic (ROC) curve., Subjects: Seventy-five consecutive outpatient Japanese obese boys, ranging in age from 6 to 14 y, were studied., Measurements: Anthropometric indices measured were height, body weight, waist girth, hip girth, triceps and subscapular skinfold thicknesses. Classical criteria for obesity used were percentage overweight (POW), body mass index (BMI) and percentage body fat. Waist girth, sagittal diameter by CT and waist-hip ratio (WHR) were evaluated as anthropometric surrogates for VAT. The areas of total abdominal fat (TAF), VAT and subcutaneous adipose tissue (SAT) were measured by CT at the level of the umbilicus. Clinical blood biochemistry was analyzed in fasting blood samples of obese boys., Results: Thirty-three boys were classified into a no-complication group, and 42 into a complication group. TAF, VAT and SAT areas were closely associated with age, body size and degree of overweight and adiposity, while VAT/SAT was not. VAT area, sagittal diameter, TAF area and waist girth were closely correlated with alanine aminotransferase, insulin, TG and HDL-C. VAT/SAT, BMI, SAT area, WHR, percentage body fat and POW were less closely associated with these biochemical indices. The descending order of the values of area under the curve for the ROC curves were as follows: VAT>sagittal diameter>TAF>VAT/SAT>waist girth>BMI>WHR>percentage body fat>POW. Both VAT area and VAT/SAT gave >80% of sensitivity and specificity. Among the anthropometric indices studied, the sagittal diameter was the best surrogate of visceral fat measure. The sensitivity and specificity for the rest of the anthropometric indices were in an unsatisfactory range. The threshold values for VAT area, VAT/SAT and sagittal diameter were 58.0 cm(2), 0.276 and 19.2 cm, respectively., Conclusion: The threshold values for VAT area, VAT/SAT and sagittal diameter for detecting biochemical complication in Japanese obese boys were lower than the respective values reported in adults. These values can be used for classifying the obese boys into two types: those with medical problem and those without.

The relationship between the risk of endometrial cancer and the use of noncontraceptive estrogens by Japanese postmenopausal women was investigated in a hospital-based case-control study of 1025 women with endometrial cancer and 1267 with other conditions. The overall odds ratio (OR) for estrogen use with or without progestins, compared with never use of any type of estrogens, was 0.917 (95% confidence interval (CI) 0.622-1.353), suggesting that hormone replacement therapy is not a causative agent for endometrial cancer in Japanese women, and that a recent increase in the incidence of endometrial cancer in Japanese women may be related to changes in their life-style. However, although not statistically significant, women who used estrogen without progestin for 12 or more months had an OR of 2.552 (CI 0.231-28.192), while those who used estrogen with progestin for 12 or more months had an OR of 0.425 (CI 0.086-2.113). These results indicate that the addition of a progestin should be considered for reducing the risk of endometrial cancer in Japanese women.

The frequency profile of tuberculin skin testing among employees of a hospital was studied. In the analysis, tuberculin skin testing was defined as "negative" if skin rash is measured < or = 9 mm, and as "positive" if skin rash is measured > or = 10 mm, and as "strongly positive" if skin rash is measured > or = 10 mm, with induration, and double skin rash or bulla. Boosting was defined as initial skin rash was measured < or = 9 mm, with second skin rash measured > or = 10 mm and at least 6 mm increase of rash than the initial one. 544 employees were tested initially, and 81 were retested. Initial tuberculin positivity was associated with older age (p < 0.001); but boosting was not associated with age and occupation. Comparing pharmacists with other groups, the adjusted odds ratio of an initial strongly positive tuberculin reaction as significantly higher, namely 2.8 (95% confidence interval 1.2-6.7), but that of a booster reaction was 4.8 (0.7-32.1) which was insignificant.

5-Fluorouracil (5-FU) is used widely in the treatment of several common neoplasms. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-FU. Several recent studies have described a pharmacogenetic disorder in which cancer patients with decreased DPD activity develop life-threatening toxicity following exposure to 5-FU. We reported recently the first Japanese case of decreased DPD activity accompanied by severe 5-FU toxicity. The present study describes the results of molecular analysis of this patient and her family, in which three novel mutations (Arg21Gln, Val335Leu, and Glu386Ter) of the gene coding for DPD were identified. We also revealed that Arg21Gln and Glu386Ter are on the same allele and that Val335Leu is on the other allele, on the basis of analysis of the family genome. Expression analysis in Escherichia coli showed that Val335Leu and Glu386Ter led to mutant DPD protein with significant loss of enzymatic activity and no activity, respectively. The Arg21Gln mutation, however, resulted in no decrease in enzymatic activity compared with the wild type. The present data represent the first molecular genetic analysis of DPD deficiency accompanied by severe 5-FU toxicity in a Japanese patient.

Objective: To determine the anthropometric indices linked to the biochemical risk factors for atherosclerosis in Japanese obese elementary school children, ages ranging from 6 to 12 years., Design: Cross-sectional study of obese children based on fasting blood samples., Setting: Outpatient clinic of University Hospital., Subjects: 65 consecutive patients with simple obesity (38 boys and 27 girls), and age-matched controls, 184 boys and 205 girls., Main Outcome Measures: Percent obesity and body mass index as indices of being overweight; percent body fat and the sum of four skinfold thicknesses as indices of adiposity; waist-to-hip circumference ratio and waist-to-thigh circumference ratio as indices of body fat distribution. The anthropometric indices were standardized by calculating standard deviation scores based on data from control children., Results: In the obese boys, all six anthropometric indices studied correlated closely with serum biochemical indices, and strong correlations were observed among the indices of overweight, adiposity and body fat distribution. In contrast, only the indices of body fat distribution, not those of overweight or of adiposity, were correlated with serum biochemical indices in the obese girls. No relationship was found between the indices of body fat distribution and the other anthropometric indices in the obese girls. Thus, the profile of the obese girls differed from that of their male counterparts., Conclusion: The results suggest that body fat distribution is related to certain biochemical complications of childhood obesity, and that androgyny in fat patterns induces metabolic derangements in children.