Large scale replication analysis of loci associated with lipid concentrations in a Japanese population.

BACKGROUND: Recent genome wide association studies discovered seven novel loci that influence plasma concentrations of triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in Europeans. To date, large scale replication studies using populations with known differences in genome-wide linkage disequilibrium (LD) pattern have not been undertaken. METHODS: To address this issue, we tested associations between single nucleotide polymorphisms (SNPs) within the seven novel loci and plasma lipid profiles in 21 010 Japanese individuals. RESULTS: Multiple linear regression analyses showed that the rs3812316 in MLXIPL was strongly associated with triglyceride concentrations (p approximately 3.0x10(-11), 7.1 mg/dl decrease per minor C allele) and that rs599839 in CELSR2/PSRC1/SORT1 was strongly associated with LDL cholesterol concentrations (p approximately 3.1x10(-11), 4.7 mg/dl decrease per minor G allele) in the Japanese population. SNPs near ANGPTL3, TRIB1 and GALNT2 showed evidence for associations with triglyceride concentrations (3.6x10(-6)

Developmental expression of a unique carbohydrate antigen, Tn antigen, in mouse central nervous tissues.

Using an anti-Tn monoclonal antibody, the Tn antigen was detected immunohistochemically in prenatal and early postnatal central nervous tissues. On embryonic day 9 (E9), the antigen was distributed throughout the single neuroepithelial layer in the neocortex and then became more prominent in the preplate than in the ventricular zone along with formation of the preplate. Following division of the preplate and concomitant formation of the cortical plate, distinct labeling of the neocortex occurred in the marginal, subplate and intermediate zones, whereas in the cortical plate and ventricular zone were virtually not immunostained. It is notable that thalamocortical afferent fibers were also immunostained specifically on E14. After birth, the localization of the antigen became less noticeable and by 3 weeks after birth, the antigen had substantially disappeared. In the developing cerebellum, prominent labeling was also observed in the molecular layer and outskirts of the cerebellar nuclei on early postnatal days. To characterize the glycoprotein bearing the Tn antigen biochemically, immunoblot analysis was performed. The glycoprotein, most of which was extracted with a salt solution, migrated as a broad smeared band corresponding to a molecular weight of about 250 kDa on SDS-PAGE. Among the various tissues examined, this glycoprotein was only detected in the brain and its amount increased until an early postnatal stage with a peak on postnatal day 3 (P3), and then decreased gradually with age. This spatially and developmentally regulated expression of the Tn antigen suggests that this antigen plays a significant role in brain development.

Accidents associated with bathing in home care services for the aged in Japan.

OBJECTIVES: To reveal what kinds of accidents happen associated with bathing in home care services for the aged in Japan. METHODS: The study was cross-sectional in design. In November 1999, a postal questionnaire survey was conducted of 828 councils selected from the list of the National Council of Social Welfare of Japan by a systematic sampling method (extraction rate was 25%). The main outcome measures were characteristics of cases of accidents associated with bathing service for the aged, including patient age, sex, time of occurrence, symptoms, and results of accidents. RESULTS: Replies were received from 683 (82%) councils. Of the councils that replied, 430 (63%) reported providing bathing service for the aged. Of these 430 councils, 108 (25%) have experienced accidents, and 130 cases were analyzed. Affected patients had a mean age of 80.7 years (SD: 9.0 years), and 71 were females (55%). Sixty-two (48%) had symptoms of a disease or had accidents after bathing, and 42 (32%) presented with loss of consciousness. In results of accidents, 14 (11%) were reported to have died. CONCLUSION: This study revealed that there were not a few accidents associated with bathing in home care services for the aged in Japan, the most frequent symptom was loss of consciousness, most accidents occurred after bathing, and that some patients died as a result of bathing provided by home care services.

Identification of the core protein carrying the Tn antigen in mouse brain: specific expression on syndecan-3.

We isolated glycoproteins carrying the Tn antigen, which was expressed spatiotemporally in the developing mouse brain. The Tn antigen was expressed on two molecular species with a molecular weight from 200 to 350 kDa and 110 to 160 kDa, as judged on SDS-PAGE. Although the two glycoproteins showed different susceptibilities to heparitinase I and solubilities in a salt solution, after treatment with V8 protease they showed the same mobility corresponding to a molecular weight of 90 kDa on SDS-PAGE, suggesting that these two molecules shared a common core protein. Partial N-terminal sequences of the glycoproteins were determined, i.e. AQRXRNENFERPV and ALAAPXAPAMLP, which were identified as the sequences of the N-terminal and central portions of syndecan-3, respectively. Both glycoproteins were reactive to anti-mouse syndecan-3 antibody. These results suggest that one is a soluble syndecan-3 cleaved between mucin-like domain and transmembrane domain, and the other is a membrane-bound syndecan-3 lacking N-terminal glycosaminoglycan attachment sites, and that both glycoproteins have a mucin-like domain characteristic of syndecan-3, in which the Tn antigen may be expressed.

Possible contaminant origins of the red cosmetics decorating ancient burial sites in Japan.

Marker elements were estimated from the red cosmetics collected from different ancient burials and mine ruins in three separate districts of Japan. Element levels were displayed in reference to the relative amount to sulfur (RA/S), by which the cosmetics were divided into five types: I--a low Hg/S with a low Fe/S; II--both moderate Hg/S and Fe/S; III--a moderate Hg/S with a high Fe/S; III 2--a high Hg/S with a moderate Fe/S; IV--a high Hg/S with a high Fe/S. The cosmetics can be further characterized by referring to other contaminants such as Zn, Cu, and Mn. These combined analyses with contaminant metals were capable of characterizing the origins of the cosmetics; it is useful to compare them to each other. The cosmetics were identified as being due to several groups of contaminants from ancient mines in Japan, and also with this system analysis of the markers it is possible to identify them from neighboring countries.

Japanese paediatricians' judgement of the appropriateness of bathing for children with colds.

OBJECTIVES: This study investigated the decisions which Japanese paediatricians make regarding bathing a child with a common cold. METHODS: A total of 486 printed questionnaires were mailed to paediatricians systematically sampled from the list of members of the Japanese Pediatric Association. The questionnaire included two main questions. (i) Do you permit a 2- to 4-year-old child with a common cold to take a bath? (ii) If the answer to (i) was 'yes', what conditions should limit bathing of such children, and if the answer was 'no', why do you forbid bathing? In addition, the questionnaire included the age and sex of the practitioner, and the type and location of the practice. RESULTS: A total of 269 paediatricians returned questionnaires (response rate 55%); of these, 88% permitted a child with a cold to take a bath. Of these paediatricians, 5% permitted it without any conditions. The main conditions for taking a bath indicated by these paediatricians were 'no fever' (72%), 'not in a severe physical condition' (27%) and 'after 2 or 3 days from onset' (19%). Thirty-nine paediatricians indicated a specific body temperature at which bathing was appropriate. One-third of these paediatricians did not permit bathing at body temperatures above 38 degrees C. Of the 31 paediatricians (12%) who answered that a child with a cold should not take a bath, 61% were concerned for the physical well-being of the child. However, 29% provided no supporting evidence. CONCLUSIONS: Japanese paediatricians' judgements concerning bathing of a child with a cold are related to the effects of bathing on physical condition. Bathing immersed up to the neck does not always affect physical conditions. It is necessary to establish appropriate parental and patient education concerning bathing of children with colds.

Participation of syndecan 2 in the induction of stress fiber formation in cooperation with integrin alpha5beta1: structural characteristics of heparan sulfate chains with avidity to COOH-terminal heparin-binding domain of fibronectin.

The present study provides direct evidence that syndecan 2 participates selectively in the induction of stress fiber formation in cooperation with integrin alpha5beta1 through specific binding of its heparan sulfate side chains to the fibronectin substrate. Our previous study with Lewis lung carcinoma-derived P29 cells demonstrated that the cell surface heparan sulfate proteoglycan, which binds to fibronectin, is syndecan 2 (N. Itano et al., 1996, Biochem. J. 315, 925-930). We here report that in vitro treatment of the cells by antisense oligonucleotide for syndecan 2 resulted in a failure to form stress fibers on fibronectin substrate in association with specific suppression of its cell surface expression. Instead, localization of actin filaments in the cytoplasmic cortex occurred. A similar response of the cells was observed when the cells were treated to eliminate functions of cell surface heparan sulfates, including exogenous addition of heparin and pretreatment with anti-heparan sulfate antibody, F58-10E4, and with proteinase-free heparitinase I. Size- and structure-defined oligosaccharides prepared from heparin and chemically modified heparins were utilized as competitive inhibitors to examine the structural characteristics of the cell surface heparan sulfates involved in organization of the actin cytoskeleton. Their affinity chromatography on a column linked with a recombinant H-271 peptide containing a C-terminal heparin-binding domain of fibronectin demonstrated that 2-O-sulfated iduronates were essential for the binding. Inhibition studies revealed that a heparin-derived dodecasaccharide sample enriched with an IdoA(2OS)-GlcNS(6OS) disaccharide completely blocked binding of the syndecan 2 ectodomain to immobilized H-271 peptide. Finally, the dodecasaccharide sample was shown to inhibit stress fiber formation, triggered by adhesion of P29 cells to a CH-271 polypeptide consisting of both the RGD cell-binding and the C-terminal heparin-binding domains of fibronectin in a fused form. All these results consistently suggest that syndecan 2 proteoglycan interacts with the C-terminal heparin-binding domain of fibronectin at the highly sulfated cluster(s), such as [IdoA(2OS)-GlcNS(6OS)](6) present in its heparan sulfate chains, to result in the induction of stress fiber formation in cooperation with integrin alpha5beta1.

[A study of mental health in community-dwelling older persons--influence of cared elderly].

This study aimed to evaluate mental health of elderly persons living in the community and understand the various backgrounds and effects of care giving. The study used a questionnaire from similar to the one used by Matsubayashi et al in the Kahoku-cho study. The Japanese Version of General Health Questionnaire 12 (GHQ-12) was used to evaluate mental health. Responses were received from 2,799 (81.5%) of 3,432 Numura-cho residents (81.5%). After removing inadequate responses, 1,268 (36.9%) (575 men and 693 women) were analyzed. Fifty-five men (9.6%) and 69 women (10.0%) were caring for someone at home. Multiple logistic regression analysis which examined the relation between mental health and the background factors such as having someone to care for, revealed that their mental health was significantly poor compared to those having no one to care for (odds ratio (OR) = 2.01, 95% confidence interval (CI), 1.29-3.15). As for the relation between the degree of care giving and their mental health, the subjective burden was significantly poor at 72-100% (OR = 3.40, 95% CI, 1.71-6.78) and for those with three to eight years of care-giving (OR = 2.22, 95% CI, 1.00-4.90), disabled activity of daily living (almost bed ridden) of the cared for person (OR = 5.53, 95% CI, 2.23-13.7), severely demented state (OR = 5.13, 95% CI, 2.14-12.3), their mental health was significantly poor. However, being able to participate in an event (OR = 0.12, 95% CI, 0.03-0.49) and strong emotional support (OR = 0.12, 95% CI, 0.03-0.49) were negatively associated with caregivers' psychiatric distress. Having someone to care for largely affected mental health of the elderly to subjects living in the community. Services should be devised to serve the needs such as psychological care of care-givers as well as those being cared for.

[A study of depressive state and background factors in community-dwelling older persons].

In order to maintain and improve the mental health of elderly people living in the community, a cross-sectional survey was conducted to elucidate their depressive state and its background factors. Subjects were elderly persons living in the community who were able to fill in the questionnaire themselves. The study used the self-recording questionnaire sheets used in the Kahoku Longitudinal Aging Study by Matsubayashi et al and the Zung Self-rating Depression Scale (SDS). Out of 2,379 elderly persons who were able to fill in the questionnaire by themselves in the community, 2,361 (99.2%) returned the questionnaire sheets. After removing inadequate responses, analysis was possible for 1,181 (49.6%) (542 males (average age 72.3 +/- 5.5) and 639 females (average age 73.0 +/- 6.3). Degree of depressive state as evaluated by SDS was normal for 731 persons (61.9%); mild, 240 (20.3%); moderate, 181 (15.3%); and severe, 29 (2.5%). The average age became higher as the SDS became high, of being indicating the seriousness of the depressive state (p = 0.0155), with the ratio women significantly higher (p = 0.0077). Among those with severe SDS, the ratio of single persons was high (p < 0.001) as well as those who were non-drinkers (p = 0.0015), without regular habit of walking (p < 0.001), or without work (p < 0.001). The ratio of those receiving medication regularly was also significantly high (p = 0.0022). As for the relation of SDS with various of the scores, the higher the SDS score became, the scores for ADL, information-related function, functional and emotional support network, family relationship, friendship, economic condition became significantly lower (p < 0.001, respectively). In logistic regression analysis using the background factors for SDS as explanatory variables, factors such as being women (odds ratio, 1.73; 95% confidence interval, 1.10-2.72). ADL (0.80; 0.69-0.93), emotional support network (0.88; 0.81-0.96), friendship (0.98; 0.96-0.99) were significant independent contributing factors. As for the relation between SDS and subjective senses, the more serious the SDS score became, the scores for feelings of healthiness and satisfaction became significantly smaller (both p < 0.001). For prevention and amelioration of the depressive state of elderly persons living in the community, attempts should be made to improve the background factors which were clarified by the present study by efficiently utilizing health, medical and welfare services and following the future course with a positive attitude.

The role of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 genotypes in alcohol-induced vasospastic angina.

Alcohol ingestion often provokes attacks in patients with vasospastic angina. Type 2 aldehyde dehydrogenase (ALDH2) deficiency, which is based on a single point mutation (Glu487Lys) of the ALDH2 gene, is common in the Japanese population, but rare among the Caucasian population. We investigated how the genotype of ALDH2 affects the characteristics of alcohol-induced vasospastic angina. Ninety-one patients with vasospastic angina who had ingested alcohol daily or occasionally were studied. Patients had been diagnosed as vasospastic angina by a provocation test with an intracoronary injection of ergonovine or acetylcholine during coronary angiography. The Glu487Lys mutation was detected by allele specific PCR. We interviewed the patients to obtain information concerning the relationship between alcohol ingestion and anginal attacks. Alcohol ingestion induced attacks in 16 of 66 patients without the Glu487Lys mutation, 8 of 22 in heterozygotes, and 1 of 3 in mutant homozygotes. The intervals between alcohol ingestion and the onset of anginal attacks were shorter in homozygotes (0.17 hours) and heterozygotes (1.5+/-0.6 hours) for ALDH2*2 than in normal homozygotes for ALDH2*1 (5.4+/-0.6 hours). The amount of ethanol which induced attacks was significantly greater in normal homozygotes than in homozygotes (11 ml) and heterozygotes (42.5+/-7.1 ml) for ALDH2*2 (96.1+/-13.4 ml in normal patients). The frequency of anginal attacks induced by alcohol ingestion did not differ between ALDH deficient and normal homozygotes. In ALDH deficient patients, however, anginal attacks were induced by a smaller amount of alcohol immediately after its ingestion. Thus, the ALDH2 genotype modifies the characteristics of the anginal attacks as a co-factor for the induction of vasospastic angina after alcohol ingestion.

[Happiness and background factors in community-dwelling older persons].

In order to maintain and improve mental health of elderly people living in the community, a cross sectional survey was conducted to elucidate their happiness and background factors. The subjects were elderly persons living in the community who were able to fill in the questionnaire themselves. The study employed the self-recording questionnaire forms used in Kahoku Longitudinal Aging Study by Matsubayashi et al. Happiness was assessed using a visual analogue scale. Out of 2,379 elderly persons who were able to fill in the questionnaire by themselves in 2,361 (99.2%) returned the questionnaire sheets. After removing inadequate responses, analysis was possible for 1,873 (78.7%) (860 men (average age 72.7 years) and 1,013 women (average age 72.8 years). Among those with greater happiness, the ratio of those living with others (p = 0.0051) was high as well as those with spouses (p = 0.0240), without a history of hypertension (p = 0.0096) and apoplexy (p = 0.0039), not receiving medication regularly (p = 0.0039), with regular habit of walking (p < 0.001), or with work (p < 0.001). As for the relationship between happiness and various scores, the higher the happiness scale became, the scores for ADL, information-related function, functional and emotional support network, healthy condition, appetite condition, sleep condition, memory condition, family relationships, friendship, economic condition became significantly higher (p < 0.001, respectively). On multiple regression analysis using the background factors for happiness as explanatory variables, factors such as functional support network (p < 0.001), emotional support network (p = 0.0254), healthy condition (p < 0.001), good memory condition (p = 0.0027), friendship (p < 0.001), good economic condition (p < 0.001) were significant independent contributing factors. As for the relation between SDS and happiness, the more serious the SDS score (higher score) became, the scores for the feeling of happiness became significantly smaller (p < 0.001). For amelioration of the happiness of elderly persons living in the community, attempts should be made to improve the background factors clarified by the present study by efficiently utilizing health, medical and welfare services.

Methacholine bronchial hyperresponsiveness in chronic sinusitis.

The coexistence of chronic sinusitis (CS) may deteriorate the clinical condition of lower airway diseases such as bronchial asthma (BA) or chronic bronchitis (CB). However, the bronchial hyperresponsiveness (BH) in CS without any apparent lower airway disease is not fully understood nor are the effects of treatment. We examined lower airway hyperresponsiveness to methacholine (MCh) in 42 subjects with CS but without allergic rhinitis (AR) who had normal lung functions without any pulmonary symptoms, comparing it with that of 50 subjects with stable BA, 50 subjects with simple CB and 40 subjects with AR, and further examined the effect of endoscopic sinus surgery in 7 CS subjects with BH. The BH to MCh was measured in terms of the minimum dose (Dmin), defined as the cumulative dose at the point where respiratory conductance began to decrease. A Dmin <50 units was defined as BH. Seventy-one percent of CS subjects showed BH without relation to the severity or duration of CS, or atopic status. BH in CS subjects, which was less than that in BA subjects, was similar to that in simple CB or AR in both its prevalence and degree. After the surgical treatment of CS, BH significantly decreased (p < 0.01) with improvements in both nasal symptoms and sinus lesions. These findings suggest that CS itself induces BH to a degree similar to simple CB and AR without any relationship to the clinical background, and that adequate treatment of CS reduces BH.

A study of clinical features and treatment of acute bronchitis by Japanese primary care physicians.

OBJECTIVE: This study aimed to examine the factors affecting prescription of antibiotics for acute bronchitis in ambulatory care settings in Japan. METHOD: A prospective study was conducted on 92 physicians engaged in primary care regarding their prescription behaviour for a series of 20 new patients with acute respiratory diseases seen during November 1996 and the background factors affecting the behaviour. RESULTS: A total of 1755 patients were registered during the study period, 302 (17.2%) of whom were diagnosed with acute bronchitis and 1165 (66.4%) with upper respiratory tract infection. Independent background factors related to diagnosis of acute bronchitis included self-care prior to visit (odds ratio 1.93, 95% CI 1.33-2.80), complaints such as cough (8.80, 4.77-16.2), sputum (2.24, 1.59-3.14) and purulent sputum (6.47, 3.02-13.9). The odds ratio was high in patients with more severe findings of the chest (5.00, 3.64-6.85), given chest X-ray (2.68, 1.33-5.38) while it was low in those feeling cold (0.68, 0.48-0.96), and those with a sore throat (0.63, 0.45-0.90), nasal symptoms (0.75, 0.54-1.04) and more severe findings of the pharynx (0.74, 0.58-0.92). In those with an upper respiratory tract infection, the odds ratio was high for complaints such as feeling cold (1.51, 1.11-2.05) and nasal symptoms (1.39, 1.04-1.86), while it was low for complaints such as cough (0.67, 0.48-0.95), sputum (0.43, 0.30-0.62), purulent sputum (0.19, 0.08-0.44), wheeze (0.34, 0.13-0.92), in those with more severe findings of the tonsil (0.36, 0.29-0.44) and the chest (0.30, 0.19-0.47) and given chest X-rays (0.29, 0.12-0.66). For acute bronchitis, antibiotics were administered to 67.5% and symptomatic therapy concurrently given to 64.9%. As for independent background factors related to prescription of antibiotics for acute bronchitis, the odds ratio was higher in physicians denying the efficacy of antibiotics for treating a cold (4.58, 1.94-10.8), and the patients with complaints such as purulent sputum (22.9, 2.66-197.2), more severe findings of the pharynx (2.26, 1.34-3.79) and of the chest (2.73, 1.53-4.88), and those who had a body temperature measurement taken (4.42, 1.71-11.4) and a chest X-ray (6.11, 1.07-34.9), but was lower in those complaining of chills (0.16, 0.04-0.66) and diarrhoea (0.11, 0.01-1.11). CONCLUSIONS: A majority of patients receiving medical care for acute bronchitis are given an unnecessary antibiotic prescription. The result of this study may be useful for the finding of appropriate forms of intervention for changing physicians' prescription behaviour.

[A case of thymic cyst differentiated from cardiac cyst with immunostaining].

This is a case of a 70-year-old woman with thymic cyst which was found by chance on admission for treatment of acute bronchial asthma and diagnosed by pathological examination. After remission of the asthma she was asymptomatic and no pathological physical findings were found except of cervical thyroid tumor of adenomatous goiter. Chest X-ray films revealed a large mediastinal mass with a sharp margin at the right cardiophrenic angle. Chest CT and MRI revealed that it occupied a space from upper anterior mediastinum to right cardiophrenic angle, and that it showed low density area without enhancement, suggesting a mediastinal cyst. A multilocular cyst, 15 cm in diameter, containing serous liquid was excised using thoracotomy. Pathological and immunohistochemical examination of the cyst revealed that its inner surface was lined with benign cylindrical epithelium and that thymic tissues existed in the walls of the cyst, resulting in a thymic cyst. The thymic cyst, of which reports have increased, should be considered in the differential diagnosis of anterior mediastinal cysts.

An association of human T-cell lymphotropic virus type I infection with vascular dementia.

Subjects ranging in age from 50 to 89 years old, either with or without dementia were studied by both ELISA for anti-human T-cell lymphotropic virus type I (HTLV-I) gag 100-130 antibody and by cranial CT in order to clarify the relationship between HTLV-I infection and dementia. The frequency of anti-HTLV-I antibody was found to be significantly higher in the patients with dementia (24/130, 18.5%) than in those without dementia (11/139, 7.9%) (P=0.0169). Among the various types of dementia, HTLV-I seropositivity was found to be significantly associated with vascular dementia (11/48, 23%) (P=0.0087), but not with Alzheimer type dementia. In addition, HTLV-I seropositivity was also associated with Babinski sign, and the severity of cerebral infarction, ventricular dilatation and periventricular lucency on CT. The presence of HTLV-I therefore appears to be one of the risk factors for vascular dementia in HTLV-I endemic areas.

[The efficacy of HFJV (high frequency jet ventilation) for ARDS (adult respiratory distress syndrome) following total arch replacement].

A 40-year-old man was admitted to the hospital with shock due to acute aortic dissection (type A of Stanford classification). The emergent total arch replacement was performed with the retrograde cerebral perfusion uneventfully. At the 3rd day after the operation, bilateral infiltrates were recognized on the frontal chest radiograph. The oxygenation was gradually decreased to less than 200 mmHg of PaO2/FiO2 in proportion with the growth of infiltrates and increase of LDH in blood. Steroid therapy was not effective. So then HFJV was introduced to improvement of hypoxygenation at the 16th day after the operation. HFJV made PaO2/FiO2 improve immediately to more than 300 mmHg and the inspiratrory pressure decrease to less than 30 mmHg. Bilateral infiltrates were diminished by HFJV. LDH in blood decreased apparently. HFJV had been used together during 15 days. The respirator was weaned at the 46th day after the operation. In this clinical course, the change of PaO2/FiO2 had the negative correlation with that of LDH in blood.