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Reiko Kishi

Publications and source records attributed to Reiko Kishi.

At least 37 records · Page 2Linked to original sources

[Exposure to endocrine disrupting chemicals and human health: a review of epidemiological studies focused on hypospadias and cryptorchidism].

Hypospadias and cryptorchidism are common congenital anomalies. Recently, increases in the prevalence of hypospadias and cryptorchidism have been reported in various countries, including Japan. As male sexual differentiation is critically dependent on normal androgen concentrations, increased exposure to environmental factors affecting androgen homeostasis during fetal life (i.e. EDCs with estrogenic or anti-androgenic effects) may cause hypospadias or cryptorchidism. However, the results from the International Clearinghouse for Birth Defects Monitoring System (ICBDMS), hospital-based studies in each country and population-based studies in Japan are different, because in the present system there are some problems such as the standardization of diagnostic criteria and the difference of the time of diagnosis, we hope to improve the monitoring system method. Previous papers have reported that hypospadias and cryptorchidism were associated with maternal exposure to progesterone, estrogen, diethylstilbestrol (DES) and pesticide. However, there are few studies evaluating the quantity of endocrine disrupting chemicals, using biological samples. In the future, a well-designed epidemiological study is needed to elucidate the relation between endocrine disrupting chemicals and genital development.

Agrochemicals↗

[Significance of laboratory studies of neurobehavioral and developmental toxicities--transgenerational effects of styrene exposure].

Recently, health problems caused by environmental chemical substances present in daily life have been increasing, particularly developmental toxicities, the effects of which often become apparent only after a long developmental period. It is difficult to determine adverse transgenerational effects. Therefore, we must recognize important indices to measure neurobehavioral and developmental effects. The assessment of such effects indices, is difficult and few neurobehavioral data are available compared to teratological data. Thus, through studies using laboratory animals, analyses of the mechanisms, exposure periods, doses and neurobehavioral effects are necessary. We have reviewed studies of the volatile monomer of the organic solvent styrene with regard to reproductive and developmental toxicities in laboratory animals. The styrene monomer crosses through the placenta; however, fetal excretion is less than maternal excretion. Therefore, it seems that a dose of styrene that does not affect the mother may be toxic for the fetus. We reported that exposure to low-dose styrene results in physical and neurobehavioral developmental delays, as well as decreases in enzyme activity and neurotransmitter secretion level. To prevent neurobehavioral toxicity, we need further studies to obtain precise data on chemical-biological interactions developmental toxicity and dose-response relationships. A key step towards effective prevention can also be obtained from studies in which animals are continuously exposed to chemicals for one or more generations. Thereafter, we must extrapolate developmental toxicity data from animals to humans. In this paper, we provide the information on developmental toxicity.

Animals↗

Relationship of Helicobacter pylori infection to arterial stiffness in Japanese subjects.

The role of Helicobacter pylori in the pathogenesis of atherosclerosis remains controversial, and the relationship between H. pylori and the early stage of atherosclerosis has not been fully investigated. We investigated the influence of H. pylori infection on arterial stiffness to clarify whether H. pylori infection is related to early-stage atherosclerosis. The subjects were 3,412 males and 854 females. Anti-H. pylori antibody and C-reactive protein (CRP) level were measured. Arterial stiffness was evaluated using the brachial-ankle pulse wave velocity (PWV). In multivariate logistic repression analyses of male subjects, H. pylori seropositivity (odds ratio [OR] 1.27 [95% confidence interval, 1.05-1.52]) and H. pylori seropositivity with a high CRP value (>0.045 mg/dl) (OR 1.50 [1.14-1.98]) were significantly related to a high value of PWV. In the analyses of male subjects aged < or = 49 years, H. pylori seropositivity (OR 1.40 [1.04-1.88]) and H. pylori seropositivity with a high CRP value (OR 1.81 [1.16-2.80]) were also significantly related to a high value of PWV. However, in male subjects aged > or = 50 years and female subjects, no associations were found. These results suggest that inflammation following H. pylori infection contributes to the early stage of atherosclerosis in younger males.

Adult↗

Relationship of beta2-microglobulin to arterial stiffness in Japanese subjects.

Beta2-Microglobulin (beta2m) is related to inflammatory diseases, but there have been few reports of a relationship between beta2m and atherosclerosis. We have examined the influence of beta2m on brachial-ankle pulse wave velocity (baPWV) to clarify whether it is related to arterial stiffness. baPWV, beta2m, C-reactive protein (CRP), and conventional risk factors were measured in 614 males and 158 females. The adjusted means of baPWV were compared with the quartiles of beta2m, and significant differences in baPWV were observed across the quartiles of beta2m (p = 0.037). After being adjusted for potential confounders, quartile 4 of beta2m, quartile 4 of CRP, and the combination of high beta2m plus high CRP were significantly associated with a high value of PWV (quartile 4 of beta2m: odds ratio [OR] 2.53, 95% confidence interval [CI], 1.31-4.89; quartile 4 of CRP: OR 2.27, 95% CI, 1.18-4.34; high beta2m plus high CRP: OR 5.60, 95% CI, 2.38-13.2). These results suggest that beta2m is associated with an increase of arterial stiffness. Further studies are needed to clarify whether beta2m is related to atherosclerotic diseases, and whether the combination of beta2m and CRP measurement is a useful predictor for the development of atherosclerosis.

Adult↗

The effects of subacute inhalation of di (2-ethylhexyl) phthalate (DEHP) on the testes of prepubertal Wistar rats.

In animal studies using oral dosing for short periods, di (2-ethylhexyl) phthalate (DEHP) is well known for its reproductive toxicity, especially for its testicular toxicity. However, extending the period of DEHP exposure in prepubertal rats resulted in significant increases in testosterone. This suggests that the reproductive effect of DEHP might be associated with the timing and the term of exposure. Moreover, the route of exposure may induce differences in its effect because tissue levels of metabolites of DEHP after inhalation are thought to be different from those after oral administration. We researched the effects of inhalation of DEHP on testes of prepubertal rats. Our results showed that inhalation of DEHP by 4-wk-old male Wistar rats at doses of 5 or 25 mg/m(3), 6 h per day, for 4 and 8 wk significantly increased the concentration of plasma testosterone and weight of seminal vesicles. However, the concentration of luteinizing hormone (LH), follicular stimulating hormone (FSH) and the expression of mRNAs of androgen biosynthesis enzyme, cytochrome P450 cholesterol side-chain-cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450 17alpha-hydroxylase/17, 20 lyase (CYP17) and aromatase (CYP19) did not change. Rats with precocious testes did not increase in any of the DEHP groups. We also found that the estimated effective dose in this study was less than those reported in previous studies which used oral dosing. Our study showed that inhaled DEHP increased plasma testosterone concentrations in prepubertal rats and suggested that their effects were more sensitive to inhalation of DEHP than oral dosing.

Administration, Inhalation↗

Effects of pregnancy, age and sex in the metabolism of styrene in rat liver in relation to the regulation of cytochrome P450 enzymes.

To elucidate the effect of maternal styrene exposure, which is due to various postnatal changes in the development and behavior of offspring, we investigated pregnancy-induced changes in the metabolism of styrene in rat liver in relation to the regulation of cytochrome P450 enzymes. We also examined age and sex-induced changes in the metabolism of styrene. Pregnancy appeared to exert a negative effect on cytochrome P450 content at the late stage, whereas microsomal protein content showed little change during pregnancy. Pregnancy significantly decreased the rate of formation of styrene glycol at the late stage. The percentage of remaining activity in microsomes exposed to anti-CYP2E1 was lower than that exposed to anti-CYP2C11/6 in pregnant and non-pregnant female rats and immature male rats, indicating that CYP2E1 contributes to the metabolism of styrene more than CYP2C11/6 in these rats. Although pregnancy seemed to decrease styrene metabolism, the contribution of CYP2E1 seemed to be slightly increasing. In conclusion, pregnancy clearly influences the metabolism of styrene as well as other characteristic factors such as age and sex. It is very important to elucidate the changes in specific P450 isozyme composition related to their characteristic modification and in their affinity for chemicals.

Age Factors↗

[A review of epidemiological studies about pulse wave velocity for prevention of cardiovascular disease].

Early arteriosclerosis can be prevented by medication and life style changes. However, late cardiac disease, called cardiovascular disease, could be fatal or have severe sequelae. Therefore, it is important to develop a method for early diagnosis. Since no symptoms become evident until endothelial/vascular dysfunction, a simple and sensitive diagnostic method using a biological parameter needs to be developed for prevention and medical treatment. Pulse wave velocity (PWV) is a noninvasive and simple measure for evaluating arterial wall stiffness and several studies have indicated this is a good marker for vascular damage, although not all results were consistent. This review concerns the following three aspects: 1. PWV as a marker of vascular damage 2. PWV as a prognostic predictor 3. Brachial-ankle PWV (baPWV) Blood pressure is strongly related with PWV, along with BMI, fasting blood glucose, and cholesterol. However, no relation was rated cigarette smoking. While many reports have shown that rise of PWV can serve as a prognostic predictor of disease, the situation with baPWV remains unclear. It is to be expected that improvements in methods for PWV will greatly contribute to primary and secondary prevention in the future.

Aging↗

[Effects of stressful life events which cause depression in the elderly, and the role of the social support network--a longitudinal study in Hokkaido prefecture].

The effects of stressful life events which cause depression in the elderly and the role of the social support network--a longitudinal study in Hokkaido prefecture It has been reported that various stressful life events experienced by the elderly increase the risk of depression, and that a support network mitigates the effects. However, reports in our country are still lacking. This research was a longitudinal study in a former coal mining area, conducting a baseline survey on 1991. Every three to four years, we followed-up the elderly in the area. The questionnaire included :1) base attributes 2) stressful life events 3) networks, 4) instrumental/emotional support, support provided themselves, 4) Zung's Self Rating Depression Scale, 5) subjective health/number of illness/hospital admission/body aches/vision and hearing/urinary incontinence/signs of dementia, 6) hobbies and motivation in life/ADL/IADL. Whether male or female, SDS scores after three years were significantly high in cases of poor health, body aches, and signs of dementia. Females who did not participate in social activities scored significantly high after three years. In cross-sectional analysis, both males and females who were not working had significantly high scores. The effect of networks on SDS scores in females was significantly recognized for items regarding children living separately, neighborhood, close friends/relatives, and groups. However, it was not significant for males. Thus, a gender difference was found. In females, the level of depression was low when there were supports, though it was not significant in males. The subjective health condition was significantly different from SDS scores in both male and female groups. Admission to hospital, existence of body aches and vision disturbance were significantly different in females. Nevertheless, those were not significant in the male group. For social activity, whether the persons possessed hobbies and motivation in life or not created a significant difference in SDS scores. For stressful life events, both males and females had significantly high SDS scores caused by aggravation of health condition. In the female group, moving against the will, illness of spouse/family, and increased borrowing showed significance, and life events experienced within a year and SDS scores were significantly related. In multivariate analysis using parameters of males in 1995, only subjective health condition significantly increased the level of depression. In females, when the number of experienced life events was large, the level of depression was higher even when adjusted for the subjective health condition. Moreover, even then when "home visits by children separately living" were rare, the level of depression tended to be higher. As future issues, (1) adequate measures for evaluation of social support networks and (2) early preventive action in each community with validated scales for stressful life events are important.

Aged↗

No difference in natural killer or natural killer T-cell population, but aberrant T-helper cell population in the endometrium of women with repeated miscarriage.

BACKGROUND: The aim of this study was to assess the natural killer (NK) cell and natural killer T (NKT) cell populations and cytokine expression of T-helper (Th) cells in the endometrium of women who suffered from unexplained repeated miscarriage (RM). METHODS: The percentages of NK cells, NKT cells and CD4(+) cells expressing intracellular interferon (IFN)-gamma, interleukin (IL)-4 and tumour necrosis factor (TNF)-alpha were measured by flow cytometry in the endometrium of 20 RM women and 17 fertile control women in the mid-luteal phase of the menstrual cycle. RESULTS: No significant differences in CD56(+) NK cell or CD3(+)CD4(-)CD8(-)Valpha24(+)Vbeta11(+) NKT cell percentages were found between RM and control women. However, in RM women compared with control women, the percentages of CD3(+) cells (mean 40.3 versus 56.5%), CD4(+)IFN-gamma(+) cells (28.4 versus 39.5%) and CD4(+)TNF-alpha(+) cells (32.9 versus 45.8%) were significantly lower. The Th1/Th2 cell balance in RM women did not differ from that of controls. CONCLUSIONS: Immunodystrophism detected as diminution of the Th cell population rather than Th1 predominance, NK cell or NKT cell accentuation in the endometrium might underlie the pathophysiology of unexplained RM. This finding provokes an additional controversy on the Th1/Th2 balance concerning RM aetiology.

Abortion, Habitual↗

Single nucleotide polymorphisms in the promoter region of the interleukin-6 gene and the risk of recurrent pregnancy loss in Japanese women.

OBJECTIVE: To investigate the relationships between recurrent pregnancy loss and single nucleotide polymorphisms (-634C-->G and -174G-->C genotypes) in the promoter region of the interleukin (IL)-6 gene in the Japanese population. DESIGN: A case-control study. SETTING: Obstetrics and gynecology department of a university hospital. PATIENT(S): Cases were 76 women with recurrent pregnancy loss; controls were 93 fertile women. INTERVENTION(S): Determination of IL-6 promoter gene polymorphisms performed by polymerase chain reaction and gel electrophoresis. MAIN OUTCOME MEASURE(S): Frequency and distribution of the promoter region of the IL-6 gene allele. RESULTS: There was a significant difference in the -634C-->G genotype frequency (CC vs. CG/GG) between women with recurrent pregnancy loss and controls. The risk of recurrent pregnancy loss was lower in the carriers of the G allele than in women with the wild type (CC) (odds ratio = 0.46; 95% confidence interval = 0.24-0.91). On the other hand, we did not detect any carrier of -174C among the 169 subjects. CONCLUSION(S): The results suggest that, in the Japanese population, women carrying the -634G allele of the IL-6 gene might have a decreased risk of recurrent pregnancy loss.

Abortion, Habitual↗

A polymorphism in the CYP17 gene and intrauterine fetal growth restriction.

Intrauterine fetal growth restriction is a multifactorial disorder, and its aetiology includes both environmental and genetic components. We aimed to investigate whether maternal genetic polymorphisms of metabolic enzymes affects fetal growth and pregnancy duration. Genomic DNA was obtained from 134 women who experienced singleton deliveries beyond 24 weeks of gestation. Maternal age, birth weight, gestational age at birth and frequencies of fetal growth restriction, prematurity and pregnancy-induced hypertension were compared among genotypic subgroups of cytochrome p450 (CYP) and glutathione S-transferase (GST) genes. The polymorphisms of CYP1A1 (MspI), CYP17 (MspAI) and GSTP1 (BsmAI) genotypes, and the presence or absence of GSTM1 and GSTT1 genes were analysed by PCR-based methods. The frequency of fetal growth restriction (<10th percentile/<-1.5 SD; 22.7%/11.4%) in 44 women who were homozygous for the A1 allele (A1A1) of CYP17 was significantly higher than that (7.8%/2.2%) in 90 women who carried the A2 allele (A1A2/A2A2) of CYP17 (P < 0.05), with an odds ratio =3.41 (95% confidence interval = 1.18-9.84). The gestational age at birth (mean +/- SD, 37.5 +/- 3.1 weeks) in 67 women with GSTM1 null genotype was significantly lower than that (38.5 +/- 2.4 weeks) in 67 women who carried GSTM1 (P < 0.05). The polymorphism of CYP17 that encodes the cytochrome p450c17alpha enzyme might be associated with the pathophysiology underlying fetal growth restriction.

Case-Control Studies↗

Genistein-induced changes in gene expression in Panc 1 cells at physiological concentrations of genistein.

OBJECTIVES: To investigate the effect of genistein on gene expression in Panc 1 cells using microarray technology. METHODS: Panc 1 cells were treated with 10 micromol/L genistein or DMSO (vehicle control) for 0, 1, 3, 6, or 12 hours. Total RNA from each sample was isolated, and biotin-labeled probes were hybridized to the human genome U133A chip, after which the chip was washed and scanned. Data were analyzed using DMT software (Affymetrix). For genes that showed large changes in expression due to genistein, these changes were confirmed using real-time PCR assays. RESULTS: Two independent microarray experiments showed that genistein significantly changed the expression of 47 genes: up-regulating of egr-1 and IL-8 and down-regulating of EGF-R AKT2, CYP1B1, NELL2, SCD, DNA ligase III, Rad as well as 18s and 28s rRNA and others. These alterations in expression were confirmed using real-time PCR, although the increase in change was not exactly the same in the 2 assays. CONCLUSIONS: Our data suggest the reported apparent ability of genistein to inhibit carcinogenesis may involve a number of pathways. The most obvious target is the EGF-R signaling pathway since the expression of 5 genes related to this pathway was reduced (EGFR, egr-1, AKT2, CYP1B1, and NELL2). Genistein may also act by disabling cancer cell self-protection by inhibiting expression of AKT2, CYP1B1, and DNA ligase III. Furthermore, genistein may inhibit car-cinogenesis by inhibiting expression of SCD. Finally, our data support findings indicating that genistein inhibits rRNA formation, which is an important mechanism by which genistein regulates tumor cell growth.

Adenocarcinoma↗

Decrease in a specific killer cell immunoglobulin-like receptor on peripheral natural killer cells in women with recurrent spontaneous abortion of unexplained etiology.

PROBLEM: The aim of this study was to investigate immunophenotypic characteristics of natural killer (NK) cells by assessing specific molecules expressed in women with recurrent spontaneous abortion (RSA) of unexplained etiology. METHOD OF STUDY: Peripheral blood cells were obtained from 20 RSA women and 15 fertile controls. The expression of perforin, CD94, CD161, CD158a, CD158b, and CD244 on CD3- CD56+ NK cells was analyzed by flow cytometry. RESULTS: A significant decrease in CD158a expression was demonstrated in RSA women (mean +/- SD, 22.9 +/- 8.7%) as compared with that in controls (33.6 +/- 15.7%) (P < 0.05). The percentage of NK cells showing dual expression of CD94 and CD161 was relatively higher in RSA women (55.1 +/- 10.2%) than in the controls (47.1 +/- 19.0%), but without statistically significant (P = 0.096). The expression of perforin, CD158b, or CD244 in RSA women did not differ from that in the controls. CONCLUSIONS: A divergence of the specific NK cell repertoire might be related to the etiology of RSA.

Abortion, Habitual↗

Interleukin-4 gene polymorphism is not involved in the risk of recurrent pregnancy loss.

PROBLEM: Enhanced secretion of type-2 T-helper (Th2) cytokine is a characteristic feature in normal physiological pregnancy. A study has demonstrated defective production of interleukine-4 (IL-4) and other Th2 cytokine in women with recurrent pregnancy loss (RPL). Several studies have suggested that IL-4 variable number of tandem repeat (VNTR) gene polymorphism is probably associated with different IL-4 production. METHODS OF STUDY: The IL-4 VNTR genotypes were assessed in 109 Japanese women with RPL and 210 ethnically matched women experiencing at least one live birth and no spontaneous abortion. RESULTS: No significant differences in IL-4 VNTR genotype frequencies were found between the RPL and the control [B1B1 genotype (reference); B1/B2 and B2/B2 genotypes, odds ratio, 0.91; 95% confidence interval, 0.58-1.45]. CONCLUSION: The present study suggests that the IL-4 VNTR allele is not a major genetic regulator in RPL.

Abortion, Habitual↗

Perfluorooctane sulfonate (PFOS) and related perfluorinated compounds in human maternal and cord blood samples: assessment of PFOS exposure in a susceptible population during pregnancy.

Fluorinated organic compounds (FOCs), such as perfluorooctane sulfonate (PFOS), perfluoro-octanoate (PFOA), and perfluorooctane sulfonylamide (PFOSA), are widely used in the manufacture of plastic, electronics, textile, and construction material in the apparel, leather, and upholstery industries. FOCs have been detected in human blood samples. Studies have indicated that FOCs may be detrimental to rodent development possibly by affecting thyroid hormone levels. In the present study, we determined the concentrations of FOCs in maternal and cord blood samples. Pregnant women 17-37 years of age were enrolled as subjects. FOCs in 15 pairs of maternal and cord blood samples were analyzed by liquid chromatography-electrospray mass spectrometry coupled with online extraction. The limits of quantification of PFOS, PFOA, and PFOSA in human plasma or serum were 0.5, 0.5, and 1.0 ng/mL, respectively. The method enables the precise determination of FOCs and can be applied to the detection of FOCs in human blood samples for monitoring human exposure. PFOS concentrations in maternal samples ranged from 4.9 to 17.6 ng/mL, whereas those in fetal samples ranged from 1.6 to 5.3 ng/mL. In contrast, PFOSA was not detected in fetal or maternal samples, whereas PFOA was detected only in maternal samples (range, < 0.5 to 2.3 ng/mL, 4 of 15). Our results revealed a high correlation between PFOS concentrations in maternal and cord blood (r2 = 0.876). However, we did not find any significant correlations between PFOS concentration in maternal and cord blood samples and age bracket, birth weight, or levels of thyroid-stimulating hormone or free thyroxine. Our study revealed that human fetuses in Japan may be exposed to relatively high levels of FOCs. Further investigation is required to determine the postnatal effects of fetal exposure to FOCs. Key words: cord blood, fluorinated organic compounds, human, PFOA, PFOS, PFOSA, pregnancy.

Adolescent↗

The estimated prevalence of hypospadias in Hokkaido, Japan.

BACKGROUND: Hypospadias is one of the most common congenital anomalies in the world. Recently, increases in the prevalence of hypospadias have been reported in various countries including Japan. In this study, we examined whether the prevalence of hypospadias in Hokkaido, Japan, increased or not, using standardized diagnostic criteria. We also investigated the degree of its severity. METHODS: We calculated prevalence of hypospadias using hospital records of hypospadias repair in Hokkaido. The prevalence from 1985 through 1997 by dividing the number of patients obtained from hospital records by the number of births. RESULTS: The average prevalence of hypospadias in Hokkaido was 3.9 per 10,000 births, and did not significantly change (p=0.7). The average proportions of distal, proximal and chordee alone were 56.7%, 39.6% and 3.7%, respectively. The decrease in the proportion of the proximal type was statistically significant (p=0.05) for the entire time period, whereas the proportion of the distal type did not have a significant upward trend for the observed 13 years (p=0.1). CONCLUSION: No significant changes in the prevalence of hypospadias existed in Hokkaido.

Child↗

Urinary catecholamines and salivary cortisol on workdays and days off in relation to job strain among female health care providers.

OBJECTIVES: This study examined the effects of psychosocial job strain on the excretion of neuroendocrine stress hormones (adrenaline, noradrenaline, and cortisol) on workdays and days off. METHODS: Japanese female health care providers (N=16) filled out Karasek's job content questionnaire and had their neuroendocrine excretions (ie, urinary catecholamines and salivary cortisol) measured on a day off and on two workdays (one day shift and one night shift). After control for age and job experience as covariates, a repeated-measures analysis of variance was carried out. RESULTS: Noradrenaline excretion was significantly greater over time in the high-strain group than in the low-strain group, and that of the high-demand group was significantly greater over time than that of the low-demand group. Adrenaline excretion did not significantly differ between the groups. The group with high supervisory support had significantly higher adrenaline excretion than the group with low supervisory support. The concentration of salivary cortisol on a dayshift was significantly lower, but marginally, in the high-strain group than in the low-strain group. CONCLUSIONS: Psychosocial job strain is associated with greater noradrenaline excretion over time. This finding suggests unwinding sympathetic nervous activity. The low cortisol levels of the high-strain group may indicate circadian rhythm disturbance induced by job strain. Supervisory relationships may have a particular influence for the studied occupation because the participants had more administrative contact with supervisors than support at the worksite; therefore, supervisory support may increase adrenaline excretion.

Adult↗

[Role of the social support network which influences age of death and physical function of elderly people: study of trends in and outside of Japan and future problems].

Concerning associations between the social support network and physical health of the elderly, longitudinal studies have been conducted using various measurement indexes. The studies indicated that the support network influences on physical function and life expectancy. In this study we compared research papers from Japan and elsewhere that appeared after 1980, from the viewpoint of 1) social support effects, and 2) social network effects, to examine potential problems in the future. The main knowledge obtained was that the receipt of emotional support, wide network size, and participation in social activities reduced the risk of early death and decrease in physical function of elderly people. Sex differences were indicated, and in many cases, the effects were more remarkable in men than women. In addition the positive influence of receiving help from a support network, a major subject of conventional research, the effects of offering help to others and negative findings were also examined. It has been indicated that participation in volunteer groups and offer of support to other people can prevent decrease in physical function or early death. As negative effects, improper instrumental support rather disturbs the mental and physical independence of elderly people. As future issues, it is necessary to focus on both positive/negative and receipt/offer effects of support network, and to clarify how to provide example which best match the life of elderly people by comparing sexes and regions. It is also important to actually apply the knowledge gained from observational studies to prevent the elderly from becoming a condition requiring care, and to develop intervention studies which can increase the social contacts of elderly people at the same time as conducting health education and medical treatment.

Aged↗