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Biomedical subjects

Y Kubo

Publications and source records attributed to Y Kubo.

At least 19 recordsLinked to original sources
PubMed2006

Regulatory mechanisms of ethylene biosynthesis in response to various stimuli during maturation and ripening in fig fruit (Ficus carica L.).

In order to obtain a greater uniformity of maturation, the growth of the fig fruit (Ficus carica L.) can be stimulated by the application of either olive oil, ethrel/ethephon or auxin. The three treatments induce ethylene production in figs. In this study, we investigated the regulatory mechanisms responsible for oil, auxin and ethylene induced ethylene production in figs. The ethylene production in response to olive oil, auxin, and propylene treatments and during ripening were all induced by 1-methylcyclopropene (1-MCP) and inhibited by propylene indicating a negative feedback regulation mechanism. Three 1-aminocyclopropane-1-carboxylic acid (ACC) synthase genes (Fc-ACS1, Fc-ACS2 and Fc-ACS3) and one ACC oxidase gene (Fc-ACO1) were isolated and their expression patterns in response to either oil, propylene or auxin treatment in figs determined. The expression patterns of Fc-ACS1 and Fc-ACO1 were clearly inhibited by 1-MCP and induced by propylene in oil treated and ripe fruits indicating positive regulation by ethylene, whereas Fc-ACS2 gene expression was induced by 1-MCP and inhibited by propylene indicating negative regulation by ethylene. The Fc-ACS3 mRNA showed high level accumulation in the auxin treated fruit. The inhibition of Fc-ACS3 gene by 1-MCP in oil treated and in ripe fruits suggests that auxin and ethylene modulate the expression of this gene by multi-responsive signal transduction pathway mechanisms. We further report that the olive oil-induced ethylene in figs involves the ACC-dependent pathway and that multiple ethylene regulatory pathways are involved during maturation and ripening in figs and each specific pathway depends on the inducer/stimulus.

Alkenes↗
PubMed2006

Effects of tetrabromobisphenol A, brominated flame retardant, in ICR mice after prenatal and postnatal exposure.

Tetrabromobisphenol A (TBBPA), brominated flame retardant, is produced in the largest amounts globally for use in plastics or building materials. TBBPA has been detected in sediment, air at the dismantling plant or human serum samples. In the present study, we examined the effects of prenatal and postnatal exposure to TBBPA in mice. TBBPA (99.1% pure) in diet was administered to pregnant ICR mice at doses of 0% (control), 0.01%, 0.1% or 1.0% from gestational day 0 to weaning at postnatal day 27. The average daily food intake and body weight of dams showed no significant differences between the control and treated groups. There were no dose-related effects on reproductive data. Serum concentrations of total-cholesterol and liver weights of treated dams and offspring were higher than those of the control mice. Histological findings in treated dams or offspring showed the increase of focal necrosis of hepatocytes and inflammatory cell infiltration in the liver, and increase of dilation or atrophy of renal tubules and cyst in the kidney. TBBPA was developed as a new, safe class of flame retardant and was not highly toxic. However, the present data suggested that TBBPA caused a lipid metabolic disorder and hepatic or kidney lesion, under these conditions.

Alanine Transaminase↗
PubMed2006

Evaluation of sentinel node identification with isosulfan blue in gastric cancer.

AIMS: The aim of this study was to clarify whether the metastasis of gastric cancer can be detected by identifying the sentinel lymph nodes (SNs) using only lymphatic dye. METHOD: The study was based on 101 patients clinically diagnosed with T1 and T2 gastric cancer. Isosulfan blue was intraoperatively injected within the submucosal layer around the lesion through an endoscope and blue stained nodes (BNs) were identified as SNs and harvested. Standard radical gastrectomy with D2 lymphadenectomy was performed on all patients and SNs and other nodes were evaluated. RESULTS: Out of 101 patients, 21 had lymph-node metastases. The accuracy of SN identification was 97.0% (98/101) and the metastasis detection rate was 85.7% (18/21). With improvement of the manoeuvre in the latter 84 cases, the detection rate was elevated up to 100.0% (18/18), as was the accuracy (84/84). CONCLUSION: The sentinel concept using lymphatic dye is applicable to gastric cancer, but the identification of SNs with lymphatic dye requires some practice. Furthermore, the issue of intraoperative metastasis detection remains to be resolved.

Adult↗
PubMed2006

Epigenetic abnormalities in cutaneous squamous cell carcinomas: frequent inactivation of the RB1/p16 and p53 pathways.

BACKGROUND: Aberrant methylation of CpG islands in the promoter regions of cancer-related genes has been demonstrated in many human tumours. However, the methylation profile of these regions in cutaneous squamous cell carcinomas (SCCs) has not been well studied. OBJECTIVES: To examine epigenetic abnormalities of a wide range of cancer-related genes in SCCs. METHODS: We investigated the methylation status of 11 candidate cancer-related genes (CDH1, p16(INK4a), p14(ARF), DAPK1, MGMT, RB1, RASSF1, p15(INK4b), PTEN, PRDM2 and p53) in 20 cases of SCC by methylation-specific polymerase chain reaction, and comparatively examined the protein production of E-cadherin (CDH1), p16, RB1, p14, BMI1 and cyclin A by immunohistochemical analysis. RESULTS: The frequency of cancer-related gene methylation in SCCs was: CDH1 (95%), p16 (20%), p14 (15%), DAPK1 (15%), MGMT (15%), RB1 (5%), RASSF1 (5%), p15 (0%), PTEN (0%), PRDM2 (0%) and p53 (0%). Almost all cases with hypermethylation of CDH1, p16, RB1 and p14 showed no obvious production of each protein, suggesting that promoter hypermethylation of these genes contributes to the loss of protein production. The results of methylation analysis, in combination with the results of our previous mutation analysis of CDKN2A locus and p53, revealed that 70% of SCCs have alterations in the RB1/p16 or p53 pathway. CONCLUSIONS: Our findings indicate that the promoter hypermethylation of cancer-related genes, especially CDH1, is frequently shown in SCCs, and dysregulation of the RB1/p16 and/or p53 pathway through either genetic or epigenetic mechanisms, except for epigenetic abnormalities of p53 itself, should contribute to the carcinogenesis of SCCs.

Aged↗
PubMed2006

Fibre-free diet leads to impairment of neuronally mediated muscle contractile response in rat distal colon.

Dietary fibre consumption is known to be beneficial to increase stool bulk and frequency. In contrast, it is unclear whether chronic dietary fibre deficiency affects colonic motor functions, especially neuronally mediated muscle contractions. In this study, rats were fed a fibre-free diet or diet containing dietary fibre (cellulose or guar gum) for 27 days. Furthermore, neurogenic and myogenic contractions were evaluated in circular and longitudinal muscle strips of the distal colon. Additionally, the number of enterochromaffin (EC) cells, which play important roles in the initiation of the peristaltic reflex, was also examined by immunohistochemistry for serotonin. Myogenic contractions induced by carbachol or substance P were examined in the presence of tetrodotoxin. Circular muscle was hyposensitive to carbachol, but longitudinal muscle was hypersensitive to substance P in the fibre-free group. Nerve-mediated circular (5-20 Hz) and longitudinal (1-2 Hz) muscle contractions evoked by electrical field stimulation were attenuated in the fibre-free group and the latter response was almost abolished by atropine, suggesting functional changes of cholinergic neurons. EC cell number was decreased in the fibre-free group. In conclusion, changes in neurogenic and myogenic contractions and a decrease in EC cell number observed may affect colonic motility of the fibre-free group.

Animal Feed↗
PubMed2005

Coupled charge-spin dynamics of the magnetoresistive pyrochlore TI2Mn2O7 probed using ultrafast midinfrared spectroscopy.

Optical-pump midinfrared probe spectroscopy is used to investigate coupled charge-spin dynamics in the magnetoresistive pyrochlore TI(2)Mn(2)O(7). We find that the temporal persistence of the photoexcited carrier density is strongly influenced by spin disorder above and below the ferromagnetic Curie temperature. Our results are consistent with a picture whereby spin disorder leads to spatial segregation of the initially excited Tl 6s-O 2p electron-hole pairs, effectively reducing the probability for recombination. This further implies that colossal magnetoresistance in these materials may be driven primarily by Mn t(2g) spin disorder.

Journal Article↗
PubMed2005

Depressive mood is independently related to stroke and cardiovascular events in a community.

By means of a multivariate Cox model, we investigated the predictive value of a depressive mood on vascular disease risk in middle-aged community-dwelling people. In 224 people (88 men and 136 women; mean age: 56.8 +/- 11.2 years) of U town, Hokkaido (latitude: 43.45 degrees N, longitude: 141.85 degrees E), a chronoecological health watch was started in April 2001. Consultations were repeated every 3 months. Results at the November 30, 2004 follow-up are presented herein. 7-day/24-h blood pressure (BP) and heart rate (HR) monitoring started on a Thursday, with readings taken at 30-min intervals between 07:00 h and 22:00 h and at 60-min intervals between 22:00 h and 07:00 h. Data stored in the memory of the monitor (TM-2430-15, A and D company, Japan) were retrieved and analyzed on a personal computer with a commercial software for this device. Subjects were asked to answer a self-administered questionnaire inquiring about 15 items of a depression scale, at the start of study and again after 1-2 years. Subjects with a score higher by at least two points at the second versus first screening were classified as having a depressive mood. The other subjects served as the control group. The mean follow-up time was 1064 days, during which four subjects suffered an adverse vascular outcome (myocardial infarction: one man and one woman; stroke: two men). Among the variables used in the Cox proportional hazard models, a depressive mood, assessed by the Geriatric Depression Scale (GDS), as well as the MESOR of diastolic (D) BP (DBP-MESOR) and the circadian amplitude of systolic (S) BP (SBP-Amplitude) showed a statistically significant association with the occurrence of adverse vascular outcomes. The GDS score during the second but not during the first session was statistically significantly associated with the adverse vascular outcome. In univariate analyses, the relative risk (RR) of developing outcomes was predicted by a three-point increase in the GDS scale (RR = 3.088, 95% CI: 1.375-6.935, P = 0.0063). Increases of 5 mmHg in DBP-MESOR and of 3 mmHg in SBP-Amplitude were associated with RRs of 2.143 (95% CI: 1.232-3.727, P = 0.0070) and 0.700 (95% CI: 0.495-0.989, P = 0.0430), respectively. In multivariate analyses, when both the second GDS score and the DBP-MESOR were used as continuous variables in the same model, GDS remained statistically significantly associated with the occurrence of cardiovascular death. After adjustment for DBP-MESOR, a three-point increase in GDS score was associated with a RR of 2.172 (95% CI: 1.123-4.200). Monday endpoints of the 7-day profile showed a statistically significant association with adverse vascular outcomes. A 5 mmHg increase in DBP on Monday was associated with a RR of 1.576 (95% CI: 1.011-2.457, P = 0.0446). The main result of the present study is that in middle-aged community-dwelling people, a depressive mood predicted the occurrence of vascular diseases beyond the prediction provided by age, gender, ABP, lifestyle and environmental conditions, as assessed by means of a multivariate Cox model. A depressive mood, especially enhanced for 1-2 years, was associated with adverse vascular outcomes. Results herein suggest the clinical importance of repetitive assessments of a depressive mood and the need to take sufficient care of depressed subjects. Another result herein is that circadian and circaseptan characteristics of BP variability measured 7-day/24-h predicted the occurrence of vascular disease beyond the prediction provided by age, gender, depressive mood and lifestyle, as assessed by means of a multivariate Cox model. Earlier, we showed that the morning surge in BP on Mondays was statistically significantly higher compared with other weekdays. Although a direct association between the Monday surge in BP and cardiovascular events could not be demonstrated herein, it is possible that the BP surge on Monday mornings may also trigger cardiovascular events. We have shown that depressive people exhibit a more prominent circaseptan variation in SBP, DBP and the double product (DP) compared to non-depressed subjects. In view of the strong relation between depression and adverse cardiac events, studies should be done to ascertain that depression is properly diagnosed and treated. Chronodiagnosis and chronotherapy can reduce an elevated blood pressure and improve the altered variability in BP and HR, thus reducing the incidence of adverse cardiac events. This recommendation stands at the basis of chronomics, focusing on prehabilitation in preference to rehabilitation, as a public service offered in several Japanese towns.

Adult↗
PubMed2005

Arterial stiffness independently predicts cardiovascular events in an elderly community -- Longitudinal Investigation for the Longevity and Aging in Hokkaido County (LILAC) study.

We investigated the predictive value of arterial stiffness to assess cardiovascular risk in elderly community-dwelling people by means of a multivariate Cox model. In 298 people older than 75 years (120 men and 178 women, average age: 79.6 years), brachial-ankle pulse wave velocity (baPWV) was measured between the right arm and ankle in a supine position. The LILAC study started on July 25, 2000, consultation was repeated yearly, and the last follow-up ended on November 30, 2004. During this follow-up span of 1227 days, there were nine cardiovascular deaths, the cause of death being myocardial infarction for two men and three women or stroke for two men and two women. In Cox proportional hazard models, baPWV as well as age, Mini-Mental State Examination (MMSE), Hasegawa Dementia Scale Revised (HDSR) and the low-frequency/high-frequency (LF/HF) ratio showed a statistically significant association with the occurrence of cardiovascular death. A two-point increase in MMSE and HDSR score significantly protected against cardiovascular death, the relative risk (RR) being 0.776 (P = 0.0369) and 0.753 (P = 0.0029), respectively. The LF/HF ratio also was significant (P = 0.025), but the other indices of HRV were not. After adjustment for age and HDSR, a 200 cm/s increase in baPWV was associated with a 30.2% increase in risk (RR = 1.302, 95% CI: 1.110-1.525), and a 500 cm/s increase in baPWV with a 93.3% increase in risk (RR = 1.933, 95% CI: 1.300-2.874, P = 0.0011), whereas the LF/HF ratio was no longer associated with a statistically significant increase in cardiovascular mortality. In elderly community-dwelling people, arterial stiffness measured by means of baPWV predicted the occurrence of cardiovascular death beyond the prediction provided by age, gender, blood pressure and cognitive functions. baPWV should be added to the cardiovascular assessment in various clinical settings, including field medical surveys and preventive screening. The early detection of risk by chronomics allows the timely institution of prophylactic measures, thereby shifting the focus from rehabilitation to prehabilitation medicine, as a public service to several Japanese towns.

Aged↗
PubMed2005

Fractal analysis of heart rate variability and mortality in elderly community-dwelling people -- Longitudinal Investigation for the Longevity and Aging in Hokkaido County (LILAC) study.

AIM: Fractal analysis of heart rate (HR) variability (HRV) has been used as a new approach to evaluate the risk of mortality in various patient groups. Aim of this study is to examine the prognostic power of detrended fluctuation analysis (DFA) and traditional time- and frequency-domain analyses of HR dynamics as predictors of mortality among elderly people in a community. METHODS: We examined 298 people older than 75 years (average age: 79.6 years) and 1-h ambulatory ECG was monitored. During the last 10 min, deep respiration (6-s expiration and 4-s inspiration) was repeated six times in a supine position. Time-domain and frequency-domain measures were determined by the maximum entropy method. Scaling exponents of short-term (<11 beats, alpha 1) and longer-term (>11 beats, alpha 2) were determined by the DFA method. Six estimates, obtained from 10-min segments, were averaged to derive mean values for the entire recording span. These average values were denoted Alpha 1 and Alpha 2, estimates obtained during the first 10-min segment Alpha 1 S and Alpha 2 S, and those during the last 10-min segment Alpha 1E and Alpha 2E, respectively. The LILAC study started on July 25, 2000 and ended on November 30, 2004. We used Cox regression analysis to calculate relative risk (RR) and 95% confidence interval (CI) for all-cause mortality. Significance was considered at a value of P < 0.05. RESULTS: Gender, age and Alpha 2E showed a statistically significant association with all-cause mortality. In univariate analyses, gender was significantly associated with all-cause mortality, being associated with a RR of 3.59 (P = 0.00136). Age also significantly predicted all-cause mortality and a 5-year increase in age was associated with a RR of 1.49 (P = 0.01809). The RR of developing all-cause mortality predicted by a 0.2-unit increase in Alpha 2E was 0.58 (P = 0.00390). Other indices of fractal analysis of HRV did not have predictive value. In multivariate analyses, when both Alpha 2E and gender were used as continuous variables in the same model, Alpha 2E remained significantly associated with the occurrence of all-cause mortality (P = 0.02999). After adjustment for both gender and age, a 0.2-unit increase in Alpha 2E was associated with a RR of 0.61 (95% CI: 0.42-0.90, p = 0.01151). CONCLUSION: An intermediate-term fractal-like scaling exponent of RR intervals was a better predictor of death than the traditional measures of HR variability in elderly community-dwelling people. It is noteworthy that the longer-term (alpha 2) rather than the short-term fractal component (alpha 1) showed predictive value for all-cause mortality, which suggests that an increase in the randomness of intermediate-term HR behavior may be a specific marker of neurohumoral and sympathetic activation and therefore may also be associated with an increased risk of mortality.

Aged↗
PubMed2005

Common carotid intima-media thickness is predictive of all-cause and cardiovascular mortality in elderly community-dwelling people: Longitudinal Investigation for the Longevity and Aging in Hokkaido County (LILAC) study.

Several cohort studies have examined the association of carotid intima-media thickness (IMT) with the risk of stroke or myocardial infarction in apparently healthy persons. We investigated the predictive value of IMT of cardiovascular mortality in elderly community-dwelling people, beyond the prediction provided by age and MMSE, assessed by means of a multivariate Cox model. Carotid IMT and plaque were evaluated bilaterally with ultrasonography in 298 people older than 75 years (120 men and 178 women, average age: 79.6 years). The LILAC study started on July 25, 2000. Consultations were repeated every year. The follow-up ended on November 30, 2004. During the mean follow-up span of 1152 days, 30 subjects (21 men and nine women) died. Nine deaths were attributable to cardiovascular causes (myocardial infarction: two men and three women; stroke: two men and two women). The age- and MMSE-adjusted relative risk (RR) and 95% confidence interval (95% CI) of developing all-cause mortality was assessed. A 0.3 mm increase in left IMT was associated with a RR of predicted 1.647 (1.075-2.524), and a similar increase in right IMT with a RR of 3.327 (1.429-7.746). For cardiovascular mortality, the corresponding RR values were 2.351 (1.029-5.372) and 2.890 (1.059-7.891), respectively. Carotid IMT assessed by ultrasonography is positively associated with an increased risk of all-cause and cardiovascular death in elderly community-dwelling people.

Age Factors↗
PubMed2005

Bowen's disease on the sole: p16INK4a overexpression associated with human papillomavirus type 16.

We report a case of Bowen's disease on the sole presenting clinically as an exophytic, blackish-grey, verrucous tumour, and showing human papillomavirus (HPV) type 16 on analysis with polymerase chain reaction. Positive stains for HPV particles by immunohistochemical analysis were limited to several cell nuclei at the upper stratum Malpighii. However, all the tumour cells in the epidermis exhibited strong and diffuse nuclear and cytoplasmic stains for the tumour suppressor protein p16INK4a. We speculate that dysregulation of the retinoblastoma/p16INK4a pathway may be involved in the pathogenesis of the lesion, and p16INK4a overexpression might serve as a useful surrogate marker for identifying Bowen's disease harbouring high-risk types of HPV infection.

Adult↗
PubMed2004

Positive impact of social intervention on disturbed neurobehavioral function in an elderly community-dwelling population: longitudinal investigation for longevity and aging in Hokkaido County (LILAC).

Several kinds of health consultation and rehabilitation for functional disorders aimed at stroke prevention and maintenance of cognitive function in an elderly population in Hokkaido county, Japan. Changes in cardiovascular and neurobehavioral endpoints between 2000 and 2002 were assessed in 72 of 115 subjects over 75 years of age. Direct social intervention, including lifestyle modification can have a positive impact, notably on subjects with cardiovascular disorders.

Aged↗
PubMed2004

Type I interferon receptor and response to interferon therapy in chronic hepatitis C patients: a prospective study.

The type I interferon (IFN) receptor consists of at least two subunits, IFNAR1 and IFNAR2. We previously found a correlation between IFNAR1 and IFNAR2 expression in liver, and a correlation in IFNAR2 expression, but not in IFNAR1, between liver and peripheral blood mononuclear cells (PBMCs). The aim of this study was to prospectively assess whether IFNAR2 expression levels in PBMCs as well as in liver act as markers for predicting response to IFN therapy in chronic hepatitis C patients. Fifty-two Japanese patients with chronic hepatitis C, were enrolled. IFNAR2 mRNA was quantified using competitive polymerase chain reaction, in liver and PBMC specimens, and of the 52 patients assigned to receive a 6-month course of interferon-alpha therapy, 36 patients who received more than 300 million units of interferon were analysed. IFNAR2 mRNA expression levels were significantly higher in liver than in PBMCs in all 36 patients (P = 0.016). Seventeen sustained virologic responders showed lower pretreatment hepatitis C virus (HCV)-RNA levels (P = 0.017) in serum and higher pretreatment levels of IFNAR2 mRNA in liver (P = 0.007), but not in PBMCs, compared with nonsustained virologic responders. In multivariate analysis, these factors were independently associated with a sustained virologic response (i.e. HCV-RNA level: odds ratio 0.23, 95% CI 0.038-0.864; and IFNAR2 in liver: odds ratio 1.116, 95% CI 1.015-1.227). Hence, IFNAR2 expression levels in liver, but not in PBMCs, is predictive of response to IFN treatment in chronic hepatitis C patients.

Adult↗
PubMed2003

Genistein, a protein tyrosine kinase inhibitor, suppresses the fusogenicity of Moloney murine leukemia virus envelope protein in XC cells.

XC cells are highly susceptible to syncytium formation by infection of ecotropic murine leukemia viruses (MLVs) and by expression of their envelope protein (Env). By this property, XC cells are widely used to determine titers of ecotropic MLVs. Number of plaques resulted from the syncytium formation in XC cells by ecotropic MLV infection is corresponding to number of the viral particles. XC cells had been established from a v-src-induced rat tumor. It has been reported that transformed cells are more sensitive to Mo-MLV-induced syncytium formation than non-transformed cells. To assess whether the transformation by v-src oncogene in XC cells is involved in the high sensitivity to ecotropic MLV-induced syncytium formation, XC cells were treated with genistein, a protein tyrosine kinase inhibitor. Genistein suppressed the syncytium formation between XC cells and ecotropic Env-expressing 293T cells. This result indicates that protein tyrosine kinase activity is associated with the high sensitivity of XC cells to ecotropic Env-induced syncytium formation.

Animals↗
PubMed2003

Chronomics for chronoastrobiology with immediate spin-offs for life quality and longevity.

Effects of geomagnetic disturbance on heart rate variability (HRV), the 1/f fractal scaling in particular, are being assessed in adults living at high latitude, where magnetic storms are more frequent and more intense than at lower latitudes. The latter may constitute a signal or a proxy, and possibly a mechanism underlying both undesirable and desirable effects, depending upon circumstances yet to be elucidated. Any circadecadal stage-dependence of morbidity and/or mortality from certain conditions such as myocardial infarctions remains to be studied in both adult and pediatric populations. Further work could thus examine whether any associations of geomagnetic disturbances may account, at least in part, through effects upon the circulation, for long-term infra-annual changes, possibly anchored in the population's gene pool, observed in a number of anthropologic measurements at birth as well as in other population statistics. In order to assess the development of several chronome components of the electrocardiogram (ECG), around-the-clock ambulatory ECG were recorded from 19 infants (25 days-3 months of age), 22 children (3-9 years of age), 18 boys and girls (10-14 years of age), pubertal boys (15-20 years of age), and 10 young men (21-29 years of age). Time- and frequency-domain measures of HRV were obtained by spectral analysis, using the maximal entropy method (MEM). The frequency of detection of the circadian, circasemidian and circaoctohoran components, with periods of about 24, 12 and 8 h, respectively, was compared among the five groups for several HRV endpoints, notably 1/f fractal scaling, total spectral power within a 5-min span, and its distribution into several frequency regions. A circadian component is already detectable in a sizeable proportion of infants and children for most of the HRV indices considered. The incidence of detection of the circadian component increases with age for the spectral power in different frequency regions, notably around 10.5 s ("LF") and around 3.6 s ("HF"); it peaks around puberty for 1/f in our data; and it did not detectably change with age for the total spectral power. Similar changes with age are not observed for the circasemidian or circaoctohoran components. The latter characterizes primarily 1/f and less so the about 3.6 s power ("HF"). Several aspects of the HRV chronome may thus develop differently as a function of age. In 2000, we began a community-based study named "Longitudinal Investigation of Longevity and Aging in Hokkaido County (LILAC study)". The ambulatory blood pressure (BP) of middle-aged subjects, aged 40-74 years, was monitored 7-day/24-h, and the cardiovascular and neurobehavioral functions of elderly people above 75 years were evaluated. Our goal was the prevention of stroke and myocardial infarction and the decline in cognitive function of the elderly in a community. Of 115 elderly people recruited in a longitudinal community-based study in 2000, 72 completed yearly follow-ups in 2002. A cardiovascular score based on BP, pulse wave velocity, and 1-h ECG-based HRV endpoints served to distinguish between normal, mildly disordered, or disordered participants. A comparison of cognitive function in 2002 vs. 2000, assessed with the MMSE, HDSR, the Up & Go and Functional Reach tests, gauged any effect of social intervention. Cognitive function was maintained or improved, especially for people suffering from hypertension, tachycardia, or a decreased HRV, suggesting that cardiovascular function is a major factor affecting cognitive function.

Cardiovascular Diseases↗
PubMed2003

Radiation dose-dependent increases in inflammatory response markers in A-bomb survivors.

PURPOSE: The well-documented increases in malignant tumours in the A-bomb survivors have recently been supplemented by reports that non-cancer diseases, including cardiovascular disease, may also have increased in incidence with increasing radiation dose. Given that low-level inflammatory responses are widely accepted as a significant risk factor for such diseases, we undertook a detailed investigation of the long-term effects of ionizing radiation on the levels of the inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) in A-bomb survivors. MATERIALS AND METHODS: Blood samples were taken from 453 participants in a long-term epidemiological cohort of A-bomb survivors. Plasma levels of CRP and IL-6 were measured using standard antibody-mediated procedures. Relationships between CRP or IL-6 levels and radiation dose were then investigated by multivariate regression analysis. Blood lymphocytes from each individual were used for immunophenotyping by flow cytometry with murine monoclonal antibodies to CD3, CD4 and CD8. RESULTS: CRP levels were significantly increased by about 31% Gy(-1) of estimated A-bomb radiation (p=0.0001). Higher CRP levels also correlated with age, male gender, body mass index and a history of myocardial infarction. After adjustments for these factors, CRP levels still appeared to have increased significantly with increasing radiation dose (about 28% increase at 1Gy, p=0.0002). IL-6 levels also appeared to have increased with radiation dose by 9.3% at 1Gy (p=0.0003) and after multiple adjustments by 9.8% at 1Gy (p=0.0007). The elevated CRP and IL-6 levels were associated with decreases in the percentages of CD4(+) helper T-cells in peripheral blood lymphocyte populations. CONCLUSIONS: Our results appear to indicate that exposure to A-bomb radiation has caused significant increases in inflammatory activity that are still demonstrable in the blood of A-bomb survivors and which may lead to increased risks of cardiovascular disease and other non-cancer diseases.

Aged↗