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Biomedical subjects

S Murakami

Publications and source records attributed to S Murakami.

At least 19 recordsLinked to original sources
PubMed2006

Extranuclear expression of hormone receptors in primary breast cancer.

BACKGROUND: Hormone receptor (HR)-positive breast cancer cells grow through estrogen receptor (ER)-signaling pathways that mediate both genomic and nongenomic actions, which cross-talk with growth factors associated with resistance to tamoxifen. The aim of this study was to explore the cross-talk between extranuclear expression of ER and progesterone receptor (PR) and growth factor signaling pathways in primary breast cancer. PATIENTS AND METHODS: The extranuclear expression of ER and PR was examined in 219 primary breast cancers by immunohistochemical staining. Specimens showing such expression were further examined for the expression of pAkt and aromatase. Staining reactions were scored on the basis of intensity and distribution in the tumors. RESULTS: Extranuclear expression of ER or PR was observed in 21 cases (9.5%), which included four cases for ER and 20 cases for PR. Among these patients, HER-2, pAkt, and aromatase-positivity were observed in 14 cases (66.6%), 13 cases (61.9%), and 14 cases (66.6%), respectively. On the basis of nuclear HR expression, 11 of these cases were categorized as ER-positive/PR-negative, while two were ER-negative/PR-positive. Of these 13 cases, increased pAkt staining was found in 11 cases (84.6%). In particular, among the 11 ER-positive/PR-negative cases, elevated pAkt and aromatase were found in 10 (90.9%; P<0.01) and nine cases (81.8%), respectively. CONCLUSIONS: PR is expressed extranuclearly more frequently than ER in primary breast cancer, and extranuclear HRs cross-talk with the Akt/HER-2-signaling pathways and activation of aromatase. These observations may explain the more beneficial effects of aromatase inhibitors than tamoxifen for ER-positive/PR-negative patients.

Adult↗
PubMed2006

Regulation and interplay of apoptotic and non-apoptotic cell death.

Various death triggers including DNA damage, oxidative stress, and growth factor deprivation promote the loss of mitochondrial membrane potential, leading to the production of reactive oxidative species (ROS) or enhanced permeability of the mitochondrial membrane, otherwise known as mitochondrial membrane permeabilization, by insertion of Bax/Bak into the outer membrane where it interacts with voltage-dependent anion channel (VDAC)/adenine nucleotide transporter (ANT). MMP leads to the release of small pro-apoptotic molecules, which induce caspase-dependent and -independent apoptotic cell death. The production of ROS due to the loss of mitochondrial membrane potential enhances the permeability of lysosomal membranes, resulting in the release of lysosomal proteases, which contribute to mitochondrial membrane permeabilization and the lysosomal degradation mechanism of autophagic cell death. Although defects in apoptotic and non-apoptotic cell death pathways can be carcinogenic, these pathways are more or less preserved within cancer cells and can therefore influence cell death and mediate resistance to cancer treatment. This paper discusses recent advances in determining the molecular mechanisms behind regulation of apoptotic and non-apoptotic cell death, as well as the interplay between these two processes, which may lead to the development of new strategies by which to enhance the therapeutic effects of chemotherapeutic agents.

Animals↗
PubMed2006

Role of the unfolded protein response in cell death.

Unfolded protein response (UPR) is an important genomic response to endoplasmic reticulum (ER) stress. The ER chaperones, GRP78 and Gadd153, play critical roles in cell survival or cell death as part of the UPR, which is regulated by three signaling pathways: PERK/ATF4, IRE1/XBP1 and ATF6. During the UPR, accumulated unfolded protein is either correctly refolded, or unsuccessfully refolded and degraded by the ubiquitin-proteasome pathway. When the unfolded protein exceeds a threshold, damaged cells are committed to cell death, which is mediated by ATF4 and ATF6, as well as activation of the JNK/AP-1/Gadd153-signaling pathway. Gadd153 suppresses activation of Bcl-2 and NF-kappaB. UPR-mediated cell survival or cell death is regulated by the balance of GRP78 and Gadd153 expression, which is coregulated by NF-kappaB in accordance with the magnitude of ER stress. Less susceptibility to cell death upon activation of the UPR may contribute to tumor progression and drug resistance of solid tumors.

Animals↗
PubMed2006

Effect of diglucosamine on the entrapment of protein into liposomes.

Liposomes, which had entrapped bovine serum albumin (BSA), were modified with diglucosamine by two methods. The liposome was prepared by a freeze-thawing method in the presence of the disaccharide, or the disaccharide was added to the liposome prepared in advance without it. To examine the effects of diglucosamine, the morphology, mean particle size, and zeta potential of both liposomes were compared with those of BSA-entrapping liposome prepared without the disaccharide. Diglucosamine caused no remarkable change in shape and no aggregation of the liposome. The presence of the disaccharide was confirmed on the surfaces of modified liposomes, and the entrapment of BSA into the liposomes was increased by the disaccharide. The entrapment behavior was affected by the way the disaccharide was added, and the difference in the way the BSA was entrapped was also indicated.

Animals↗
PubMed2006

Regulation of PLAP-1 expression in periodontal ligament cells.

Periodontal-ligament-associated protein-1 (PLAP-1) is preferentially expressed in the periodontal ligament (PDL) and encodes a novel small leucine-rich repeat proteoglycan protein. PLAP-1 expression was induced during the course of cytodifferentiation of PDL cells into mineralized-tissue-forming cells in vitro, suggesting the possible involvement of PLAP-1 in the mineralization process of PDL cells. In this study, we hypothesized that PLAP-1 expression is regulated by mineralization-related cytokines in PDL cells. PLAP-1 expression was clearly down-regulated when the cytodifferentiation of PDL cells was reversibly inhibited by fibroblast growth factor-2 (FGF-2). In contrast, bone morphogenetic protein-2 (BMP-2) enhanced PLAP-1 expression. Up-regulation of PLAP-1 expression by BMP-2 was confirmed at the protein level when PDL cells were immunostained with anti-PLAP-1 polyclonal antibody. These results revealed the cytokine-mediated regulatory mechanisms of PLAP-1 expression and suggested that PLAP-1 expression may be associated with the process of cytodifferentiation of PDL cells.

Amino Acid Sequence↗
PubMed2006

Activation of adenosine receptor on gingival fibroblasts.

CD73 (ecto-5'-nucleotidase) on human gingival fibroblasts plays a role in the regulation of intracellular cAMP levels through the generation of adenosine, which subsequently activates adenosine receptors. In this study, we examined the involvement of ecto-adenosine deaminase, which can be anchored to CD26 on human gingival fibroblasts, in metabolizing adenosine generated by CD73, and thus attenuating adenosine receptor activation. Ecto-adenosine deaminase expression on fibroblasts could be increased by pre-treatment with a lysate of Jurkat cells, a cell line rich in cytoplasmic adenosine deaminase. Interestingly, the cAMP response to adenosine generated from 5'-AMP via CD73 and the ability of 5'-AMP to induce hyaluronan synthase 1 mRNA were significantly decreased by the pre-treatment of fibroblasts with Jurkat cell lysate. This inhibitory effect was reversed by the specific adenosine deaminase inhibitor. These results suggest that ecto-adenosine deaminase metabolizes CD73-generated adenosine and regulates adenosine receptor activation.

5'-Nucleotidase↗
PubMed2006

Resource recovery from excess sludge by subcritical water combined with magnesium ammonium phosphate process.

The amount of excess sludge produced in municipal wastewater treatment plants in Japan is increasing every year as the urban population increases. Phosphorus in excess sludge could be a potential phosphorus resource since at present, phosphate rock is being exhausted all over the world. Every year, Japan imports large quantities of phosphorus from abroad but much is discharged as excess sludge. Therefore, the solubilization process, one method of recovering phosphorus from sludge, could be a promising solution. In this study, a subcritical water process, a new technology that solubilizes sludge under subcritical conditions, was applied before the phosphorus in sludge was recovered with the magnesium ammonium phosphate (MAP) process. As a result, the solubilization rate of excess sludge achieved approximately 80% and about 94-97% of the phosphorus could be recovered.

Cities↗
PubMed2005

Regulation of prostaglandin synthesis by interleukin-1alpha in bovine endometrium during the estrous cycle.

Interleukin (IL)-1 has been suggested to participate in regulation of many reproductive functions. To investigate the possible role of IL-1alpha as a local regulator in bovine endometrium, we determined the effects of IL-1alpha on prostaglandin (PG) E2 and PGF(2alpha) output by the bovine endometrium at different stages of the estrous cycle. The expressions of IL-1alpha and IL-1 receptor type 1 (IL-1RT1) mRNA in bovine endometrium were also studied. Bovine uteri were classified into six stages (estrus: day 0; early luteal: days 2-3; developing luteal: days 5-6; mid luteal: days 8-12; late luteal: days 15-17; and follicular: days 19-21). After 1h of pre-incubation, endometrial tissues (20-30mg) were exposed to 0 or 10ng/ml IL-1alpha for 4h. IL-1alpha significantly stimulated PGE2 output throughout the luteal stages, with the highest response during the mid luteal stage, while it did not stimulate PGE2 output during the estrus and the follicular stage. On the other hand, IL-1alpha significantly enhanced PGF(2alpha) output throughout the estrous cycle except in the endometrium from the mid luteal stage, with the highest response at the follicular stage (P<0.001). The treatment of endometrial tissue with IL-1alpha resulted in an increase of the PGE2:PGF(2alpha) ratio at the mid luteal stage, and in a decrease during the late luteal and follicular stages of the estrous cycle. A semiquantitative reverse transcription-polymerase chain reaction revealed that IL-1alpha and IL-1RT1 mRNA are expressed in the endometrium throughout the estrous cycle. IL-1alpha mRNA expression was greater in the early luteal stage than in the estrus, late luteal, and follicular stages (P<0.05). IL-1RT1 mRNA was greater in the late luteal stage than in the other stages (P<0.05). The overall results suggest that IL-1alpha is produced in bovine endometrium throughout the estrous cycle, and plays some roles not only in maintenance of CL, but also in luteolysis by regulating the local PGE2:PGF(2alpha) ratio in bovine endometrium during the estrous cycle.

Animals↗
PubMed2005

Inhibition of endogenous SHIP2 ameliorates insulin resistance caused by chronic insulin treatment in 3T3-L1 adipocytes.

AIMS/HYPOTHESIS: SHIP2 is a physiologically important negative regulator of insulin signalling hydrolysing the PI3-kinase product, PI(3,4,5)P3, which also has an impact on insulin resistance. In the present study, we examined the effect of inhibiting the endogenous SHIP2 function on the insulin resistance caused by chronic insulin treatment. METHODS: The endogenous function of SHIP2 was inhibited by expressing a catalytically inactive SHIP2 (DeltaIP-SHIP), and compared with the effect of treatments designed to restore the levels of IRS-1 in insulin signalling systems of 3T3-L1 adipocytes. RESULTS: Chronic insulin treatment induced the large (86%) down-regulation of IRS-1 and the modest (36%) up-regulation of SHIP2. Subsequent stimulation by insulin of Akt phosphorylation, PKClambda activity, and 2-deoxyglucose (2-DOG) uptake was markedly decreased by the chronic insulin treatment. Coincubation with the mTOR inhibitor, rapamycin, effectively inhibited the proteosomal degradation of IRS-1 caused by the chronic insulin treatment. Although the coincubation with rapamycin and advanced overexpression of IRS-1 effectively ameliorated subsequent insulin-induced phosphorylation of Akt, insulin stimulation of PKClambda activity and 2-DOG uptake was partly restored by these treatments. Similarly, expression of DeltaIP-SHIP2 effectively ameliorated the insulin-induced phosphorylation of Akt without affecting the amount of IRS-1. Furthermore, the decreased insulin-induced PKClambda activity and 2-DOG uptake following chronic insulin treatment were ameliorated by the expression of DeltaIP-SHIP2 more effectively than by the treatment with rapamycin. CONCLUSIONS/INTERPRETATION: Our results indicate that the inhibition of endogenous SHIP2 is effective in improving the state of insulin resistance caused by chronic insulin treatment.

3T3 Cells↗
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

Effect of aging on blood pressure in Leh, Ladakh, a high-altitude (3524 m) community, by comparison with a Japanese town.

The effect of aging on blood pressure (BP) and heart rate (HR) was investigated in a cross-sectional study in the high-altitude community of Leh, Ladakh (altitude: 3524 m) and a Japanese community in U town, Hokkaido (altitude: 25 m). BP and HR were obtained in a sitting position from 332 subjects 13-81 years of age in Ladakh, and from 216 Japanese citizens, 24-79 years of age. Measurements were taken after a 2-min rest, using a semi-automated BP device (UA-767 PC, A and D Co. LTD, Tokyo). High-altitude people showed higher diastolic BP and HR values than lowland people (83.2 vs. 76.9 mmHg and 78.6 vs. 69.2 bpm, P < 0.001), but no difference in systolic BP. Highland people also showed a steeper BP increase with age than the lowland people (systolic BP: 0.7476 vs. 0.3179 mmHg/year, P < 0.0005; diastolic BP: 0.3196 vs. 0.0750 mmHg/year, P < 0.001). This chronoecologic investigation in Ladakh examined the circulation as a physiological system at high-altitude. Our data indicate the need for a more comprehensive cardiovascular assessment for a better diagnosis and a more fruitful treatment. Longitudinal observations of effects of socio-ecologic factors on the cardiovascular system should help prevent strokes and other cardiovascular events, especially at high altitude.

Adolescent↗
PubMed2005

Chronoecological health watch of arterial stiffness and neuro-cardio-pulmonary function in elderly community at high altitude (3524 m), compared with Japanese town.

Effects of high altitude on arterial stiffness and neuro-cardio-pulmonary function were studied. Blood pressure (BP) and heart rate (HR) were measured in a sitting position on resting Ladakhis, living at an altitude of 3250-4647 m (Phey village, 3250 m: 17 men and 55 women; Chumathang village, 4193 m: 29 men and 47 women; Sumdo village, 4540 m: 38 men and 57 women; and Korzok village, 4647 m: 84 men and 70 women). The neuro-cardio-pulmonary function, including the Kohs block design test, the Up and Go, the Functional Reach and the Button tests, was examined in 40 elderly subjects (19 men and 21 women, mean age: 74.7 +/- 3.3 years) in Leh, Ladakh (altitude: 3524 m), for comparison with 324 elderly citizens (97 men and 227 women, mean age: 80.7 +/- 4.7 years) of Tosa, Japan (altitude: 250 m). Cardio-Ankle Vascular Index (CAVI) was measured as the heart-ankle pulse wave velocity (PWV) in these subjects using a VaSera CAVI instrument (Fukuda Denshi, Tokyo). SpO(2) decreased while Hb and diastolic BP increased with increasing altitude. At higher altitude, residents were younger and leaner. Women in Leh vs. Tosa had a poorer cognitive function, estimated by the Kohs block design test (3.7 +/- 3.6 vs. 16.4 +/- 9.6 points, P < 0.0001) and poorer ADL functions (Functional Reach: 13.7 +/- 7.0 cm vs. 25.3 +/- 8.7 cm, P < 0.0001; Button test: 22.5 +/- 4.8 vs. 14.8 +/- 5.7 s, P < 0.0001). Time estimation was shorter at high altitude (60-s estimation with counting: 41.1% shorter in men and 23.0% shorter in women). A higher voltage of the QRS complex was observed in the ECG of Leh residents, but two times measurement of CAVI showed no statistically significant differences between Leh and Tosa (two times of CAVI measures; 9.49 vs. 10.01 m/s and 9.41 vs. 10.05 m/s, respectively), suggesting that most residents succeed to adapt sufficiently to the high-altitude environment. However, correlation of CAVI with age shows several cases who show an extreme increase in CAVI. Thus, for the prevention of stroke and other adverse cardiovascular outcomes, including dementia, CAVI may be very useful, especially at high altitude. In conclusion, elderly people living at high altitude have a higher risk of cardiovascular disease than low-latitude peers. To determine how these indices are associated with maintained cognitive function deserves further study by the longitudinal follow-up of these communities in terms of longevity and aging in relation to their neuro-cardio-pulmonary function.

Adolescent↗
PubMed2005

Yearly and perhaps transyearly human natality patterns near the equator and at higher latitudes.

Data on the daily numbers of births in Davao, Philippines, available from 1993 to 2003 are re-analyzed herein by linear-nonlinear rhythmometry, as are data from Italy and Japan. A transyear, characterizing the solar wind and other non-photic physical environmental factors, corresponds to a spectral peak of the near-equatorial natality series. This component with a period of about 1.3 years is found to have an amplitude larger than the calendar year, the amplitude ratio being 134%. Whereas the transyear is validated nonlinearly, the 95% confidence interval for the period extending from 1.21 to 1.38 years and the 95% confidence interval for the amplitude not overlapping zero (P < 0.05), the annual variation is only demonstrable by linear least squares analysis. The results bring added evidence for an influence of non-photic environmental effects on human physiology, in this case data collected near the equatorial region, Davao being situated at 7 degrees N, 126 degrees E. They are in keeping with some degree of generality of a rule of reciprocity among mutually supporting physical and biological periodicities. They do not detract from the fact that in other longer data sets at higher latitudes, the calendar year, presumably reflecting climatic influences, dominates the spectrum.

Adult↗
PubMed2004

DARPP-32 expression arises after a phase of dysplasia in oesophageal squamous cell carcinoma.

This is the first report to correlate DARPP-32 immunoreactivity (dopamine and cAMP-regulated phosphoprotein, M(r) 32 000) to clinicopathological status in human cancer. DARPP-32 is recognised as a neuronal protein. A recent study demonstrated that DARPP-32, and a truncated isoform t-DARPP, are overexpressed in gastric carcinoma during the process of carcinogenesis. The biological function of DARPP-32, however, is still unclear. The purpose of this study was to clarify the roles of DARPP-32 and t-DARPP in oesophageal squamous cell carcinoma (OSCC). Initially, we investigated DARPP-32 and t-DARPP expression in OSCC cell lines by Reverse transcription-polymerase chain reaction and Western blot. DARPP-32 expression was observed in four out of seven (57.1%) cell lines, but t-DARPP expression was not observed in any cell lines. In oesophageal tissue sample, DARPP-32 expression was observed in four out of seven (57.1%) tumour tissues, while t-DARPP was not observed in any tissues. Subsequently, DARPP expression was assessed by immunohistochemistry, using a polyclonal antibody, in tissue sections from 122 patients with primary OSCC. DARPP immunoreactivity was not observed in any normal oesophageal mucous membranes. On the other hand, positive DARPP immunostaining was detected in 37 patients (30.3%) and correlated inversely with pathologic stage (P=0.0284), pT (P=0.0438), pN (P=0.0303) and tumour size (P=0.012). The overall survival rate was worse in patients with DARPP-negative tumours than in patients with DARPP-positive tumours (P=0.0453). Interestingly, DARPP expression was observed in only one out of 45 cases of dysplasia. These observations suggest that DARPP-32 (rather than t-DARPP) expression arises after a phase of dysplasia in OSCC, and that tumours expressing DARPP-32 progress less rapidly than DARPP-32-negative tumours.

Adult↗