Biomedical subjects

K Shibata

Publications and source records attributed to K Shibata.

At least 19 recordsLinked to original sources

PubMed2007

Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients.

Twist is a transcription factor that regulates the expression of tumour suppressors such as E-cadherin. We examined the distribution and expression of Twist in human epithelial ovarian carcinoma (EOC) to examine its clinical significance. Paraffin sections from EOC tissues (n=82) were immunostained with Twist antibody, and the staining intensity was evaluated. The clinicopathological factors examined were age, International Federation of Gynecology and Obstetrics staging, histological type, tumour grade, preoperative value of CA125, peritoneal cytology, volume of ascites and residual tumour after cytoreductive surgery. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Of the 82 carcinomas, 49 (59.8%) cases were negative for Twist immunoexpression, and 33 (40.2%) were positive immunoexpression. When categorized into negative vs positive expression, Twist was not associated with any of the clinicopathological parameters examined. However, positive Twist expression significantly predicted poorer OS and PFS when compared with negative expression (P<0.0001). In the multivariate analyses, positive Twist expression was the only independent prognostic factor for survival in this study (P<0.0001). Positive Twist expression seems to be a useful marker in patients with EOC likely to have an unfavourable clinical outcome.

Blotting, Western↗

PubMed2006

Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer.

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolising enzyme inducing immune tolerance. The present study aimed to investigate IDO expression and its prognostic significance in endometrial cancer. Indoleamine 2,3-dioxygenase expression in endometrial cancer tissues (n = 80) was immunohistochemically scored as four groups (IDO-, 1+, 2+, and 3+). The high IDO expression (IDO2+ or 3+) in tumour cells was found in 37 (46.3%) of the 80 cases, and was positively correlated with surgical stage, myometrial invasion, lymph-vascular space involvement, and lymph node metastasis, but not with the histological grade. Patients with high IDO expression had significantly impaired overall survival and progression-free survival (PFS) (P = 0.002 and P = 0.001, respectively) compared to patients with no or weak expression of IDO (IDO- or 1+). The 5-year PFS for IDO-/1+, 2+, and 3+ were 97.7, 72.9, and 36.4%, respectively. Even in patients with early-stage disease (International Federation of Gynecology and Obstetrics I/II, n = 64), the PFS for IDO2+/3+ was significantly poor (P = 0.001) compared to that for IDO-/1+. On multivariate analysis, IDO expression was an independent prognostic factor for PFS (P = 0.020). These results indicated that the high IDO expression was involved in the progression of endometrial cancer and correlated with the impaired clinical outcome, suggesting that IDO is a novel and reliable prognostic indicator for endometrial cancer.

Biomarkers, Tumor↗

PubMed2006

Surface phase transition of C12E1 at the air/water interface: a study by dynamic surface tension, external RA FT-IR, and 2D IR correlation methods.

The surface conformational states of the Gibbs monolayer of ethylene glycol mono-n-dodecyl ether (C(12)E(1)) at the air/water interface was studied using dynamic surface tension, external reflection-absorption FT-IR spectroscopy (ERA FT-IR), and two-dimensional infrared (2D IR) correlation methods at constant temperature. The dynamic surface tensions were measured at different bulk concentrations of C(12)E(1), and it was observed that a constant surface tension region appears at approximately 38.5 mN m(-1) in a dynamic surface tension profile at concentrations higher than 11 micromol kg(-1). This constant surface tension region corresponds to the surface phase transition from liquid expanded (LE) to liquid condensed (LC). Two sets of ERA FT-IR spectra were collected, one at different bulk concentrations but after equilibrium time (equilibrium measurements) and another at constant bulk concentration (m = 16 micromol kg(-1)) but at different times (dynamic measurements). The first set of these measurements show that the peak area increases in the range of 11 < m < or = 16 micromol kg(-1), which means the increase in the number of surfactant molecules at the air/water interface. Also, the wavenumber of antisymmetric CH(2) stretching decreases gradually from approximately 2923 cm(-1) (for 10 and 11 micromol kg(-1)) to approximately 2918 cm(-1) (for m > or = 16 micromol kg(-1)) with increasing concentration. The wavenumbers of 2923 and 2918 cm(-1) were assigned to LE and LC phases, respectively, and the decrease of wavenumber in the concentration range of 11 < m < or = 16 micromol kg(-1) were correlated to the surface phase transition (LE --> LC), or in other words, in the mentioned concentration range, two phases coexist. The dynamic ERA FT-IR measurements at 16 micromol kg(-1) also confirm the surface phase transition from LE to LC. The 2D IR correlation method was applied to the both equilibrium and dynamic IR spectra of the C(12)E(1) monolayer. The synchronous correlation maps show two strong autopeaks at approximately 2922 and approximately 2851 cm(-1) and also show a strong correlation (cross-peaks) between antisymmetric CH(2) stretching (nu(a)) and symmetric CH(2) stretching (nu(s)). The asynchronous correlation maps show that both observed bands of nu(a) and nu(s) in one-dimensional IR split into two components with the characteristic of overlapped bands, which reveals the coexistence of two phases (LE and LC) at the interface at 11 < m < or = 16 micromol kg(-1). The synchronous and asynchronous maps that were obtained from dynamic IR spectra closely resembled the equilibrium map.

Journal Article↗

PubMed2006

Preoperative transcatheter arterial chemoembolization reduces long-term survival rate after hepatic resection for resectable hepatocellular carcinoma.

AIMS: To study the effect of preoperative transcatheter arterial chemoembolization (TACE) on long-term survival after hepatic resection for hepatocellular carcinoma (HCC), we conducted a comparative analysis in 235 HCC patients who underwent hepatic resection with a curative intent. METHODS: We compared clinicopathologic background, mortality, and survival rates after hepatic resection between those who underwent preoperative TACE (n=109) and those who did not (n=126). RESULTS: One hundred and two patients in the TACE group (93.6%) received TACE only once. The mean interval between TACE and hepatic resection was 33.1days. Patients in the TACE group were younger than those in the non-TACE group, and liver cirrhosis and non-anatomical hepatic resection were more prevalent in this group. The 5-year overall survival rate after hepatic resection was significantly lower in the TACE group (28.6%) than in the non-TACE group (50.6%), especially in patients without cirrhosis or with stage I or II tumor. There was no difference between the two groups in mortality or disease-free survival after hepatic resection. Multivariate analysis showed preoperative TACE, preoperative aspartate aminotransferase elevation, and microscopic portal invasion to be independent risk factors for a poor outcome after hepatic resection. CONCLUSIONS: Preoperative TACE should be avoided for patients with resectable HCC, especially for those without cirrhosis or with an early stage tumor.

Adult↗

PubMed2006

Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival.

Angiotensin II, a main effector peptide in the renin-angiotensin system, acts as a growth-promoting and angiogenic factor via type 1 angiotensin II receptors (AT(1)R). We have recently demonstrated that angiotensin II enhanced tumour cell invasion and vascular endothelial growth factor (VEGF) secretion via AT1R in ovarian cancer cell lines in vitro. The aim of the present study was to determine whether AT1R expression in ovarian cancer is correlated with clinicopathological parameters, angiogenic factors and patient survival. Immunohistochemical staining for AT1R, VEGF, CD34 and proliferating cell nuclear antigen (PCNA) were analysed in ovarian cancer tissues (n = 67). Intratumour microvessel density (MVD) was analysed by counting the CD34-positive endothelial cells. Type 1 angiotensin II receptors were expressed in 85% of the cases examined, of which 55% were strongly positive. Type 1 angiotensin II receptors expression was positively correlated with VEGF expression intensity and MVD, but not with histological subtype, grade, FIGO stage or PCNA labelling index. In patients who had positive staining for AT1R, the overall survival and progression-free survival were significantly poor (P = 0.041 and 0.017, respectively) as compared to those in patients who had negative staining for AT1R, although VEGF, but not AT1R, was an independent prognostic factor on multivariate analysis. These results demonstrated that AT1R correlated with tumour angiogenesis and poor patient outcome in ovarian cancer, suggesting its clinical potential for a novel molecular target in strategies for ovarian cancer treatment.

Disease Progression↗

PubMed2006

Toll-like receptors, NOD1, and NOD2 in oral epithelial cells.

Oral epithelium might be the first barrier against oral bacteria in periodontal tissue. We hypothesized that oral epithelium is endowed with innate immune receptors for bacterial components, which play roles in host defense against bacterial infection without being accompanied by excessive inflammatory responses. We found clear expression of Toll-like receptor (TLR)4 as well as TLR2, and strong expression of NOD1 and NOD2 in normal oral epithelial tissues by immunohistochemical analysis. We also showed that primary oral epithelial cells in culture expressed these molecules using PCR, flow cytometry, and immunostaining. In inflamed oral epithelium, cell-surface localizations of TLR2 and TLR4 were more clearly observed than in healthy tissue. Upon stimulation with synthetic ligands for these receptors, the expression of beta-defensin 2 was markedly up-regulated. These findings indicate that these molecules in oral epithelial cells are functional receptors that induce antibacterial responses.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Effects of hypoxic and osmotic stress on the free D-aspartate level in the muscle of blood shell Scapharca broughtonii.

Blood shell, Scapharca broughtonii, contains large quantities of free D-aspartate comparable to free L-aspartate in its tissues. When the shell was reared in hypoxic seawater, D-aspartate as well as L-aspartate in the foot muscle decreased rapidly, and their total level became about one-fourth within 24 hr. None of the other amino acids examined showed a similar behavior, but many of them rather increased during the same period. The increase in L-alanine was especially remarkable and was almost equal to the sum of the decrease in aspartate enantiomers. When the shell that had been acclimated to hypoxic seawater for 96 hr was transferred to normoxic seawater, all the amino acid levels mostly returned to the control levels within 96 hr. In contrast to these effects of hypoxic stress, hyperosmotic stress of 150% seawater had no effect on the D- and L-aspartate levels in the same tissue. These results suggest that D-aspartate is involved in anaerobic energy metabolism of this bivalve as well as L-aspartate, whose vital role in anoxia-tolerant bivalves is well known.

Animals↗

PubMed2005

Evaluating the effects of spatial frequency on migraines by using pattern-reversal visual evoked potentials.

OBJECTIVE: To clarify the effects of contrast and spatial frequency in patients with migraine by means of pattern-reversal visual evoked potentials (PVEPs). METHODS: PVEPs were obtained from 14 patients who had migraine without aura (MO), 11 patients who had migraine with aura (MA), and 25 age-matched, healthy controls (CO). PVEPs were binocularly recorded with a reversal rate of 1Hz (2 reversal/s) at 3 spatial frequencies (0.5, 1.0 and 4.0 cpd) at high (98%), medium (83%) and low (29%) contrast. N75, P100 and N135 latency and the amplitudes of P50-N75, N75-P100 and P100-N135 were analyzed. RESULTS: Increased amplitude of PVEPs in patients with migraines were revealed at 3 different spatial frequencies in all components. The MO and the MA showed increased amplitudes mostly in high contrasts (98%). These findings were detected more at a high spatial frequency (4.0 cpd) than at a low spatial frequency (0.5 cpd). Increased amplitude with prolonged latency of N135 were found both in MO and MA at 4.0 cpd. CONCLUSIONS: We conclude that pattern stimuli of high contrasts may be particularly effective in uncovering abnormal cortical reactivity which may be modified in the primary and secondary visual cortex in the interictal state of migraine. SIGNIFICANCE: These findings indicate that there is abnormal visual cortex processing in patients with migraine.

Adult↗

PubMed2005

Comparative study of survival of patients with hepatocellular carcinoma predicted by different staging systems using multivariate analysis.

AIMS: In a previous pilot study, we reported the usefulness of the modified the Cancer of the Liver Italian Program (CLIP) score for patients with hepatocellular carcinoma (HCC). To determine the best staging system for predicting the survival of HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 210 Japanese HCC patients who underwent hepatic resection. METHODS: We compared the survival as predicted by various staging systems, including tumour node metastasis (TNM) stage of the American Joint Commission on Cancer (AJCC) and the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), CLIP score and our modified CLIP score using protein induced by vitamin K absence or antagonist II (PIVKA-II). RESULTS: Univariate analysis showed that discrimination of disease-free survival in the early and advanced stages by the JIS score and modified CLIP score was clearer than by the Japanese or AJCC TNM or the original CLIP score. Discrimination between stages of overall survival by all staging systems was significant. Multivariate analysis showed that the JIS, CLIP and modified CLIP scores were better staging systems for predicting survival than the Japanese and AJCC TNM. The modified CLIP score showed the lowest Akaike information criteria statistical value for disease-free and overall survival, which means the best discrimination ability for patient survival compared with the JIS score and CLIP score. CONCLUSIONS: A staging system that combines tumour factors, sensitive tumour marker(s) and hepatic function is the best predictor of prognosis of HCC patients.

Adult↗

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

Oculomotor nerve schwannoma mimicking ophthalmoplegic migraine.

Ophthalmoplegic migraine (OM) is a rare variant of migraine characterized by recurrent attacks of severe headache followed by oculomotor nerve palsy. The recent revision of the International Headache Classification has reclassified OM from a subtype of migraine, defined as a functional headache, to the neuralgia category. We describe a case of an 11-year-old girl with pathologically confirmed oculomotor nerve schwannoma who had been suffering from symptoms mimicking OM. For five years, she has been under treatment for OM, an initial diagnosis which was corroborated by brain magnetic resonance imaging (MRI). Usually, most OM attacks occur during one period in a lifetime and remit completely. In contrast, however, her attacks became more frequent and were not controlled by medication. After surgery, the frequency of OM attacks was reduced. From this experience, we hypothesize that optic nerve tumor is one condition that can mimic OM, without apparent signs suggestive of intracranial mass. To our knowledge, this is the first report to describe a pathologically confirmed case of oculomotor nerve schwannoma mimicking OM.

Child↗

PubMed2005

Development of a simple method to evaluate medical staff radiation dose and its application to a software system supporting PET facility operation.

In recent years, positron-emitting labelled radiopharmaceuticals have come to be used in conjunction with positron emission tomography (PET) in various clinical diagnoses. Radiation exposure of the medical staff is a key issue in the design of PET facilities intended to handle large numbers of persons for PET diagnosis. As a first step, the radiation dose to individuals who received radiopharmaceuticals was calculated using a mathematical phantom model and the EGS4 electromagnetic cascade Monte Carlo code and MCNP Monte Carlo code. Dose rate behind a lead shield was also calculated for various lead thicknesses. The radiation dose distribution around a syringe containing a positron emitter was calculated. The calculated dose distributions were fitted to polynomial equations. These calculations were evaluated against measurements. The second step was to evaluate medical staff dose at a specified time by superimposing dose distribution from each person who received radioisotopes taking into account radioactive decay. In this way, we developed software to support PET facility operation, namely, planning, prediction, control of medical staff dose and facility operation. This system was also designed to schedule daily radiopharmaceuticals production and to manage radioactive wastes by taking decay time into account.

Body Burden↗

PubMed2005

Muramyldipeptide and diaminopimelic acid-containing desmuramylpeptides in combination with chemically synthesized Toll-like receptor agonists synergistically induced production of interleukin-8 in a NOD2- and NOD1-dependent manner, respectively, in human monocytic cells in culture.

Two types of synthetic peptidoglycan fragments, diaminopimelic acid (DAP)-containing desmuramylpeptides (DMP) and muramyldipeptide (MDP), induced secretion of interleukin (IL)-8 in a dose-dependent manner in human monocytic THP-1 cells, although high concentrations of compounds are required as compared with chemically synthesized Toll-like receptor (TLR) agonists mimicking bacterial components: TLR2 agonistic lipopeptide (Pam3CSSNA), TLR4 agonistic lipid A (LA-15-PP) and TLR9 agonistic bacterial CpG DNA. We found marked synergistic IL-8 secretion induced by MDP or DAP-containing DMP in combination with synthetic TLR agonists in THP-1 cells. Suppression of the mRNA expression of nucleotide-binding oligomerization domain (NOD)1 and NOD2 by RNA interference specifically inhibited the synergistic IL-8 secretion induced by DMP and MDP with these TLR agonists respectively. In accordance with the above results, enhanced IL-8 mRNA expression and the activation of nuclear factor (NF)-kappaB induced by MDP or DMP in combination with synthetic TLR agonists were markedly suppressed in NOD2- and NOD1-silenced cells respectively. These findings indicated that NOD2 and NOD1 are specifically responsible for the synergistic effects of MDP and DMP with TLR agonists, and suggested that in host innate immune responses to invading bacteria, combinatory dual signalling through extracellular TLRs and intracellular NODs might lead to the synergistic activation of host cells.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2004

Distribution of adrenomedullin-containing perivascular nerves in the rat mesenteric artery.

Distribution of adrenomedullin (AM)-containing perivascular nerve fibers was studied in rat mesenteric arteries. Many fibers containing AM-like immunoreactivity (LI) were observed in the adventitia. AM-LI fibers were abolished by cold storage denervation or capsaicin but not 6-hydroxydopamine. Double immunostainings showed colocalization of AM-LI with calcitonin gene-related peptide (CGRP)-LI. The dorsal root ganglia had many AM-positive cells and AM mRNA detected by RT-PCR. Electron microscopy study revealed high proportions of immunogold labeling for AM and colocalization of both AM-LI and CGRP-LI in unmyelinated nerve axons. These results suggest that AM-containing perivascular nerves are distributed in the rat mesenteric artery.

Adrenomedullin↗

PubMed2004

Chronomic community screening reveals about 31% depression, elevated blood pressure and infradian vascular rhythm alteration.

Depression, which is a risk factor for cardiac morbidity and mortality, is not an unusual occurrence among individuals with coronary heart disease (CHD), but evidence concerning its role in the pathogenesis of this condition is less clear. Ambulatory blood pressure monitoring (ABPM) has become an important tool in the diagnosis and management of hypertension. Several previous studies have indicated that various kinds of target organ damage and cardiovascular morbidity are more strongly associated with a diagnosis by ABPM than through spot-checks in a clinical setting. This study investigated whether depressive mood was associated with changes in the about-weekly (circaseptan) and half-weekly (circasemiseptan) variations in blood pressure (BP) and heart rate (HR), including a BP surge on Mondays, in community-dwelling subjects monitored chronomically for the time structure (chronome) of their BP and HR variabilities. From April 2001 to April 2003, 217 subjects (85 men and 132 women; mean age: 56.8 +/- 11.3 yr) from U town, Hokkaido (latitude: 43.45 degrees N, longitude: 141.85 degrees E), self-monitored their BP and HR for 7 days starting around 11 a.m. on Thursday, and took readings at 30-minute intervals between 7 a.m. and 10 p.m., then at 60-minute intervals between 10 p.m. and 7 a.m. The data were retrieved and analyzed on a PC with appropriate commercial software (TM-2430-15; A&D Co., Japan). Subjects were asked about 15 items on a depression rating scale through a self-administered questionnaire. When the score amounted to 5 or higher, subjects were considered to be depressive. Student's t-test, a one-way analysis of variance (ANOVA), and cosinor methods with parametric tests were also used. A p-value below 0.05 was considered to indicate statistical significance (below 0.10: borderline statistical significance). Depression rating scales were obtained for 192 out of the 217 subjects enrolled in this study. Depression scores were (>) 5 in 72 subjects. The average values of systolic (S) and diastolic (D) BP were statistically significantly higher in depressed subjects (SBP: 129.2 vs 124.5 mmHg; p = 0.034; DBP: 79.0 vs 76.5 mmHg; p = 0.041). The 7-day average for HR did not differ between subjects with depression scores of < 5 or > 5. DBP dipping was less in the depressed subjects (16.30 vs 18.22%; p = 0.048). The dipping ratios of SBP and HR showed no statistically significant difference. In the group with depression scores of < 5, HR variability (estimated by the SD of HR and HR dip) was higher during vacations and lower on Mondays. The 24-h BP measures showed a novelty effect and a surge on Mondays. In the depressed group, a prominent circaseptan rhythm appeared to replace the novelty effect, vacation dip, and Monday surge. The results of this investigation indicate the clinical importance of the monitoring of depressed subjects. Fewer than 7 days of monitoring means a greater risk of false diagnosis, and thus a therapeutic decision including potentially unnecessary or inappropriate long-term treatment. Records shorter than 7 days would not have detected circaseptan BP dysrhythmia associated with a depressive state. Prominent circaseptans can provide new indications on the mechanisms underlying the strong relation between depression and adverse cardiac events. Future studies should aim at determining whether the treatment of depression, especially from the standpoint of a chronodiagnosis and chronotherapy, can reduce the incidence of adverse cardiac events, and whether this depends upon restoring normal BP and HR variability, i.e. anormal BP and HR chronome.

Blood Pressure Monitoring, Ambulatory↗