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Biomedical subjects

T Shibata

Publications and source records attributed to T Shibata.

At least 37 records · Page 2Linked to original sources

Radiation safety design for the J-PARC Project.

The High-Intensity Proton Accelerator Project, named J-PARC, is in progress, with the aim of enabling studies on the latest basic science and the advancement of nuclear technology. In the project, a high-energy proton accelerator complex with the world's highest instantaneous intensity is under construction. In order to establish a reasonable shielding design, both simplified and detailed design methods were used in the shielding design of J-PARC. This paper reviews the present status of the radiation safety design study for J-PARC.

Computer Simulation↗

Type II collagen and aggrecan mRNA expressions in rabbit condyle following disc displacement.

The aim of this investigation was to study the remodelling of cartilage in the mandibular condyle following disc displacement (DD) of the temporomandibular joint (TMJ). Forty adult Japanese white rabbits were used in this study. The right joints of 28 of the 40 rabbits had their discs surgically displaced. Four of the 28 were killed at 4 days or 1, 2, 4, 6, 8 and 12 weeks after surgery. The messenger RNA (mRNA) expression levels of aggrecan and type II collagen in cartilages were measured using in situ hybridization techniques. Results showed that aggrecan mRNA expression reduced in the first week after DD. The expression began to recover after 4 weeks and reached a normal level after 6 weeks. Type II collagen mRNA expression reduced from 4 weeks and the expression recovered after 8 weeks. This suggests that the chondrocyte reacting to the displacement of the TMJ disc, alters its matrix gene expression patterns and it is may be the cause of the shape changes of TMJ after DD.

Aggrecans↗

Purification and characterization of extracellular alkaline serine protease from Stenotrophomonas maltophilia strain S-1.

AIMS: The present study was conducted by screening soil bacteria in an attempt to isolate a bacterium that produced extracellular alkaline protease, and for purification and characterization of the protease. METHODS AND RESULTS: Soil bacteria were screened by growth on casein as the sole carbon source. Characterization of a strain isolated from soil of Abashiri, Japan indicated a taxonomic affiliation to Stenotrophomonas maltophilia, and was named S-1 strain. The purified S-1 protease, designed S. maltophilia Protease-1 (SmP-1), exhibited an optimal pH of 12.0, optimal reaction temperature of 50 degrees C and a molecular mass of approximately 40 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The cleavage sites of the oxidized-insulin B chain by SmP-1 were identified as Leu6-Cys7, Cys7-Gly8, Tyr16-Leu17 and Leu17-Val18. The N-terminal amino acid sequence of the purified alkaline protease was determined as NH2-SASAPMVSGVAALVLE. CONCLUSION: A novel extracellular alkaline serine protease was isolated from S. maltophilia strain S-1. The optimal pH of the proteolytic activity was pH 12.0. SIGNIFICANCE AND IMPACT OF THE STUDY: The extremely high optimal pH and heat stability of the alkaline serine protease SmP-1 might make it widely applicable to food and other industries.

Amino Acid Sequence↗

Genetic parameter estimates of meat quality traits in Duroc pigs selected for average daily gain, longissimus muscle area, backfat thickness, and intramuscular fat content.

Using a multitrait animal model BLUP, selection was conducted over seven generations for growth rate (ADG), real-time ultrasound LM area (LMA), backfat thickness (BF), and intramuscular fat content (IMF) to develop a new line of purebred Duroc pigs with enhanced meat production and meat quality. This selection experiment examined 543 slaughtered pigs (394 barrows and 153 gilts) from the first to the seventh generation for meat quality traits. Further, electric impedance and collagen content of loin meat were measured from the fourth to sixth generation. The present study was intended to estimate genetic parameters of the correlated traits of tenderness (TEND), meat color (pork color standard: PCS; lightness = L*), drip loss (DL), cooking loss (CL), pH (PH), electric impedance (IMP), and collagen (COL) of the LM, and the genetic trends of these traits. Respective heritability estimates for IMF, TEND, DL, CL, PCS, L*, PH, IMP, and COL were 0.39, 0.45, 0.14, 0.09, 0.18, 0.16, 0.07, 0.22, and 0.23. Genetic correlations of IMF with ADG and BF were low and positive, but low and negative with LMA. Tenderness was correlated negatively with ADG (-0.44) and BF (-0.59), but positively correlated with LMA (0.32). The genetic correlation between LMA and DL was positive and high (0.64). The genetic correlations of TEND with IMF and COL were low (-0.09 and 0.26, respectively), but a moderate genetic correlation (0.43) between COL and IMF was estimated, suggesting related increases of IMF and connective tissue. Genetic correlations among meat quality traits suggested that when IMF increases, the water holding capacity improves. Genetic trends of meat quality traits showed increased IMF and lighter meat color.

Adipose Tissue↗

A case of elderly-onset systemic lupus erythematosus presenting as acute renal failure due to disseminated intravascular coagulation.

Herein we describe a case of a patient with elderly-onset systemic lupus erythematosus presenting as acute renal failure due to disseminated intravascular coagulation. A 78-year-old man was admitted to our hospital with fever and generalized lymphadenopathy. He was diagnosed as having systemic lupus erythematosus on the basis of renal involvement, hematological abnormality and positivity for antinuclear and anti-double-stranded DNA antibodies. Renal biopsy revealed lupus nephritis (class III and V (A/C)) with focal glomerular thrombosis. He responded to hemodialysis and corticosteroid therapy with remission of serological values and renal function. Possible mechanisms underlying the coexistence of these conditions are discussed.

Acute Kidney Injury↗

[Off-pump coronary artery bypass for old myocardial infarction associated with jejunotomy for obstructive ileus due to gall bladder stone; report of a case].

In non-cardiac operative cases with inflammatory digestive organ disease, bacterial translocation (BT) often results from non-enteral nutrition postoperatively. If coronary artery bypass grafting (CABG) is performed in the case having old myocardial infarction (OMI) and inflammatory digestive organ disease at first before non-cardiac operation, he seems vulnerable to have severe complications such as multiple organ failure due to systemic inflammatory response syndrome (SIRS) and preexisting BT postoperatively. We performed a off-pump CABG (OPCAB) for OMI associated with jejunotomy for obstructive ileus due to gall bladder stone. No complication was found in the postoperative course. We conclude that combined operation, non-cardiac surgery after OPCAB is worth considering in those cases. And we think OPCAB is better than conventional CABG in such cases, because cardiopulmonary bypass is known to ponder comparable damages to immune system, coagulation system and others.

Aged↗

Maternal genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 and the risk of hypospadias.

Hypospadias is one of the most common congenital anomalies. Increased exposure to environmental factors (endocrine-disrupting chemicals and smoking) or maternal endogenous estrogen may cause hypospadias because male sexual differentiation is dependent on normal androgen homeostasis. Moreover, interactions between genetic factors and cigarette smoking and other chemicals have been suggested. It has been demonstrated that the CYP1A1 metabolizes not only environmental chemicals but also estrogens, and glutathione-S-transferases (GSTs) are detoxification enzymes that protect cells from toxicants by conjugation with glutathione. In this study, to investigate the association of CYP1A1 (MspI), GSTM1 and GSTT1 polymorphisms with hypospadias, a case-control study of 31 case mothers who had boys with hypospadias and 64 control mothers was performed in Japan. These polymorphisms were investigated by PCR-based methods using DNA from peripheral lymphocytes. We found that the heterozygous CYP1A1 and heterozygous and homozygous CYP1A1 were less frequent in the case mothers than in the control mothers [adjusted odds ratio (OR)=0.17, 95% confidence interval (CI)=0.04-0.74, OR = 0.28, 95% CI = 0.08-0.97, respectively]. We found no effect of maternal smoking on the hypospadias risks among the gene polymorphisms. The results suggest that mothers with the CYP1A1 MspI variant allele may have a decreased risk for hypospadias.

Adult↗

Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas.

Dysregulation of apoptosis plays an important role in tumour progression and resistance to chemotherapy. The X-linked inhibitor of apoptosis (XIAP) is considered to be the most potent caspase inhibitor of all known inhibitor of apoptosis-family members. Only recently, an antagonist of XIAP has been identified, termed Smac/DIABLO. To explore the relevance of antiapoptotic XIAP and proapoptotic Smac/DIABLO for tumour progression in renal cell carcinomas (RCCs), we analysed XIAP and Smac/DIABLO mRNA and protein expression in the primary tumour tissue from 66 RCCs of all major histological types by quantitative real-time PCR, Western blot and ELISA. X-linked inhibitor of apoptosis and Smac/DIABLO mRNA expression was found in all RCCs. Importantly, the relative XIAP mRNA expression levels significantly increased from early (pT1) to advanced (pT3) tumour stages (P=0.0002) and also with tumour dedifferentiation (P=0.04). Western blot analysis confirmed the tumour stage-dependent increase of XIAP expression on the protein level. In contrast, mRNA and protein expression levels of Smac/DIABLO did not significantly change between early and advanced tumour stages or between low and high tumour grades. Consequently, the mRNA expression ratio between antiapoptotic XIAP and proapoptotic Smac/DIABLO markedly increased during progression from early (pT1) to advanced (pT3) tumour stages. Moreover, RCCs confined within the organ capsule (pT1 and pT2) exhibited a significantly lower XIAP to Smac/DIABLO expression ratio when compared with RCCs infiltrating beyond the kidney (pT3; P=0.01). Thus, our investigation demonstrates that the delicate balance between XIAP and Smac/DIABLO expression is gradually disturbed during progression of RCCs, resulting in a relative increase of antiapoptotic XIAP over proapoptotic Smac/DIABLO, thereby probably contributing to the marked apoptosis resistance of RCC.

Apoptosis↗

Involvement of SAPK/JNK in prostaglandin E(1)-induced VEGF synthesis in osteoblast-like cells.

We previously reported that prostaglandin E(1) (PGE(1)) activates both p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase via cAMP-dependent protein kinase in osteoblast-like MC3T3-E1 cells, and that p38 MAP kinase but not p42/p44 MAP kinase is involved in PGE(1)-induced synthesis of vascular endothelial growth factor (VEGF). In the present study, we investigated the involvement of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in the PGE(1)-induced VEGF synthesis in MC3T3-E1 cells. PGE(1) induced the phosphorylation of SAPK/JNK. SP600125, a specific inhibitor of SAPK/JNK, markedly reduced the PGE(1)-induced VEGF synthesis. Forskolin, a direct activator of adenylyl cyclase, elicited the phosphorylation of SAPK/JNK, and 8bromo-cAMP, a plasma membrane-permeable cAMP analogue-stimulated VEGF synthesis was significantly reduced by SP600125. SP600125 suppressed the PGE(1)-induced phosphorylation of SAPK/JNK without affecting the phosphorylation of p38 MAP kinase induced by PGE(1). The phosphorylation of c-Jun induced by PGE(1) was also inhibited by SP600125. SB203580, a p38 MAP kinase inhibitor, failed to reduce the PGE(1) induced phosphorylation of SAPK/JNK. A combination of SP600125 and SB203580 suppressed the PGE(1)-stimulated VEGF synthesis in an additive manner. These results strongly suggest that PGE(1) activates SAPK/JNK in osteoblasts, and that SAPK/JNK plays a part in PGE(1)-induced VEGF synthesis.

8-Bromo Cyclic Adenosine Monophosphate↗

Activation of p38 mitogen-activated protein kinase mediates thyroid hormone-stimulated osteocalcin synthesis in osteoblasts.

It is well known that thyroid hormone modulates osteoblast cell function. We have previously shown that triiodothyronine (T(3)) activates p44/p42 mitogen-activated protein (MAP) kinase, which limits T(3)-induced alkaline phosphatase activity in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether p44/p42 MAP kinase or p38 MAP kinase is involved in the thyroid hormone-stimulated osteocalcin synthesis in these cells. T(3) markedly induced the phosphorylation of p38 MAP kinase in addition to p44/p42 MAP kinase. PD98059 and U0126, inhibitors of the upstream kinase that activates p44/p42 MAP kinase, had little effect on the T(3)-induced synthesis of osteocalcin. On the contrary, the T(3)-induced osteocalcin synthesis was significantly reduced by SB203580 and PD169316, inhibitors of p38 MAP kinase. SB203580, PD169316 or PD98059 suppressed the T(3)-phosphorylation of myelin basic protein. T(3)-induced osteocalcin synthesis was significantly reduced by SB203580 or PD169316 also in primary cultured mouse osteoblasts. These results strongly suggest that p38 MAP kinase but not p44/p42 MAP kinase takes part in the thyroid hormone-stimulated osteocalcin synthesis in osteoblasts.

3T3 Cells↗

Relationship between the tooth eruption and regional blood flow in angiotensin II-induced hypertensive rats.

OBJECTIVE: The mechanism of action of vasoactive drugs on tooth movement is unknown. The purpose of the present study was to measure simultaneously the axial movement of the mandibular incisor, regional blood flow at the base of the incisor, and systemic arterial blood pressure in angiotensin II-induced hypertensive rats to determine the possible cause of tooth displacement. DESIGN: The measurements were made under artificial respiration with halothane anaesthesia. In the experimental animals, 2.5 microg of angiotensin II in 1 ml of Ringer's solution was infused at 0.83 ml/h for 12 h from the femoral vein. In the control animals, only Ringer's solution was infused. RESULTS: Angiotensin II caused an increase of the mean arterial blood pressure from 86 to 119 mm Hg, and decreases of the eruption rate from 667 to 494 microm/24 h and the regional blood flow from 262 to 214 mV. There was a positive correlation between the eruption rate and regional blood flow, and a negative correlation between the blood pressure and regional blood flow. CONCLUSION: These results suggest that angiotensin II caused constriction of the peripheral vascular smooth muscle resulting in an increase of arterial blood pressure and a decrease of regional blood flow, followed by a decrease of fluid volume and then a reduction of either the pressure within the socket or of the eruptive force. We assume that the regional vascular pressure within the socket plays an important role in determining the position of the rat incisor.

Angiotensin II↗

Effects of age on the stress-strain and stress-relaxation properties of the rat molar periodontal ligament.

OBJECTIVE: We examined the stress-strain and stress-relaxation properties of the periodontal ligament (PDL) in the rat molar at 2, 6, 12, and 24 months of age to elucidate age-related changes in the tooth support function of the PDL. DESIGN: From the dissected left and right mandibles in each rat, a pair of transverse sections (ca. 0.45 mm in thickness) of the first molar was cut at the middle part of the mesial root. We then obtained a load-deformation curve for the PDL, using one of the paired sections. The other section was loaded to as much as 50% of the maximum load as determined from the contralateral section, and keeping the deformation constant for 10 min, a load-relaxation curve was obtained and analysed. RESULTS: The maximum shear stress and tangent modulus decreased between 2 and 24 months of age. As the maximum shear strain increased with age (P < 0.001), the failure strain energy density did not change between 2 and 24 months of age. The stress-relaxation during the 10 min period decreased from 2 to 24 months of age (P < 0.01). The relaxation process of the PDL in each age was well described by a sum of three exponential decay functions. The age-related decrease in the relaxation was found to be mainly due to the increase in the relaxation time for the long-term relaxation component. CONCLUSION: These results indicate that the maximum shear stress and stiffness of the rat molar PDL decrease between 2 and 24 months of age; but its toughness remains unchanged due to an increase in the extensibility. Our findings further indicate that the fluid flow and movements of macromolecules within the stretched PDL fibres during the stress-relaxation decrease with advancing age.

Aging↗

Intra-articular oxidative state correlated with the pathogenesis of disorders of the temporomandibular joint.

We investigated the redox state of albumin in the synovial fluid from patients with temporomandibular joint (TMJ) disorders (TMD) to evaluate the relation between the cause of the TMD and the number of types of oxygen in synovial fluid. The albumin was fractionated into three components, human mercaptalbumin (HMA, reduced form) and two types human non-mercaptalbumin (HNA, oxidized form), by high-performance liquid chromatography (HPLC). The 63 patients were divided into three groups radiologically, and the ratios of the redox state of the synovial fluid in each group were compared. The fraction of HNA was significantly higher in patients with advanced disease than in patients with early disease. This indicates that the TMJ is affected by intra-articlular oxidative stress, and the severity of TMD correlates closely with the number of oxidative factors. Oxidative stress was thought to be responsible for the genesis of TMD.

Adolescent↗

Age-related and regional differences in the stress-strain and stress-relaxation behaviours of the rat incisor periodontal ligament.

Groups of rats were killed at 2, 6, 12, and 24 months of age. From dissected left and right mandibles in each rat, three pairs of transverse sections were cut at the incisal, middle, and basal regions of the incisor. One section in each pair was loaded until failure and a stress-strain curve for the periodontal ligament (PDL) was obtained. The other section was loaded to up to 50% of the maximum shear stress as determined from the contralateral section and then kept at a constant strain for 10 min, to obtain the stress-relaxation curve at the same region of the PDL. The maximum shear stress and toughness increased with age at the incisal region and the maximum shear strain increased with age at the incisal and middle regions. The tangent modulus decreased with advancing age at the middle region. The stress-relaxation during 10 min decreased with advancing age at the incisal and basal regions, but not at the middle region. The relaxation process was well described by a sum of three exponential decay functions, reflecting the short-, medium-, and long-term relaxation components. The age-related decrease in the relaxation was mainly attributable to increases in the ratio and relaxation time of the long-term relaxation component. These results suggest that with advancing age the mechanical strength and toughness of the PDL are enhanced mostly at the incisal region and that the viscous fraction is relatively decreased at the incisal and basal regions along the long axis of the rat incisor.

Aging↗

Pool of dust particles over the Asian continent: balloon-borne optical particle counter and ground-based lidar measurements at Dunhuang, China.

Measurements of aerosols were made in 2001 and 2002 at Dunhuang (40 degrees 00'N, 94 degrees 30'E), China to understand the nature of atmospheric particles over the desert areas in the Asian continent. Balloon-borne measurements with an optical particle counter suggested that particle size and concentration had noticeable peaks in super micron size range not only in the boundary mixing layer but also in the free troposphere. Super-micron particle concentration largely decreased in the mid tropopause (from 5 to 10 km; above sea level, a.s.l.). Lidar measurements made during August 2002 at Dunhuang suggested the possibility that mixing of dust particles occurred from near the ground to about 6 km even under calm weather conditions, and a large depolarization ratio of particulate matter was found in the aerosol layer. The top of the aerosol layer was found at heights of nearly 6 km (a.s.l.). It is strongly suggested that nonspherical dust particles (Kosa particles) frequently diffused in the free atmosphere over the Taklamakan desert through small-scale turbulences and are possible sources of dust particles of weak Kosa events that have been identified in the free troposphere not only in spring but also in summer over Japanese archipelago. Electron microscopic experiments of the particles collected in the free troposphere confirmed that coarse and nonspherical particles observed by the mineral particle were major components of coarse mode (diameter larger than 1 microm) below about 5 km over Dunhuang, China.

Aerosols↗

Impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas: a single-institution retrospective study.

Neuronavigation has become an effective therapeutic modality and is used routinely for intra-axial tumor removal. This retrospective study was conducted to evaluate the clinical impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas. Between 1990 and 2002, 76 adult patients with pathologically confirmed malignant astrocytomas underwent craniotomy and removal of the tumors at the Toyama Medical and Pharmaceutical University Hospital. Of these 76 patients, 42 were treated using neuronavigation with conventional microneurosurgery and the other 34 were treated with conventional microneurosurgery alone. Postoperative early MRI with contrast enhancement was done, and gross total resection was defined as the complete absence of residual tumor. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. In univariate analysis, age (< 65), grade 3, preoperative KPS (>/= 80), use of neuronavigation, and gross total resection were significantly associated with longer survival. However, when the data were submitted to multivariate analysis, grade 3, preoperative KPS (>/= 80), and gross total resection were independent prognostic factors. The median survival periods of patients receiving gross total resection (vs. partial resection) and neuronavigation (vs. no neuronavigation) were 16 (vs. 9) months and 16 (vs. 10) months, respectively. The percentage of a gross total resection was significantly higher in the neuronavigation group compared to that in the no-navigation group (64.3 % vs. 38.2 %, p < 0.05). Neurological deterioration occurred in 4 of 42 (9.5 %) and in 6 of 34 (17.6 %) patients after surgery with neuronavigation and surgery without neuronavigation, respectively, although this difference was not statistically significant. Our results showed that neuronavigation increases the radicality in the resection of malignant astrocytomas and is objectively useful for improving survival time.

Adolescent↗

Expression of enamel proteins and LEF1 in adamantinomatous craniopharyngioma: evidence for its odontogenic epithelial differentiation.

AIMS: Adamantinomatous craniopharyngioma (ACP) resembles histologically some odontogenic tumours, such as ameloblastoma and calcifying odontogenic cyst. However, there has been no evidence that ACP differentiates also functionally as odontogenic epithelium. The aim of this study was to gain evidence of odontogenic epithelial differentiation in ACP by means of immunohistochemistry. Among normal human tissues, enamel proteins are expressed exclusively in teeth, and lymphoid enhancer factor 1 (LEF1), in co-operation with beta-catenin, play an important role in tooth development. The expression of these proteins is therefore indicative of odontogenic epithelial differentiation. METHODS AND RESULTS: The expression of enamel proteins and LEF1 was examined in 10 adamantinomatous and six papillary craniopharyngiomas. All the ACPs showed a variable degree of enamel protein expression, including amelogenin, enamelin and enamelysin, mainly in ghost cells. LEF1 was also heterogeneously expressed in ACPs; remarkably, its expression pattern was identical to that of nuclear beta-catenin accumulation. In contrast, none of the papillary craniopharyngiomas expressed enamel proteins or LEF1. CONCLUSIONS: These results suggest that ACP consistently shows odontogenic epithelial differentiation. Since ACPs harbour beta-catenin mutation, the inappropriate activation of beta-catenin/LEF1 complex-dependent transcription may play a critical role in ACP tumorigenesis.

Adult↗

Effects of alendronate on restoration of biomechanical properties of periodontium in replanted rat molars.

OBJECTIVE: We examined the effect of the pretreatment of roots with alendronate on the restoration of the support function of the healing periodontal ligament in replanted rat molars. METHODS: The left maxillary first molars were extracted, placed in 0.9% NaCl containing 1 mm alendronate (alendronate group) or 0.9% NaCl (control group) for 5 min, and were replanted into their sockets. Groups of animals were killed at 7, 14, and 21 days after replantation. Normal control rats were also killed on the same days. The force required to extract the replanted or normal tooth from its socket was measured, and a load-deformation curve was developed and analyzed. Micro-computed tomography and histologic analyses were also made. RESULTS: The mechanical properties of the healing periodontal ligament in the alendronate group were gradually restored from 7 to 21 days. However, fractures of the roots and bones during mechanical testing occurred in most of the replanted teeth in the control group at 21 days. The rates of restoration of the mechanical strength, extensibility, stiffness, and toughness for the alendronate group at 21 days were 67, 98, 74, and 68% of the normal controls, respectively. Micro-computed tomography and histologic observations revealed that bone-like structures within the pulp and ankylosis between the roots and socket bones occurred commonly in the control group, but were uncommon in the alendronate group. CONCLUSIONS: Our findings suggest that the pretreatment with alendronate inhibits the formation of abnormal mineralized tissues and results in better restoration of the support function of the healing periodontal ligament in replanted teeth.

Alendronate↗