Biomedical subjects

J Saito

Publications and source records attributed to J Saito.

At least 19 recordsLinked to original sources

PubMed2007

Effects of the short chain sugar acid 2-buten-4-olide on the hypothalamo-pituitary-adrenal axis in normal and adjuvant-induced arthritic rats.

The effects of intraperitoneal (i.p.) administration of 2-buten-4-olide (2-B4O), an endogenous sugar acid, on the hypothalamo-adenohypophysial system were examined in Lewis rats that were normal and in adjuvant-induced arthritic (AA) rats. In comparison with vehicle-treated rats, the plasma corticosterone and c-fos mRNA levels in the paraventricular nucleus (PVN) of normal rats increased significantly after i.p. administration of 2-B4O. Dual immunostaining revealed that almost all corticotrophin-releasing factor (CRF)-immunopositive neurones in the parvocellular division of the PVN exhibited Fos-like immunoreactivity (LI) 120 min after i.p. administration of 2-B4O (100 mg/kg). In the AA rats, repeated i.p. administration of 2-B4O (100 mg/kg) after immunisation significantly suppressed the expression of clinical symptoms and significantly increased plasma concentrations of corticosterone. Further, repeated i.p. administration of 2-B4O significantly increased CRF mRNA levels in the PVN and pro-opiomelanocortin mRNA levels in the anterior pituitary; however, they did not change arginine vasopressin mRNA levels in the parvocellular division of the PVN. These results suggest that i.p. administration of 2-B4O activates the hypothalamo-pituitary-adrenal (HPA) axis via the activation of CRF neurones in the PVN, and the activation of the HPA axis by i.p. administration of 2-B4O may be associated with the inhibition of AA in rats.

4-Butyrolactone↗

PubMed2006

Risk stratification for in-hospital mortality in spontaneous intracerebral haemorrhage: a Classification and Regression Tree analysis.

BACKGROUND: Risk stratification for mortality in intracerebral haemorrhage (ICH) helps guide care, but existing clinical prediction rules are too cumbersome for clinical practice because of their complexity. AIM: To develop a simple decision tree model of in-hospital mortality risk stratification for ICH patients. METHODS: We collected information on spontaneous ICH patients hospitalized in a teaching hospital in Japan from August, 1998 to December, 2001 (n = 374). All variables were abstracted from data available at the time of initial evaluation. A prediction rule for in-hospital mortality was developed by the Classification and Regression Tree (CART) methodology. The accuracy of the model was evaluated using the area under receiver-operator characteristic curve. RESULTS: Overall in-hospital mortality rate was 20.2%. The CART methodology identified four groups for mortality risk, varying from low (2.1%) to high (58.9%). Level of consciousness (coma) was the best single predictor for mortality, followed by high ICH volume (cut-off 10.4 ml), and then age (cut-off 75 years). The accuracy of our CART model (0.86) exceeded that of a multivariate logistic regression model (0.81). DISCUSSION: ICH patients can easily be stratified for mortality risk, based on three predictors available on admission. This simple decision tree model provides clinicians with a reliable and practical tool.

Adult↗

PubMed2006

Genetic linkage analysis of pulmonary fibrotic response to silica in mice.

Inter-individual variations in the development of silicosis, even within the same environments, have been reported, which suggest the contribution of genetic factors in silicosis aetiology. The aim of the present study was to determine whether there is any significant genetic influence on the development of silicosis. Furthermore, which genetic loci are responsible for the pulmonary response to silica exposure? Eight strains of inbred mice were used to examine the genetic influence on the lung fibrotic response to silica exposure. After intercross-breeding between the most susceptible and most resistant strains, a genome-wide linkage analysis of quantitative trait loci (QTL) was performed. Hydroxyproline was applied as an index, and genotypes of 167 marker genes were analysed by fragment analysis using a capillary-type sequencer. There was significant inter-strain difference in the mean concentration of hydroxyproline contents among the eight strains of mice. Breeding studies were conducted between the most susceptible, C57BL/6J, and the most resistant strain, CBA/J. A genome-wide linkage analysis of silica-exposed intercrossed cohorts identified significant QTL on chromosome 4 and suggestive QTL on chromosomes 3 and 18. The present study demonstrates that genetic factors may play a significant role in fibrotic-lung responses to silica; one significant and two suggestive quantitative trait loci were identified.

Air Pollutants, Occupational↗

PubMed2006

Detailed images of asteroid 25143 Itokawa from Hayabusa.

Rendezvous of the Japanese spacecraft Hayabusa with the near-Earth asteroid 25143 Itokawa took place during the interval September through November 2005. The onboard camera imaged the solid surface of this tiny asteroid (535 meters by 294 meters by 209 meters) with a spatial resolution of 70 centimeters per pixel, revealing diverse surface morphologies. Unlike previously explored asteroids, the surface of Itokawa reveals both rough and smooth terrains. Craters generally show unclear morphologies. Numerous boulders on Itokawa's surface suggest a rubble-pile structure.

Journal Article↗

PubMed2006

The rubble-pile asteroid Itokawa as observed by Hayabusa.

During the interval from September through early December 2005, the Hayabusa spacecraft was in close proximity to near-Earth asteroid 25143 Itokawa, and a variety of data were taken on its shape, mass, and surface topography as well as its mineralogic and elemental abundances. The asteroid's orthogonal axes are 535, 294, and 209 meters, the mass is 3.51 x 10(10) kilograms, and the estimated bulk density is 1.9 +/- 0.13 grams per cubic centimeter. The correspondence between the smooth areas on the surface (Muses Sea and Sagamihara) and the gravitationally low regions suggests mass movement and an effective resurfacing process by impact jolting. Itokawa is considered to be a rubble-pile body because of its low bulk density, high porosity, boulder-rich appearance, and shape. The existence of very large boulders and pillars suggests an early collisional breakup of a preexisting parent asteroid followed by a re-agglomeration into a rubble-pile object.

Journal Article↗

PubMed2006

Touchdown of the Hayabusa spacecraft at the Muses Sea on Itokawa.

After global observations of asteroid 25143 Itokawa by the Hayabusa spacecraft, we selected the smooth terrain of the Muses Sea for two touchdowns carried out on 19 and 25 November 2005 UTC for the first asteroid sample collection with an impact sampling mechanism. Here, we report initial findings about geological features, surface condition, regolith grain size, compositional variation, and constraints on the physical properties of this site by using both scientific and housekeeping data during the descent sequence of the first touchdown. Close-up images revealed the first touchdown site as a regolith field densely filled with size-sorted, millimeter- to centimeter-sized grains.

Journal Article↗

PubMed2006

Prolactin-releasing peptide is a potent mediator of stress responses in the brain through the hypothalamic paraventricular nucleus.

The effects of i.c.v. administration of prolactin-releasing peptide on neurons in the paraventricular nucleus of rats and plasma corticosterone levels were examined by measuring changes in Fos-like immunoreactivity, c-fos mRNA using in situ hybridization histochemistry, and plasma corticosterone using a specific radioimmunoassay. Approximately 80% of corticotropin-releasing hormone immunoreactive cells exhibited Fos-like immunoreactivity in the parvocellular division of the paraventricular nucleus 90 min after i.c.v. administration of prolactin-releasing peptide. The greatest induction of the c-fos mRNA expression in the paraventricular nucleus was observed 30 min after administration of prolactin-releasing peptide, and occurred in a dose-related manner. Plasma corticosterone levels were also significantly increased 30 min after administration of prolactin-releasing peptide. Next, the effects of restraint stress, nociceptive stimulus and acute inflammatory stress on the expression of the prolactin-releasing peptide mRNA in the dorsomedial hypothalamic nucleus, nucleus of the solitary tract and ventrolateral medulla were examined using in situ hybridization histochemistry for prolactin-releasing peptide mRNA. Restraint stress and acute inflammatory stress upregulated the prolactin-releasing peptide mRNA expression in the nucleus of the solitary tract and ventrolateral medulla. Nociceptive stimulus upregulated the prolactin-releasing peptide mRNA expression in the ventrolateral medulla. Finally, we observed that pretreatment (i.c.v. administration) with an anti-prolactin-releasing peptide antibody significantly attenuated nociceptive stimulus-induced c-fos mRNA expression in the paraventricular nucleus. These results suggest that prolactin-releasing peptide is a potent and important mediator of the stress response in the brain through the hypothalamic paraventricular nucleus.

Analysis of Variance↗

PubMed2005

Expression of immediate early genes and vasopressin heteronuclear RNA in the paraventricular and supraoptic nuclei of rats after acute osmotic stimulus.

Monitoring the expression of immediate early genes (IEGs) is useful for following stress-induced cellular responses in the neuroendocrine system. We have examined the transcriptional activities of four IEGs (c-fos, junB, NGFI-A and NGFI-B) and of the arginine vasopressin (AVP) gene in the hypothalamic paraventicular (PVN) and supraoptic nuclei (SON) of rats after acute osmotic stimuli, using in situ hybridization histochemistry. After intraperitoneal (i.p.) administration of hypertonic saline (2% body weight, 900 mOsm/kg), the expression levels of all IEG mRNAs were increased significantly both in the PVN and SON at as early as 10 min, peaked at 30 min and remained elevated until 60 min. The expression of AVP heteronuclear (hn)RNA also peaked at 30 min, and remained elevated until 180 min. Thirty min after i.p. administration of hypertonic saline (600 mOsm/kg), the expression levels of all IEG mRNAs in the PVN and SON were significantly increased in comparison with those after i.p. administration of isotonic saline (290 mOsm/kg). Regression analysis revealed that expression levels of the IEG mRNAs and AVP hnRNA were positively correlated with the plasma concentration of sodium, and the rates of increase of the expression levels of all IEG mRNAs were similar. The expression levels of all IEG mRNAs examined are useful markers for following the changes of the AVP gene transcription in the PVN and SON after acute osmotic stimuli in rats.

Animals↗

PubMed2004

Novel G-protein coupled receptor ligands and neurohypophysial hormones.

Recently, novel peptides have been identified as unknown ligands of orphan G-protein coupled receptors. In the paraventicular (PVN) and supraoptic nuclei (SON), the expression of the G-protein genes are abundant. In this review, we focus on the physiological role of neuromedin U and galanin-like peptide, which were recently identified as ligands of G-protein coupled receptors, in the regulation of neurohypophysial hormones. Intracerebroventricular (i.c.v) administration of neuromedin U induced the expression of c-fos mRNA in both the magnocellular and parvocellular division of the PVN and throughout the SON. Administration of i.c.v. neuromedin U caused a significant increase in plasma concentrations of vasopressin and oxytocin as well as adrenocorticotropic hormone. The expression of galanin-like peptide mRNA was observed in the pituicytes of rat posterior pituitary gland. The expression of galanin-like peptide mRNA in the posterior pituitary gland was markedly increased after dehydration, salt loading and intraperitoneal administration of lipopolysaccaride, challenges that stimulate the secretion of vasopressin and oxytocin, and which activate the hypothalamic-pituitary adrenal axis. These results suggest that neuromedin U and galanin-like peptide may have an important role in the regulation of both the hypothalamic-neurohypophysial system and the hypothalamic-adrenohypophysial system.

Animals↗

PubMed2004

Expression of the arginine vasopressin gene in response to salt loading in oxytocin gene knockout mice.

Accumulating evidence suggests that both oxytocin and arginine vasopressin (AVP) are vital components in the regulation of body fluid balance. However, the physiological role of oxytocin and possible cooperative interactions between oxytocin and AVP in sodium balance remain obscure, even though recent studies using oxytocin knockout (OTKO) mice suggested that oxytocin may contribute to the regulation of salt appetite. In the present study, we examined the effects of salt loading (drinking 2% NaCl for 5 days) on the expression of the AVP gene in the paraventricular (PVN) and supraoptic nuclei (SON) of wild-type, OTKO and heterozygous littermates using in situ hybridization histochemistry. In addition, the effects of salt loading on the expression of the oxytocin gene were also examined in wild-type and heterozygous mice. Under the non salt-loaded condition, the levels of AVP mRNA in the PVN and SON of OTKO mice were significantly decreased compared to those in wild-type mice. Nevertheless, the up-regulation of the expression of the AVP gene in response to salt loading was preserved in OTKO mice. The degree of the up-regulation in OTKO mice tended to be greater compared to those in wild-type mice, suggesting compensatory up-regulation of the expression of the AVP gene in OTKO mice after salt loading. The basal levels of oxytocin mRNA in the PVN and SON of heterozygous mice were significantly lower than those in wild-type mice. Salt loading caused an increase of oxytocin mRNA levels in the PVN and SON of both wild-type and heterozygous mice. The ratios of increase of oxytocin mRNA levels were very similar between wild-type and heterozygous mice, suggesting that the single remaining oxytocin gene in heterozygous mice responds normally to an osmotic cue. Finally, salt loading tended to increase the serum concentration of sodium regardless of genotype, and there were no genotype differences in both the control and salt-loaded groups. These results suggest ways in which oxytocin may play a cooperative role together with AVP in the regulation of sodium balance.

Animals↗

PubMed2003

Different spatial processing for stimulus-centered and body-centered representations.

The authors describe a patient who experienced two successive strokes in the right hemisphere. After the first stroke, she showed stimulus-centered left neglect confined to right space on a circle discrimination task, which resolved. After the second stroke, she showed body-centered left neglect on the same task. These observations of two types of left neglect in the same patient suggest there are at least two distinct spatial attentional systems in the brain: global and focal attentional systems.

Aged↗

PubMed2003

Emergency endovascular stent-grafting for infected pseudoaneurysm of brachial artery.

The use of covered stents in an infected field is controversial. It is generally recommended that infected aneurysms be treated using autografts or allografts. We report a case of infected brachial pseudoaneurysms that developed after medical debridement of a methicillin-resistant Staphylococcus aureus (MRSA)-infected wound of the right arm and emergency brachial artery bypass-grafting using the saphenous vein, which was successfully treated by endovascular stent-grafting followed by antibiotic administration. The present case suggests that endovascular stent-grafting prevents rupture and occlusion of infected aneurysms and enables the continued administration of antibiotics.

Adult↗

PubMed2003

Enhanced up-regulation of corticotropin-releasing hormone gene expression in response to restraint stress in the hypothalamic paraventricular nucleus of oxytocin gene-deficient male mice.

The neuropeptide oxytocin is released not only into the blood, but also within the brain in response to various stressors. Accumulating evidence suggests that central oxytocin may play a major role in the regulation of neuroendocrine responses to stress. In the present study, using the oxytocin knockout mouse model, we tested whether oxytocin might act to attenuate stress-induced up-regulation of corticotropin-releasing hormone (CRH) mRNA expression in the brain. The expression of CRH mRNA in the paraventricular nucleus (PVN) after 4 h of restraint stress was examined in oxytocin gene-deficient (OTKO), wild-type and heterozygous male mice using in situ hybridization histochemistry. We found that basal levels of CRH mRNA were not different among the three genotypes. Although restraint stress resulted in a significant increase of CRH mRNA expression in the PVN regardless of genotype, the degree of stress induced-up-regulation was significantly higher in OTKO mice than in wild-type mice. The effects of restraint stress on the expression of the arginine vasopressin (AVP) and the oxytocin genes were also examined. Unlike CRH mRNA, basal expression (in nonstressed control groups) of AVP mRNA in OTKO mice, as well as oxytocin mRNA in heterozygous mice, was significantly lower in the PVN and the supraoptic nucleus than in wild-type mice. After restraint stress, the expression of AVP mRNA was significantly increased in the PVN of OTKO mice compared to the nonstressed control group, whereas the expression of both AVP and oxytocin mRNA were unchanged in the PVN and the supraoptic nucleus of wild-type and heterozygous mice. Finally, in a separate set of mice, restraint stress-induced Fos expression was also examined in several brain regions involved in stress response, including the lateral septum, the bed nucleus of the stria terminalis (BNST), the medial preoptic area, the PVN, the medial and central amygdala using immunohistochemistry. After 90 min of restraint stress, the number of Fos-expressing cells significantly increased in all brain regions examined regardless of genotype. However, the number of stress-induced Fos-expressing cells in the BNST and the medial amygdala of OTKO mice was significantly lower than in wild-type mice. Collectively, the findings in the present study suggest that oxytocin may regulate stress-induced CRH gene expression in the PVN. Furthermore, neuronal activity in the BNST and the medial amygdala may be involved in this neuroendocrine regulatory system.

Animals↗

PubMed2001

The core of the motor domain determines the direction of myosin movement.

Myosins constitute a superfamily of at least 18 known classes of molecular motors that move along actin filaments. Myosins move towards the plus end of F-actin filaments; however, it was shown recently that a certain class of myosin, class VI myosin, moves towards the opposite end of F-actin, that is, in the minus direction. As there is a large, unique insertion in the myosin VI head domain between the motor domain and the light-chain-binding domain (the lever arm), it was thought that this insertion alters the angle of the lever-arm switch movement, thereby changing the direction of motility. Here we determine the direction of motility of chimaeric myosins that comprise the motor domain and the lever-arm domain (containing an insert) from myosins that have movement in the opposite direction. The results show that the motor core domain, but neither the large insert nor the converter domain, determines the direction of myosin motility.

Animals↗

PubMed2001

Dual regulation of mammalian myosin VI motor function.

Myosin VI is expressed in a variety of cell types and is thought to play a role in membrane trafficking and endocytosis, yet its motor function and regulation are not understood. The present study clarified mammalian myosin VI motor function and regulation at a molecular level. Myosin VI ATPase activity was highly activated by actin with K(actin) of 9 microm. A predominant amount of myosin VI bound to actin in the presence of ATP unlike conventional myosins. K(ATP) was much higher than those of other known myosins, suggesting that myosin VI has a weak affinity or slow binding for ATP. On the other hand, ADP markedly inhibited the actin-activated ATPase activity, suggesting a high affinity for ADP. These results suggested that myosin VI is predominantly in a strong actin binding state during the ATPase cycle. p21-activated kinase 3 phosphorylated myosin VI, and the site was identified as Thr(406). The phosphorylation of myosin VI significantly facilitated the actin-translocating activity of myosin VI. On the other hand, Ca(2+) diminished the actin-translocating activity of myosin VI although the actin-activated ATPase activity was not affected by Ca(2+). Calmodulin was not dissociated from the heavy chain at high Ca(2+), suggesting that a conformational change of calmodulin upon Ca(2+) binding, but not its physical dissociation, determines the inhibition of the motility activity. The present results revealed the dual regulation of myosin VI by phosphorylation and Ca(2+) binding to calmodulin light chain.

Actin Cytoskeleton↗

PubMed2001

Overexpression and overactivation of Akt in thyroid carcinoma.

Enhanced activation of Akt occurs in Cowden's disease, an inherited syndrome of follicular thyroid, breast, colon, and skin tumors, via inactivation of its regulatory protein, PTEN. Whereas PTEN inactivation is uncommon in sporadic thyroid cancer, activation of growth factor pathways that signal through Akt is frequently identified. We hypothesized that Akt overactivation could be a common finding in sporadic thyroid cancer and might be important in thyroid cancer biology. We examined thyroid cancer cells lines and benign and malignant thyroid tissue for total Akt activation and isoform-specific Akt expression. In thyroid cancer cells, Akt 1, 2, and 3 proteins were expressed, total Akt was activated by insulin phosphatidylinositol 3'-kinase, and inhibition of phosphatidylinositol 3'-kinase reduced cell viability. In human thyroid tissue, increased levels of phosphorylated total Akt were identified in follicular but not papillary cancers compared with normal tissue. Levels of Akt 1 and 2 proteins and Akt 2 RNA were elevated only in the follicular cancers. In paired samples, Akt 1, 2, 3, and phospho-Akt levels were higher in five of six cancers, including three of three follicular cancers. These data suggest that Akt activation may play a role in the pathogenesis or progression of sporadic thyroid cancer.

Adenocarcinoma, Follicular↗

PubMed2001

Motor function and regulation of myosin X.

Myosin X is a member of the diverse myosin superfamily that is ubiquitously expressed in various mammalian tissues. Although its association with actin in cells has been shown, little is known about its biochemical and mechanoenzymatic function at the molecular level. We expressed bovine myosin X containing the entire head, neck, and coiled-coil domain and purified bovine myosin X in Sf9 cells. The Mg(2+)-ATPase activity of myosin X was significantly activated by actin with low K(ATP). The actin-activated ATPase activity was reduced at Ca(2+) concentrations above pCa 5 in which 1 mol of calmodulin light chain dissociates from the heavy chain. Myosin X translocates F-actin filaments with the velocity of 0.3 microm/s with the direction toward the barbed end. The actin translocating activity was inhibited at concentrations of Ca(2+) at pCa 6 in which no calmodulin dissociation takes place, suggesting that the calmodulin dissociation is not required for the inhibition of the motility. Unlike class V myosin, which shows a high affinity for F-actin in the presence of ATP, the K(actin) of the myosin X ATPase was much higher than that of myosin V. Consistently nearly all actin dissociated from myosin X in the presence of ATP. ADP did not significantly inhibit the actin-activated ATPase activity of myosin X, suggesting that the ADP release step is not rate-limiting. These results suggest that myosin X is a nonprocessive motor. Consistently myosin X failed to support the actin translocation at low density in an in vitro motility assay where myosin V, a processive motor, supports the actin filament movement.

Actins↗

PubMed2001

The tip of the coiled-coil rod determines the filament formation of smooth muscle and nonmuscle myosin.

Myosin II self-assembles to form thick filaments that are attributed to its long coiled-coil tail domain. The present study has determined a region critical for filament formation of vertebrate smooth muscle and nonmuscle myosin II. A monoclonal antibody recognizing the 28 residues from the C-terminal end of the coiled-coil domain of smooth muscle myosin II completely inhibited filament formation, whereas other antibodies recognizing other parts of the coiled-coil did not. To determine the importance of this region in the filament assembly in vivo, green fluorescent protein (GFP)-tagged smooth muscle myosin was expressed in COS-7 cells, and the filamentous localization of the GFP signal was monitored by fluorescence microscopy. Wild type GFP-tagged smooth muscle myosin colocalized with F-actin during interphase and was also recruited into the contractile ring during cytokinesis. Myosin with the nonhelical tail piece deleted showed similar behavior, whereas deletion of the 28 residues at the C-terminal end of the coiled-coil domain abolished this localization. Deletion of the corresponding region of GFP-tagged nonmuscle myosin IIA also abolished this localization. We conclude that the C-terminal end of the coiled-coil domain, but not the nonhelical tail piece, of myosin II is critical for myosin filament formation both in vitro and in vivo.

Actins↗