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Biomedical subjects

Y Ohashi

Publications and source records attributed to Y Ohashi.

At least 199 records · Page 11Linked to original sources

[Evaluation of mortality of patients admitted to ICU for the last 12 years].

We evaluated mortality of 2689 patients admitted to the Intensive Care Unit, Osaka University Hospital from January, 1987 to December, 1998. The patients were divided into 3 groups. Group A consisted of 1408 patients who underwent cardiovascular surgery, group B, 1082 patients who underwent other surgical procedures and group C, 199 patients who were transferred from the department of medicine. We studied mortality rate, causes of death, correlation between length of ICU stay and mortality rate, and mortality rate among age groups for 12 years. The main causes of death were cardiac failure and sepsis in group A, and respiratory failure and sepsis in group B and C. Mortality rate in each group showed no significant change for the last 12 years. Those who stayed more than 2 weeks in ICU showed a significantly higher mortality rate (p < 0.0001). Thus, length of ICU stay and mortality rate showed a positive correlation (p < 0.0001). The youngest group (age 0-1) showed a significantly higher mortality rate than other age groups (p < 0.0001). As sepsis was the most important cause of death in all the groups, the prevention and treatment of infection are the most important issue in our ICU to reduce mortality rate.

Adolescent↗

Hypotension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase.

Nitric oxide (NO), constitutively produced by endothelial nitric oxide synthase (eNOS), plays a major role in the regulation of blood pressure and vascular tone. We generated transgenic mice overexpressing bovine eNOS in the vascular wall using murine preproendothelin-1 promoter. In transgenic lineages with three to eight transgene copies, bovine eNOS-specific mRNA, protein expression in the particulate fractions, and calcium-dependent NOS activity were confirmed by RNase protection assay, immunoblotting, and L-arginine/citrulline conversion. Immunohistochemical studies revealed that eNOS protein was predominantly localized in the endothelial cells of aorta, heart, and lung. Blood pressure was significantly lower in eNOS-overexpressing mice than in control littermates. In the transgenic aorta, basal NO release (estimated by Nomega-nitro-L-arginine-induced facilitation of the contraction by prostaglandin F2alpha) and basal cGMP levels (measured by enzyme immunoassay) were significantly increased. In contrast, relaxations of transgenic aorta in response to acetylcholine and sodium nitroprusside were significantly attenuated, and the reduced vascular reactivity was associated with reduced response of cGMP elevation to these agents as compared with control aortas. Thus, our novel mouse model of chronic eNOS overexpression demonstrates that, in addition to the essential role of eNOS in blood pressure regulation, tonic NO release by eNOS in the endothelium induces the reduced vascular reactivity to NO-mediated vasodilators, providing several insights into the pathogenesis of nitrate tolerance.

Animals↗

A Bayesian hierarchical survival model for the institutional effects in a multi-centre cancer clinical trial.

In randomized clinical trials comparing treatment effects on diseases such as cancer, a multi-centre trial is usually conducted to accrue the required number of patients in a reasonable period of time. While we interpret the average treatment effect, it is necessary to examine the homogeneity of the observed treatment effects across institutions, that is, treatment-by-institution interaction. If the homogeneity is confirmed, the conclusions concerning treatment effects can be generalized to a broader patient population. In this paper, a Bayesian hierarchical survival model is used to investigate the institutional effects on the efficacy of treatment as well as on the baseline risk. The marginal posterior distributions are estimated by a Markov chain Monte Carlo method, that is, Gibbs sampling, to overcome current computational limitations. The robustness of the inferences to the distributional assumption for the random effects is also examined. We illustrate the methods with analyses of data from a multi-centre cancer clinical trial, which investigated the efficacy of immunochemotherapy as an adjuvant treatment after curative resection of gastric cancer. In this trial there is little difference in the treatment effects across institutions and the treatment is shown to be effective, while there appears to be substantial variation in the baseline risk across institutions. This result indicates that the observed treatment effects might be generalized to a broader patient population.

Adjuvants, Immunologic↗

A novel sporulation-control gene (spo0M) of Bacillus subtilis with a sigmaH-regulated promoter.

A novel sporulation-control gene (spo0M) of Bacillus subtilis was cloned, sequenced and analyzed. The spo0M gene is located at the end of large tRNA gene clusters including rrnD and codes for a 257-amino-acid protein with a calculated size of 29.6kDa. The protein Spo0M has a strong negative charge (calculated pI=4.3) and shows no significant sequence homology to any known proteins. Gene disruption experiments revealed that spo0M is not essential for cell viability, but its disruption results in considerable impairments (decreasing by 20- to 100-fold) in sporulation. The morphological stage blocked in sporulation was stage 0 as observed by electron microscopy, and expression analysis using spo0Aps-bgaB fusion revealed an impaired gene expression of spo0A in the spo0M mutant. In contrast, spo0M disruption had no effect on antibiotic productivity. Propagation of the spo0M gene in wild-type cells using a high-copy-number plasmid also impaired sporulation, indicating that overproduction of Spo0M exerts certain negative effects on sporulation. spo0M gene expression is controlled by sigmaH, as demonstrated: (1) by monitoring expression of a bgaB transcriptional fusion integrated into the amyE locus on the chromosome of the wild-type or spo0H mutant cells, and (2) by in-vitro transcription of spo0M gene with EsigmaH.

Amino Acid Sequence↗

RF system of the SPring-8 storage ring.

Construction of three RF stations in the storage ring of SPring-8 has been completed. The design concept concentrates on avoiding a coupled-bunch instability which limits the stored current or makes the synchrotron radiation beam unstable. The cavity is bell-shaped to reduce the coupling impedance of the higher-order modes. The cavity dimensions are trimmed systematically to distribute the higher-order mode frequencies. Each cavity has two movable tuners. The temperature of the cavity cooling water is controlled within 0.02 K and the water flow is kept constant. The construction and commissioning of the SPring-8 storage ring RF system is reported.

Journal Article↗

X-ray triple refraction and triple absorption in a cobalt-complex crystal.

X-ray triple refraction and triple absorption have been quantitatively measured for the first time. The samples were (100)-, (010)- and (001)-oriented plates of a cobalt-complex monoclinic crystal. The apparatus used was an energy-tunable X-ray polarimeter with a phase retarder. The X-ray energy was scanned over a range of 150 eV near the cobalt K-absorption edge. Both the spectra of ellipticity and rotation of polarization were completely different for each crystal plate, which revealed that the biaxial crystal had three refractive indices and three absorption coefficients in the X-ray region. The Kramers-Kronig relation between the real and imaginary parts of the dielectric anisotropy has been quantitatively confirmed for all three different orientations.

Journal Article↗

T cell receptor-mediated tyrosine phosphorylation of Cas-L, a 105-kDa Crk-associated substrate-related protein, and its association of Crk and C3G.

Cas-L (pp105), a Crk-associated substrate (p130(Cas))-related protein, was first identified as a 105-kDa protein that is tyrosine-phosphorylated following beta1 integrin cross-linking in T cells. Cas-L contains possible multiple binding sites for the Src homology (SH) 2 domains of various signaling molecules, and appears to be involved in signal transduction through phosphorylated tyrosine-mediated protein-protein interaction. Since Cas-L is preferentially expressed in lymphocytes, it is conceivable that Cas-L plays an important role in lymphocyte-specific signals. Here, we show the involvement of Cas-L in the T cell receptor (TCR)/CD3 signaling pathway. Cas-L is transiently phosphorylated following CD3 cross-linking, and tyrosine-phosphorylated Cas-L binds to Crk and C3G. Furthermore, a Cas-L mutant that lacks the SH3 domain, the binding site for focal adhesion kinase (FAK), is also tyrosine-phosphorylated upon CD3 cross-linking, but not upon beta1 integrin crosslinking, suggesting that FAK is not involved in CD3-dependent Cas-L phosphorylation. Taken together, the present study indicates a novel signaling pathway mediated by tyrosine-phosphorylated Cas-L upon the TCR/CD3 stimulation.

Adaptor Proteins, Signal Transducing↗

Clinical role of soluble adhesion molecules during immunotherapy for perennial allergic rhinitis.

BACKGROUND: Soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) have recently been identified in serum samples from atopic patients, but their clinical significance in the treatment of allergic diseases remains to be established. OBJECTIVE: To study the clinical roles of serum sICAM-1 and sVCAM-1 during immunotherapy for perennial allergic rhinitis. DESIGN: Our study included 30 nonatopic volunteers and 60 patients with perennial allergic rhinitis due to Dermatophagoides farinae. The 60 patients had been treated for variable periods (7.3+/-3.0 years [mean+/-SD]) with immunotherapy using a standardized D. farinae antigen. Serum samples were collected from each patient before and after immunotherapy to determine sICAM-1 and sVCAM-1 with sandwich enzyme-linked immunosorbent assays. RESULTS: Serum levels of sICAM-1 in the patients before immunotherapy were higher than those in the nonatopic volunteers (P<.001). The levels of sICAM-1 in the patients' serum samples were decreased significantly after immunotherapy (P<.001), and the percentage of the decrease in the sICAM-1 levels was significantly correlated with the duration of immunotherapy (P=.04) and with the percentage of the decrease in symptom scores (P<.001). The levels of sVCAM-1 in the serum samples from the patients with severe symptoms were significantly higher before immunotherapy than those in the nonatopic volunteers (P=.002) and were significantly decreased after immunotherapy (P=.05). However, the percentage of the decrease in the sVCAM-1 levels was not correlated with the duration of immunotherapy (P=.89) or with the percentage of the decrease in symptom scores (P=.89). CONCLUSION: Decrease in serum sICAM-1 levels during immunotherapy is probably involved in the working mechanisms of immunotherapy, but modulation of serum sVCAM-1 levels is not likely related to the clinical effect of immunotherapy.

Adult↗

Serologic study of the working mechanisms of immunotherapy for children with perennial allergic rhinitis.

BACKGROUND: Recent double-blind placebo-controlled trials have clearly shown the efficacy of immunotherapy for perennial allergic rhinitis. However, the exact working mechanisms related to the clinical effect of immunotherapy remain unclear. OBJECTIVES: To monitor the changes over time in immunologic parameters in children who received immunotherapy for perennial allergic rhinitis, and to elucidate the working mechanisms of immunotherapy related to its clinical efficacy. DESIGN: Nineteen children with perennial allergic rhinitis due to Dermatophagoides farinae enrolled in this prospective open study. Venous blood was collected to determine levels of specific IgE, specific IgG4, soluble interleukin 2 receptor, interleukin 4, soluble intercellular adhesion molecule 1, and soluble vascular cell adhesion molecule 1 at enrollment and 1, 2, 3, 5, and 10 years after enrollment. RESULTS: Immunotherapy affected serum levels of specific IgE, specific IgG4, soluble interleukin 2 receptor, interleukin 4, and soluble intercellular adhesion molecule 1, but not soluble vascular cell adhesion molecule 1. The rates of increase of levels of specific IgG4 and the rates of decrease of levels of soluble interleukin 2 receptor were correlated with the rates of decrease of symptom scores during the first 3 years of treatment, but not after 5 years. The rates of decrease in levels of soluble intercellular adhesion molecule 1 were correlated with the rates of decrease in symptom scores at 3 and 5 years after the beginning of the course of immunotherapy. The rates of decrease in levels of specific IgE and interleukin 4 were correlated with the rates of decrease in symptom scores after 5 and 10 years of treatment, but not during the first 3 years. CONCLUSION: Each modulation in levels of specific IgE, specific IgG4, soluble interleukin 2 receptor, interleukin 4, and soluble intercellular adhesion molecule 1 contributed to the clinical effect of immunotherapy in particular phases of treatment for children with perennial allergic rhinitis.

Anti-Asthmatic Agents↗

Characterization of the sulfated fucose-containing trisaccharides by fast atom bombardment tandem mass spectrometry in the study of the acrosome reaction-inducing substance of the starfish, Asterias amurensis.

Fast atom bombardment mass spectrometry (FABMS) and collision-induced dissociation tandem mass spectrometry (CID-MS/MS) were applied to the investigation of the anomeric isomerism of synthetic trisaccharides consisting of xylose, galactose and sulfated fucose {Xyl1-->3Gal alpha 1-->3(4-OSO3Na)Fuc} and {Xyl1-->3Gal alpha 1-->4(3-OSO3Na)Fuc} and the linkage position of the sulfate group. It was possible to differentiate between various glycosidic linkages in several synthetic trisaccharides. The position of a sulfate group in synthetic methyl O-sulfo-alpha-L-fucopyranoside isomers was elucidated from the fragmentation patterns. Comparing the data from the synthetic sulfated trisaccharides with the spectra from the natural compound derived from glycan chains of the acrosome reaction-inducing substance (ARIS) from starfish, the anomeric structure and the position of the sulfate group in the natural sample were determined without ambiguity as Xyl beta 1-->3Gal alpha 1-->3(4-OSO3-)Fuc, in agreement with the result from an independent study based on nuclear magnetic resonance.

Animals↗

Transforming growth factor-beta1 and protein kinase C synergistically activate the c-fos serum response element in myocardial cells.

We previously reported that transforming growth factor-beta1 (TGF-beta1) potentiated alpha1-adrenergic and stretch-induced c-fos mRNA expression and norepinephrine (NE)-induced amino acid incorporation in rat cultured myocardial cells (MCs). In the present study, we attempted to explore the mode of TGF-beta1 action for c-fos gene expression in MCs. In the transient transfection assay, TGF-beta1 potentiated NE- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated c-fos promoter/enhancer, but not forskolin-activated c-fos promoter/enhancer. The c-fos serum response element (SRE) and the TPA response element (TRE) were responsible for TGF-beta1-induced potentiation of the NE or TPA action. Although TGF-beta1 activated not only the wild-type c-fos SRE, but also the mutated c-fos SRE, which contains an intact binding site for the serum response factor (SRF) but lacks the ternary complex factor (TCF) binding site, TPA activated the wild-type c-fos SRE but not the mutated c-fos SRE. TGF-beta1 did not potentiate the effects of TPA on the activation of mitogen-activated protein kinase (MAPK) and the phosphorylation of Elk-1 and SAP-1a, which belong to TCF at the c-fos SRE. These results indicate that TGF-betaf potentiates the c-fos SRE activated by PKC through the SRF binding site. TGF-beta1 is involved in the regulation of c-fos gene expression through the c-fos SRE and is subsequently involved in the regulation of the gene which has the TRE in the promoter/enhancer region.

Animals↗

Osteolipoma in the parapharyngeal space.

We report our experience in managing a 58-year-old Japanese woman with a rare parapharyngeal interstitial cell tumor. Her main complaint was that of a submandibular swelling, which was diagnosed as osteolipoma histologically after resection.

Adipose Tissue↗

Prolonged secretion of IL-15 in patients with severe forms of acute graft-versus-host disease after allogeneic bone marrow transplantation in children.

Graft-versus-host disease (GVHD) is one of the most common and fatal complications that follows allogeneic bone marrow transplantation (BMT). Donor origin T cells are responsible for the initiation of GVHD. In this report, we demonstrate that conditioning regimens for BMT resulted in elevated serum levels of interleukin-15 (IL-15), which reached maximum levels within 15 days and returned to basal levels within 25 days after allogeneic BMT, in all patients examined. Thereafter, circulating IL-15 was detected only in patients with grade III or IV acute GVHD with gut involvement. In contrast, IL-2 was not detected at any time in these patients. Since IL-15 is able to activate antigen-stimulated T cells and natural killer (NK) cells, IL-15 may play an important role in the development of severe forms of acute GVHD.

Acute Disease↗

Influence of absorption enhancers (bile salts) and the preservative (benzalkonium chloride) on mucociliary function and permeation barrier function in rabbit tracheas.

Effects of bile salts and benzalkonium chloride on the ciliary beat activity (frequency) and the mucociliary transport rate of tracheas, and permeabilities of 6-carboxyfluorescein (6-CF; Mw 376) and FITC-dextrans (FD-4; Mw 4300) as hydrophilic compounds through trachea were investigated for intratracheal delivery of drugs. Ciliary beat activity was measured by an in vitro photoelectric method by using excised rabbit tracheas. Transport rate was determined by an in vivo endoscopic method in rabbit tracheas. Permeation test was carried out by using excised rabbit tracheas. The ciliary beat activities and mucociliary transport rates were not significantly affected by 1, 10 and 20 mM sodium glycocholate, while they were significantly decreased by 1 and 10 mM sodium taurodeoxycholate and immediately halted after application of 20 mM taurodeoxycholate. They were not significantly affected by 0.02% of benzalkonium chloride, whereas they were completely halted by 0.05% of benzalkonium chloride. The apparent permeability coefficients (Papp) of 6-CF and FD-4 were 2.35x10(-7) and 2.22x10(-8) cm/s, respectively. One mmol of glycocholate did not significantly increase the Papp of 6-CF and FD-4, while, 10 mM of glycocholate and 1 and 10 mM of taurodeoxycholate significantly increased the Papp. Benzalkonium chloride (0.01%) did not significantly increase the Papp of 6-CF, whereas 0.03% significantly increased the Papp of 6-CF. Benzalkonium chloride (0.01 and 0.03%) slightly increased the Papp of FD-4. Therefore, sodium glycocholate may be a safe and useful absorption enhancer for intratracheal delivery of drugs.

Animals↗

Value of mild hypothermia in patients who have severe circulatory insufficiency even after intra-aortic balloon pump.

STUDY OBJECTIVE: To evaluate the effectiveness of mild hypothermia in postcardiac surgical patients with severe heart failure in spite of conventional medical therapy and the use of intra-aortic balloon pumping (IABP). DESIGN: Prospective, clinical study. SETTING: Teaching hospital. PATIENTS: 10 postcardiac surgical patients with severe heart failure despite the use of IABP with massive doses of catecholamine. INTERVENTIONS: Patients underwent mild hypothermia produced by surface cooling (to approximately 34.5 degrees C). Hemodynamic criteria for the induction of hypothermia included a cardiac index (CI) of less than 2.2 L/min/m2 with a pulmonary capillary wedge pressure (PCWP) of up to 18 mmHg despite the use of IABP with massive doses of catecholamine. MEASUREMENTS AND MAIN RESULTS: After control measurements had been taken at normal core body temperature (37 degrees C), patients were cooled to approximately 34.5 degrees C (using a cooling blanket and gastric lavage with cold water) to decrease tissue oxygen (O2) demand. Patients showed significant improvements in CI (1.9 +/- 0.3 to 2.2 +/- 0.3 L/min/m2), mixed venous O2 saturation, (SvO2; 55 +/- 7 to 64 +/- 6%), and urine output (2.1 +/- 1.1 to 3.4 +/- 2.2 ml/kg/hr). Patients were rewarmed while SvO2 was being monitored. The duration of the hypothermia was 38 +/- 41 hours. Oxygen delivery increased in 8 of the 10 patients, the mean value (+/- SD) for the group rising from 309 +/- 65 ml/min/m2 to 358 +/- 57 ml/min/m2 as temperature was reduced from 36.7 +/- 0.4 degrees C to 34.7 +/- 0.3 degrees C. All patients were successfully weaned from IABP at 140 +/- 107 hours after admission to the intensive care unit. CONCLUSIONS: Mild hypothermia is a simple and useful procedure for improving the circulation of postcardiac surgical patients with severe heart failure despite the use of IABP.

Aged↗

The clinical role of specific IgE and IgG4 antibodies in patients having immunotherapy for seasonal allergic rhinitis.

This study was designed to investigate the clinical role of specific IgG4 and IgE responses in patients during immunotherapy for seasonal allergy. The study included 109 patients with seasonal allergic rhinitis due to Japanese cedar pollens. They were divided into the control group and the immunotherapy group. Serum samples were obtained at the start of immunotherapy, before the pollen season and during the season, to determine serum specific IgE and IgG4. In the control group specific IgE was significantly increased, but specific IgG4 was not changed during the pollen season. In the immunotherapy group specific IgE was not significantly increased, but specific IgG4 was significantly increased during the season. In the patients having immunotherapy for 2 years or less, the seasonal increase in specific IgG4 related to the magnitude of the clinical effect. In the patients having immunotherapy for 3 years or more, the seasonal increase in specific IgE related to the magnitude of the clinical effect. In conclusion, the specific IgG4 response and specific IgE response during the pollen season make a significant contribution to the clinical effect of immunotherapy. However, modulation of specific IgE and IgG4 responses out of the pollen season was unlikely to be an important phenomenon related to the clinical effect of immunotherapy.

Adolescent↗