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Biomedical subjects

T Matsui

Publications and source records attributed to T Matsui.

At least 199 records · Page 11Linked to original sources

Central role for cdc45 in establishing an initiation complex of DNA replication in Xenopus egg extracts.

BACKGROUND: In eukaryotes, chromosomal DNA is licensed to be replicated through the sequential loading of the origin recognition complex, Cdc6 and mini-chromosome maintenance protein complex (MCM) onto chromatin. However, how the replication machinery is assembled onto the licensed chromatin during initiation of replication is poorly understood. RESULTS: Using Xenopus egg extracts, we have investigated the role of Cdc45 in the loading of various replication proteins onto chromatin at the onset of S phase, and found that Cdc45, which required MCM for its loading, was essential for the sequential loading of replication protein A (RPA), DNA polymerase alpha and proliferating cell nuclear antigen (PCNA) onto chromatin. The assembly of DNA polymerase epsilon onto chromatin required Cdc45 but did not require DNA polymerase alpha. Analysis of nuclease-digested chromatin fractions shows that Cdc45 formed a stable complex with either MCM or DNA polymerase alpha on chromatin. CONCLUSIONS: These results demonstrate a central role for Cdc45 in activation of the licensed chromatin to form replication complexes at the onset of S phase, and suggest that Cdc45 has a dual role in the initiation of DNA replication: the unwinding of DNA and the recruiting of DNA polymerases onto DNA.

Animals↗

Relation between incidence of pneumonia and protective reflexes in post-stroke patients with oral or tube feeding.

OBJECTIVES: Although attenuated protective reflexes have been implicated in the development of aspiration pneumonia, the relation between the incidence of pneumonia and the state of these reflexes has not been investigated. Furthermore, the role of feeding tube placement in preventing pneumonia in patients with attenuated protective reflexes is unknown. We studied the relationship between the incidence of pneumonia and the state of cough and swallowing reflexes in post-stroke patients with oral or tube feeding. DESIGN: The incidence of pneumonia was prospectively analysed for 1 year in three groups of post-stroke patients on the basis of the following clinical conditions: oral feeding without dysphagia (n = 43); oral feeding with dysphagia (n = 48); and nasogastric tube feeding with dysphagia (n = 52). We also studied the incidence of pneumonia in bedridden patients with nasogastric tube feeding (n = 14). Before the start of the study, the swallowing and cough reflexes of each patient were measured. The swallowing reflex was evaluated according to latency of response, which was timed from the injection of 1 mL of distilled water into the pharynx through a nasal catheter to the onset of swallowing. The cough threshold of citric acid aerosols was defined as the concentration at which the patient coughed five times. RESULTS.;: The incidence of pneumonia was observed in patients having both a latency of response longer than 5 s and a cough threshold for citric acid higher than a concentration of 1.35 (log mg mL-1). The incidence of pneumonia was significantly higher in patients with oral feeding than in those with tube feeding (54.3 vs. 13.2%, P < 0.001). In bedridden patients with tube feeding, the latency of response was longer than 20 s and no patient coughed at the highest concentration of citric acid. The incidence of pneumonia was 64.3% in such patients. CONCLUSIONS: The state of protective reflexes had a significant relation to the incidence of pneumonia. Feeding tube placement may have a beneficial role in preventing aspiration pneumonia in mildly or moderately disabled post-stroke patients with attenuated protective reflexes. Bedridden patients who were tube-fed had the highest incidence of pneumonia.

Aged↗

Possible role of the superoxide anion in the development of neuronal tolerance following ischaemic preconditioning in rats.

There is a large body of evidence that reactive oxygen species play a major role in the pathogenesis of ischaemic brain damage. On the other hand, it has recently been suggested that superoxide anions participate in the development of neuronal tolerance against lethal ischaemia following ischaemic preconditioning (PC). The present study aimed to examine whether or not the intravenous administration of human recombinant Cu/Zn superoxide dismutase (hr SOD) prior to PC would affect the subsequent development of neuronal tolerance. Animals were randomly assigned to the following three groups: group 1, sham PC treated with vehicle; group 2, PC treated with hr SOD and group 3, PC treated with vehicle. For PC, 10 min occlusion of the middle cerebral artery (MCA) by a modified intraluminal suture method was followed by 60 min recirculation and this procedure was successively repeated three times. The procedures were similar for sham PC except that the MCA was kept unoccluded. Just prior to PC or sham PC, a bolus of hr SOD (6 x 103 IU/2 ml/kg) was administered intravenously. Seventy-two hours thereafter, rats were subjected to lethal ischaemia, i.e. MCA occlusion for 100 min followed by recirculation for 48 h. The infarct area and volume were assessed with the 2,3,5-triphenyltetrazolium stain. A significant difference in the infarct volume was revealed between the sham PC/vehicle and the PC/vehicle groups (total and cortex P < 0.01; striatum P < 0.05), showing that PC induced a marked neuronal tolerance against lethal ischaemia. The infarct volume in the PC/SOD group was close to that in the sham PC/vehicle group, being significantly greater than that in the PC/vehicle group (total and cortex P < 0.01) and showing that the administration of hr SOD suppressed the development of neuronal tolerance induced by PC. In a parallel experiment, expression of 72-kDa heat-shock protein (hsp 72) at 72 h after PC was considerably reduced in rats treated with hr SOD compared with those treated with vehicle. These results suggest that superoxide anions intraluminally generated within cerebral microvessels participate in the development of neuronal tolerance as well as the induction of hsp 72 following PC.

Animals↗

A clinical use of the Kyocera Gyro C1E3 centrifugal pump.

The Kyocera Gyro C1E3 centrifugal blood pump was clinically applied for a cardiopulmonary bypass (CPB) of coronary artery bypass grafting (CABG). The patient was 72-year-old male with postinfarction unstable angina. The surgery was carried out on November 20, 1998. The air inside the pump was easily and quickly removed, and its controllability was excellent. The pump flow during operation was maintained 2.2 L/m2. Total CPB time was 173 min. Perioperative parameters of hemolysis and cytotoxicity were not remarkably changed. Macroscopically and microscopically, there were no thrombi inside the pump after usage. This is the first reported case of clinical use of the Kyocera Gyro C1E3 pump.

Aged↗

Jostra Rota Flow RF-30 pump system: a new centrifugal blood pump for cardiopulmonary bypass.

The Rota Flow pump is a fully integrated centrifugal pump system in the Jostra heart-lung machine HL-20 with features such as a less friction mono-pivot bearing system, sealless pump housing, and spiral housing. To evaluate its biocompatibility, antithrombogenesity, and hemolysis, we used it as a main pump of cardiopulmonary bypass (CPB) in coronary artery bypass grafting (CABG) cases and compared it with the BioMedicus pump. From February 1999 to May 1999, 30 consecutive patients underwent CABG under conventional CPB. Fifteen cases were supported by the Rota Flow RF-32 (Group R), and the remaining 15 were pumped by the BioMedicus BP-80 (Group B). In both groups, the flow rate was controlled in an equivalent value. Blood sampling was as follows: preoperative, 60 min after, postoperative Days (POD) 0, 1, and 2. We evaluated the plasma free hemoglobin (fHb) as the hemolysis parameter, beta-thromboglobulin (beta-TG) and platelet factor IV (PF-4) as the platelet deterioration index, C3, C4, and CH50 as complement activation, coagulation function, fibrinolytic factor and thrombomodulin, nitric oxide (NO), and endothelin as endothelial deterioration. This system was very easily and simply controlled and had excellent response. Perioperative laboratory data were not markedly changed in either group. The Rota Flow demonstrated equivalent value of biocompatibility and hemolysis as compared with the BioMedicus BP-80, which is a standard centrifugal pump. After pumping, no thrombus formation or pivot wear was observed inside the pump. This atraumatic, small centrifugal pump is suitable not only for CPB but also for long-term circulatory support.

Analysis of Variance↗

Retroviral gene transfer of signaling molecules into murine fetal hepatocytes defines distinct roles for the STAT3 and ras pathways during hepatic development.

We recently demonstrated that oncostatin M (OSM) in the presence of glucocorticoid promotes development of fetal hepatic cells in a primary culture system. Our results also suggested that OSM transduces differentiation signals through gp130, a common subunit of the interleukin (IL)-6 family cytokine receptors. However, an essential downstream pathway required for hepatic development remains unknown. To address this issue, we expressed signal molecules by a retroviral expression vector in primary fetal hepatic cells and investigated a signaling pathway essential for OSM-mediated hepatic development. Expression of a dominant-negative form of STAT3 (DeltaSTAT3), but not DeltaSTAT5, suppressed differentiated phenotypes of hepatocytes induced by OSM. On the other hand, dominant-negative forms of Ras (RasN17) and SHP-2(C463A) rather augmented the expression of hepatic differentiation markers, suggesting that the Ras pathway negatively regulates hepatic development. Consistently, expression of a constitutively activated form of Ras (RasV12) inhibited cellular responses to OSM. Our results indicate that STAT3 is an essential signaling component for OSM-induced hepatic development, while activation of Ras appears to negatively regulate this process. Thus, retrovirus-mediated gene transfer is an effective means to analyze function of a gene in primary fetal hepatic culture.

Animals↗

Magnetic resonance angiography for monitoring prophylactic endoscopic treatment of high risk esophageal varices.

BACKGROUND AND STUDY AIMS: Endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) are used worldwide as the treatment for esophageal varices. We evaluated portal hemodynamics using magnetic resonance angiography (MRA) in these two forms of treatment. PATIENTS AND METHODS: The study was carried out in 50 cirrhotic patients. MRA was performed to identify the hepatofugal supply vein selectively for esophageal varices. Those who showed a positive MR angiogram for the supply vein were randomly allocated to one of two groups, using the sealed envelope method, and underwent either EIS or EVL. On the other hand, those with a negative angiogram received only EVL. EIS was done to embolize esophageal varices as well as their feeders by intravariceal injection of sclerosant under fluoroscopic guidance. RESULTS: A positive MR angiogram of the hepatofugal left gastric vein as the supply vein was observed in 41 patients. Nine patients showed negative MRA results. Among those with positive angiograms, the rate of eradication of the left gastric vein was higher in the EIS-treated group than in the EVL treated group (50% vs. 8.6%). After either treatment, the recurrence-free rate for high risk esophageal varices was higher in patients with complete eradication of the left gastric vein than in those without (88% vs. 35%). In patients with negative angiogram results, who only underwent EVL, high risk esophageal varices did not reappear over a long period. CONCLUSION: MRA is useful for evaluating portal hemodynamics. With the aim of avoiding recurrence of esophageal varices, EIS was suitable for patients who had a hepatofugal supply vein for the varices because recurrence could be prevented by embolization of the supply vein. EVL may be expected to be efficacious in patients where no image of a hepatofugal supply vein is found on MRA.

Adult↗

Hemoglobin content in intramucosal gastric carcinoma as a marker of histologic differentiation: a clinical application of quantitative electronic endoscopy.

BACKGROUND: It has been suggested that the endoscopic color of intramucosal gastric carcinoma is correlated with mucosal vascularity within the carcinomatous tissue. The development of electronic endoscopy has made it possible to quantitatively measure the mucosal hemoglobin volume, using a hemoglobin index. The aims of the present study were to investigate whether this hemoglobin index is useful for evaluating the change in color of early gastric carcinoma and to verify the diagnostic value of this index for distinguishing between histologic degrees of differentiation. METHODS: The ratios of the hemoglobin index of cancerous and non-cancerous mucosa for 26 differentiated and 18 undifferentiated intramucosal gastric carcinomas were determined from electronic endoscopic imaging data. RESULTS: The mean ratio of the hemoglobin index of cancerous and non-cancerous mucosa in the differentiated gastric carcinomas was higher than it was in the undifferentiated carcinomas (1.23: 95% CI [1.15, 1.31] versus 0.84: 95% CI [0.81, 0. 88]). The sensitivity and specificity for discriminating undifferentiated from differentiated carcinoma were 100% and 85%, respectively. CONCLUSION: Measurement of mucosal hemoglobin volume (hemoglobin index) is useful for evaluating the endoscopic color of early gastric carcinoma quantitatively and may be helpful in distinguishing differentiated from undifferentiated carcinoma.

Adult↗

Relationship between infiltrating cells and adhesion molecules in the nasal mucosa of patients with allergic rhinitis.

Antigen-induced changes of cell adhesion molecules and their relationships to infiltrating cells were investigated immunohistochemically in nasal mucosa of perennial allergic rhinitis patients. An increased expression of E-selectin and VCAM-1 was noted on the vascular endothelium of the nasal mucosa 15-25 h after the topical antigen challenge. Although there was no increased expression of ICAM-1, we noted a positive correlation between the expression of E-selectin and ICAM-1. The expression of E-selectin and VCAM-1 as well as ICAM-1 was revealed to be correlated with the number of EG2-positive cells and CD4-positive cells, but not with elastase-positive cells. These findings suggest that all these adhesion molecules play a role in the topical influxes of eosinophils and CD4-positive cells in allergic nasal mucosa.

Adolescent↗

Effects of anti-VLA-4 monoclonal antibody treatment in murine model of allergic rhinitis.

In order to study the role of VLA-4 in allergic rhinitis, the effects of anti-mouse VLA-4 monoclonal antibody (mAb) were evaluated in a murine model. BALB/c mice were sensitized first by i.p. injections (general sensitization) and then by daily nasal dripping of antigen (local sensitization) before performing a nasal antigen challenge. The mAb was applied either before the antigen challenge (BC group), before the local sensitization (BL group) or before the general sensitization (BS group). The effects were evaluated in terms of antigen-induced early-phase nasal symptoms (sneezing), late-phase nasal eosinophilia and the serum level of antigen-specific IgE. Antigen-induced nasal eosinophilia was significantly (p = 0.009) reduced in the BL group but not in the BC group (number of eosinophils = 114 +/- 15.1, 244 +/- 52.8 and 347 +/- 50.5 in the BL, BC and control groups, respectively). The serum level of the specific IgE was also significantly (p = 0.038) reduced in the BL group but not in the BC group (optical density = 1.18 +/- 0.07, 1.28 +/- 0.13 and 1.58 +/- 0.14 in the BL, BC and control groups, respectively). The suppressive effect on sneezing was not significant in either the BL or BC groups. In the BS group, suppressive effects on antigen-induced nasal responses and the specific IgE level were not statistically significant. These findings suggest that VLA-4 plays an important role in the topical booster or priming effects during repeated nasal antigen exposures in pre-sensitized animals.

Animals↗

The ratio of splicing variants of MGC-24/CD164, a sialomucin, correlates with the metastatic potential of colorectal carcinomas.

MGC-24/CD164 is a sialomucin expressed in many normal and cancerous tissues. In humans, soluble and transmembrane forms of MGC-24 are produced by alternative splicing. The total MGC-24 RNA level was found to be lower in human colorectal carcinomas as compared with the adjacent normal mucosal tissues. Lower MGC-24 mRNA levels in colon carcinomas and in the adjacent normal mucosa epithelium correlate with lymphatic vessel invasion by the carcinoma. The ratio of the soluble form to the transmembrane form of the mRNA in colorectal carcinomas was determined by ribonuclease protection assay. Higher ratios were correlated with less venous invasion and less remote metastasis, which became evident during postoperative observation.

Alternative Splicing↗

Study on the secretion of cytokines from osteoblasts stimulated with prostaglandin E1.

In previous studies, prostaglandin (PG) E1 was found not only to enhance the effect of rhBMP, but also to increase orthotopic osteoconduction and enhance bone formation, even when used alone, as well as increasing the physical strength of implanted porous hydroxyapatite ceramics (HAP). In the present study, the secretion of cytokines from MC3T3-E1 cells was investigated, which is a cell line of osteoblasts derived from the mouse skull, stimulated in vitro by 10(-5) M and 10(-6) M PGE1, in order to elucidate the mechanism of action of PGE1. The cytokines examined included transforming growth factor (TGF) beta 1, interleukin (IL)-6, and IL-1 beta. The results of this study clarify the mechanism of enhancement of osteogenesis by PGE1. Elevated TGF beta 1 plays a very important role, and the findings are significant because they may provide the basis for the establishment of a rational clinical combined application of these materials.

3T3 Cells↗

Effects of intravenous nicorandil on coronary circulation in humans: plasma concentration and action mechanism.

We investigated the cardiovascular profile of nicorandil, an antianginal agent, in humans. Pharmacologically, nicorandil acts as both an adenosine triphosphate (ATP)-sensitive K+ (K(ATP)) channel opener and a nitrate. We examined which of these mechanistic components has a predominant vasodilatory effect at clinical doses. Fourteen patients underwent cardiac catheterization. The effects of the continuous intravenous infusion of nicorandil (12 mg/45 min) were examined in angiographically normal coronary arteries. Coronary vascular resistance was calculated from coronary artery diameter and coronary blood flow velocity measured using an intravascular Doppler catheter. We compared the hemodynamic responses to nicorandil with those to the intracoronary injection of nitroglycerin (250 microg) and papaverine (12 mg). The epicardial coronary arteries responded to nicorandil at the lowest plasma concentration examined (dilation of +14.0 +/- 3.3% at approximately 170 ng/ml), whereas dilation of the coronary resistance arteries (i.e., a decrease in coronary vascular resistance) took place only at higher concentrations (>200 ng/ml). Nitroglycerin caused no further changes in coronary artery diameter or coronary vascular resistance. Papaverine caused no further increase in coronary artery diameter, but markedly decreased coronary vascular resistance (1.6 +/- 0.3 to 0.4 +/- 0.1 mm Hg/ml/min; p < 0.05). Nicorandil significantly decreased pulmonary capillary wedge pressure (i.e., reduced cardiac preload) at a plasma level of >200 ng/ml, but did not change either systemic or pulmonary vascular resistance. Thus nicorandil preferentially dilated epicardial coronary arteries rather than coronary resistance arteries, and had a stronger effect on preload than on afterload. These changes in human coronary hemodynamics suggest that the nitrate actions of nicorandil as a coronary vasodilator predominate over those as a K(ATP) opener.

Adult↗

Crystallographic characterization of the membrane-binding domain of radixin.

Radixin is a protein which cross-links plasma membranes and actin filaments and thus forms membrane-associated cytoskeleton. The radixin N-terminal domain, which is responsible for membrane association, has been purified and crystallized by vapour diffusion with polyethylene glycol 6000. The crystals belong to space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b = 96.36, c = 133.16 A, and diffract to a resolution of 3.0 A.

Binding Sites↗

Microaggregate of immunostained macrophages in noninflamed gastroduodenal mucosa: a new useful histological marker for differentiating Crohn's colitis from ulcerative colitis.

OBJECTIVE: In 10% of cases it may be difficult to differentiate Crohn's colitis from ulcerative colitis. Distinguishing the two conditions is important because they are distinct entities with different therapeutic implications. Noncaseating granulomas are usually considered diagnostic of Crohn's disease. We previously reported that the presence of a microaggregate of immunostained macrophages within the noninflamed gastroduodenal mucosa was a characteristic finding of Crohn's disease. The aim of this study was to determine whether a microaggregate of immunostained macrophages can be a reliable marker for differentiating Crohn's colitis from ulcerative colitis. METHODS: We investigated the presence of microaggregates of immunostained macrophages and epithelioid cell granulomas in biopsy specimens taken from the noninflamed gastroduodenal mucosa of 22 known Crohn's colitis patients and 23 established ulcerative colitis patients. The incidence of microaggregates and granulomas was compared between these two groups. RESULTS: Microaggregates and granulomas were detected only in the Crohn's colitis patients. In addition, the presence of microaggregates was more frequent than that of granulomas in Crohn's colitis patients (54.5% and 18.2%, respectively, 95% confidence interval for the difference: 10.0-62.7%). CONCLUSION: Detecting a microaggregate of immunostained macrophages in a biopsy specimen taken from noninflamed gastroduodenal mucosa seems to be a useful method for differentiating Crohn's colitis from ulcerative colitis.

Adolescent↗

Transfusion-acquired, autochthonous human babesiosis in Japan: isolation of Babesia microti-like parasites with hu-RBC-SCID mice.

We have isolated piroplasms from a patient who developed the first case of human babesiosis in Japan by using NOD/shi-scid mice whose circulating erythrocytes (RBCs) had been replaced with human RBCs (hu-RBC-SCID mice). Following inoculation of the patient's blood specimen into hu-RBC-SCID mice, parasites proliferated within the human RBCs in the mice, resulting in a high level of parasitemia. Parasite DNA was prepared from blood samples of the patient and the mice, and the nuclear small-subunit rRNA gene (rDNA) was amplified and sequenced. Both DNA samples gave rise to identical sequences which showed the highest degree of homology (99.2%) with the Babesia microti rDNA. Because the patient had received a blood transfusion before the onset of babesiosis, we investigated the eight donors who were involved. Their archived blood samples were analyzed for specific antibody and parasite DNA; only a single donor was found to be positive by both tests, and the parasite rDNA sequence from the donor coincided with that derived from the patient. The donor's serum exhibited a high antibody titer against the isolate from the patient, whereas it exhibited only a weak cross-reaction against B. microti strains isolated in the United States. We conclude that the first Japanese babesiosis case occurred due to a blood transfusion and that the etiological agent is an indigenous Japanese parasite which may be a geographical variant of B. microti. Our results also demonstrated the usefulness of hu-RBC-SCID mice for isolation of parasites from humans and for maintenance of the parasite infectivity for human RBCs.

Animals↗

Phlebosclerotic colitis: value of radiography in diagnosis--report of three cases.

Three cases sharing the following radiologic features are reported: (a) abdominal conventional radiography-vascular calcifications at the right hemicolon, (b) abdominal computed tomography-colonic wall thickening and venous calcifications, and (c) barium enema examination-luminal narrowing of the right hemicolon and thumbprinting. There were no clinical or laboratory findings suggestive of portal hypertension. The disease entity, "phlebosclerotic colitis," should be differentiated from ordinary ischemic colitis.

Abdomen, Acute↗