Search PubMed⌕ Search

Biomedical subjects

T Sawai

Publications and source records attributed to T Sawai.

At least 73 records · Page 4Linked to original sources

The redistribution of Ca2+ stores with inositol 1,4,5-trisphosphate receptor to the cleavage furrow in a microtubule-dependent manner.

We reported that microinjection of Ca2+ store-enriched microsome fractions from cultured CHO cells and mouse cerebella to dividing newt eggs induced extra-cleavage furrows via inositol 1,4,5-trisphosphate-induced Ca2+ release (Mitsuyama et al., 1999). Our observation strongly suggested that Ca2+ stores with inositol 1,4,5-trisphosphate receptor (IP3R) induce and position a cleavage furrow, as Ca2+-releasing machinery, and that such is itself a putative cleavage stimulus. For confirmation, we immunocytochemically examined mitotic CHO cells using antibodies against Ca2+ store-related proteins. We found that polar dominant Ca2+ stores with IP3R during metaphase were re-distributed to the future cleavage cortex just preceding the onset of furrowing, and that this redistributing IP3R was present on microtubule bundles. When a microsome fraction from sacro/endoplasmic reticulum Ca2+-ATPase (SERCA)-GFP stably expressing CHO cells was microinjected into dividing newt eggs and observed by confocal microscopy, the microinjected Ca2+ stores with IP3R moved linearly toward the next cleavage furrow and this movement was blocked by nocodazole, a microtubule-depolarizing agent, but not by cytochalasin B, an F-actin-depolarizing agent. These observations strongly suggest that Ca2+ stores with IP3R are transferred and accumulate to the cleavage furrow by microtubule-based motility, as a cleavage stimulus.

Animals↗

Difference in prognostic value between sialyl Lewis(a) and sialyl lewis(x) antigens in blood samples obtained from the drainage veins of the colorectal tumors.

Subtraction values, (i.e. values obtained by subtracting the serum titer of sialyl Lewis(a) (CA19-9) and sialyl Lewis(x) (SLX) antigens in peripheral venous blood from the serum titer of the same antigen in the tumor's drainage venous blood) were determined in order to clarify whether or not such values for these specific antigens (d-CA19-9 and d-SLX) are prognostic factors after resection for colorectal cancer. The blood samples were obtained from 144 colorectal cancer patients during surgical excisions of the tumors. Univariate and multivariate analyses revealed that d-SLX level was an independent prognostic factor, separate from stage, while d-CA19-9 level did not have any additional prognostic value. In conclusion, a high d-SLX level is a predictor of poor outcome after surgery.

Adult↗

Increased expression of sialyl Le(x) antigen in non-polypoid growth type of colorectal carcinoma.

Colorectal carcinoma can be morphologically divided into two different categories, namely polypoid growth (PG-type) and non-polypoid growth (NPG-type). To ascertain whether the expression of sialyl Le(x) antigen correlates with biologically and clinically important differences, an immunohistochemical assay was performed in 30 PG-type and 119 NPG-type cancers. In contrast to PG-type, the characteristics of the NPG-type include (1) an increased expression of sialyl Le(x); (2) a high rate of lymph node metastasis; (3) a high proportion of moderately differentiated adenocarcinoma cells; (4) young age of onset. It is concluded that differences in sialyl Le(x) expression between the PG-type and NPG-type cancers may be at least partly responsible for different tumor progression behavior.

Adenocarcinoma↗

Expression of blood group antigens A, B and H in carcinoma tissue correlates with a poor prognosis for colorectal cancer patients.

The deletion of blood group ABH isoantigens on tumor tissues has been reported to be an adverse prognostic marker for patients with various solid tumors. In the present study, we evaluated the prognostic value of altered expression of ABH isoantigens in colorectal carcinomas. Using monoclonal antibodies, the expression of A, B, and H antigens was assessed by immunohistochemistry on paraffin-embedded carcinoma samples from 82 patients who had undergone surgery for colorectal cancer. ABH isoantigens were found to be deleted in 36 carcinomas (43.9%) and expressed in 46 (56.1%). Univariate and multivariate analysis using a logistic regression model revealed that N factor (lymph node metastasis) and blood group type were independently related to the expression of ABH isoantigens. In contrast to previous reports on other cancers, patients whose colorectal carcinomas express ABH isoantigens had a poorer prognosis than those whose carcinomas showed deletion of ABH isoantigens (P = 0.0008). The expression of ABH isoantigens was an independent prognostic variable, in addition to T (depth of tumor invasion), N, and M (distant metastasis) factors, as shown by means of Cox regression analysis. In conclusion, the expression of ABH isoantigens in carcinoma tissue is an important poor prognostic factor in patients with colorectal cancer. This variable needs to be considered in the design of future trials of therapy.

ABO Blood-Group System↗

Extralobar pulmonary sequestration with venous drainage to the portal vein: a case report.

Venous drainage to the portal vein in pulmonary sequestration is rare. A 7-month-old girl was referred to our hospital following surgery for ventricular septal defect because of a left upper abdominal mass with a large feeding artery from the abdominal aorta and venous drainage to the portal vein. She had had frequent pulmonary infections and was growth retarded. MRI demonstrated that the mass was above the left diaphragm, suggesting extralobar sequestration. An extralobar sequestered lung was resected at thoracotomy. Diagnostic problems and clinical features are presented.

Abnormalities, Multiple↗

Meconium peritonitis in utero.

To clarify the relationship between clinical features in utero and postnatal prognosis, 20 fetuses who underwent ultrasonic (US) evaluation for meconium peritonitis (MP) over a 17-year period were reviewed. According to final US findings in utero, patients were classified into three types. Type I (massive meconium ascites) was noted is 5 cases, type II (giant pseudocyst) in 4, and the other 11 were classified as type III (calcification and/or small pseudocyst). Abdominal calcifications were identified in only 5 cases (2 type I, 1 type II, 2 type III). Seven fetuses who had associated polyhydramnios (1 Type I, 1 Type II, 2 Type III) and fetal hydrops (3 Type II) were delivered before 36 weeks' gestation. Cardiopulmonary resuscitation at birth was required in 9 cases (5 type I, 4 type II) who underwent abdominal drainage before delivery and/or immediately after birth. Although dilatation of the intestine was identified in 10 fetuses (2 type II, 8 Type III), 18 had intestinal atresia and 2 had fecal obstruction of the distal ileum. Four infants (2 type I, 1 type II, 1 type III) died of respiratory failure and postoperative complications. These results indicated that careful fetal US may be useful for perinatal management of MP.

Ascites↗

The effect of phospholipase A2 on bacterial translocation in a cell culture model.

The activity of phospholipase (PL)A2 is elevated in the intestinal epithelia of patients with inflammatory bowel disease (IBD). Recently, we reported that lysophosphatidylcholine (L-PC), the PLA2 hydrolysis product of phosphatidylcholine (PC), stimulates bacterial translocation (BT) in an enterocyte cell-culture model. These two observations stimulated us to examine the effects of extracellular PLA2 on intestinal epithelial permeability. Human Caco-2 enterocytes were grown to confluence on porous filters in the apical chamber of a two-chamber cell-culture system. Monolayer integrity and tight-junction permeability were measured by dextran blue (DB) permeability and transepithelial electric resistance (TEER). Monolayers were treated with PC, L-PC, or PLA2 with and without PC. The magnitude of BT was determined 2 h after treatment by adding Escherichia coli to the apical chamber followed by quantitatively culturing basal chamber samples. Thin-layer chromatography (TLC) was utilized to verify PLA2 hydrolysis of PC to L-PC. Statistical analysis was performed by one-way analysis of variance. The magnitude of BT across monolayers pretreated with PLA2 + PC significantly increased compared to either PC or PLA2 (6.83 +/- 0.069, 2.41 +/- 0.46, and 3.06 +/- 1.14 log10 colony forming units/ml, respectively, P < 0.05). Absence of DB-permeability in any group confirmed monolayer integrity. TLC of PL samples harvested from the apical monolayer surface confirmed PC hydrolysis. PLA2 mediates hydrolysis of PC to L-PC when both are applied to the apical surface of cultured enterocyte monolayers, resulting in increased BT and increased TEER with no damage to monolayer integrity. These observations may have implications in the pathogenesis and treatment strategies for IBD.

Bacterial Translocation↗

The relationship between circulating sialyl Tn antigen and polypoid or nonpolypoid growth characteristics in colorectal cancer.

Recent studies delineated two different patterns of tumor growth in colorectal carcinoma characterized as polypoid and nonpolypoid (PG-type and NPG-type, respectively). We quantified serum sialyl Lewis (Le)a (CA19-9), sialyl Lex (SLX), sialyl Tn (STN), and carcinoembryonic antigen (CEA) in 269 colorectal cancer patients to establish whether their levels correlated with any biological or clinical differences between PG-type and NPG-type cancer. Patients were divided into high and low antigen groups (higher or lower than a selected diagnostic-based cut-off value) and compared. Statistical testing was by univariate and multivariate (logistic regression) analyses. Forty-seven (17.5%) patients with PG-type and 222 (82.5%) with NPG-type cancer were studied. In contrast to NPG-type, the characteristics of the PG-type cancers included a low rate of lymph node metastasis and a high serum STN level. In contrast to a low STN level, a high STN level was independently related to the presence of distant metastasis in patients with PG-type cancer, and also to the presence of distant metastasis and large-sized tumor in patients with NPG-type cancer. These data suggest that differences in STN levels in the serum of patients with PG-type or NPG-type colorectal carcinomas may be at least partly responsible for different tumor progression behavior.

Antigens, Tumor-Associated, Carbohydrate↗

Differences in release mechanisms and distributions for sialyl Le(a) and sialyl Le(x) antigens in colorectal cancer.

BACKGROUND: To investigate colorectal cancer-related carbohydrate antigen release and distribution, we evaluated serum levels of sialyl Le(a) (CA19-9) and sialyl Le(x) antigen (SLX) in blood samples obtained from both a peripheral vein and a tumor's draining vein. METHODS: Blood samples were obtained during surgery from 126 patients. Based on these samples, patients were placed into a high-antigen group, with a concentration above a selected cutoff value, or into a low-antigen group, with a tumor marker concentration below that same value. The blood samples obtained from peripheral veins were designated by the "p" prefix, and samples from drainage veins were designated by the "d." RESULTS: Serum d-SLX levels were significantly higher than p-SLX levels (P < .0001), although there was no difference between those of d-CA19-9 and p-CA19-9. Only 1 (3.6%) of 28 patients in the high d-CA19-9 group had a low p-CA19-9. In contrast, 6 (33.3%) of 18 patients in the high d-SLX group had low p-SLX levels (P = .0103). Correlations between pathological variables and either p-CA19-9 levels or d-CA19-9 levels were similar. However, both distant metastasis and venous invasion did prove to be independent variables related to d-SLX levels, as shown by logistic regression analysis. CONCLUSIONS: SLX may drain predominantly via the draining veins of colorectal tumors into portal circulation, whereas CA19-9 may drain via another route.

Aged↗

Pexis of the great vessels for patients with tracheobronchomalacia in infancy.

BACKGROUND/PURPOSE: Aortopexy has been established as a surgical treatment for tracheobronchomalacia in infancy. However, the effects in patients with bronchial involvement remain controversial. The authors performed aortopexy and pexis of the pulmonary artery trunk (PApexy) for patients with tracheobronchomalacia. METHODS: Between 1992 and 1997, 14 infants with tracheobronchomalacia were treated. Patients ranged in age from 4 months to 7 years (median, 3.5 years). Using patients' records, intraoperative bronchofiberscopic results and clinical outcomes were analyzed retrospectively. RESULTS: Concerning tracheomalacia, aortopexy eliminated airway collapse as shown by intraoperative fiberscopic results and clinical outcome in 4 patients. Regarding tracheobronchomalacia, aortopexy eliminated collapse of the trachea and the right main bronchus in 3 patients but did not improve collapse of the lower half of the left main bronchus in 3 patients, which was eliminated by PApexy. Aortopexy eliminated airway collapse of the left main bronchus in 1 of 3 patients with bronchomalacia. PApexy eliminated collapse of the lower half of the left main bronchus in 1 patient. CONCLUSIONS: These results indicate that intraoperative bronchofiberscopic results were closely correlated to the clinical outcome, and suggest that aortopexy is helpful for eliminating collapse of the right main bronchus and the proximal half of the left main bronchus and that PApexy eliminates collapse of the distal half of the left main bronchus.

Abnormalities, Multiple↗

Intrapulmonary concentrations of inflammatory cytokines in a mouse model of chronic respiratory infection caused by Pseudomonas aeruginosa.

We investigated the role of inflammatory cytokines in a mouse model of chronic Pseudomonas aeruginosa infection mimicking diffuse panbronchiolitis (DPB), and determined the effects of clarithromycin therapy on the production of these cytokines. The concentrations of IL-1beta, IL-2, IL-4, IL-5, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were measured serially in the lungs of mice with experimentally induced chronic respiratory P. aeruginosa infection until 60 days after inoculation. The concentrations of these cytokines during the course of the disease were significantly higher than baseline (before inoculation, P<0.01 for all cytokines). Clarithromycin significantly inhibited the production of IL-1beta and TNF-alpha in the lung (P<0.01). The same treatment also reduced the levels of other cytokines, albeit insignificantly. Treatment with anti-TNF-alpha antibody significantly reduced the number of pulmonary lymphocytes and concentration of IL-1beta in the lung (P<0.01), but did not change the number of viable bacteria. Our findings resemble those detected in bronchoalveolar lavage fluid of patients with DPB and indicate that inflammatory cytokines play an important role in chronic P. aeruginosa lung infection. Our results also show that macrolides modulated the production of these cytokines, ultimately reducing lymphocyte accumulation in the lung. Our data suggest that anti-TNF-alpha antibody might be a useful new strategy for the treatment of chronic respiratory P. aeruginosa infection.

Animals↗

Desmoplastic cerebral astrocytoma of infancy intermingling with atypical glial cells.

Despite the rarity of desmoplastic cerebral astrocytoma of infancy (DCAI), it has distinct clinical and pathological features. The present case is a typical DCAI except for its detection and operational age and intermingling with pleomorphic glial cells. In this case, although a cystic lesion of the right temporal lobe was noticed when the patient was 6 months old, it was not regarded as a tumor and wasn't removed until he was 9 years old. It is quite unusual that a DCAI was able to exist in the cerebrum for 9 years. However, no metastasis occurred and distinct macroscopic and microscopic features of the tumor were not different from typical DCAI except for an intermingling with pleomorphic glial cells. Furthermore, even in the pleomorphic areas, the absence of necrosis and an MIB-1 index of 2.9% indicated non-aggressive growth. These features of the present case may provide additional information as to the character of DCAI, which generally has a favorable prognosis.

Antigens, Nuclear↗

Dilated cardiomyopathy in Noonan's syndrome: a first autopsy case.

The first autopsy case of dilated cardiomyopathy associated with Noonan's syndrome is described. A 9-month-old girl with Noonan's syndrome died from cardiac failure. Autopsy showed biatrial and biventricular enlargement of the heart. The posterior half of the ventricular septum and right ventricular wall were remarkably thin. Other parts of the wall were nearly normal in thickness, but both ventricular cavities were dilated. Microscopically, the myocardium of both ventricles consisted of mainly abnormally thinned, elongated, and loosely arranged myocardial fibers lacking immunoreactivity to anti-dystrophin antibody. Myocardial disarray was not found except for where it normally existed. The abnormal changes of the myocardial fibers were considered to be primary. Common cardiomyopathy associated with Noonan's syndrome is a hypertrophic type. Various types of cardiovascular abnormality associated with Noonan's syndrome, including dilated cardiomyopathy, might be disclosed by further investigation and precise diagnosis of Noonan's syndrome.

Cardiomyopathy, Dilated↗

Patent ductus venosus with a hypoplastic intrahepatic portal system presenting intrapulmonary shunt: a case treated with banding of the ductus venosus.

A case of patent ductus venosus (PDV) presenting intrapulmonary shunting is described. Although retrograde venography of ductus venosus showed few intrahepatic branches, banding of PDV resulted in increased intrahepatic portal branches and disappearance of symptoms 10 months after the operation. Banding of the ductus venosus may be effective in PDV even with hypoplastic intrahepatic portal system.

Child↗

Airway anomalies in patients with congenital diaphragmatic hernia.

PURPOSE: Congenital diaphragmatic hernias (CDH) sometimes are associated with airway anomalies such as congenital stenosis, abnormal branching of the bronchi, and pulmonary hypoplasia. The incidence of these associated airway anomalies has not been reported previously. METHODS: Bronchoscopy was performed in all neonates with CDH from 1987 to 1999. In addition to anatomic anomalies, bronchial hypoplasia was defined as narrowing and shortening of the bronchi at bronchoscopy. RESULTS: Anatomic anomalies were identified in 7 of 39 patients with CDH: 1 had congenital tracheal stenosis with pulmonary artery sling, 1 had a defect of the right upper lobe bronchus, 2 had a tracheal bronchus, and 3 had a trifurcated trachea. Bronchial hypoplasia on the affected side was identified in 15 patients and was seen in all patients with anatomic anomalies of the tracheobronchial tree except the 2 with tracheal bronchus. After excluding 5 patients with severe associated anomalies, 6 of 14 patients with an abnormal tracheobronchial tree died, whereas 1 of 20 patients without airway abnormalities died. CONCLUSIONS: Anatomic anomalies of the tracheobronchial tree and bronchial hypoplasia on the affected side were identified in 17.9% and 38.4% of patients with CDH, respectively. CDH patients who exhibited these abnormalities showed a poor outcome.

Bronchial Diseases↗

Thrombin inhibitor ameliorates secondary damage in rat brain injury: suppression of inflammatory cells and vimentin-positive astrocytes.

The effects of the thrombin inhibitor argatroban on the number of inflammatory cells and reactive astrocytes were investigated in a rat brain injury model. Gelatin sponge soaked with thrombin inhibitor (treatment group) or saline (control group) was placed in the brain defect to assess the infiltration of inflammatory cells by hematoxylin-eosin and immunohistochemical staining. Expression of polymorphonuclear leukocytes (PMNs) and monocyte/macrophage (Mo/Mo) cells, and vimentin (VIM)-positive astrocytes and glial fibrillary acidic protein (GFAP)-positive astrocytes were compared between groups. In the treatment group, infiltration of both PMNs and Mo/Mo cells, and the number of VIM-positive astrocytes were significantly reduced, but the number of GFAP-positive astrocytes was not different from the control group. Thrombin inhibitor suppresses the infiltration of inflammatory cells and excessive gliosis caused by VIM-positive astrocytes, but not expression of GFAP-positive astrocytes, suggesting minimization of secondary brain damage and promotion of the conditions required for neural regeneration.

Animals↗

Combination therapy for chronic Pseudomonas aeruginosa respiratory infection associated with biofilm formation.

There had been no reports of investigations into biofilms in chronic respiratory infection in vivo. Recently, we established a new murine model of chronic respiratory infection with Pseudomonas aeruginosa. In the present study, we examined the bacteriological effect of combined clarithromycin and levofloxacin against chronic respiratory infection with P. aeruginosa. Scanning electron micrograph of the surface of the catheter intubated in mouse bronchus for 7 days demonstrated in vivo formation of a biofilm containing blood cells, complex fibrous structures and bacteria. Treatment with either clarithromycin alone or levofloxacin alone had no statistical effect on the number of viable bacteria in lung. The combined use of both drugs resulted in a significant decrease in the number of viable bacteria. The present experiment demonstrates that the newly established murine model was useful to investigate the treatment of biofilm-associated chronic respiratory infection with P. aeruginosa, and combination therapy with clarithromycin and levofloxacin was effective in biofilm-associated chronic respiratory infection.

Animals↗

Preoperative UFT administration for patients with advanced colorectal cancer--increased uptake of 5-fluorouracil by tumor tissue is a prognostic factor.

The aim of this study was to clarify whether increased 5-fluorouracil (5-FU) uptake by tumor tissue following preoperative UFT administration is a prognostic factor after surgery in colorectal cancer patients. We examined the concentrations of 5-FU in tumor or normal tissue of 96 colorectal cancer patients who received UFT (400 mg/day) orally for 7 days prior to surgery. Patients were divided into two groups with high or low 5-FU concentrations in tumor tissue (defined as higher or lower than the cut-off value, respectively). The cut-off value of 5-FU was established based on the upper limit of the 95% confidence interval of the median of the concentration found in normal tissue (0.106 microg/g). Of the 96 patients, 62 (64.6%) were in the low-5-FU group and 34 (35.4%) in the high-5-FU group. The latter had a more favorable clinical outcome (p=0.0465). Cox regression analysis revealed that two independent variables, stage and 5-FU status in tumor tissue, were significant for prediction of survival. These findings suggest that increased uptake of 5-FU by tumor tissue following preoperative oral administration of UFT is an independent prognostic factor in colorectal cancer patients. This variable needs to be considered in the design of future therapeutic trials.

Administration, Oral↗