Search PubMed⌕ Search

Biomedical subjects

S Sawada

Publications and source records attributed to S Sawada.

At least 145 records · Page 8Linked to original sources
PubMed1997

Quinoline-induced chromosome aberrations and sister chromatid exchanges in rat liver.

Induction of chromosome aberrations and sister chromatid exchanges (SCEs) was studied in hepatocytes of F344 rats exposed in vivo to the hepatocarcinogen quinoline (Q). Hepatocytes were isolated 4-48 hr after a single dose of 200 mg/kg body weight or 24 hr after 28 repeated doses (once a day) of 25-200 mg/kg body weight/day by gastric intubation, and allowed to proliferate in Williams' medium E supplemented with epidermal growth factor. Cells were fixed after a culture period of 48 hr. A single dose of Q induced chromosome aberrations in up to 22% of metaphase cells, and SCEs with a frequency of up to 1.27 per chromosome 12 hr after the dose, while the control values were 1% and 0.63 per chromosome, respectively. Treatment with 28 repeated doses of Q induced significant chromosome aberrations and SCEs dose-dependently. Cytogenetic damage induced induced in the liver by repeated doses of Q was greater than induced by a single dose. Furthermore, Q induced replicative DNA synthesis in the liver, but failed to induce micronucleus formation in the bone marrow. The noncarcinogen 8-hydroxyquinoline was also examined and found to be essentially non-genotoxic to rat liver. These results show that Q is a genotoxic carcinogen to rat liver and the present method of in vivo cytogenetic assay should be useful for evaluating the genotoxicity of hepatocarcinogens.

Animals↗
PubMed1997

Analysis of cytogenetic effects and DNA adduct formation induced by safrole in Chinese hamster lung cells.

Safrole (1-allyl-3,4-methylenedioxybenzene) was tested for its ability to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) and to form DNA adducts in Chinese hamster lung (CHL) cells, in order to investigate the relationship between cytogenetic effects and DNA adduct formation under the same treatment conditions. The cells were treated with 0.025-0.2 mg/ml safrole in the presence or absence of rat liver postmitochondrial supernatant fraction (S9). Safrole induced significant SCEs and CAs dose-dependently in the presence of S9. SCEs ranged in number from 15.6 to 21.1 SCEs/cell and CAs were observed in 4-37% of cells. Using the 32P-postlabeling assay, two major and two minor safrole-DNA adducts were detected in DNA digests obtained from CHL cells in the presence of S9. The levels of total DNA adducts ranged from 1.3 to 22.8 adducts/10(7) nucleotides. The two major adducts were shown to be guanine derivatives since these adducts comigrated on polyethylenimine plates with the adducts produced by the reaction of safrole with 2'-deoxyguanosine 3'-monophosphate. A correlation was seen between DNA adducts and SCEs or CAs. Neither induction of SCEs and CAs nor formation of DNA adducts was observed in the absence of S9. These findings suggest that SCEs and CAs induced by safrole result from covalent DNA modification metabolically activated by S9 in cultured cells.

Animals↗
PubMed1997

Therapeutic value of neoadjuvant intra-arterial chemotherapy (cisplatin) and irradiation for locally advanced uterine cervical cancer.

We analyzed long-term treatment results in 51 patients with locally advanced uterine cervical carcinoma (IIB, 4; IIIB, 43; IVA, 4) treated with neoadjuvant intra-arterial (I-A) chemotherapy (cisplatin) via the uterine artery and irradiation. Thirty patients (58.8%) developed recurrence. Twelve had pelvic recurrence alone, 8 had distant metastases alone, and 10 had both pelvic and distant failure. The 5-year cumulative pelvic control rate, absolute survival rate, and disease-free survival rate were 55.3, 47.1, and 39.4%, respectively. Eight of 51 patients (15.7%) suffered late complications. These results suggest that our neoadjuvant I-A chemotherapy prior to irradiation has limited additional value for long-term prognosis in patients with locally advanced uterine cervical carcinoma.

Adult↗
PubMed1997

Evaluation of patterns of perfusion and metabolism in dobutamine-responsive myocardium.

OBJECTIVES: We investigated the patterns of perfusion and metabolism in dysfunctional myocardium whose contractility improved with dobutamine. BACKGROUND: Clinical studies have suggested that dobutamine echocardiography can identify hibernating myocardium, but laboratory studies suggest that reduced perfusion limits the response to dobutamine. METHODS: Twenty-five patients with coronary disease and ventricular dysfunction underwent low (5 and 10 micrograms/kg body weight per min) and high dose (maximum of 50 micrograms/kg per min) dobutamine echocardiography and positron emission tomography (PET) using nitrogen-13 (N-13) ammonia and fluorine-18 fluorodeoxyglucose (FDG) for imaging of perfusion and metabolism. Wall motion and tracer uptake were scored in 16 left ventricular segments. RESULTS: Perfusion and metabolism were normal in 56.4%, mildly reduced in 29.1% and mismatched (reduced perfusion, preserved FDG uptake) in 14.5% of dysfunctional segments viable on PET. Wall motion improved with dobutamine in 89 dysfunctional segments (62 at low dose, 27 only at peak dose), and 86 of these (97%) were viable on PET. Improvement in wall motion with dobutamine was more common in segments with normal perfusion and metabolism (56.5%) than in those with mildly reduced tracer uptake (28.5%, p < 0.001) and those with mismatch (32%, p = 0.03). All the segments with a biphasic response were supplied by vessels with > or = 70% stenosis, and 88% had normal perfusion and metabolism. CONCLUSIONS: The majority of viable segments with rest dysfunction had normal perfusion and metabolism, suggesting that myocardial stunning was common. Improvement of wall motion at low and high doses of dobutamine was highly correlated with myocardial viability on PET and was more common in myocardium with normal perfusion. A biphasic response to dobutamine identified segments with normal perfusion and metabolism supplied by severely diseased vessels.

Ammonia↗
PubMed1997

Mechanisms of lymphocyte adhesion to cultured human corneal epithelial cells.

PURPOSE: The authors studied the adhesion mechanisms between peripheral blood lymphocytes (PBL) and cultured human corneal epithelial (HCE) cells to investigate the lymphocyte interaction with corneal epithelial cells in the corneal immune response. METHODS: First, the authors examined the expression of intercellular adhesion molecule (ICAM)-1 or lymphocyte function-associated antigen (LFA)-3 on the normal human corneal epithelium and cultured HCE cells by an immunostaining technique and flow cytometry. Effects of inflammatory cytokines such as interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, on ICAM-1 or LFA-3 expression on cultured HCE cells were also examined. Second, the authors performed an adhesion assay with 51Cr-labeled monocyte-depleted PBL from normal, healthy volunteers and cultured HCE cells, with and without treatment of IFN-gamma or TNF-alpha in 96-well-plates for 1 hour at 37 degrees C in 5% CO2. After unbound PBL were removed, the radioactivity of the sample in each well was counted with a scintillation counter. In addition, the authors evaluated the blocking effects of monoclonal antibodies (mAbs) on the adhesion of PBL to the cultured HCE cells. RESULTS: ICAM-1 expression was not detected in the normal human corneal epithelium. However, the expression of ICAM-1 was detected on the cultured HCE cells with Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum. In addition, both IFN-gamma and TNF-alpha increased ICAM-1 expression on the cultured HCE cells dramatically. LFA-3 expression was detected in all cell layers of the normal human corneal epithelia. Neither IFN-gamma nor TNF-alpha had any effect on LFA-3 expression on the cultured HCE cells. The PBL adhesion to the HCE cells with and without treatment of IFN-gamma or TNF-alpha was blocked dominantly by anti-ICAM-1 or anti-LFA-1 alpha mAb. Anti-LFA-3 mAb also blocked the PBL adhesion but had less blocking effect than anti-ICAM-1 or anti-LFA-1 alpha mAb. Anti-very late activation antigen beta, or anti-human leukocyte antigen (HLA)-class I or HLA-class II mAb had no effect on the PBL adhesion to the HCE cells. The adhesion percentile of the PBL applied to the HCE cells pretreated with IFN-gamma or TNF-alpha showed a dose-response curve dependent on the concentration of these cytokines. CONCLUSIONS: The results in the present study demonstrate that (i) adhesion of lymphocytes to HCE cells could be mediated by the LFA-1-ICAM-1 pathway and/or the CD2-LFA-3 pathway; (ii) the LFA-1-ICAM-1 pathway could be crucial in lymphocyte adhesion to HCE cells; (iii) IFN-gamma or TNF-alpha exerts an enhancing effect not only on the ICAM-1 expression on HCE cells but also on the adhesion of lymphocytes to HCE cells.

Antibodies, Monoclonal↗
PubMed1997

Olive oil increases the magnitude of postprandial chylomicron remnants compared to milk fat and safflower oil.

OBJECTIVE: The acute effects of olive oil, milk fat and safflower oil on postprandial lipemia and remnant lipoprotein metabolism were investigated. METHODS: Eight Healthy male volunteers randomly underwent three types of oral fat-vitamin A loading tests. The test drink was a mixture of retinyl palmitate (RP)(50,000 IU of aqueous vitamin A/m2 body surface area) and one of the three types of oils (40 g of fat/m2 body surface area): olive oil (70.7% oleic acid of total fatty acids); milk fat (69.3% saturated fatty acid); safflower oil (74.2% linoleic acid). RESULTS: Olive oil significantly increased plasma triacylglycerol and RP concentrations 4 hours after fat loading, as compared to other fats. Increases of remnant like particle concentrations were higher after olive oil than after the other two fats. CONCLUSION: These results show that olive oil increases the magnitude of postprandial chylomicrons and chylomicron remnants compared to milk fat and safflower oil.

Adult↗
PubMed1997

Detection of Epstein-Barr virus-encoded small RNA 1 and latent membrane protein 1 in synovial lining cells from rheumatoid arthritis patients.

Several investigators have demonstrated an association between Epstein-Barr virus (EBV) and the pathogenesis of rheumatoid arthritis (RA). However, there is no direct evidence that this virus exists in the synovial cells of patients with RA. We attempted to detect EBV in synovial cells from RA patients. Specimens of synovial tissues from 34 patients with RA and from 20 patients with osteoarthritis (OA), and from one patient with psoriatic arthritis as controls, were examined for evidence of the EBV by in situ hybridization. The specimens were also tested by immunoperoxidase staining for expression of the CD21 molecule (EBV receptor), EBV nuclear antigen (EBNA)-2 and latent membrane protein (LMP)-1. EBV-encoded small RNA-1 (EBER) was demonstrated in synovial lining cells from eight (23.5%) out of 34 RA patients but in none of 20 OA patients (P < 0.05) nor in the one psoriatic arthritis patient. Interestingly, EBER localized in synovial lining cells that were located at the apex of villus proliferating lesions. Furthermore, LMP-1 was also detected in synovial lining cells at the top of villus lesions. Nevertheless, CD19 and CD21 molecules, and EBNA-2 were not demonstrated in such lesions. The incidence of EBV-positive in synovial lining cells with severely infiltrated lymphocytes tended to be higher than that in moderately infiltrated ones. This is the first evidence that EBV exists in chronically inflamed synovial lining cells of human joints in RA.

Antigens, Viral↗
PubMed1997

Crossover trial of simvastatin versus pravastatin in patients with primary hypercholesterolemia.

The effects of simvastatin and pravastatin administered alone at initial doses of 5 and 10 mg/day, respectively, on normalization of abnormal lipid metabolism in patients with hypercholesterolemia were evaluated by a crossover method. Patients whose serum levels of total cholesterol (TC) were > or = 220 mg/dl were randomly divided into two groups, and one of the groups (group S-P: 17 patients) was treated with simvastatin first and then with pravastatin whereas the other group (group P-S: 19 patients) was treated with pravastatin first and then with simvastatin. Simvastatin or pravastatin was replaced with the other drug after 8-week administration in each group. These drugs were administered for 8 weeks each. Simvastatin and pravastatin significantly reduced the following serum lipids as compared with the levels in the observation period: TC by 23.2 +/- 8.1% and 18.1 +/- 10.9%, triglyceride (TG) by 13.0 +/- 24.7% and 5.8 +/- 47.1%, and low-density lipoprotein cholesterol (LDL-C) by 31.3 +/- 10.1% and 23.1 +/- 14.3%, respectively. TC and LDL-C levels were significantly (p < 0.001) lower and decreased to significantly (p < 0.001) greater degrees after simvastatin treatment than after pravastatin treatment. TC was normalized in 77.8% of the patients (28 of 36) after simvastatin treatment and in 68.9% of the patients (23 of 36) after pravastatin treatment. LDL-C was normalized in 63.9% of the patients (23 of 36) after simvastatin treatment and in 44.4% of the patients (16 of 36) after pravastatin treatment. The percentage of patients whose LDL-C was normalized by simvastatin was significantly (p < 0.05) higher as compared with pravastatin. Results of this trial, which was conducted by a crossover method, show that the initial dose of simvastatin reduces serum cholesterol and LDL-C more potently than the initial dose of pravastatin in patients with hypercholesterolemia.

Adult↗
PubMed1997

[Pathological examination of the lung in leprosy patients].

To study pulmonary lesions in leprosy, five autopsy cases were histopathologically examined. Case 1 (BL type) died of renal failure, case 2 (LL type) of myocardial infarction, case 3 (TT type) and 4 (BL type) of cerebral hemorrhage and case 5 (BL type) of pancreas cancer. The mean age was 78 years old. Uremic lung (case 1), old tuberculous lesion (case 3) and metastatic adenocarcinoma (case 5) were demonstrated. Pulmonary congestion and mild emphysema were seen in all cases. Aspiration pneumonia was found in all but case 4. Small foci of adenomatous hyperplasia were found in cases 1 and 5. In addition, pulmonary findings of 13 outpatients with leprosy were roentgenologically examined. No patient except one with mild emphysema showed any abnormality in the lung. In our cases, no characteristic pulmonary lesion to leprosy was found.

Aged↗
PubMed1997

Genetic analysis in Japanese kindreds of congenital type I antithrombin deficiency causing thrombosis.

We have identified two novel minor deletions (case 1; -TA or -AT at nucleotide 9831-3 in exon 5 and case 2; -A at nucleotide 7640-1 in exon 4), one novel nonsense mutation (case 3; TAT to TAA at nucleotide 7491 in exon 4), and one recurrent nonsense mutation (case 4; CGA to TGA at nucleotide 5381 in exon 3A) in Japanese kindreds with congenital type I antithrombin deficiency. The deletion detected in case 1 represented a symmetric element (CTCTGTCTC) and possessed a direct repeat (CTCTATGTCTC). The deletion in case 2 was recognized in a consensus sequence (TGAAT) and possessed a direct repeat (GATGAA). The nonsense mutation in case 3 formed a palindrome (CCGTTAACGG) and that in case 4 was caused by a CpG dinucleotide mutation. These results confirm that the mutations of congenital type I antithrombin deficiency are not random events but are influenced strongly by DNA sequences.

Adult↗
PubMed1997

Audiological findings of sensorineural deafness associated with a mutation in the mitochondrial DNA.

OBJECTIVE: The aim of this study was to investigate audiologic features and the lesion site of sensorineural deafness with mitochondrial DNA mutation at position 3243. STUDY DESIGN: Case review. SETTING: The study was conducted at the Kochi Medical School. PATIENTS: A case of sensorineural deafness in a patient who had a mitochondrial DNA mutation was presented. The incidence of deafness and diabetes mellitus (DM) was very high in the patient's family, but she did not have DM. MAIN OUTCOME MEASURES: The patient's mitochondrial DNA was examined. Furthermore, the pure-tone audiogram, the Bekesy audiogram, an auditory brain stem response, and the electrocochleogram were analyzed. RESULTS: The patient's mitochondrial DNA had a point mutation at codon 3243 (A-->G). The pure-tone audiogram showed moderate sensorineural deafness. An auditory brain stem response showed normal latencies. The electrocochleogram showed an enhanced negative summating potential. CONCLUSIONS: It was speculated that the lesion site of the auditory system was the inner ear. The possible sites in the inner ear were hair cells, the stria vascularis, and the endolymphatic sac.

Adult↗
PubMed1997

[Comparison of calculated and measured rectal doses in HDR brachytherapy with Ir-192 source].

Two orthogonal radiographs are used to reconstruct the three-dimensional positions of applicators (sources) and their dosemeter for assessing afterloading techniques. It has always been assumed that the applicators are perfectly fixed and unchanged during irradiation. In a review comparing measurements by a five-detector dosemeter and calculated doses in our institution, a relatively poor correlation (correlation coefficient = 0.79) was observed. The purpose of this study was to investigate the sources of this difference between calculated and measured rectal doses in HDR brachytherapy with Ir-192 source. In this study, the calculated dose was used as a reference value. The overall percentage difference between calculated and measured rectal doses was estimated at 9%. The major source of the difference between calculated and measured rectal doses was applicators and dosemeter movement during irradiation. This was verified by X-ray fluoroscopy during irradiation. It was found that loose fastening of the applicators caused a change in the position of the applicators and dosemeter during irradiation. By improving the fastening of the applicators and dosemeter, the correlation (correlation coefficient = 0.90) between calculated and measured doses was improved. The results demonstrate the importance of the fastening of the applicators and dosemeter.

Brachytherapy↗
PubMed1997

[A case of atrial septal defect complicated by persistent left superior vena cava in whom hemophagocytic syndrome appeared after operation].

The patient was a 22-year-old woman and suffered from atrial septal defect (ASD) complicated by persistent left superior vena cava (PLSVT). The patient underwent a patch closure using calf pericardium. Despite favorable progress immediately after the operation, fever, enlarged cervical lymph nodes, and leukocytopenia appeared beginning day 8 after the operation. Based on the results of cytodiagnosis of myeloaspiration specimen, the diagnosis of hemophagocytic syndrome (HPS) was made. Since an elevation of 2-5 oligo A synthetase (2-5 AS) levels was observed, the patient was diagnosed to suffer from virus-associated hemophagocytic syndrome (VAHS), and steroid was administered. The patient exhibited a good response to the treatment. The fever declined 3 days after the start of administration. Leukocyte counts were also increased gradually. The patient condition was improved and she was discharged from the hospital on day 28. At present, seven months after the operation, there is no evidence of recurrence and the patient's condition is still monitored.

Adult↗
PubMed1997

Angiotensin II increases plasminogen activator inhibitor-1 and tissue factor mRNA expression without changing that of tissue type plasminogen activator or tissue factor pathway inhibitor in cultured rat aortic endothelial cells.

Angiotensin converting enzyme inhibitors (ACE-I) have been reported to prevent the recurrence of cardiovascular events. The mechanism of this decrease, however, can not be completely explained by anti-hypertensive and anti-hypertrophic effects of ACE-I. To investigate the mechanism of this decrease, we studied the regulation of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (TPA), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) by angiotensin II (Ang II) in cultured rat aortic endothelial cells. Ang II increased PAI-1 and TF mRNA expression without affecting that of TPA or TFPI. These inductions were accompanied by increases in PAI-1 and TF activities and were inhibited by a type I Ang II receptor antagonist. The results suggest that Ang II decreases the antithrombotic properties of endothelial cells which increases the chance of thrombosis. Thus, inhibition of the renin-angiotensin system may be beneficial to prevent thrombus formation in treatment of ischemic heart disease.

Angiotensin II↗
PubMed1997

Computed radiographic measurement of the dimensions of the vestibular aqueduct in Menière's disease.

Lateral polytomography of the vestibular aqueduct by computed radiography was carried out in 30 normal subjects and 25 patients with Meniere's disease, 14 of whom had bilateral involvement. The vestibular aqueduct could be identified clearly not only in normal subjects but also in patients with Menière's disease. Normal vestibular aqueducts were funnel-shaped or tubular, and the width of the external aperture was 6.0 mm on average. In contrast, a hypoplastic vestibular aqueduct with a narrow external aperture was often observed in patients with Menière's disease. Especially, in affected ears of patients with unilateral Menière's disease, the external aperture was very narrow; its mean width was 2.2 mm. In these cases, the most common radiographic configuration of the vestibular aqueduct was filiform. Meanwhile bilateral Menière's disease had a relatively wide external aperture compared with that of unilateral Menière's disease, although a hypoplastic vestibular aqueduct was also observed in patients with bilateral Menière's disease. As to the distribution of radiographic configuration types, bilateral Menière's disease had almost the same distribution as in normal ears. From these results, it was concluded that a hypoplastic development of the vestibular aqueduct was based on the etiology of Menière's disease, but general factors as well as a hypoplastic vestibular aqueduct seem to be responsible for bilateral involvement.

Constriction, Pathologic↗
PubMed1997

Antidiuretic hormone and psychosomatic aspects in Menière's disease.

We studied the relation between psychosomatic profiles of patients with Menière's disease and antidiuretic hormone (ADH). For investigation of the psychosomatic aspects, we used the Cornell Medical Index (CMI), Yatabe-Guilford personality (Y-G) test and the originally produced stress questionnaire. In Y-G test, patients with Menière's disease are classified in normal group. In the CMI test, on the other hand, types III and IV were significantly more often observed in Menière's disease than normal control (chi 2 test, p < 0.05). However, the CMI test results have no correlation to plasma ADH (p-ADH) levels. The survey of our original questionnaire revealed that stress has a close relationship to vertiginous attacks. Further, high p-ADH levels were significantly frequently observed in cases with stress compared with cases without stress (t-test, p < 0.05).

Adult↗