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Biomedical subjects

M Kawamura

Publications and source records attributed to M Kawamura.

At least 145 records · Page 8Linked to original sources

Present state of dental health knowledge, attitudes/behaviour and perceived oral health of Japanese employees.

The aim of this survey was to assess the present state of dental health knowledge, attitudes/behaviour and perceived oral health of Japanese employees. A 60-item questionnaire was used in a dental health project in the work place. The subjects comprised 77,845 employees, 76 per cent of whom reported delaying a dental visit until they had toothache, with about 60 per cent delaying even when they discovered a decayed tooth. The majority did not regard decayed teeth as a disease and only a minority reported regular dental visits. About three quarters reported bleeding gums on brushing, although more than half had never been taught professionally how to clean their teeth and less than 5 per cent flossed daily. More than half believed that false teeth were inevitable in old age, and that their teeth were getting worse despite daily brushing. About 70 per cent of the employees thought that it was impossible to prevent gum disease with toothbrushing alone, and nearly half believed a toothpaste with fluoride was effective in preventing periodontal disease. Reorientation of oral health care in Japan, therefore, is urgently needed and dental services have to be provided for the implementation of systematic oral health promotion for employees in the workplace.

Adolescent↗

Age-dependent abnormalities of hematopoietic stem cells in (NZW x BXSB)F1 mice.

The (NZW x BXSB)F1 (W/BF1) mouse is known as an autoimmune-prone strain which develops lupus nephritis, thrombocytopenia due to platelet-specific autoantibodies, leukocytosis, and myocardial infarction. In this experiment, we investigated the age-dependent abnormalities of the hematopoietic stem cells (HSCs) and hematopoiesis in this mouse. White blood cell counts (especially Mac-1- or Gr-1-positive cells) in the peripheral blood of 12-week-old W/BF1 mice increased in comparison with those of four-week-old W/BF1 or normal mice. To investigate whether the abnormal hematopoiesis can be attributed to the HSCs of W/BF1 mice, colony-forming unit in spleen (CFU-S) and colony-forming unit in culture (CFU-C) assays were performed. Day 12 CFU-S counts of 12-week-old W/BF1 mice significantly increased in comparison with those of four-week-old W/BF1 mice or normal mice. In the CFU-C assay, CFU-GEMM and CFU-GM counts in 12-week-old W/BF1 mice increased in comparison with those of four-week-old W/BF1 or control mice. The bone marrow cells (BMCs) from 12-week-old W/BF1 mice showed a high level of G-CSF and a low level of GM-CSF in mRNA expression. To examine the effect of HSCs from 12-week-old W/BF1 mice on the onset of autoimmune diseases and the abnormal hematopoiesis, T- and B-cell-depleted BMCs of four-week-old or 12-week-old W/BF1 mice were transplanted to C3H mice. Recipient C3H mice that had received the BMCs from 12-week-old W/BF1 mice showed an earlier onset of autoimmune diseases and a shorter survival rate than those that had received the BMCs from four-week-old W/BF1 mice. These data suggest that the HSCs from 12-week-old W/BF1 mice showing the symptoms of autoimmune diseases have the capacity to induce autoimmune diseases earlier than the HSCs from four-week-old W/BF1 mice.

Age of Onset↗

Non-mycotic pseudoaneurysm in the ascending aorta following cardiac surgery.

Cannulation of the ascending aorta is the recognized method to achieve arterial return during cardiopulmonary bypass. Mediastinal infection after cardiac surgery can cause disruption at the point of insertion, and give rise to a pseudoaneurysm in the ascending aorta. Although rare, a pseudoaneurysm can occur without clear evidence of infection. Here we report two cases that received aortic valve replacement and that developed ascending aortic aneurysms after surgery. Based on our clinical findings, these aneurysms were related to the arterial cannulation into the aorta and not to any infection.

Aneurysm, False↗

Protective effect of nisoldipine on myocardial ischemia during coronary bypass surgery.

BACKGROUND: Nisoldipine, a calcium antagonist, was assessed for myocardial protection and the prevention of reperfusion injury in patients undergoing CABG. METHODS: Of the 34 subjects undergoing CABG in this study, 20 were given nisoldipine orally at 10 mg/day for 2 weeks before surgery (N group) and the other 14 untreated controls (C group). Myocardial protection was conducted via ante-grade cold blood cardioplegia at 20-minute intervals. RESULTS: Myocardial blood flow was significantly higher in the N group (67.8 +/- 21.8 ml/100 g vs. 47.2 +/- 14.4 ml/100 g, p < 0.05) after cardiopulmonary bypass. Serum interleukin-6 levels were significantly lower in the N group 1 hour after reperfusion (116 +/- 58 vs. 409 +/- 362 pg/ml, p < 0.05), as were serum lactate dehydrogenase levels immediately after surgery (888 +/- 268 vs. 1350 +/- 486 IU/L, p < 0.05). The N Group showed a better left ventricle stroke work index 6 hours after surgery (43 +/- 8 vs. 36 +/- 9 g.m/m2). Dopamine dosage in the N group on postoperative day 1 was lower than in controls (5.3 +/- 1.9 vs. 3.0 +/- 2.4 micrograms/kg/min). CONCLUSIONS: Preoperative nisoldipine treatment increased blood flow in the postischemic myocardium and prevented myocardial damage and reperfusion injury to some extent.

Administration, Oral↗

Production of functional human alpha 1-antitrypsin by plant cell culture.

Recombinant human alpha 1-antitrypsin (rAAT) was expressed and secreted from transgenic rice cell suspension cultures in its biologically active form. This was accomplished by transforming rice callus tissues with an expression vector, p3D-AAT, containing the cDNA for mature human AAT protein. Regulated expression and secretion of rAAT from this vector was achieved using the promoter, signal peptide, and terminator from a rice alpha-amylase gene Amy3D. The Amy3D gene of rice is tightly controlled by simple sugars such as sucrose. It was possible, therefore, to induce the expression of the rAAT by removing sucrose from the cultured media or by allowing the rice suspension cells to deplete sucrose catabolically. Although transgenic rice cell produced a heterogeneous population of the rAAT molecules, they had the same N-terminal amino acids as those found in serum-derived (native) AAT from humans. This result indicates that the rice signal peptidase recognizes and cleaves the novel sequence between the Amy3D signal peptide and the first amino acid of the mature human AAT. The highest molecular weight band seen on Western blots (AAT top band) was found to have the correct C-terminal amino acid sequence and normal elastase binding activity. Staining with biotin-concanavalin A and avidin horseradish peroxidase confirmed the glycosylation of the rAAT, albeit to a lesser extent than that observed with native AAT. The rAAT, purified by immunoaffinity chromatography, had the same association rate constant for porcine pancreatic elastase as the native AAT. Thermostability studies revealed that the rAAT and native AAT decayed at the same rate, suggesting that the rAAT is correctly folded. The productivity of rice suspension cells expressing rAAT was 4.6-5.7 mg/g dry cell. Taken together, these results support the use of rice cell culture as a promising new expression system for production of biologically active recombinant proteins.

Amino Acid Sequence↗

Antiatherogenic effect of angiotensin converting enzyme inhibitor (benazepril) and angiotensin II receptor antagonist (valsartan) in the cholesterol-fed rabbits.

The purpose of this study was to determine whether an angiotensin converting enzyme (ACE) inhibitor, benazepril, and an angiotensin receptor antagonist, valsartan, would decrease atherosclerotic severity in cholesterol-fed rabbits. Male rabbits were fed either: (a) normal rabbit chow; (b) 2% cholesterol diet; (c) 2% cholesterol diet supplemented by benazepril (3 mg/kg per day, subcutaneous injection); or (d) 2% cholesterol diet supplemented by valsartan (1 mg/kg per day, subcutaneous injection). After 12 weeks, the arteries were harvested for histomorphometry and immunohistochemistry. We observed that decreases in serum triglyceride (TG) and total cholesterol (TC) and ACE activity with benazepril-treatment were more than 60, 30, and 84%, respectively, in comparison with the cholesterol group; with valsartan-treatment, TG levels were 53% lower than in the cholesterol group, however, there was no significant difference in TC and ACE activity. The percentage of aortic surface atherosclerotic area, intimal thickness and the ratio of aortic intimal area to medial area were about 40% lower in the benazepril-treated group in comparison with those of the cholesterol group; the difference was more than 60% in the thoracic aorta. The valsartan-treated group had 23% less atherosclerotic area, less effective than benazepril treatment. The percent of PCNA-positive cells and the number of intimal proliferative cells/mm2 were significantly less in the benazepril-treated group compared with the cholesterol group (by 55 and 63%); these parameters were 35 and 17% lower, respectively, with valsartan. The ratio of proliferating macrophages to smooth muscle cells (SMCs) was 3:1 in the cholesterol group, 1:1 in the benazepril and 2:1 in the valsartan-treated group. These results indicate that benazepril could reduce atherosclerotic progression by decreasing macrophage proliferation and accumulation in the arterial wall. The mechanisms for reducing atherosclerotic progression by benazepril and valsartan may be related to reduction of TG and blockade of the angiotensin II action.

Analysis of Variance↗

Surgical treatment for both pulmonary and hepatic metastases from colorectal cancer.

OBJECTIVE: The role of surgery in the treatment of patients with pulmonary and hepatic metastases from colorectal cancer has not been delineated. METHODS: Of the 351 patients enrolled in the Metastatic Lung Tumor Study Group of Japan between June 1988 and June 1996 who underwent thoracotomy for pulmonary metastases from colorectal cancer, 47 also underwent hepatic resection for metastatic tumors. The records of these patients were studied. RESULTS: The 47 patients who underwent pulmonary and hepatic resection had a 3-year survival of 36% +/- 8%, a 5-year survival of 31% +/- 8%, and an 8-year survival of 23% +/- 9%. The longest survival was 98 months. This patient was alive without recurrence. There was a significant difference in the cumulative survival of the patients with a solitary pulmonary metastasis and the patients with multiple pulmonary metastases (P =.04). Neither age, sex, location of the primary tumor, maximum diameter of the pulmonary metastases, method of pulmonary resection, number of hepatic metastases, nor method of hepatic resection was correlated with survival. However, 9 of 10 patients who survived 3 years or more after the initial thoracotomy had only one or two hepatic metastases. CONCLUSION: Surgical treatment of a solitary pulmonary metastasis concurrent with or after resection of hepatic metastases from colorectal cancer may be appropriate if the hepatic metastases are resectable for cure. Patients with a solitary pulmonary metastasis and a small number of hepatic metastases are good candidates for resection. Long-term survival can be expected.

Age Factors↗

Expression and function of cyclooxygenase-2 in mesothelial cells during late phase of rat carrageenin-induced pleurisy.

We have previously shown that the inducible isoform of the cyclooxygenases, COX-2, is strongly expressed in pleural exudate leukocytes early (between 3 and 7 hr after irritation) during rat carrageenin-induced pleurisy. The present study further examined COX-2 expression and disclosed that mesothelial cells expressed COX-2 later (12 to 24 hr after irritation) in this model. A COX-2 inhibitor, nimesulide, lowered the intrapleural level of 6-keto-PGF1alpha and inhibited hyperplasia of the pleural matrix, suggesting that COX-2 expressed in mesothelial cells may play a role in the synthesis of extracellular matrix through formation of PGI2.

Animals↗

Alterations of the p53, p21, p16, p15 and RAS genes in childhood T-cell acute lymphoblastic leukemia.

We investigated the alterations of the p53, p21, p16, p15 and RAS genes in childhood T-cell acute lymphoblastic leukemia (T-ALL) and T-ALL cell lines by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. Mutations of the p53 gene were found in three of 57 (5%) patients at diagnosis, one of 14 (7%) patients at relapse and in 12 of 18 (67%) cell lines. In these 12 cell lines, four had more than two mutations of the p53 gene. The p53 mutations were found in four of five cell lines whose original fresh leukemic cells were simultaneously examined original fresh leukemic cells. However, only one of the four fresh leukemic cells had the same mutation. All patients with p53 mutations in the course of disease died. Mutations of the p21 gene were not identified in 71 fresh samples and in 18 cell lines. N-RAS mutations were found in two of 57 (4%) fresh T-ALL patients at diagnosis, and four of 18 cell lines (22%), whereas no mutations were detected in any samples at relapse. Alterations of the p16 gene were found in 18 of 47 (38%) patients at diagnosis and in seven of 14 (50%) at relapse. These differences were not statistically significant. There were no differences in the frequency of alteration of the p16 and p15 genes between event-free patients and the remaining patients. Furthermore, we found the methylation of p16 gene in three of seven patients lacking homozygous deletions, suggesting higher frequency of p16 inactivation than previous reports in T-ALL. Interestingly, we found that one allele is inactivated by methylation and another allele had nonsense mutation in one cell line (KOPT-KI), resulting in loss of protein expression of p16. This type of p16 inactivation has not been so far reported in leukemia. We conclude that, (1) p53 mutations are infrequent at diagnosis but tend to be associated with poor clinical outcome; (2) RAS and p21 mutations may not be involved in the pathogenesis of T-ALL; (3) not only frequent alterations of p16 and p15 genes but also methylation of p16 gene are involved in initiating the leukemogenesis of T-ALLs, and (4) these 5 genes are independently involved in T-ALL.

Adolescent↗

Cell-dependent replication potentials of HIV-1 gag mutants.

An infectious molecular clone of human immunodeficiency virus type 1 (HIV-1), designated pNLaiKH, which is tropic for both lymphocytic and monocytic cells, was constructed. To study the early function of HIV-1 Gag proteins in two types of cells, the mutations known to give host cell-dependent early defects were introduced into pNLaiKH, and the replication potentials and defective replication sites in the cells of the resultant mutants were monitored. All mutants grew in some lymphocytic cells, but not at all in monocytic cells. A nucleocapsid mutant was found to be defective at an early replication phase in all the cell lines to various extent, as expected. In contrast, a matrix mutant and a capsid mutant displayed a replication defect in a producer-cell-dependent manner. These results demonstrated that complex interactions of cell factors and Gag proteins are involved in an early process of HIV-1 replication.

Cell Line↗

Differential effects of chemical sympathectomy on expression and activity of tyrosine hydroxylase and levels of catecholamines and DOPA in peripheral tissues of rats.

Tyrosine hydroxylase (TH) mRNA and activity and concentrations of 3,4-dihydroxyphenylalanine (DOPA) and catecholamines were examined as markers of sympathetic innervation and catecholamine synthesis in peripheral tissues of sympathectomized and intact rats. Chemical sympathectomy with 6-hydroxydopamine (6-OHDA) markedly decreased norepinephrine and to a generally lesser extent TH activities and dopamine in most peripheral tissues (stomach, lung, testis, duodenum, pancreas, salivary gland, spleen, heart, kidney, thymus). Superior cervical ganglia, adrenals and descending aorta were unaffected and vas deferens showed a large 92% decrease in norepinephrine, but only a small 38% decrease in TH activity after 6-OHDA. Presence of chromaffin cells or neuronal cell bodies in these latter tissues, indicated by consistent expression of TH mRNA, explained the relative resistance of these tissues to 6-OHDA. Stomach also showed consistent expression of TH mRNA before, but not after 6-OHDA, suggesting that catecholamine synthesizing cells in gastric tissue are sensitive to the toxic effects of 6-OHDA. Tissue concentrations of DOPA were mainly unaffected by 6-OHDA, indicating that much of the DOPA in peripheral tissues is synthesized independently of local TH or sympathetic innervation. The differential effects of chemical sympathectomy on tissue catecholamines, DOPA, TH mRNA and TH activity demonstrate that these variables are not simple markers of sympathetic innervation or catecholamine synthesis. Other factors, including presence of neuronal cell bodies, parenchymal chromaffin cells, non-neuronal sites of catecholamine synthesis and alternative sources of tissue DOPA, must also be considered when tissue catecholamines, DOPA and TH are examined as markers of sympathetic innervation and local catecholamine synthesis.

Animals↗

Inter- and intra-individual variation of food and nutrient consumption in a rural Japanese population.

OBJECTIVES: To determine the relative contribution of intra- and inter-individual variation in the consumption of foods and nutrients. DESIGN: Cross-sectional study. SETTING: Two rural towns in the Miyagi Prefecture, a northeastern part of Japan. SUBJECTS: Fifty-nine men and sixty women. METHODS: Four 3-d food records were collected in four seasons within a year. The total variance in the consumption of 15 nutrient variables and 16 food groups was partitioned by analysis of variance into its inter- and intra-individual components, separately for men and women. RESULTS: The ratio of the intra- to inter-individual variance was larger than unity in 87% (13/15) of the nutrients in men and 100% (15/15) in women. The ratio was largest for retinol (52.9 in men and infinity in women) and smallest for carbohydrates (0.8 in men and 1.5 in women). The ratio was larger than unity in 88% (14/16) of the food groups in men and 94% (15/16) in women, which was smallest for cereals (0.6 in men and 0.9 in women). CONCLUSIONS: The results were consistent with previous western studies in that intra-individual variation was generally larger than inter-individual variation for the consumption of both foods and nutrients. SPONSORSHIP: This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture (09470106) and by Health Sciences Research Grants for Research on Health Services (H10-25) from the Ministry of Health and Welfare in Japan.

Aged↗

Management of acute metabolic decompensation in maple syrup urine disease: a multi-center study.

BACKGROUND: Therapeutic modalities in acute metabolic decompensation in maple syrup urine disease (MSUD) are variable, and outcomes of each therapeutic measure have been known only individually. Factors that affect neurological outcome are not clear. METHODS: A questionnaire was sent throughout Japan to each pediatrician treating any of the 42 MSUD patients. RESULTS: Necessary information was available for 13 patients through the questionnaire, and through a publication for one patient. In nine of the 14 patients episodes of metabolic decompensation developed in the neonatal period. In the other five, the onset of disease was delayed until infancy or later. In the nine patients with neonatal onset, a pretreatment level of plasma leucine greater than 40 mg/100 mL or a duration of altered level of alertness longer than 10 days was associated with a poor neurological outcome. The therapeutic measures employed included intravenous infusion of glucose and electrolyte solution or hypertonic glucose and electrolyte solution, exchange transfusion, peritoneal dialysis, a large dose of thiamine and intravenous hyperalimentation. All patients had survived the episodes and were alive at the time of the survey. Five of the nine patients with neonatal onset have developed neurological sequelae to varying degrees. Episodes of metabolic decompensation in infancy or thereafter did not affect, or only minimally affected, the neurological outcome. CONCLUSION: Therapeutic goals to improve neurological outcome are to shorten the duration of the altered level of consciousness, and to minimize the peak plasma leucine level as much as possible.

Acute Disease↗

Heparin coating extends the durability of oxygenators used for cardiopulmonary support.

Acomparative study was performed between a noncoated and heparin-coated cardiopulmonary support (CPS) systems with the same design and structure (Terumo Corporation, Capiox-SX series) to evaluate whether or not heparin coating extends oxygenator service life. Fifty patients underwent CPS from January 1993 until December 1997, and 54 oxygenators (Capiox-SX series) were used. There were 35 noncoated oxygenators (Group NC) and 19 heparin-coated ones (Group HC). Significant predictors for the durability of oxygenators were evaluated by a nonparametric survival analysis and a proportional hazards regression analysis. Thirteen of 35 Capiox-SX and only 2 of 19 Capiox SX-HP revealed gas transfer failure and had to be exchanged. The average life span of the Capiox-SX and Capiox-SX-HP were calculated to be 78.6 +/- 16.8 and 168 +/- 15.4 h, respectively. Group HP showed significantly longer durability than Group NC (p = 0.0017), although there were differences of perfusion index and platelet counts between the 2 groups. Heparin coating of the CPS system remained one of the 2 significant predictors (hazards ratio 8. 871, p = 0.0449) to determine the durability of oxygenators by increasing stepwise multivariate proportional hazards regression analysis, along with anemia with less than 8 g/dl hemoglobin (hazards ratio 9.438, p = 0.0173). Heparin coating of the CPS system assures improved durability because heparin-coated oxygenators have a longer service life than noncoated ones.

Anemia↗

Analysis of 8-hydroxyguanine in rat kidney genomic DNA after administration of a renal carcinogen, ferric nitrilotriacetate.

The frequency of oxidative base damage, such as 8-hydroxyguanine (8-OH-Gua), was determined at the nucleotide level of resolution using the ligation-mediated PCR technique. Administration of a renal carcinogen, ferric nitrilotriacetate (Fe-NTA), is known to induce oxidative stress and subsequent formation of 8-OH-Gua in the rat kidney. Whole genomic DNA was isolated from the rat kidney after or without Fe-NTA treatment and then cleaved with hot piperidine. In order to assess the frequency of 8-OH-Gua formation, we chose three genes, the tumor suppressor gene p53, the heat shock protein 70 (HSP70-1) gene and the Na,K-ATPase alpha1 subunit gene. No alteration in the cleavage profile was observed in the p53 and HSP70 genes after Fe-NTA treatment. In the case of the p53 gene, a low incidence of point mutations has been observed in this carcinogenesis system. On the other hand, time-dependent alterations, corresponding to the time course of overall 8-OH-Gua formation and repair, were detected in the promoter region of the Na,K-ATPase alpha1 subunit gene. GpG and GpGpG in specific regions seem to be hotspots for the formation of 8-OH-Gua. These results were confirmed by formamidopyrimidine-DNA glycosylase-dependent DNA cleavage patterns. Thus, oxidative base damage, such as 8-OH-Gua, was not distributed uniformly along the whole genome, but seemed to be restricted to particular genes and regions.

Animals↗

Down-regulation of protein tyrosine phosphatase gene expression in lactating mouse mammary gland.

Detailed analysis of protein tyrosine phosphatase (PTP) expression in mouse mammary gland and mammary epithelial cells using a set of degenerate primers corresponding to the PTP core domain sequence revealed the presence of 16 different receptor-type and intracellular PTPs. Northern blot and RT-PCR analyses revealed that some PTPs were up-regulated during gestation, suggesting that these enzymes are involved in development of mammary gland. However, expression of most PTPs dramatically decreased during lactation, whereas the beta-casein gene expression was increased and remained at a high level. At the involution stage after weaning, most PTPs were up-regulated and their expression returned almost to the virgin level. Such up-regulation was also induced by forced weaning in lactating mother mice. These results suggest the possible contribution of PTPs to the development, involution, and remodeling of mammary gland and their possible inhibitory action on maintaining high expression of milk genes during lactation.

Animals↗