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Biomedical subjects

H Oda

Publications and source records attributed to H Oda.

At least 91 records · Page 5Linked to original sources

[Actual conditions of occupational health administration of small-scale enterprises in Japan: (II). Occupational health controls for hazardous and musculo-skeletally stressful working factors].

In order to clarify the actual condition of occupational health management for hazardous and musculo-skeletally stressful work factors in small-scale enterprises (SSEs) in Japan, a questionnaire survey was conducted in an area near Osaka city. The hazardous work factors examined were dust, organic solvents, lead, specified chemical substances, anoxia, noise, hand-arm vibration, ionizing radiation, high and low temperatures, and high air pressure. The musculo-skeletally stressful work factors examined were VDT work, prolonged standing, unnatural postures, handling of heavy weights, and stress on neck, shoulders and arms. The number of SSEs that replied to the questionnaire was 765 (recovery rate: 69.3%). Enterprises with noise, dust, hand-arm vibration and organic solvents numbered 14.0%, 10.7%, 6.9% and 6.4%, respectively, and those with other hazardous factors numbered less than 3%. Special medical examinations and working environment measurements for hazardous factors were conducted in 0.0% to 26.7% and 0.0% to 13.3%, respectively, of the enterprises. Working environment controls were conducted in 0.0% to 40.2%. Enterprises with prolonged standing and VDT work, were 42.0% and 35.8%, whereas those with other stressful factors were approximately 30%. Special medical examinations for musculo-skeletally stressful factors were conducted in 3.0% to 5.1% of the enterprises, and work controls were conducted in 20.4% to 25.3%. Non execution of the special medical examinations and working environment measurements were mainly due to "lack of knowledge of the law (19.7% and 30.2%)" and "lack of time to perform (16.0% and 23.3%)". Non execution of the controls for the hazardous work factors was due to "lack of knowledge as to how to control (9.0%)", "high costs (7.4%)", "lack of time to perform (6.4%)" and "absence of a suitable adviser (5.9%)". Non execution of the controls for stressful work factors was due to "lack of knowledge as to how to control (15.6%)" and "lack of time to perform (10.2%)". Consequently, as a result of the survey, it was suggested that it is necessary to enlighten the employers of SEEs as to the importance of occupational health controls. It is also necessary to propose low-cost, feasible control methods.

Computer Terminals↗

Is heavy alcohol consumption an attributable risk factor for cancer-related deaths among Japanese men?

BACKGROUND: Over the past four decades, per capita alcohol consumption in Japan has increased 4-fold. Age-adjusted cirrhosis mortality rates for men have also increased, whereas the rates for women have declined gradually. This widening difference in mortality could be due to a decreasing prevalence of viral hepatitis infection for both sexes and to differences in alcohol consumption between the sexes. Difficulties in estimating the impact of increased alcohol consumption on mortality rates in Japan also arise from changes in the prevalence of non-alcohol-related risk factors. METHODS: To measure the relative contribution of alcohol to death from cirrhosis, liver cancer, esophageal cancer, and head and neck cancer among Japanese men, we used the mortality rate for Japanese women as the standard because alcohol consumption for women has been low. We used published vital statistics data from 1992 to 1996 to calculate the attributable risk percent (ARP) in 5-year cohorts of Japanese men age 20 and older. RESULTS: Among Japanese men, heavy alcohol consumption accounted for 70.7% of deaths due to cirrhosis, 76.8% of liver cancer deaths, 88.5% of esophageal cancer deaths, and 87.4% of head and neck cancer deaths. When we examined ARPs by age group, ARPs for these four diseases were approximately 80% in the middle age groups. However, for older groups, the ARPs for cirrhosis and liver cancer were much lower than those for esophageal cancer and head and neck cancer. The prevalence of previous hepatitis C virus infection, considered to be the major cause of cirrhosis and liver cancer, increased with age. CONCLUSIONS: The results support previous epidemiologic studies conducted in Japan. Heavy alcohol consumption is a major public health problem among younger Japanese men, accounting for approximately 80% of the deaths for the four diseases examined.

Adult↗

Mice deficient in the nucleotide excision repair gene XPA have elevated sensitivity to benzo[a]pyrene induction of lung tumors.

This study is focused on chemical induction of lung tumors in xeroderma pigmentosum group A gene (XPA)-deficient mice to clarify the role of nucleotide excision repair (NER) in internal organs. Six-week-old female XPA-/-, XPA(+/-) and XPA(+/+) mice were instilled intratracheally with benzo[a] pyrene (B[a]P). A total of 68 surviving XPA mice treated with B[a]P were examined at month 16. The pulmonary adenoma incidence in XPA(-/-) mice was significantly higher than that in XPA(+/+) mice (71 versus 35%). Similarly, tumor multiplicity was elevated and, in addition, only XPA(-/-) mice had lung carcinomas. These results provide the first evidence that a deficiency in the NER gene XPA leads to enhanced tumorigenesis in the lung after exposure to B[a]P.

Animals↗

[p53 transgenic and knockout mice].

Li-Fraumeni syndrome(LFS) and its relation to the p53 gene and p53 gene transgenic and targeting mice are reviewed. LFS is a hereditary cancer-prone syndrome mainly with germ line mutation of p53 gene. p53 deficient mice, especially heterozygous mice, may serve as a model for human LFS, although there are several discrepancies between them. Carcinogenesis experiment using p53 deficient mice may be important to clarify the role of p53 in tumorigenesis in vivo.

Animals↗

Anatomic basis for selective nervi-spinales infiltration in the treatment of articular back pain.

The purpose of this paper is to describe the radiologic anatomy for selective medial branch block for low back pain resulting from facet joints. A groove between the mammillary process and the accessory process (M-A groove) was chosen as the target point for this nerve block. The position of M-A groove was constant on X-rays at each level of the lumbar spine. Confirming this position under the fluoroscope. the medial branch nerves can be blocked selectively. This method clarifies the features of low back pain related to the medial branch.

Adult↗

Coagulation and fibrinolysis factors in dialysis patients with and without ischemic heart disease.

Cardiovascular disease is the leading cause of death in patients with end-stage renal disease. In addition, abnormalities of coagulation and fibrinolysis have been reported in patients with uremia. However, whether these hemostatic abnormalities lead to cardiovascular disease in dialysis patients is currently unknown. Therefore, we investigated the association of hemostatic factors with ischemic heart disease (IHD) in patients on peritoneal dialysis and hemodialysis. The study patients comprised 30 continuous ambulatory peritoneal dialysis patients and 18 hemodialysis patients. Twenty healthy subjects served as controls. We evaluated each subject's hemostatic factors, including factor VII, factor XII, thrombin-antithrombin III complex (TAT), fibrinogen, plasmin-antiplasmin complex (PIC), plasminogen activator inhibitor (PAI-1), and D-dimer. In dialysis patients, IHD was diagnosed by documented myocardial infarction or positive result on coronary angiogram or by positive thallium myocardial scintigraphy. Factor VII, fibrinogen, PIC, and D-dimer levels were significantly higher in the two dialysis groups than in controls. All hemostatic variables were similar between the two dialysis groups. Subject age (p = 0.005), PIC (p = 0.005), and D-dimer level (p = 0.003) were significantly higher in patients with IHD than in patients without IHD in the dialysis groups. Multiple logistic regression analysis showed that only patient age and D-dimer levels were independent predictors of IHD. Adjusted odds ratio for IHD was 1.06 for each 10 ng/mL increase of D-dimer (p = 0.06). In CAPD patients, only D-dimer was independently associated with IHD (odds ratio: 1.06, p = 0.03). We conclude that multiple hemostatic abnormalities are present in dialysis patients and that elevated D-dimer levels are independently associated with prevalent IHD.

Antifibrinolytic Agents↗

[Acute eosinophilic pneumonia induced by cigarette smoking: positive lymphocyte stimulation test of a cigarette extract].

A 21-year-old man was admitted to our hospital with high fever, general fatigue and dyspnea. Chest radiography on admission showed diffuse bilateral infiltrate shadows with Kerley's B lines, and a CT scan showed patches of infiltrates with thickened interlobular septa in both lungs. Examination of the bronchoalveolar lavage fluid and the clinical course led to a diagnosis of acute eosinophilic pneumonia. The patient improved without steroid therapy. We suspected that the disease was related to smoking because the patient had started smoking seven days before the onset of the symptoms. Because a lymphocyte stimulation test gave a positive reaction to a cigarette extract, a challenge test was done. After this, the patient had fever and hypoxemia. These findings suggest that cigarette smoking induces acute eosinophilic pneumonia.

Acute Disease↗

Lipid-lowering therapy and coagulation/fibrinolysis parameters in patients on peritoneal dialysis.

Patients on continuous ambulatory peritoneal dialysis (CAPD) often have abnormalities of lipid metabolism or coagulation and fibrinolysis, these patients may thus be more susceptible to atherosclerosis than those on hemodialysis. It has been reported that hypercoagulability and hyperfibrinolysis are correlated with abnormalities of lipid metabolism. Therefore, we investigated the effect of a decrease in lipids on the coagulation and fibrinolysis system in CAPD patients with hyperlipidemia who received lipid-lowering therapy. The patients included 5 men and 13 women, with a mean age of 52.5 years. Pravastatin sodium (10 mg/day) and ethyl icosapentate (1800 mg/day) were administered concomitantly for 8 weeks. Lipid levels and coagulation/fibrinolysis parameters were measured before and after therapy. The patients were divided into two groups depending on their response to therapy: responders showed a decrease in total cholesterol or triglycerides by at least 20% and non-responders showed less improvement. In the responders, the levels of protein C, tissue plasminogen activator/plasminogen activator inhibitor-I complex, factor XIII, alpha2-plasmin inhibitor, and D-dimer were significantly lower after therapy than before therapy. Protein C, factor XIII, and alpha2-plasmin inhibitor were also significantly decreased after therapy in non-responders, but the extent of the decrease was smaller. The plasminogen level was significantly increased after therapy in non-responders. These findings suggest that a decrease in lipid levels and/or some other action by lipid-lowering agents may correct abnormalities of coagulation and fibrinolysis in CAPD patients.

Adult↗

Interaction of PKN with a neuron-specific basic helix-loop-helix transcription factor, NDRF/NeuroD2.

By the yeast two-hybrid screening of a human brain cDNA library with the amino-terminal regulatory region of PKN as a bait, a clone encoding a neuron-specific basic Helix-Loop-Helix (bHLH) transcription factor, NDRF/NeuroD2 was isolated. NDRF/NeuroD2 was co-precipitated with PKN from the lysate of COS-7 cells transfected with both expression constructs for NDRF/NeuroD2 and PKN. In vitro binding studies using the deletion mutants of NDRF/NeuroD2 synthesized in a rabbit reticulocyte lysate indicated that the internal region containing the bHLH domain of NDRF/NeuroD2 was necessary and sufficient for the interaction with PKN. In addition, recombinant NDRF/NeuroD2 purified from Escherichia coli could bind PKN, suggesting the direct interaction between NDRF/NeuroD2 and PKN. Transient transfection assays using P19 cells revealed that expression of NDRF/NeuroD2 increased the transactivation of the rat insulin promoter element 3 (RIPE3) enhancer up to approximately 12-fold and that co-expression of catalytically active form of PKN, but not kinase-deficient derivative, resulted in a further threefold increase of NDRF/NeuroD2-mediated transcription. These findings suggest that PKN may contribute to transcriptional responses through the post-translational modification of the NDRF/NeuroD2-dependent transcriptional machinery.

Animals↗

Nonchordate classic cadherins have a structurally and functionally unique domain that is absent from chordate classic cadherins.

Classic cadherins, which are adhesion molecules in cell-cell adherens junctions, have a large contribution to the construction of the animal body. Their molecular structures show clear differences between chordate and nonchordate metazoans. Although nonchordate classic cadherins have cadherin superfamily-specific extracellular repeats (CRs) and a highly conserved cytoplasmic domain (CP), these cadherins have a unique extracellular domain that is absent from vertebrate and ascidian classic cadherins. We called this the primitive classic cadherin domain (PCCD). To understand the roles of the PCCD, we constructed and characterized a series of mutant forms of the Drosophila classic cadherin DE-cadherin. Biochemical analyses indicated that the last two CRs and PCCD form a special structure with proteolytic cleavage. Mutations in the PCCD did not eliminate the cell-cell-binding function of DE-cadherin in cultured cells, but prevented the cadherin from efficiently translocating to the plasma membrane in epithelial cells of the developing embryo. In addition, genetic rescue assays suggested that although CP-mediated control plays a central role in tracheal fusion, the role of the PCCD in efficient recruitment of DE-cadherin to apical areas of the plasma membranes is also important for dynamic epithelial morphogenesis. We propose that there is a fundamental difference in the mode of classic cadherin-mediated cell-cell adhesion between chordate and nonchordate metazoans.

Amino Acid Sequence↗

Ubiquitin-mediated degradation of active Src tyrosine kinase.

Src family tyrosine kinases are involved in modulating various signal transduction pathways leading to the induction of DNA synthesis and cytoskeletal reorganization in response to cell-cell or cell-matrix adhesion. The critical role of these kinases in regulating cellular signaling pathways requires that their activity be tightly controlled. Src family proteins are regulated through reversible phosphorylation and dephosphorylation events that alter the conformation of the kinase. We have found evidence that Src also is regulated by ubiquitination. Activated forms of Src are less stable than either wild-type or kinase-inactive Src mutants and can be stabilized by proteasome inhibitors. In addition, poly-ubiquitinated forms of active Src have been detected in vivo. Taken together, our results establish ubiquitin-mediated proteolysis as a previously unidentified mechanism for irreversibly attenuating the effects of active Src kinase.

Animals↗

Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism.

The human MTH1 gene for 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase, produces seven types (types 1, 2A, 2B, 3A, 3B, 4A and 4B) of mRNAs. The B-type mRNAs with exon 2b-2c segments have three additional in-frame AUGs in their 5' regions. We report here that these transcripts produce three forms of MTH1 polypeptides (p22, p21 and p18) in in vitro translation reactions. Three polypeptides were also detected in extracts of human cells, using western blotting. B-type mRNAs with a polymorphic alteration (GU-->GC) at the beginning of exon 2c that converts an in-frame UGA to CGA yielding another in-frame AUG further upstream, produced an additional polypeptide (p26) in vitro. Substitution of each AUG abolished the production of each corresponding polypeptide. Cell lines from individuals with the GC allele contain more B-type mRNAs than do those of GT homozygotes, and the former produce all of four polypeptides but the latter lack p26. Amounts of each polypeptide reflected copy number of the GC allele in each cell line. There is an apparent linkage dis-equilibrium between the two polymorphic sites, GT/GC at exon 2c and Val83/Met83 at codon 83 for p18.

Base Sequence↗

Phosphorylation/Dephosphorylation steps are crucial for the induction of CYP2B1 and CYP2B2 gene expression by phenobarbital.

The effects of several protein kinase activators and protein phosphatase inhibitors on the phenobarbital (PB)-induced gene expression of CYP2B1 and CYP2B2 (CYP2B1/2B2) in adult rat hepatocytes were investigated. Insulin, epidermal growth factor, interleukin 6, cAMP, phorbol 12-myristate 13-acetate, tumor necrosis factor alpha, vanadate, and okadaic acid were found to suppress the induction of CYP2B1/2B2 at mRNA and protein levels in hepatocytes. cAMP and vanadate completely suppressed the induction of CYP2B1/2B2 gene expression in both rat hepatocytes and liver. The addition of genistein to vanadate-treated hepatocytes partially recovered the induction of CYP2B1/2B1 gene expression by PB. These results of the present study demonstrate that phosphorylation/dephosphorylation steps are crucial for the induction of CYP2B1/2B2 gene expression by PB.

Animals↗

Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination.

The Src family of nonreceptor tyrosine kinases are important regulators of a variety of cellular processes, including cytoskeletal organization, cell-cell contact, and cell-matrix adhesion. Activation of Src family kinases also can induce DNA synthesis and cellular proliferation; therefore, tight regulation of their kinase activities is important for the cell to maintain proliferative control. Posttranslational phosphorylation and dephosphorylation are recognized as the principle modifications by which the activities of the Src family of tyrosine kinases are regulated. We have discovered that this family of kinases also is regulated by ubiquitin-mediated proteolysis. Studies aimed at the identification of cellular targets for E6AP, an E3 ubiquitin protein ligase involved in ubquitin-mediated degradation, led us to the identification of members of the Src family kinases as potential substrates for E6AP. We have found that E6AP can bind to several of the Src family tyrosine kinases. Here we show that activated Blk is preferentially degraded by the ubiquitin-proteasome pathway and that its ubiquitination is mediated by E6AP. Identification of members of the Src tyrosine kinase family as substrates of the E6AP ubiquitin-protein ligase implicates a role for the ubiquitin pathway in regulating the activities of individual members of this important family of signaling molecules.

Animals↗

Cloning, expression profile, and genomic organization of the mouse STAP/A170 gene.

The preferential screening of cDNA libraries derived from the mouse osteoblastic cell line MC3T3-E1 has yielded a cDNA clone encoding a 442-amino-acid protein designated STAP (signal transduction and adaptor protein), which contains several motifs shared among transcription factors and adaptors such as a Zn-finger like motif, a proline-rich domain, and a PEST sequence. The amino acid sequence homology search also reveals that STAP is identical to a mouse oxidative stress protein, A170, and has 90% homology with a human p62 protein that binds to the tyrosine kinase p56(lck) SH2 domain. Northern blot analysis indicated a broad expression profile of STAP mRNA in various tissues and cell lines. In MC3T3-E1 cells, STAP mRNA was induced by treatment with TGF-beta, but not with BMP-2 or GDF-5. Analysis of the mouse STAP gene isolated from the genomic library revealed that the STAP gene spans a region of over 11 kb and comprises eight exons. The transcription start site was identified by primer extension analysis to be located 35 bp upstream from the translation initiation site. Sequencing analysis of the 5' flanking region of the STAP gene revealed multiple consensus motifs/sequences for several DNA binding transcription factors. The STAP gene had a TATA box, but no CCAAT box. Potential Sp1, AP-1, NF-E2, MyoD, and NF-kappaB binding sites were found in the 5' flanking region (1.4 kb) of the STAP gene.

3T3 Cells↗

Acute and transient increase of lipocalin-type prostaglandin D synthase (beta-trace) level in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage.

We measured the concentration of lipocalin-type prostaglandin D synthase (PGDS) in cerebrospinal fluid (CSF) and serum in patients 1, 3, 5, 7, 9, 11, 14 and 17 days after subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysms. The PGDS level in lumbar CSF increased about two-fold at day 3 (20.85 +/- 2.71 microg/ml, mean +/- SE) and at day 5 (25.24 +/- 3.76), as compared with the level at day 1 (11.25 +/- 1.07). The CSF level gradually decreased and returned to the day 1 level at day 17. The serum PGDS level was much lower than the CSF level (0.39 +/- 0.06 at day 1) and almost unchanged until day 17. The neuron-specific enolase level in CSF, as an index of brain damage, was maximum at day 1 (29.83 +/- 7.32 ng/ml) and decreased at day 3 and at day 5 (18.28 +/- 2.65 and 11.95 +/- 1.82, respectively). These results suggest that the transient and delayed increase in the PGDS level in CSF is due to its induction of PGDS in the arachnoid membrane after SAH.

Aged↗

Casein kinase II inhibitors isolated from two Brazilian plants Hymenaea parvifolia and Wulffia baccata.

Two dihydroflavonol rhamnosides (1 and 2) isolated from the bark of Hymenaea parvifolia and two pentacyclic triterpenoids (3 and 6) obtained from the leaves of Wulffia baccata have been found to exhibit inhibitory effects of casein kinase II (CK-II) dose-dependently, suggesting that at higher doses more than 10 microM, these four compounds may act as potent CK-II suppressors of the CK-II-mediated activation of 60S acidic ribosomal P proteins in vitro.

Brazil↗