PubMed Health⌕ Search

Biomedical subjects

T Arimoto

Publications and source records attributed to T Arimoto.

At least 19 recordsLinked to original sources

The DNA mismatch repair gene hMSH2 is a potent coactivator of oestrogen receptor alpha.

The DNA mismatch repair gene is a key regulator in the elimination of base-base mismatches and insertion/deletion loops (IDLs). Human MutS homologue 2 (hMSH2), originally identified as a human homologue of the bacterial MutS, is a tumour suppressor gene frequently mutated in hereditary non-polyposis colorectal cancer. Hereditary non-polyposis colorectal cancer is characterised by the early onset of colorectal cancer and the development of extracolonic cancers such as endometrial, ovarian, and urological cancers. Oestrogen receptor (ER) alpha and beta are members of a nuclear receptor (NR) superfamily. Ligand-dependent transcription of ER is regulated by the p160 steroid receptor coactivator family, the thyroid hormone receptor-associated proteins/the vitamin D receptor-interacting proteins (TRAP/DRIP) mediator complex, and the TATA box-binding protein (TBP)-free TBP associated factor complex (TFTC) type histone acetyltransferase complex. Here, we report the interaction between ER alpha/beta and hMSH2. Immunoprecipitation and glutathione-S-transferase pull-down assay revealed that ER alpha and hMSH2 interacted in a ligand-dependent manner, whereas ER beta and hMSH2 interacted in a ligand-independent manner. Oestrogen receptor alpha/beta bound to hMSH2 through the hMSH3/hMSH6 interaction domain of hMSH2. In a transient expression assay, hMSH2 potentiated the transactivation function of liganded ER alpha, but not that of ER beta. These results suggest that hMSH2 may play an important role as a putative coactivator in ER alpha dependent gene expression.

Base Pair Mismatch↗

Activation of distinct signal transduction pathways in hypertrophied hearts by pressure and volume overload.

OBJECTIVE: Two types of hemodynamic overload, pressure and volume overload, result in morphologically distinct types of cardiac remodeling. We explored the possibility that distinct hemodynamic overload may differentially activate the signal transduction pathway. METHODS: Pressure and volume overload were induced by thoracic aortic banding and carotid-jugular shunt formation in rabbits, respectively. Phosphorylation activities of mitogen-activated protein (MAP) kinase families, Akt, and signal transducer and activator of transcription (STAT) 3 in the left ventricular myocardium were determined by Western blotting using phospho-specific antibodies and were compared between hypertrophied hearts by pressure and volume overload. RESULTS: Pressure and volume overload produced concentric and eccentric cardiac hypertrophy in rabbits, respectively. In pressure-overloaded hearts, extracellular signal-regulated kinase (ERK) 1/2, p38 MAP kinase, and STAT3 were transiently activated prior to hypertrophic changes. In contrast, activation of ERK1/2, but not p38 MAP kinase and STAT3, was observed only at 12 weeks after shunt surgery. Pressure overload evoked short and biphasic activation of Akt at 15 min and 1 day after aortic banding. In contrast, volume overload induced sustained activation of Akt from 1 day to 1 week. Concordant phosphorylation of downstream targets of Akt, glycogen synthase kinase-3beta (GSK-3beta) and p70 ribosomal S6 kinase (p70(S6K)), in response to Akt activation was observed at 15 min after pressure overload. However in volume-overloaded hearts, phosphorylation of GSK-3beta and p70(S6K) was observed at 6 weeks and at 6 and 12 weeks, respectively, and was not coincident with Akt activation. These findings suggest that phosphorylation of GSK-3beta and p70(S6K) is regulated by an alternative pathway other than Akt in volume-overloaded hearts. CONCLUSION: Pressure and volume overload-induced cardiac hypertrophy is associated with distinct patterns of activation of signal transduction pathways. These data may suggest that stimulus-specific heterogeneity in the signaling pathway plays a role in determining the type of cardiac hypertrophy.

Animals↗

Protein kinase C and extracellular signal regulated kinase are involved in cardiac hypertrophy of rats with progressive renal injury.

Increased cardiovascular mortality is an unresolved problem in patients with chronic renal failure. Cardiac hypertrophy is observed in the majority of patients with chronic renal failure undergoing haemodialysis. However, the mechanisms, including signal transduction pathways, responsible for cardiac hypertrophy in renal failure remain unknown. We examined the subcellular localization of protein kinase C (PKC) isoforms and phosphorylation activities of 3 mitogen-activated protein (MAP) kinase families in hypertrophied hearts of progressive renal injury rat model by subtotal nephrectomy (SNx). We also examined the effects of a novel angiotensin II type-1 receptor antagonist, CS-866, on the PKC translocation, MAP kinase activity and cardiac hypertrophy in SNx rats. The left ventricle/body weight ratios were significantly larger in SNx rats than in sham rats at 1, 2, and 4 weeks after surgery. The translocation of PKCalpha and epsilon isoforms to membranous fraction was observed in SNx rat hearts at 1, 2, and 4 weeks after surgery. Activation of extracellular signal regulated kinase (ERK) 1/2, but not p38 MAP kinase and c-Jun N-terminal kinase (JNK), was observed at 1 and 2 weeks after surgery. Angiotensin II receptor blockade with CS-866 (1 mg kg-1 day-1) prevented cardiac hypertrophy, PKC translocation and ERK1/2 activation in SNx rats without significant changes in blood pressure. These data suggest that PKC and ERK1/2 are activated by an angiotensin II receptor-mediated pathway and might play an important role in the progression of cardiac hypertrophy in renal failure.

Angiotensin II Type 1 Receptor Blockers↗

Fatty acid metabolism assessed by 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) and expression of fatty acid utilization enzymes in volume-overloaded hearts.

BACKGROUND: The peroxisome proliferator-activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily and regulates gene expression of fatty acid utilization enzymes. In cardiac hypertrophy and heart failure by pressure-overload, myocardial energy utilization reverts to the fetal pattern, and metabolic substrate switches from fatty acid to glucose. However, myocardial metabolism in volume-overloaded hearts has not been rigorously studied. The aim of the present study was to examine fatty acid metabolism and protein expressions of PPARalpha and fatty acid oxidation enzymes in volume-overloaded rabbit hearts. METHODS: Volume-overload was induced by carotid-jugular shunt formation. Sham-operated rabbits were used as control. Chronic volume-overload increased left ventricular weight and ventricular cavity size, and relative wall thickness was decreased, indicating eccentric cardiac hypertrophy. (125)I-iodophenyl 9-methylpentadecanoic acid (9MPA) was intravenously administered, and animals were sacrificed at 5 min after injection. The 9MPA was rapidly metabolized to iodophenyl-3-methylnonanoic acid (3MNA) by beta-oxidation. Lipid extraction from the myocardium was performed by the Folch method, and radioactivity distribution of metabolites was assayed by thin-layer chromatography. The protein was extracted from the left ventricular myocardium, and levels of PPARalpha and fatty acid oxidation enzymes were examined by Western blotting. RESULTS: Myocardial distribution of 9MPA tended to be more heterogeneous in shunt than in sham rabbits (P = 0.06). In volume-overloaded hearts by shunt, the conversion from 9MPA to 3MNA by beta-oxidation was faster than the sham-control hearts (P < 0.05). However, protein levels of PPARalpha and fatty acid utilization enzymes were unchanged in shunt rabbits compared with sham rabbits. CONCLUSIONS: These data suggest that myocardial fatty acid metabolism is enhanced in eccentric cardiac hypertrophy by volume-overload without changes in protein expressions of PPARalpha and fatty acid utilization enzymes. Our data may provide a novel insight into the subcellular mechanisms for the pathological process of cardiac remodelling in response to mechanical stimuli.

Animals↗

The genetic relatedness of Porphyromonas gingivalis clinical and laboratory strains assessed by analysis of insertion sequence (IS) element distribution.

OBJECTIVES: Porphyromonas gingivalis is frequently found in periodontitis lesions. This organism contains a large number of insertion sequence (IS) elements. We sought to determine the distribution of seven IS elements from strain W83 among nine P. gingivalis laboratory strains and nine clinical isolates and to use these findings to determine strain relationships. METHODS: Southern blots of BamHI digested genomic DNA digests were probed with insertion sequence elements ISPg1-7. RESULTS: The restriction fragment length polymorphism (RFLP) patterns revealed that five of the nine laboratory strains, including strain W83, were nearly identical for all seven IS elements. Two of nine clinical isolates were similar to the five laboratory strains. Two of the four remaining laboratory strains had similar or identical RFLP patterns. The remaining two laboratory strains had limited similarity to clinical strains. Four of the clinical isolates had identical RFLP patterns for all seven IS elements. The three remaining clinical isolates were unique in their RFLP patterns. Several strains lacked from one to four of the IS elements. Similar strain relationships were suggested regardless of the IS element examined. CONCLUSIONS: Transposition and recombination between IS elements are not sufficiently pervasive to obscure strain relationships, though this does not preclude the possibility that such events play an important role in allowing P. gingivalis to adapt to new environments. Given the level of genetic diversity observed, it may be especially important to examine genetically diverse strains when drawing conclusions based on the W83 P. gingivalis genomic database.

Adaptation, Physiological↗

Angiotensin-converting enzyme inhibition improves cardiac fatty acid metabolism in patients with congestive heart failure.

This study aimed to examine whether angiotensin-converting enzyme (ACE) inhibition improved cardiac fatty acid metabolism in patients with congestive heart failure (CHF). Myocardial 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging was performed in 25 patients with CHF and in 10 control subjects. Myocardial 123I-BMIPP images were obtained 30 min and 4 h after tracer injection. The heart-to-mediastinum (H/M) ratio of 123I-BMIPP uptake and the washout rate of 123I-BMIPP from the myocardium were calculated. Patients were given enalapril for 6 months, and 123I-BMIPP imaging was repeated. H/M ratios on early and delayed images were lower in CHF patients than in normal controls (P<0.01). The washout rate of 123I-BMIPP from the myocardium was faster in CHF patients than in controls (P<0.01). As the severity of the New York Heart Association (NYHA) functional class increased, the H/M ratio decreased and the washout rate increased. The washout rate of 123I-BMIPP was inversely correlated with left ventricular fractional shortening (R=-0.62, P<0.01). ACE inhibition with enalapril increased the H/M ratio on delayed images (P<0.05) and reduced the washout rate of 123I-BMIPP (P<0.05) in CHF patients. These data suggest that: (1) angiotensin II-mediated intracellular signalling activation may be a possible mechanism for the decreased myocardial uptake and enhanced washout of 123I-BMIPP in heart failure patients; and (2) the improvement in fatty acid metabolism by ACE inhibition may represent a new mechanism for the beneficial effect of this therapy in heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

Pulsed Doppler tissue imaging for the assessment of myocardial viability: comparison with 99mTc sestamibi perfusion imaging.

The aim of the present study was to examine whether Doppler tissue imaging demonstrated comparable diagnostic performance for the detection of viable myocardium compared to myocardial perfusion imaging with Tc hexakis-2-methoxyisobutylisonitrile (MIBI). We studied 30 patients with old myocardial infarction who underwent percutaneous transluminal coronary angioplasty (PTCA). Myocardial single photon emission computed tomography (SPECT) with Tc-MIBI and two-dimensional echocardiography were carried out within 7 days before PTCA. We measured regional Tc-MIBI uptake for each myocardial segment from SPECT and peak systolic velocity and a ratio of regional pre-ejection period to regional ejection time (PEP/ET) from pulsed Doppler tissue imaging. Biplane left ventriculography was performed before interventional procedures and repeated 3 months after PTCA. Myocardial viability was determined when wall motion was improved at least one grade after PTCA. The peak systolic velocity was positively correlated with regional Tc-MIBI uptake (R =0.59, P<0.01). The PEP/ET demonstrated inverse correlation with Tc-MIBI uptake ( R=-0.59, P<0.01). Peak systolic velocity of viable segments was higher than that of non-viable segments ( P<0.05). The PEP/ET was lower in viable segments than in non-viable segments ( P<0.05). Peak systolic velocity and PEP/ET demonstrated high diagnostic accuracy for detecting viable myocardium compared with Tc-MIBI perfusion imaging (80% and 79% vs 90%). These data indicate that measurements of regional peak systolic velocity and PEP/ET by Doppler tissue imaging are useful for evaluating myocardial viability quantitatively and provide helpful information for a clinical judgment in an interventional strategy.

Adult↗

[Results of questionnaire on open disclosure to patients with malignant lung tumors comparison of responses before and after chemotherapy].

To investigate patient attitudes towards open disclosure of malignant disease, we conducted a questionnaire survey of 17 patients with malignant lung tumors, to whom the nature of their disease was revealed. The questionnaire used a 100 mm analog scale. Ten of the patients were treated by chemotherapy and their questionnaire results before and after treatment were compared. It was found that they were mostly satisfied about being truthfully informed and that, indeed, they were anxious to know their true diagnoses. They were also keen to have their true prognosis revealed, but not as much as the diagnosis. They also wished to be informed about treatment and its effects. These attitudes showed no marked changes resulting from the administration of chemotherapy, and we therefore concluded that chemotherapy itself had no influence on patients' feelings about disclosure. The questionnaire was well accepted and was useful in judging attitudes to open disclosure.

Female↗

[Ganglioneuroma detected in a patient over age 60].

We report a case of ganglioneuroma in a 67-year-old woman who presented with an abnormal shadow at a medical examination. She was admitted and chest radiography disclosed a mass in the upper right mediastinum. We suspected a mediastinal tumor after chest CT, chest MRI and bronchofiberscopic examination, and so surgical treatment was performed. The histopathological diagnosis was ganglioneuroma. Ganglioneuroma is thought of as a children's disease and adult onset is rare. We reasoned that ganglioneuroma should be included among the mediastinal tumors in patients over 60.

Aged↗

Light intensity distribution in the externally illuminated cylindrical photo-bioreactor and its application to hydrogen production by Rhodobacter capsulatus.

The light distribution in the externally illuminated cylindrical photo-bioreactor for production of hydrogen by a photosynthetic bacterium Rhodobacter capsulatus ST-410 was estimated. The estimation was performed on the basis of the Matsuura and Smith's diffuse model [1]. In the diffuse model, the incident light rays are assumed to proceed in every direction and the local intensity is calculated as the sum of the intensities of light. Since Lambert-Beer's law, extensively used in photometry, was not useful for explaining the decrease in the intensity of light by the biomass, an empirical expression was used. The measurement of the intensities from every direction was conducted in an externally illuminated cylindrical photo-bioreactor having an inner diameter of 60mm and a working volume of 550ml. The obtained results confirmed our estimation. The light distribution was applied to estimate the hydrogen production by R. capsulatus ST-410 using the same photo-bioreactor. The overall hydrogen-production rate was successfully estimated.

Journal Article↗

Gq protein level increases concurrently with antigen-induced airway hyperresponsiveness in rats.

In the present study, bronchial Gq protein level of the airway hyperresponsive rats was determined by using immunoblot analysis. In the airway hyperresponsive rats that were sensitized and repeatedly antigen challenged, the in vitro bronchial responsiveness to acetylcholine was significantly enhanced as compared with that in the sensitized control group. Moreover, the bronchial contraction induced by 10 microM AlF(4)(-) (generated by 10 microM AlCl(3) plus 10 mM NaF) was significantly elevated after repeated antigen challenge (0.44+/-0.13 and 1.09+/-0.09 g tension in the control and airway hyperresponsive groups, respectively; P<0.01). In both groups, immunoblotting with the antibody against G alpha q gave a single 42 kD band. The G alpha q protein levels in the airway hyperresponsive group (0.58+/-0.12) estimated by G alpha q/beta-actin ratio was significantly greater than those in the control group (0.30+/-0.10; P<0.05). These findings suggest that the increase in G alpha q protein level may be involved in the pathogenesis of antigen-induced airway hyperresponsiveness in rats.

Animals↗

Ipsilateral irradiation for carcinomas of tonsillar region and soft palate based on computed tomographic simulation.

PURPOSE: To reduce xerostomia in selected patients with carcinomas of the tonsillar region and soft palate. METHODS AND MATERIALS: We evaluated the treatment results of 32 patients with tonsillar region and soft palate carcinoma treated by radical radiotherapy between May 1989 and December 1996. They have a unilateral tumor that did not cross midline and have no contralateral neck lymphnode metastasis and treated with an ipsilateral technique (an anterior oblique and a posterior oblique field). All patients were planned with computed tomographic (CT) simulation and given 65 Gy in 26 fractions in 6.5 weeks with or without 5-15 Gy boost irradiation. The median follow-up was 44 months (4-86 months). RESULTS: Five-year overall, cause-specific survival, local control, and regional control rate was 64, 79, 74 and 81%. No failure at the contralateral neck occurred. Moderate or severe symptomatic xerostomia was seen in 3 (9%) patients and ostero-radionecrosis requiring surgery occurred in one (3.3%) of 32 patients. CONCLUSION: It is suggested that the ipsilateral technique is indicated in patients who had an unilateral tonsillar region or soft palate carcinoma that did not cross midline and have no contralateral neck lymphnode metastasis.

Adult↗

Effect of the natural antioxidant 2"-O-glycosylisovitexin on superoxide and hydroxyl radical generation.

The inhibitory effect of 2"-O-glycosyl isovitexin (2"-O-GIV) isolated from green barley leaves on superoxide and hydroxyl radical generation was investigated using electron spin resonance spectroscopy. 2"-O-GIV exhibited dose-related inhibitory activity both towards superoxide generation and hydroxyl radical generation. 2"-O-GIV inhibited superoxide formation by 97% at a level of 25 mM and inhibited hydroxyl radical formation by 91% at a level of 500 microM. The results suggest that the inhibitory activity of 2"-O-GIV is due to trapping radicals.

Antioxidants↗

Intraoperative radiation therapy to the upper mediastinum and nerve-sparing three-field lymphadenectomy followed by external beam radiotherapy for patients with thoracic esophageal carcinoma.

BACKGROUND: In patients with thoracic esophageal carcinoma, radical dissection of the upper mediastinal lymph nodes often leads to complications such as recurrent laryngeal nerve palsy and subsequent pulmonary disorders. Intraoperative radiation therapy (IORT) to the upper mediastinum and nerve-sparing three-field lymphadenectomy followed by external beam radiotherapy has been developed to improve the locoregional control rate without resulting in these major postoperative complications. METHODS: Three-field lymphadenectomy, including cervical, mediastinal, and abdominal lymph node dissection, was performed. Dissection of the upper mediastinum was conservative to preserve recurrent laryngeal nerve function. IORT of 12-25 grays (Gy) was applied to the upper mediastinum. Postoperative radiation therapy (PORT) of 45 Gy in 16 fractions over 4 weeks was applied to the entire neck and upper mediastinum using an external X-ray beam. Between 1989-1996, 121 patients with thoracic esophageal carcinoma underwent surgery and received IORT, and 103 of these patients underwent PORT as part of their treatment schedule. RESULTS: The surgical mortality rate was 0.8% (1 of 121 cases). The overall 5-year survival rate was 34.4% and the cause specific 5-year survival rate was 54.8%. The cause specific 5-year survival rate for pN0 tumors was 79.4% and was 43.8% for pN1 tumors. No patients died with locoregional recurrence in the mediastinal lymph nodes. Recurrent laryngeal nerve palsy was observed in 25 patients (21%), but the palsy remained for > 1 month in only 13 patients (11%). Mechanical ventilation support for > 48 hours was required for 22 patients (18.2%). Fatal tracheal ulcers occurred in 4 of 18 patients who received the highest IORT dose of 25 Gy. CONCLUSIONS: Three-field lymphadenectomy to preserve recurrent laryngeal nerves and IORT using 12-20 Gy followed by 45-Gy PORT effectively reduced locoregional recurrence, recurrent laryngeal nerve palsy, and pulmonary complications caused by radical surgical dissections. The minimally effective dose of IORT appears to be < or = 15 Gy, a factor that will be further evaluated with longer follow-up.

Adult↗

A phase II study of concomitant chemoradiotherapy for laryngeal carcinoma using carboplatin.

PURPOSE: We conducted a phase II study of concomitant chemoradiotherapy with carboplatin for laryngeal carcinoma. MATERIALS AND METHODS: Sixty-four patients with stage II-IV (stage II, 36; III, 19; IV 9) laryngeal carcinoma were treated with concomitant administration of carboplatin (CBDCA) during radiotherapy (CRT group) between 1991 and 1994. There were 36 supraglottic, 25 glottic, and 3 subglottic carcinomas. Patients with stage II and stage III-IV received intravenous CBDCA of 100 mg/m2 and 120 mg/m2 once a week, respectively. Tumor response was assessed at 40 Gy in 16 fractions to select the patients suitable for total laryngectomy or radical radiotherapy of 65 Gy in 26 fractions in 6.5 weeks. The treatment results were compared with the historical control consisting of 56 patients consecutively treated from 1988 to 1990 without chemotherapy (RT group). The two studies were comparable with regard to patient characteristics, including age distribution, gender, tumor location, size, and clinical stage. RESULTS: The actuarial 5-year survival rate was 80.3% for the CRT group and 81.3% for the RT group. A favorable response (complete response or partial response) at 40 Gy was observed in 87.5% of the patients of the CRT group and in 62.5% of the patients of the RT group (chi2 = 7.566, p < 0.01). The actuarial 5-year larynx preservation rate for the CRT group (75%) was significantly higher than that for the RT group (57%) in patients with T2 supraglottic carcinoma (p < 0.05). There was no difference in the larynx preservation rate between the two treatment arms for any T stage of glottic carcinomas. CONCLUSION: CRT using carboplatin improved the tumor response at 40 Gy and consequently achieved a higher larynx preservation rate for T2 supraglottic carcinoma. A clinical randomized trial is indicated to certify the findings of this phase II study.

Antineoplastic Agents↗

Generation of reactive oxygen species and 8-hydroxy-2'-deoxyguanosine formation from diesel exhaust particle components in L1210 cells.

The generation of the reactive oxygen species during the interaction of diesel exhaust particles (DEP) with NADPH-cytochrome P450 reductase (P450 reductase) was investigated by electron spin resonance using the spin-trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO). Addition of DEP extract to an incubation mixture of mouse lung microsomes in the presence of NADPH resulted in a time-dependent NADPH oxidation and acetylated-cytochrome c reduction. Using purified P450 reductase as the enzyme source, superoxide radicals which were detected as the spin adduct (DMPO-OOH) while metabolized by P450 reductase were dependent upon both DEP and enzyme concentrations. The ELISA method using a specific monoclonal antibody revealed that DEP produced 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is formed from deoxyguanosine in DNA by hydroxyl radicals, in the culture medium of L1210 cells. Active oxygen scavengers such as superoxide dismutase and catalase effectively blocked the formation of 8-OHdG in culture medium, and deferoxamine, which inhibits hydroxyl radicals production by chelating iron, was also effective in inhibiting the DEP-produced 8-OHdG formation. These results indicate that DEP components produce 8-OHdG through the hydroxyl radical formation via superoxide by redox cycling of P450 reductase.

8-Hydroxy-2'-Deoxyguanosine↗

[Lung cancer detected in a patient under age 40 treated for pneumothorax].

We report a case of lung cancer in a relatively young patient who presented pneumothorax. A 31-year-old man complaining of pressure in his left chest was admitted with left pneumothorax disclosed on X-ray film. Although pleural drainage was performed for a week, the left lung did not expand well, and surgical treatment was required. During surgery, a tumor (1.5 x 1.0 cm in size) was discovered in the upper lobe of the left lung (S3). Histopathological examination revealed that it was a large cell carcinoma. People under the age of 40 account for only a small fraction of the entire lung cancer patient population. Pneumothorax occurs together with lung cancer, especially in people under age 40. We reasoned that lung cancer should be considered a possible complication in patients under 40 who experience recurrent or prolonged bouts of pneumothorax.

Adult↗