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T Ohta

Publications and source records attributed to T Ohta.

At least 127 records · Page 7Linked to original sources
PubMed2001

Strong induction of phytochelatin synthesis by zinc in marine green alga, Dunaliella tertiolecta.

Synthesis of phytochelatins (PCs), heavy-metal-sequestering peptides, in the marine green alga, Dunaliella tertiolecta, was evaluated under various conditions of exposure to heavy metals. To investigate the effect of heavy metals on both PC synthesis and their upstream biosynthetic reactions, an ion-pair-HPLC system was developed in this study, by which PCs and their biosynthetic intermediates, cysteine (Cys), gamma-glutamylcysteine (gammaEC) and glutathione (GSH), could be determined simultaneously with high sensitivity. When the cells were exposed to Zn2+, the level of PCs was maximal at 200 microM and significantly higher than that obtained after exposure to 400 microM Cd2+, which is the strongest inducer of PC synthesis in higher plants in vivo and in vitro as well as in microalgae. The predominant PC subtype was PC4, followed by PC3 and PC5, whereas PC2, which is generally abundant in higher plants, has the lowest level among PC2 to PC5. These results suggest that the characteristics of PC synthase in D. tertiolecta including the requirement of heavy metals for its catalysis and substrate specificity towards GSH and PC(n) are considerably different from those in higher plants and other algae. While PC synthesis proceeded in the heavy-metal-treated cells, the level of GSH did not appreciably change. To maintain the same size of the GSH pool, GSH must be newly synthesized to balance the amount consumed for PC synthesis.

Journal Article↗
PubMed2001

Release of dopamine and ATP from PC12 cells treated with dexamethasone, reserpine and bafilomycin A1.

The amounts and time courses of dopamine and ATP released from perfused PC12 cells were examined using a simultaneous on-line recording system. High KCl (60 mM) caused dopamine and ATP release with similar time courses. The relative amount of dopamine to ATP in the effluent was 9.5. In PC12 cells cultured with dexamethasone, reserpine or bafilomycin A1 for 2 days, these drugs did not affect increases of intracellular Ca2+ in response to high KCl. Dexamethasone doubled the amount of dopamine release induced by high KCl without changing the amount of ATP release. High KCl failed to cause dopamine release in reserpine-treated cells but evoked ATP release. Bafilomycin A1 decreased both high KCl-induced dopamine and ATP release. The ratio of released ATP to total adenine nucleotides and adenosine in response to high KCl was not changed by treatment with the drugs. These results suggest that dopamine and ATP are simultaneously released from secretory vesicles of PC12 cells, in which they are stored via different pathways. Similar to dopamine uptake into secretory vesicles, the H+-gradient across the vesicular membrane developed by vacuolar ATPase may play an important role in the vesicular uptake of ATP.

Adenosine Triphosphate↗
PubMed2001

Low-intensity pulsed ultrasound accelerates rat femoral fracture healing by acting on the various cellular reactions in the fracture callus.

Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate fracture healing in both animal models and clinical trials, but the mechanism of action remains unclear. In fracture healing, various consecutive cellular reactions occurred until repair. We investigated whether the advanced effects of LIPUS depended on the duration and timing of LIPUS treatment in a rat closed femoral fracture model to determine the target of LIPUS in the healing process. Sixty-nine Long-Evans male rats that have bilateral closed femoral fractures were used. The right femur was exposed to LIPUS (30 mW/cm2 spatial and temporal average [SATA], for 20 minutes/day), and the left femur was used as a control. Rats were divided into four groups according to timing and duration of treatment (Ph-1, days 1-8; Ph-2, days 9-16; Ph-3, days 17-24; throughout [T], days 1-24 after the fracture). Animals were killed on day 25. After radiographs and microfocus X-ray computed tomography (muCT) tomograms were taken, the hard callus area (HCA), bone mineral content (BMC) at the fracture site, and mechanical torsion properties were measured, and histological analysis was conducted. Interestingly, the maximum torque of the LIPUS-treated femur was significantly greater than that of the controls in all groups without any changes in HCA and BMC. The multiviewing of three-dimensional (3D) muCT reconstructions and histology supported our findings that the partial LIPUS treatment time was able to accelerate healing, but longer treatment was more effective. These results suggest that LIPUS acts on some cellular reactions involved in each phase of the healing process such as inflammatory reaction, angiogenesis, chondrogenesis, intramembranous ossification, endochondral ossification, and bone remodeling.

Animals↗
PubMed2001

Targeted disruption of cadherin-11 leads to a reduction in bone density in calvaria and long bone metaphyses.

The migration and adhesion of osteoblasts requires several classical cadherins. Cadherin-11, one of the classical cadherins, was expressed in mouse osteoblasts in skull bone and femur, revealed by immunohistochemistry. To elucidate the function of cadherin-11 in osteoblastogenesis, cadherin-11 null mutant mice were investigated. Although apparently normal at birth, Alizarin red staining of null mutant mice showed a reduced calcified area at the frontal suture that caused a round-shaped calvaria with increasing animal age to 3 months. Consequently, there was a reduction in bone density at the femoral metaphyses and the diploë of calvaria in null mutant mice. In the in vitro culture of newborn calvarial cells, the calcified area of mutant cells was smaller than those derived from wild-type littermates. These results show that absence of cadherin-11 leads to reduced bone density in some parts of skeletons including calvaria and long bone metaphyses, and thus suggest that cadherin-11 plays roles in the regulation of osteoblast differentiation and in the mineralization of the osteoid matrix.

Animals↗
PubMed2001

Human pancreatic cancer cells disable function of Fas receptors at several levels in Fas signal transduction pathway.

The aims of this study were to evaluate the functional expression of Fas receptors (Fas) in human pancreatic cancer cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2 and to search for the mechanisms of receptor-mediated inhibition of Fas signaling in these cells. Despite the expression of Fas receptors at considerable levels, exposure of these cells to agonistic Fas antibodies (500 ng/ml) induced only minimal apoptosis in 4 cell lines. The mechanisms allowing resistance to Fas-mediated apoptosis are complex. Using RT-PCR, we identified molecules which might counteract the apoptogenic signal at several levels of Fas signal transduction pathway. The most striking findings were the overexpression of Fas decoy receptors (DcR3), Fas associated phosphatase-1 (FAP-1), and FLICE-inhibitory protein (c-FLIP) in the resistant cell lines as well as in pancreatic cancer surgical specimens. In conclusion, pancreatic cancer cells express three molecules that can abrogate Fas function at different levels of Fas signaling cascade, resulting in resistance to Fas-mediated apoptosis, and this may promote the progression of this malignancy.

Adenocarcinoma↗
PubMed2001

Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma.

S100A4 has been implicated in invasion and metastasis of cancer, but prognostic significance of its expression in esophageal squamous cell carcinoma remains unclear. In this study, we examined the expression of S100A4 by Western blot analysis and immunohistochemistry in surgically resected esophageal squamous cell carcinoma. The relationship between S100A4 tissue status and clinicopathological findings was analyzed to assess the prognostic significance of S100A4 in esophageal squamous cell carcinoma. The S100A4 protein level was significantly higher in tumor tissue than in corresponding normal esophageal mucosa (p<0.05) in 22 cases of esophageal carcinoma by Western blot analysis. S100A4 expression was detected in 25% of 52 cases of esophageal squamous cell carcinoma by immunohistochemistry and correlated with the depth of invasion (p<0.05). Patients with S100A4-positive carcinoma had significantly poorer prognosis than those with S100A4-negative carcinoma, which was also true in the cases with deep invasion of the primary cancer (T3, T4) (p<0.01 and p<0.05, respectively). Moreover, S100A4 tissue status remained the only independent prognostic parameter in the multivariate analysis. Our results suggest that S100A4 may play a key role in the progression of esophageal carcinoma and that immunohistochemical detection of S100A4 in the primary tumor may be useful for the prediction of a poor prognosis.

Adult↗
PubMed2001

Human pancreatic cancer cells express non-functional Fas receptors and counterattack lymphocytes by expressing Fas ligand; a potential mechanism for immune escape.

The aim of this study was to investigate the expression and functional status of Fas ligand (FasL) and its receptor (Fas) in human pancreatic cancers. Using RT-PCR and Western blotting, Fas and FasL were expressed in seven surgically resected pancreatic cancer specimens and five cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. In the resected specimens, pancreatic cancer cells induced apoptosis in the surrounding lymphoid cells. In coculture experiments of pancreatic cancer and Jurkat T cells, 50% of Jurkat T cells underwent apoptosis after 2 days, however, almost all pancreatic cancer cells remained viable. In addition, by testing Fas function using anti-Fas antibody (CH11), all cell lines were resistant to Fas-mediated apoptosis except Capan-1 cells which showed sensitivity similar to that of Jurkat T cells. These results suggest that pancreatic cancer cells evade immune surveillance by expression of FasL and non-functioning Fas that allow them to activated T-cells. These tumor escape mechanisms may contribute to the rapid fatal course of pancreatic cancer.

Apoptosis↗
PubMed2001

[Indications for and operative outcome of hepatopancreatoduodenectomy in the treatment of gallbladder carcinoma].

Hepatopacreatoduodenectomy (HPD) was initially performed to resect highly advanced gallbladder carcinoma with direct invasion of the liver and head of the pancreas. High operative morbidity and mortality rates and early recurrence were major problems of this procedure. However, the operative outcome gradually improved with progress in surgical procedures and perioperative management. Recently, HPD has been indicated not only for direct invasion of the liver and pancreas but also for intensive dissection of peripancreatic lymph nodes and resection of occult liver metastasis to subsegments IV and V. Evaluation of all cases in which HPD was performed in our institute suggests that advanced gallbladder carcinoma with lymph node metastasis and without high-grade infiltration of the hepatoduodenal ligament (binf) is the most suitable indication for HPD.

Gallbladder Neoplasms↗
PubMed2001

Drop in plasma brain natriuretic peptide levels after successful direct current cardioversion in chronic atrial fibrillation.

BACKGROUND: According to previous reports, plasma atrial natriuretic peptide levels increase in atrial fibrillation (AF) and decrease after successful direct current (DC) cardioversion, but there have been no reports on plasma brain natriuretic peptide (BNP). OBJECTIVE: To determine whether plasma BNP levels decrease after successful direct DC cardioversion in patients with chronic AF. PATIENTS AND METHODS: Twenty patients who remained in sinus rhythm for at least seven days after cardioversion, and 20 normal control subjects, were studied. Group A consisted of 10 patients with underlying heart disease, including dilated cardiomyopathy (n=2), hypertrophic cardiomyopathy (n=1), mitral valve disease (n=3), hypertensive heart disease (n=3) and status after atrial septal closure (n=1). Group B consisted of 10 patients with just AF. Group C (serving as controls) comprised 20 subjects with normal sinus rhythm and no risk factors. RESULTS: Before cardioversion, plasma BNP levels were higher in group A (176.7+/-128.1 ng/mL) and in group B (96.8+/-51.7 ng/ml) than in group C (6.3+/-3.8 ng/ml) (P<0.01 for all). After successful cardioversion, mean plasma BNP levels in groups A and B decreased from 136.8+/-105.5 ng/mL to 46.4+/-44.2 ng/mL (P<0.01). In group A, plasma BNP levels decreased from 176.7+/-128.1 ng/mL to 62.5+/-54.6 ng/mL (P<0.01), and in group B, plasma BNP levels decreased from 96.8+/-51.7 ng/mL to 30.3+/-23.8 ng/mL (P<0.01). CONCLUSIONS: Lone AF raises plasma BNP levels, which is more marked if there is underlying structural heart disease present, and cardioversion reduces plasma BNP levels. Therefore, high plasma BNP levels in patients with chronic AF are likely to be caused by AF and reflect cardiac overloading associated with, although contributed to in part by, underlying heart diseases.

Adult↗
PubMed2001

A novel enhancer of insulinotrophic action by high glucose (JTT-608) stimulates insulin secretion from pancreatic beta-cells via a new cellular mechanism.

Insulin secretion from MIN6 cells (a pancreatic beta-cell line) induced by high glucose (greater than 16.8 mM) was potentiated by a novel hypoglycemic agent [trans-4-(4-methylcyclohexyl)-4-oxobutyric acid (JTT-608)] (but not glibenclamide, a sulfonylurea). The extracellular Ca(2+)-free condition, a L-type Ca(2+) channel blocker (nifedipine) and an ATP-sensitive K(+) channel opener, diazoxide, completely inhibited increases in cytosolic free Ca(2+) ([Ca(2+)]i) and insulin secretion evoked by JTT-608 in the presence of extracellular Ca(2+). An electrophysiological study using single-barreled microelectrode techniques demonstrated that membrane potential (V(m)) and input resistance of the cell membrane (R(i)) are depolarized and increased by JTT-608, respectively. The apparent transference number for K(+) was also significantly decreased after the addition of JTT-608. These effects immediately occurred after addition of JTT-608 and very rapidly disappeared after removal of JTT-608, which has not been observed in sulfonylureas. Also, these effects of JTT-608 were diminished, but not completely by diazoxide. JTT-608 did not affect the specific binding of [(3)H]glibenclamide to the sulfonylurea receptor. These findings suggest that JTT-608 mainly inhibits ATP-sensitive K(+) channel activity via a binding site distinct from the sulfonylurea receptor and then depolarizes V(m) to open voltage-dependent L-type Ca(2+) channels. Subsequently, these events stimulate Ca(2+) entry to increase [Ca(2+)]i and induce insulin secretion from MIN6 cells. Therefore, JTT-608 is a unique hypoglycemic agent that enhances high glucose-induced insulin secretion. The present findings indicate that JTT-608 is a more useful new class of therapeutic drug for patients with non-insulin-dependent diabetes mellitus, compared with sulfonylurea derivatives.

ATP-Binding Cassette Transporters↗
PubMed2001

[Development and evaluation of a QOL questionnaire for elderly subject living in a community].

A comprehensive, basic and simple QOL questionnaire for elderly subjects living in a community was developed, and its validity and reliability were examined. The subjects were 2944 individuals of 65 years or older living in 5 areas of metropolitan Tokyo and in a town of Aichi Prefecture. The QOL questionnaire with 19 questions was developed based on the component of QOL by Lawton and concept of QOL by Koyano. The questionnaire consisted of 6 subscales (daily activity, satisfaction with health, satisfaction with human support, satisfaction with economic state, symptom of depression and positive mental attitude). Factor analysis revealed that the 19 questions could be clearly separated into 6 components in Tokyo and Aichi districts with total variances of 70.8% and 78.4%, respectively. Scores of daily activity and positive mental attitude were significantly lower with older subjects in both men and women. However, scores for other subscales did not differ with age. Primary factors which are considered to affect QOL were compared with the 6 QOL subscales of this study. Being an outpatient had a significant relation to daily activity and satisfaction with health, presence of a spouse to satisfaction with human support, depressive state, positive mental attitude and possession of ones own room to satisfaction with economical state, and belief in religion to positive mental attitude. The results suggest that the present questionnaire include the basic components necessary for evaluation of QOL in elderly subjects living in a community. Further research is required to examine the validity of this questionnaire with correction of questions.

Aged↗
PubMed2001

[Clinical laboratory data and reference intervals standardized in Fukuoka].

In Fukuoka whose population is approximately five million inhabitants, surveys on the accuracy of laboratory data have been performed by the Fukuoka Prefecture Medical Association for the last 30 years. We have been attempting to evaluate the data for routine use since 1988, and it has become possible to share laboratory data between all institutions in Fukuoka prefectures. As a result, reference intervals for 23 clinical chemistry analytes were established in 1995, to which were added in 1996 five serum protein constituents that have been utilized for clinical examinations. Methods for documentations and monitorings the data obtained in the prefecture were also established, standardization of the above analytes extended to 97% of the institutions in the prefecture. Results for 14 of the 23 clinical chemistry analytes have become highly reliable and clinically useful as differences between institutions in terms of results have narrowed. Standardization of other analytes is now in progress.

Aged↗
PubMed2001

Comparison of cardiac sympathetic nervous function with left ventricular function and perfusion in cardiomyopathies by (123)I-MIBG SPECT and (99m)Tc-tetrofosmin electrocardiographically gated SPECT.

UNLABELLED: The objective of this study was to clarify the relationship between cardiac sympathetic nervous function (CSNF) and left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-eight cases (32 males, 6 females; mean age, 56 +/- 15 y), consisting of 5 healthy control subjects, 15 patients with DCM, and 18 patients with HCM, were studied with (123)I-metaiodobenzylguanidine (MIBG) and (99m)Tc-tetrofosmin SPECT. CSNF was evaluated from cardiac uptake and washout of MIBG, whereas LV perfusion and function were evaluated from tetrofosmin uptake and wall thickening on electrocardiographically gated SPECT. As quantitative parameters of global cardiac MIBG uptake and washout, the heart-to-mediastinum ratio (H/M) and percentage washout were calculated from early and delayed planar images. As quantitative regional parameters, the regional uptake and percentage washout of MIBG were calculated from SPECT images dividing the left ventricle into 12 segments. In the tetrofosmin study, the H/M and LV ejection fraction were calculated as the parameters of global LV perfusion and function. As quantitative regional parameters, the regional uptake and wall thickening were also calculated for the 12 myocardial segments using the quantitative gated SPECT software. Multiple linear regression analysis was performed to investigate the correlations between the parameters from the 2 studies. RESULTS: In DCM and HCM, multiple linear regression analysis of the regional parameters showed significant correlations between LV function and CSNF (P < 0.0001) and between LV perfusion and CSNF (P < 0.0001). According to the partial correlation coefficients, washout and early uptake of MIBG were the most significant factors for predicting LV function and LV perfusion, respectively. CONCLUSION: In cardiomyopathies, CSNF was closely related to LV function. The quantitative parameters of MIBG washout could reflect cardiac functional impairment. Early MIBG uptake might be determined by myocardial perfusion in cardiomyopathies.

3-Iodobenzylguanidine↗
PubMed2001

[A case report of rectal cancer with liver and pulmonary metastases responding to TS-1].

TS-1 is an oral anticancer drug that produces biochemical modulation. TS-1 is composed of FT (tegafur), CDHP (gimestat), and Oxo (ostat potassium), in a molar ratio of 1:0.4:1. We administered TS-1 to a patient with liver and pulmonary metastasis of rectal cancer (phase II study). Each treatment course consisted of a four-week administration followed by two drug-free weeks. The daily dose was 120-150 mg/day. Before the administration, hepatic metastasis was 30 x 20 mm. After 2 courses, it was reduced to 20 x 15 mm (reduction rate: 50%). Three pulmonary metastases that were recognized in chest radiographs before the administration tended to reduction after 3 courses. The reduction rate after 4 courses was 42.5%. The reduction was judged PR for the hepatic metastasis and MR for pulmonary metastases. There was no side effect and hospitalization was not required during the treatment. Thus, the administration of TS-1 enhanced the quality of life of this patient.

Adenocarcinoma↗
PubMed2001

[Chemotherapy (low-dose CDDP + UFT) to advanced pancreatic cancer in an ambulatory setting improved survival and quality of life].

The prognosis of pancreatic cancer is very poor. Past attempts to treat advanced pancreatic cancer with single agent or combination chemotherapy have yielded low response rates and little reproducible impact on patient survival or quality of life. We performed systemic chemotherapy in case of unresectable or recurrent pancreatic cancer with CDDP 25 mg/body intravenous weekly or biweekly and oral administration of UFT (300-400 mg/day) as an outpatient treatment. Tumor markers were well controlled for about over one year or more. This ambulatory combination is a well-tolerated regimen that results in improved survival and quality of life.

Ambulatory Care↗
PubMed2000

Evolution of gene families.

In eukaryote genomes, there are many kinds of gene families. Gene duplication and conversion are sources of the evolution of gene families, including those with uniform members and those with diverse functions. Population genetics theory on identity coefficients among gene members of a gene family shows that the balance between diversification by mutation, and homogenization by unequal crossing over and gene conversion, is important. Also, evolution of new functions is due to gene duplication followed by differentiation. Positive selection is necessary for the evolution of novel functions. However, many examples of current gene families suggest that both drift and selection are at work on their evolution.

Animals↗