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Biomedical subjects

S Takeda

Publications and source records attributed to S Takeda.

At least 199 records · Page 11Linked to original sources
PubMed1999

Sister chromatid exchanges are mediated by homologous recombination in vertebrate cells.

Sister chromatid exchange (SCE) frequency is a commonly used index of chromosomal stability in response to environmental or genetic mutagens. However, the mechanism generating cytologically detectable SCEs and, therefore, their prognostic value for chromosomal stability in mitotic cells remain unclear. We examined the role of the highly conserved homologous recombination (HR) pathway in SCE by measuring SCE levels in HR-defective vertebrate cells. Spontaneous and mitomycin C-induced SCE levels were significantly reduced for chicken DT40 B cells lacking the key HR genes RAD51 and RAD54 but not for nonhomologous DNA end-joining (NHEJ)-defective KU70(-/-) cells. As measured by targeted integration efficiency, reconstitution of HR activity by expression of a human RAD51 transgene restored SCE levels to normal, confirming that HR is the mechanism responsible for SCE. Our findings show that HR uses the nascent sister chromatid to repair potentially lethal DNA lesions accompanying replication, which might explain the lethality or tumorigenic potential associated with defects in HR or HR-associated proteins.

Animals↗
PubMed1999

The relation between transaortic pressure difference and flow during dobutamine stress echocardiography in patients with aortic stenosis.

OBJECTIVE: To investigate the relation between transaortic pressure difference and flow in patients with aortic stenosis. METHODS: 50 asymptomatic patients with all grades of aortic stenosis were studied using dobutamine stress echocardiography. Individual plots of mean pressure drop against flow were drawn. Comparisons were made between grades of aortic stenosis as defined by the continuity equation. RESULTS: A significant linear relation between pressure difference and flow was found in 34 patients (68%). There was a significant curvilinear relation in four (8%), while no significant regression line could be fitted in 12 (24%). In the 34 patients with linear fits, the slopes (mean (SD)) were 0.08 (0.07) in mild, 0.10 (0.04) in moderate, and 0.22 (0.16) in severe aortic stenosis (p = 0. 0055). CONCLUSIONS: Transaortic pressure difference can be related directly to flow in many patients with all grades of aortic stenosis. However, there are individual differences in slope and intercept suggesting that resistance calculated at rest may not always be representative. Raw pressure drop/flow plots may be an alternative method of describing valve function.

Adult↗
PubMed1999

Alterations in sarcoplasmic reticulum function and gene expression in ischemic-reperfused rat heart.

In view of the critical role of sarcoplasmic reticular (SR) Ca(2+) release and the Ca(2+) pump in cardiac contraction-relaxation, this study was undertaken to assess the status of SR function, protein content, and gene expression in isolated rat hearts subjected to global ischemia for 30 min followed by 60 min of reperfusion (I/R). Attenuated recovery of contractile function in the I/R hearts was associated with reduced SR Ca(2+) uptake, Ca(2+) release, and ryanodine-binding activities. mRNA levels and protein contents for SR Ca(2+) pump ATPase and Ca(2+) release channels were markedly depressed in the I/R hearts. Perfusion of hearts with superoxide dismutase plus catalase, well-known scavengers of oxyradicals, prevented the I/R-induced alterations in cardiac function and partially prevented SR Ca(2+) transport activities and mRNA abundance. In hearts perfused with xanthine plus xanthine oxidase or H(2)O(2), changes similar to those in the I/R hearts were observed. These results indicate that oxyradicals may participate in depressing the SR Ca(2+) handling and gene expression in the I/R heart. It is suggested that treatment of hearts with antioxidants may improve the recovery of cardiac function by preserving the SR function and partially protecting the SR gene expression.

Animals↗
PubMed1999

Compensatory alveolar growth normalizes gas-exchange function in immature dogs after pneumonectomy.

To determine the extent and sources of adaptive response in gas-exchange to major lung resection during somatic maturation, immature male foxhounds underwent right pneumonectomy (R-Pnx, n = 5) or right thoracotomy without pneumonectomy (Sham, n = 6) at 2 mo of age. One year after surgery, exercise capacity and pulmonary gas-exchange were determined during treadmill exercise. Lung diffusing capacity (DL) and cardiac output were measured by a rebreathing technique. In animals after R-Pnx, maximal O2 uptake, lung volume, arterial blood gases, and DL during exercise were completely normal. Postmortem morphometric analysis 18 mo after R-Pnx (n = 3) showed a vigorous compensatory increase in alveolar septal tissue volume involving all cellular compartments of the septum compared with the control lung; as a result, alveolar-capillary surface areas and DL estimated by morphometry were restored to normal. In both groups, estimates of DL by the morphometric method agreed closely with estimates obtained by the physiological method during peak exercise. These data show that extensive lung resection in immature dogs stimulates a vigorous compensatory growth of alveolar tissue in excess of maturational lung growth, resulting in complete normalization of aerobic capacity and gas-exchange function at maturity.

Animals↗
PubMed1999

Mechanisms of Hydrogen Peroxide-Induced Increase in Intracellular Calcium in Cardiomyocytes.

BACKGROUND: Hydrogen peroxide (H(2)O(2)) in high concentrations has been implicated in heart dysfunction attributable to ischemia-reperfusion. Although H(2)O(2) is also known to increase the intracellular concentration of Ca(2+) ([Ca(2+)](i)) in cardiomyocytes, the mechanisms for such a change are not clear. In this study, the sources and mechanisms of increase in [Ca(2+)](i) caused by high concentrations of H(2)O(2) in cardiomyocytes were explored. METHODS AND RESULTS: Cardiomyocytes were isolated from adult male Sprague-Dawley rats. Cell viability was examined by trypan blue exclusion test. [Ca(2+)](i) was measured by employing cell suspension at room temperature and Fura-2 fluorescence technique. Incubation of cells with 0.25-l mmol/L H(2)O(2) increased [Ca(2+)](i) in a time- and concentration-dependent manner. Catalase attenuated the H(2)O(2)-induced increase in [Ca(2+)](i) significantly, whereas mannitol showed no effect. Neither the presence of verapamil, a sarcolemmal Ca(2+) channel blocker, nor the removal of Ca(2+) from the medium produced any significant reduction in the H(2)O(2)-induced increase in [Ca(2+)](i). Conversely, treatment of cardiomyoctes with staurosporin, a protein kinase C inhibitor, thapsigargin, a sarcoplasmic reticulum Ca(2+)-pump adenosine triphosphatase inhibitor, as well as ryanodine, a sarcoplasmic reticulum Ca(2+)-release channel blocker, markedly prevented the 0.5-mmol/L H(2)O(2)-induced increase in [Ca(2+)](i). The responses of cardiomyoctes to H(2)O(2) and other Ca(2+)-mobilizing agents, such as KCl or adenosine triphosphate, were additive. No changes in cardiomyocyte viability were seen on incubation with 0.5 and 1 mmol/L H(2)O(2). Perfusion of the isolated heart with H(2)O(2) (0.1-0.5 mmol/L) depressed the left ventricular developed pressure, rate of contraction, and rate of relaxation, whereas the left ventricular end-diastolic pressure was increased. CONCLUSIONS: These results indicate that formation of H(2)O(2) under pathophysiological conditions such as ischemic heart disease may induce changes in Ca(2+) homeostasis in cardiomyocytes and may induce contractile dysfunction. Furthermore, the sarcoplasmic reticulum involving a protein kinase C-mediated mechanism appears to be the main site of action of H(2)O(2) in cardiomyocytes.

Journal Article↗
PubMed1999

Stimulation of osteoclast formation by 1,25-dihydroxyvitamin D requires its binding to vitamin D receptor (VDR) in osteoblastic cells: studies using VDR knockout mice.

Previous studies have shown that 1,25-dihydroxyvitamin D [1,25(OH)2D] plays important roles in the formation of osteoclasts through its actions on osteoblastic cells. We have generated mice lacking vitamin D receptor (VDR) by gene targeting (VDR-/-). These mice had tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and exhibited similar levels of parameters for bone resorption to those in wild type mice. The present studies were undertaken to clarify whether effects of 1,25(OH)2D on osteoclast formation require VDR in osteoblasts, and to examine mechanisms of the formation of osteoclasts without VDR-mediated actions using VDR-/- mice. When wild-type calvarial osteoblasts and spleen cells were co-cultured with 1,25(OH)2D, TRAP-positive osteoclasts were formed regardless of the genotypes of spleen cells. In contrast, when osteoblasts from VDR-/- mice were co-cultured, no osteoclasts could be formed even with wild-type spleen cells. Parathyroid hormone and interleukin-1alpha stimulated osteoclast formation by co-cultures from VDR-/- mice, and the generated osteoclasts showed resorbing activity. These results demonstrate that VDR-mediated actions of 1,25(OH)2D in osteoblasts are essential for osteoclast formation by 1,25(OH)2D, and that functionally intact osteoclasts can be formed without 1,25(OH)2D actions under stimulations by other agents. It is suggested that osteoclastic bone resorption can be maintained without 1,25(OH)2D actions by other stimulatory agents.

Acid Phosphatase↗
PubMed1999

Cell growth and organ differentiation in cultured tobacco cells under spaceflight condition.

The responses of cultured tobacco cells to microgravity were examined. Cultured tobacco cells grew and regenerated shoots under microgravity conditions. However, such growth, especially of stems, was much more heterogeneous than that in the ground control, and the increase in fresh weight of the flight samples was less than that of ground control. In addition, multiple shoot formation was not observed in flight samples. Microscopic observation showed that the meristem of regenerating shoot under microgravity was smaller than that in the ground control. Electron microscopy showed that chloroplasts in the ground control were slightly more developed than those in flight samples and extensive arrays of microtubules were more evident in ground control than in flight samples. Analyses of enzymes involved in primary and secondary metabolism indicated that callus grown on shoot regeneration medium under microgravity conditions had a much lower activity of caffeic acid O-methyltransferase, which is involved in lignin biosynthesis, than those grown on Earth. In addition, two-dimensional polyacrylamide-gel electrophoresis analysis of 35S-labeled proteins suggested that gene expression in the flight samples may be similar to that in the ground control.

Cells, Cultured↗
PubMed1999

Sickness absence due to mental disorders in Japanese workforce.

This study was conducted to elucidate sickness absence due to mental disorders in Japanese companies. Data on sickness absence taken for seven consecutive days or more at eight companies (total number of employees: 44,816) was used for the analysis. Diagnosis of mental disorders was based on medical certificates prepared by physicians. The frequency of absence due to all diseases and mental disorders was 3.0% and 0.3%, respectively. The proportion of frequency absence due to mental disorders compared to that for all diseases was 9.4%. Figures for absence prevalence were almost the same as those for frequency absence. The average length of absence due to mental disorders and non-mental disorders was 119.5 days and 47.3 days, respectively. Rate of absence days due to mental disorders compared to that for all diseases was 21.0%. Percent of sickness absenteeism was 0.4%. In one company, the proportion of frequency absence and rate of absence days due to mental disorders compared to those for all diseases had an increasing tendency over the last six years.

Absenteeism↗
PubMed1999

Trial of prophylactic administration of TXA2 synthetase inhibitor, ozagrel hydrochloride, for preeclampsia.

OBJECTIVE: In an attempt to investigate the prophylactic effect of a thromboxane A2 (TXA2) synthetase inhibitor on pregnant women with a high risk of preeclampsia, the following clinical study was undertaken. METHODS: Forty pregnant women were randomly allocated to control or treatment groups. Ozagrel Hydrochloride (400 mg/day, orally) and placebo were started at 20 weeks of gestation and continued until delivery. RESULTS: Seventeen of 20 (85%) women in the control group developed preeclampsia, whereas 9 of 20 (45%) in the treatment group developed preeclampsia. Ozagrel Hydrochloride significantly (p < 0.01) reduced the occurrence of preeclampsia, and the incidence of both hypertension (p < 0.05) and proteinuria (p < 0.01) was significantly less in the treatment group compared with the control group. One month after administration, the mean plasma concentration of TXB2, a metabolite of TXA2, was significantly decreased (p < 0.01) to 62.4 +/- 13.6%, whereas that of 6-keto prostaglandin F1 alpha, a metabolite of PGI2, was significantly increased (p < 0.01) to 206.7 +/- 52.8%. There were no maternal or fetal side effects observed. CONCLUSIONS: It seems likely that Ozagrel Hydrochloride could be used for the prevention of preeclampsia in high-risk pregnant women.

Administration, Oral↗
PubMed1999

[Reconstruction of great vessel for patients with advanced lung cancer or malignant mediastinal tumor].

Fifteen lung cancer (LC) and 11 malignant mediastinal tumor (MMT) patients who received surgical treatment in association with a reconstruction of great vessel from 1981 to 1997 were retrospectively reviewed. The aorta was resected in 7 (AO group) of 15 LC patients and the superior vena cava in the remaining 8 patients (SVC group). Pathological examination revealed actual tumor invasion in one (14%) of AO group and 6 (75%) of SVC group. In 7 p-T4 patients, 6 (85.7%) were p-N2 or N3 diseases. Five of the 6 patients belonged to SVC group and one to AO group. Five-year survival rate was 10% in all LC patients, 20% in p-T3 patients, 0% in p-T4 cancers, 50% in p-N0 patients and 0% in p-N2 or N3 patients. Eleven MMT patients included 5 thymomas, 2 thymic cancers and 4 germ cell tumors. SVC was resected and replaced with ringed PTFE graft in all patients. Invasion of vessel wall was diagnosed pathologically in 10 of 11 patients. Fifteen-year survival rate was 60% in 5 thymoma patients but 4 of whom had distant metastasis. Five-year survival rate was 50% in thymic cancers and 0% in germ cell tumors. Since the prognosis of LC and MMT patients who have tumor invasion of the great vessel is very poor, induction therapy based on preoperatively pathological diagnosis is recommended.

Adult↗
PubMed1999

The expression of proliferating cell nuclear antigen (PCNA) and p 53 protein correlate with prognosis of patients with oral squamous cell carcinoma.

Few Data are available regarding expression of proliferating cell nuclear antigen (PCNA) versus overexpression of p 53 protein and prognosis for oral squamous cell carcinoma (O-SCC). This study evaluated the relationship between expression of PCNA and p 53 protein and certain clinical and pathologic parameters to prognosis in O-SCC. Scattered PCNA immunoreactive cells were found in 50 of 51 (98.0%) tumors. The mean PCNA-labelling index (PCNA-LI) of O-SCC was 34.7 +/- 12.0% (n = 50). The PCNA-LI was significantly high in O-SCC when compared to normal squamous epithelium (3.9 +/- 2.1%, n = 10). Altogether, 28 of 51 (54.9%) tumors showed nuclear immunoreactive for the p 53 protein. p 53-positive nuclei were clearly stained as granular or reticular in O-SCC. Microscopically, it appeared that the staining patterns of PCNA- and p 53-positive cells were quite similar. The mean value of PCNA-LI for the p 53-positive cases was 37.9 +/- 11.9% (n = 28), which was significantly higher than the 30.8 +/- 11.1% of the 23 negative cases. The survival rates at 3-year and 5-year for patients with p 53-negative O-SCC were 78.3% and 73.4%, respectively, while those for patients with p 53-positive O-SCC were 51.9% and 43.2%, respectively. No significant correlation could be found between PCNA-LI and T classification, N classification and Stage classification. The expression of p 53 was detected in 48.5% (16/33) of cases without regional lymph node metastasis, and 66.7% (12/18) with regional lymph node metastasis. There was a significant difference between PCNA-LI and p 53-positive cases, and prognosis. In PCNA-LI, the Grade 4 by mode of invasion was significantly higher than Grade 1, 2 and 3. The PCNA-LI and p 53-positive cases were significantly correlated with histological grading of malignancy. The present study shows a relationship between PCNA and p 53 protein. It also suggests that both PCNA and p 53 positive rates are the malignant potential of the O-SCC.

Adult↗
PubMed1999

Evidence for the role of oxidative stress in acute ischemic heart disease: a brief review.

BACKGROUND: Although contractile performance of the acutely damaged ischemic heart is invariably depressed on reperfusion (myocardial stunning), the mechanisms of cardiac dysfunction in stunned myocardium are poorly understood. OBJECTIVES: To review briefly the current state of knowledge and to provide further experimental evidence of whether oxidative stress plays a crucial role in cardiac dysfunction and membrane abnormalities due to ischemia-reperfusion. MATERIALS AND METHODS: Isolated rat hearts perfused in the absence or presence of superoxide dismutase (SOD) plus catalase, a well known oxyradical scavenger system, were subjected to 30 mins of global ischemia and 60 mins of reperfusion. Cardiac performance, hydrogen peroxide and calcium contents, lipid peroxidation and membrane activities associated with calcium transport were measured in the control, ischemic and ischemic- reperfused hearts. RESULTS: Cardiac dysfunction, as reflected by depressed left ventricular developed pressure, +dP/dt and -dP/dt as well as elevated left ventricular end-diastolic pressure, in the ischemic-reperfused heart was associated with increased hydrogen peroxide, calcium and malondialdehyde contents as well as increased formation of conjugated dienes. These changes due to ischemia-reperfusion were attenuated in hearts treated with SOD plus catalase. Both ischemia and ischemic-reperfused hearts showed depressions in sarcolemmal Na+/K+-ATPase and sodium-calcium exchange, as well as sarcoplasmic reticular calcium uptake and calcium release activities; these membrane abnormalities were also partially prevented by the presence of SOD plus catalase. CONCLUSIONS: Oxidative stress due to the formation of hydrogen peroxide leading to lipid peroxidation and sulfhydryl group oxidation during ischemia-reperfusion seems to be one of the mechanisms that may produce membrane defects and result in intracellular calcium overload and cardiac contractile dysfunction in the stunned myocardium.

Animals↗
PubMed1999

Liu-Jun-Zi-Tang, a kampo medicine, promotes adaptive relaxation in isolated guinea pig stomachs.

Some patients with dysmotility-like functional dyspepsia present impaired reservoir functions such as gastric adaptive relaxation. A traditional Chinese herbal medicine, Liu-Jun-Zi-Tang, has been identified as an effective drug against dyspeptic symptoms and is widely used for therapy in such patients. In this study, we examined the effects of this drug on the gastric adaptive relaxation in isolated guinea pig stomachs. The changes in intragastric volume and pressure were recorded in the presence of atropine and guanethidine. Gastric adaptive relaxation was induced by luminal distention. Liu-Jun-Zi-Tang (100 mg/ml) induced gastric adaptive relaxation at a lower intragastric pressure and increased the % volume of the gastric adaptive relaxation and the absolute intragastric volume. Metoclopramide (2 mg/ml), trimebutine (6 mg/ml) and cisapride (2 mg/ml) did not affect gastric adaptive relaxation. It was inhibited by means of the incubation of the stomach with NG-nitro-L-arginine (100 microM). Liu-Jun-Zi-Tang (100 mg/ml), but not gastroprokinetics overcame the effect of NG-nitro-L-arginine. These results suggested that Liu-Jun-Zi-Tang promoted gastric adaptive relaxation. This effect might, at least in part, contribute to the symptom relief in patients with functional dyspepsia.

Adaptation, Physiological↗
PubMed1999

[The role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein (MCP)-1 in subgroups of rapidly progressive glomerulonephritis].

To elucidate the role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein(MCP)-1 in the pathogenesis of rapidly progressive glomerulonephritis (RPGN), we determined the urinary levels of MCAF/MCP-1 in 20 healthy subjects, 30 patients showing RPGN with crescents, and 39 patients with various types of renal diseases without crescents. We divided RPGN into two subgroups, the acute type and the insidious type, with regard to the declination rate of reciprocals of serum creatinine with time as previously reported. In addition, we divided the patients with RPGN into anti-neutrophil cytoplasmic antibody(ANCA)-related diseases and immune complex(IC)-mediated diseases with regard to etiology. Urinary levels of MCAF/MCP-1 were significantly higher in patients with RPGN as compared with those of other renal diseases and healthy volunteers(21.8 +/- 4.5 vs. 11.6 +/- 3.5, 1.0 +/- 0.1 pg/ml creatinine, respectively, p < 0.01, mean +/- SEM). There was no difference in the urinary levels of MCAF/MCP-1 between the acute and insidious types of RPGN patients. In addition, there was no difference in the urinary levels of MCAF/MCP-1 between the patients with ANCA-related and IC-mediated diseases. Urinary levels of MCAF/MCP-1 in patients with RPGN were correlated well with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Immunohistochemical examinations revealed that MCAF/MCP-1 positive cells were detected in tubular epithelial and endothelial cells and mononuclear infiltrated cells in the interstitium. Moreover, elevated urinary MCAF/MCP-1 levels in patients with RPGN, regardless of subgroups, were dramatically decreased during methylprednisolone pulse therapy induced convalescence. These results suggest that MCAF/MCP-1 may be involved in the pathogenesis of RPGN via macrophage recruitment and activation.

Anti-Inflammatory Agents↗
PubMed1999

[Three cases of gastric cancer (Borrmann type IV) presenting with right back pain caused by right hydronephrosis as the first symptom].

We experienced three cases of right hydronephrosis, which were later diagnosed to have been caused by gastric cancer (Borrmann type IV). The patients were 25-, 38-, and 50-year-old women who complained of right back pain. Ultrasound sonography revealed right hydronephrosis in all three cases. We conducted drip infusion pyelography, computed tomographic scan and retrograde pyelography, but there were no signs of urinary stones or tumors, except for the presence of right ureteral stenosis. Since the patients had upper abdominal discomfort, they underwent gastrofiberscopy, which revealed scirrhous gastric cancer. We suspected that the right ureteral stenosis was caused by metastasis of gastric cancer. After a double J catheter was indwelt at the right ureter, combination chemotherapy of methetrexate + 5-fluorouracil was conducted. The right hydronephrosis diminished and all three patients became catheter-free.

Adult↗
PubMed1998

Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein.

Microtubule-dependent motor, murine KIF3B, was disrupted by gene targeting. The null mutants did not survive beyond midgestation, exhibiting growth retardation, pericardial sac ballooning, and neural tube disorganization. Prominently, the left-right asymmetry was randomized in the heart loop and the direction of embryonic turning. lefty-2 expression was either bilateral or absent. Furthermore, the node lacked monocilia while the basal bodies were present. Immunocytochemistry revealed KIF3B localization in wild-type nodal cilia. Video microscopy showed that these cilia were motile and generated a leftward flow. These data suggest that KIF3B is essential for the left-right determination through intraciliary transportation of materials for ciliogenesis of motile primary cilia that could produce a gradient of putative morphogen along the left-right axis in the node.

Animals↗