Biomedical subjects

M Osada

Publications and source records attributed to M Osada.

At least 37 records · Page 2Linked to original sources

PubMed2000

Mechanisms of ischemic preconditioning effects on Ca(2+) paradox-induced changes in heart.

The effects of ischemic preconditioning (IP) on changes in cardiac performance and sarcoplasmic reticulum (SR) function due to Ca(2+) paradox were investigated. Isolated perfused hearts were subjected to IP (three cycles of 3-min ischemia and 3-min reperfusion) followed by Ca(2+)-free perfusion and reperfusion (Ca(2+) paradox). Perfusion of hearts with Ca(2+)-free medium for 5 min followed by reperfusion with Ca(2+)-containing medium for 30 min resulted in a dramatic decrease in the left ventricular (LV) developed pressure and a marked increase in LV end-diastolic pressure. Alterations in cardiac contractile activity due to Ca(2+) paradox were associated with depressed SR Ca(2+)-uptake, Ca(2+)-pump ATPase, and Ca(2+)-release activities as well as decreased SR protein contents for Ca(2+)-pump and Ca(2+) channels. All these changes due to Ca(2+) paradox were significantly prevented in hearts subjected to IP. The protective effects of IP on Ca(2+) paradox changes in cardiac contractile activity as well as SR Ca(2+)-pump and Ca(2+)-release activities were lost when the hearts were treated with 8-(p-sulfophenyl)-theophylline, an adenosine receptor antagonist; KN-93, a specific Ca(2+)/calmodulin-dependent protein kinase II (CaMK II) inhibitor; or chelerythrine chloride, a protein kinase C (PKC) inhibitor. These results indicate that IP rendered cardioprotection by preventing a depression in SR function in Ca(2+) paradox hearts. Furthermore, these beneficial effects of IP may partly be mediated by adenosine receptors, PKC, and CaMK II.

Animals↗

PubMed2000

Ischemic preconditioning prevents I/R-induced alterations in SR calcium-calmodulin protein kinase II.

Although Ca(2+)/calmodulin-dependent protein kinase II (CaMK II) is known to modulate the function of cardiac sarcoplasmic reticulum (SR) under physiological conditions, the status of SR CaMK II in ischemic preconditioning (IP) of the heart is not known. IP was induced by subjecting the isolated perfused rat hearts to three cycles of brief ischemia-reperfusion (I/R; 5 min ischemia and 5 min reperfusion), whereas the control hearts were perfused for 30 min with oxygenated medium. Sustained I/R in control and IP groups was induced by 30 min of global ischemia followed by 30 min of reperfusion. The left ventricular developed pressure, rate of the left ventricular pressure, as well as SR Ca(2+)-uptake activity and SR Ca(2+)-pump ATPase activity were depressed in the control I/R hearts; these changes were prevented upon subjecting the hearts to IP. The beneficial effects of IP on the I/R-induced changes in contractile activity and SR Ca(2+) pump were lost upon treating the hearts with KN-93, a specific CaMK II inhibitor. IP also prevented the I/R-induced depression in Ca(2+)/calmodulin-dependent SR Ca(2+)-uptake activity and the I/R-induced decrease in the SR CaMK II activity; these effects of IP were blocked by KN-93. The results indicate that IP may prevent the I/R-induced alterations in SR Ca(2+) handling abilities by preserving the SR CaMK II activity, and it is suggested that CaMK II may play a role in mediating the beneficial effects of IP on heart function.

Animals↗

PubMed2000

Cardiac arrhythmias and left ventricular hypertrophy in dipper and nondipper patients with essential hypertension.

To evaluate the behavior of cardiac arrhythmias in dipper and nondipper hypertensive patients, 48-h ambulatory blood pressure monitoring, 24-h Holter electrocardiogram recording and echocardiographic studies were performed in 56 untreated outpatients with essential hypertension. These patients were divided into 2 groups according to the presence (dipper, n=33) or absence (nondipper, n=23) of reduction of both systolic and diastolic blood pressure during nighttime by an average of more than 10% of daytime blood pressure. Mean 48-h systolic and diastolic blood pressures did not differ between the 2 groups. Nondipper patients had a significantly larger left atrial dimension (31.9+/-3.8 vs 35.6+/-3.7 mm; p<0.01), left ventricular mass index (114+/-26 vs 136+/-36 g/m2; p<0.05), as well as a larger number of total supraventricular (16+/-19 vs 89+/-197 beats; p<0.05) and ventricular ectopic beats (7+/-14 vs 47+/-96 beats; p<0.05) during daytime as compared with dippers. In conclusion, nondipper hypertensive patients are likely to experience supraventricular and ventricular arrhythmias more frequently than dippers. A blunted nocturnal blood pressure fall may be involved in the appearance of cardiac arrhythmias in patients with essential hypertension.

Adult↗

PubMed1999

Effects of p51/p63 missense mutations on transcriptional activities of p53 downstream gene promoters.

The p51/p63 gene is a homologue of p53, the product of which acts as a transcriptional activator by binding to p53-responsive elements in the promoter regions of several p53 downstream genes. Recently, we identified four distinct mutations in the p51/p63 gene after screening >200 human tumors and cell lines. Because all of the detected p51/p63 mutations were missense mutations, the pathogenic effect of these mutations is difficult to determine without performing a functional analysis. In this study, we examined the transcriptional activity of tumor-derived p51/p63 missense mutations using a yeast-based assay and compared the data with that of artificial p51/p63 missense mutations at residues corresponding to the positions and substituted residues of p53 mutation "hotspots." Although most of the p51/p63 missense mutations at the p53 hotspot residues were unable to transactivate the promoters used in this study, the tumor-derived p51/p63 missense mutations retained their ability to transactivate the MDM2 and/or the BAX promoter but not the p21/WAF1 promoter. These results suggest that the p51/p63 mutation might be involved in an unknown tumor suppression pathway distinct from that of p53.

Amino Acid Sequence↗

PubMed1999

Involvement of singlet oxygen in cytochrome P450-dependent substrate oxidations.

Cytochrome P450 (P450)-dependent p-hydroxylation of aniline and o-deethylation of 7-ethoxycoumarin were examined in rat liver microsomes in the presence of radical scavengers. The addition of beta-carotene, a quencher of singlet oxygen species ((1)O(2)), suppressed the aniline hydroxylation, while the addition of sodium azide (NaN(3)) ((1)O(2) quencher) enhanced the reaction. No other reactive oxygen scavengers or chelating agents such as superoxide dismutase, catalase, dimethylsulfoxide, or deferoxamine altered the reaction. In contrast, the microsomal o-deethylation of 7-ethoxycoumarin was suppressed by the addition of NaN(3). (1)O(2) was detectable during the reaction of microsomes and NADPH by ESR spin-trapping when 2,2,6,6-tetramethyl-4-piperidone (TMPD) was used as a spin trap, and the (1)O(2) was quenched by the additions of beta-carotene, NaN(3), aniline, and 7-ethoxycoumarin. The enhancement effect of NaN(3) in the hydroxylation of aniline appeared to be due to the conformational change of P450 protein, which in turn enhances the binding of aniline to P450 in terms of the spectral dissociation constant (K(s)). In contrast, (1)O(2) appeared to be active in the o-deethylation of 7-ethoxycoumarin. On the basis of the results, the involvement of (1)O(2) in P450-dependent substrate oxygenations is proposed.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1999

Coronary arterial involvement and QT dispersion in Kawasaki disease.

For the early detection of myocardial ischemia in patients with severe involvement of the coronary arteries after Kawasaki disease, a method with high sensitivity and low cost is desirable because these patients require frequent follow-up and diagnostic tests. For this purpose, electrocardiographic, echocardiographic, Holter, and stress testing or angiography are repeated. However, these tests have some limitations due to cost, convenience, or sensitivity. It is uncertain that increased QT dispersion would exactly indicate progression of myocardial ischemia after Kawasaki disease, but this is the first study to present that QT dispersion of > or = 60 ms had higher sensitivity for detection of severe involvement of coronary artery after Kawasaki disease. This study is limited due to the small number of patients; larger prospective studies are required to clarify the usefulness of QT dispersion analysis in detecting the progression of myocardial ischemia after Kawasaki disease.

Adolescent↗

PubMed1999

The transcriptional activities of p53 and its homologue p51/p63: similarities and differences.

p51/p63 is a novel p53 homologue that has been shown to act as a transcriptional activator through the p53-binding sequence of the p21/WAF1 promoter and to induce apoptosis when it is expressed transiently in a human tumor cell line. We developed transcription assay systems for these two related genes in both Saccharomyces cerevisiae and mammalian cells and used them to investigate the functional similarities and differences of these genes. We found that p51/p63 trans-activated the previously identified p53 target genes, but the degree of the transactivation by p51/p63 differed from that by p53. These results suggest that the cellular signal on p51/p63 cross-talks partially but not completely with that of the p53 pathway.

Cyclin-Dependent Kinase Inhibitor p21↗

PubMed1999

Protection against tick-borne encephalitis virus isolated in Japan by active and passive immunization.

In order to establish a firm preventive measure for tick-borne encephalitis (TBE) in Japan, we evaluated the immune response of European vaccine against Japanese TBE virus strain (Oshima 5-10) for man and mouse. Furthermore, the efficacy of pre- and post-exposure protection by a polyclonal rabbit anti-TBE virus serum was examined in the mouse model. 80% of vaccinees seroconverted against Oshima 5-10 strain after the 2nd immunization of vaccine and the remaining 20% seroconverted after the 3rd immunization. Two persons with pre-existing anti-Japanese encephalitis virus (JEV) antibodies showed low immune responses against TBE virus. In mouse vaccination and challenge tests, efficient protection was observed in mice challenged with lethal doses of Oshima 5-10 strain as well as those observed in mice with the Western subtype and the Far Eastern subtype of TBE strains. Pre-exposure treatment with rabbit anti-TBE virus serum provided complete protection against lethal challenge with Oshima 5-10 strain. For post-exposure treatment with the antibody, significant protection was observed when mice were treated 24 h after virus challenge, whereas it was not observed 48 h after virus challenge. reserved.

Animals↗

PubMed1999

Activation of phospholipase C-Ca2+ system by sphingosine 1-phosphate in CHO cells transfected with Edg-3, a putative lipid receptor.

Sphingosine 1-phosphate (S1P) induces phospholipase C (PLC) activation and Ca2+ mobilization in many types of cells. We examined the possible involvement of Edg-3, one of the putative S1P receptors, in the phospholipase C (PLC)-Ca2+ system. S1P increased the cytoplasmic free Ca2+ concentration without detectable inositol phosphate production in vector-transfected CHO cells. In the Edg-3-transfected cells, however, the S1P-induced Ca2+ response was clearly enhanced, which was associated with a significant production of inositol phosphate. These S1P-induced responses in the Edg-3-transfected cells were inhibited by U73122, a potent PLC inhibitor. We conclude that Edg-3 may be one of the S1P receptors participating in the activation of the PLC-Ca2+ system.

Animals↗

PubMed1999

Implementation and evaluation of workflow based on hospital information system/radiology information system/picture archiving and communications system.

The purpose of this presentation is to review and evaluate computerized workflow of selected sites that have integrated systems of the hospital information system (HIS), radiology information system (RIS), and picture archiving and communications system (PACS). We then focus on some essential points of integration of those systems, such as avoiding multiple entries of patients demographic data, prefetching current and previous images to the correspondent workstations, and workflow management. To realize them by integrating multiple subsystems such as HIS/RIS/PACS integration, there must be exchange of the workflow control information, and consistency of the information between subsystems.

Computer Systems↗

PubMed1999

Immature megakaryocytes undergo apoptosis in the absence of thrombopoietin.

We examined withdrawal effects of recombinant mouse Tpo (rm-Tpo) on the apoptosis of mature and immature megakaryocytes in in vitro experiments. Apoptotic megakaryocytes were detected by double staining for acetylcholinesterase and by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. When the purified mature megakaryocytes were cultured with or without rm-Tpo, the numbers of viable megakaryocytes, apoptotic megakaryocytes, and megakaryocytes with cytoplasmic processes were not significantly different between the two groups. In contrast, purified immature megakaryocytes underwent apoptosis when rm-Tpo was absent from the culture system. Murine bone marrow cells were cultured with rm-Tpo (50 U/mL) on days 1-7 to generate immature megakaryocytes and subsequently were cultured with different concentrations of rm-Tpo (0-50 U/mL) on days 8-14. The number of viable megakaryocytes was decreased and that of apoptotic megakaryocytes was increased by rm-Tpo in a dose-dependent manner. These results indicated a clear relation between the rm-Tpo level and the apoptosis of immature megakaryocytes.

Animals↗

PubMed1999

Antiarrhythmic effect of magnesium sulfate against occlusion-induced arrhythmias and reperfusion-induced arrhythmias in anesthetized rats.

The antiarrhythmic effect of magnesium sulfate (Mg) as well as the hemodynamics were studied using the coronary ligation and reperfusion models in rats. In the study on coronary ligation arrhythmia, i.v. administration of Mg (0.6, 2, 6, 20 and 60 micromol) was conducted at 5 min after coronary ligation. Mg had an action to decrease the total number of premature ventricular contraction (PVC), the duration of ventricular tachycardia (VT), the frequency of VT and ventricular fibrillation (Vf) and the mortality ratio for 30 min after coronary ligation. In the 6-60 micromol groups, significant antiarrhythmic action (p < 0.01 vs. control) was attained. In the study on reperfusion arrhythmia, i.v. administration of Mg (20, 60 and 200 micromol) was conducted at 4 min after coronary ligation, and at 1 min after ligation, the coronary artery was reperfused. Mg had an action to decrease the frequency of Vf, the mortality ratio and the duration of VT and Vf and to extend the interval between the initiation of reperfusion and the occurrence of VT and Vf for 10 min after reperfusion. In the 200 micromol group, significant antiarrhythmic action (p < 0.05 vs. control) was attained. Administration of Mg decreased the heart rate and blood pressure. We concluded that Mg can control myocardial ischemia-induced and reperfusion-induced arrhythmia and that sudden cardiac death which occurs as a result of arrhythmia can be prevented.

Anesthesia↗

PubMed1999

Differential roles of Akt, Rac, and Ral in R-Ras-mediated cellular transformation, adhesion, and survival.

Multiple biological functions have been ascribed to the Ras-related G protein R-Ras. These include the ability to transform NIH 3T3 fibroblasts, the promotion of cell adhesion, and the regulation of apoptotic responses in hematopoietic cells. To investigate the signaling mechanisms responsible for these biological phenotypes, we compared three R-Ras effector loop mutants (S61, G63, and C66) for their relative biological and biochemical properties. While the S61 mutant retained the ability to cause transformation, both the G63 and the C66 mutants were defective in this biological activity. On the other hand, while both the S61 and the C66 mutants failed to promote cell adhesion and survival in 32D cells, the G63 mutant retained the ability to induce these biological activities. Thus, the ability of R-Ras to transform cells could be dissociated from its propensity to promote cell adhesion and survival. Although the transformation-competent S61 mutant bound preferentially to c-Raf, it only weakly stimulated the mitogen-activated protein kinase (MAPK) activity, and a dominant negative mutant of MEK did not significantly perturb R-Ras oncogenicity. Instead, a dominant negative mutant of phosphatidylinositol 3-kinase (PI3-K) drastically inhibited the oncogenic potential of R-Ras. Interestingly, the ability of the G63 mutant to induce cell adhesion and survival was closely associated with the PI3-K-dependent signaling cascades. To further delineate R-Ras downstream signaling events, we observed that while a dominant negative mutant of Akt/protein kinase inhibited the ability of R-Ras to promote cell survival, both dominant negative mutants of Rac and Ral suppressed cell adhesion stimulated by R-Ras. Thus, the biological actions of R-Ras are mediated by multiple effectors, with PI3-K-dependent signaling cascades being critical to its functions.

3T3 Cells↗

PubMed1999

Status of Ca2+/calmodulin protein kinase phosphorylation of cardiac SR proteins in ischemia-reperfusion.

Although the sarcoplasmic reticulum (SR) is known to regulate the intracellular concentration of Ca2+ and the SR function has been shown to become abnormal during ischemia-reperfusion in the heart, the mechanisms for this defect are not fully understood. Because phosphorylation of SR proteins plays a crucial role in the regulation of SR function, we investigated the status of endogenous Ca2+/calmodulin-dependent protein kinase (CaMK) and exogenous cAMP-dependent protein kinase (PKA) phosphorylation of the SR proteins in control, ischemic (I), and ischemia-reperfused (I/R) hearts treated or not treated with superoxide dismutase (SOD) plus catalase (CAT). SR and cytosolic fractions were isolated from control, I, and I/R hearts treated or not treated with SOD plus CAT, and the SR protein phosphorylation by CaMK and PKA, the CaMK- and PKA-stimulated Ca2+ uptake, and the CaMK, PKA, and phosphatase activities were studied. The SR CaMK and CaMK-stimulated Ca2+ uptake activities, as well as CaMK phosphorylation of Ca2+ pump ATPase (SERCA2a) and phospholamban (PLB), were significantly decreased in both I and I/R hearts. The PKA phosphorylation of PLB and PKA-stimulated Ca2+ uptake were reduced significantly in the I/R hearts only. Cytosolic CaMK and PKA activities were unaltered, whereas SR phosphatase activity in the I and I/R hearts was depressed. SOD plus CAT treatment prevented the observed alterations in SR CaMK and phosphatase activities, CaMK and PKA phosphorylations, and CaMK- and PKA-stimulated Ca2+ uptake. These results indicate that depressed CaMK phosphorylation and CaMK-stimulated Ca2+ uptake in I/R hearts may be due to a depression in the SR CaMK activity. Furthermore, prevention of the I/R-induced alterations in SR protein phosphorylation by SOD plus CAT treatment is consistent with the role of oxidative stress during ischemia-reperfusion injury in the heart.

Animals↗

PubMed1999

Exercise-induced uncommon atrioventricular nodal reentrant tachycardia with sick sinus syndrome: a case report.

Exercise seldom provokes tachycardia in patients with paroxysmal supraventricular tachycardia (PSVT). This report presents a case of exercise-induced uncommon atrioventricular nodal reentrant tachycardia (AVNRT) with sick sinus syndrome. Treadmill exercise testing provoked AVNRT of long RP' with good reproducibility. Uncommon AVNRT was confirmed by the lack of atrial pre-excitation during PSVT and para-Hisian pacing. The patient has been successfully treated with verapamil and DDD pacing for 5 years.

Aged↗

PubMed1999

Isolation of tick-borne encephalitis virus from wild rodents and a seroepizootiologic survey in Hokkaido, Japan.

To determine the vertebrate host of tick-borne encephalitis (TBE) virus in the southern part of Hokkaido, Japan, virus isolation was performed using spleens from small mammals captured in the area. Two virus strains were isolated, one strain from Apodemus speciosus and another from Clethrionomys rufocanus. Virus isolates were inoculated onto baby hamster kidney cell monolayers and antigen slides were prepared for an indirect immunofluorescent antibody assay. Two isolates were identified as TBE viruses by monoclonal antibody reactions. To specify the TBE-endemic area in Hokkaido, rodent, horse, and dog sera collected from 1992 to 1997 were tested for neutralization antibody against TBE virus previously isolated from a dog. The positive cases were distributed in four districts in the southern part of Hokkaido.

Animals↗

PubMed1999

[Congestive heart failure due to a combination of atrial fibrillation and tricuspid regurgitation: clinical course and echocardiographical analysis].

The combination of atrial fibrillation (Af) and tricuspid regurgitation (TR) may induce the congestive heart failure (HF) due to insufficient output. However, these associations have not been elucidated. We examined the clinical course with echocardiographic data in 119 patients with Af and/or TR and/or HF. Their mean age was 65 +/- 14 years. The patients were classified into 6 groups as follows: Group I contained patients with Af, TR and HF(n = 13); Group II contained patients with Af and TR, without HF(n = 59); Group III contained patients with TR and HF, without Af(n = 15); Group IV contained patients with TR and without AF and HF(n = 15); Group V contained patients with Af and HF, without TR(n = 24); Group VI contained patients with Af and without TR and HF(n = 13). The fractional shortening and ejection fraction in Group I and II were significantly (p < 0.05) decreased compared to Group IV. Moreover, the fractional shortening in Group V was significantly (p < 0.05) lower than in Group IV. Among 72 cases in Group I and II, 24 cases were followed by echocardiography for 2 to 5 years. Eight cases of HF exhibited a no HF state and 1 demonstrated had the HF state. All 9 cases (38%) showed a decreased heart rate and no alternation of TR. Four of the 24 patients (17%) had developed worsened TR and a lowered ejection fraction but none developed them became HF. Therefore, tachycardia may be an accelerative factor for HF due to the combination of Af and TR, not due to the grade of TR.

Aged↗

PubMed1999

Influence of p53 mutation on pathological grade, but not prognosis of non-Hodgkin's lymphoma.

Mutations in the p53 gene were detected in 27 of the 107 (25%) cases of non-Hodgkin's lymphoma (NHL), examined by assaying the transcriptional activity of p53 in yeast. A relatively high mutation rate of p53 was observed in B-cell intermediate-grade NHL and in T-cell high-grade immunoblastic NHL, in contrast to the relatively low mutation rate observed in other pathological classifications. However, retrospective analyses of all 76 cases revealed that the survival profile and therapeutic responses were very similar in NHL patients bearing lymphomas with a mutant p53 or with the wild-type p53 even within the subclasses characterized by frequent p53 mutation. In patients with high-intermediate grade tumors, the median survival period was 24 months in mutated p53 cases and 14 months in wild-type cases. Complete remission (CR) was observed in 9 of the 17 patients (53%) with mutated forms of p53 and 18 of the 35 patients (51%) with wild-type p53 genes. Our analyses of NHL patients revealed that the presence of p53 mutations may influence pathological grades of NHL, but did not strongly correlate with poor prognosis or reduced chemo/radiosensitivity in NHL. Hence, mutations of p53 do not serve as a prognostic, or chemo/radiosensitivity marker in NHL.

Adolescent↗