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Biomedical subjects

T Hata

Publications and source records attributed to T Hata.

At least 217 records · Page 12Linked to original sources

Relation of oxidative stress and glutathione synthesis to CD95(Fas/APO-1)-mediated apoptosis of adult T cell leukemia cells.

An IL-2 dependent adult T cell leukemia cell line (SO4) has been established that is sensitive to CD95-mediated apoptosis as well as a subline (R-SO4) that is resistant. Incubating SO4 cells with anti-CD95 IgM mAb caused concentration-dependent cell death. On the contrary, R-SO4 cells did not die even at 1000 ng/ml of anti-CD95 IgM mAb. The levels of CD95 expression on R-SO4 cells were one-third of those on SO4 cells. However a blocking Ab, anti-CD95 IgG mAb, did not induce complete resistance of SO4 cells to anti-CD95 IgM mAb as R-SO4 cells. As CD95 and TNF receptor are similar, and TNF/TNF receptor binding induces oxygen radicals, the involvement of oxidant and antioxidant systems in CD95-mediated apoptosis has been examined. The addition of anti-CD95 IgM mAb resulted in formation of intracellular oxygen radical species in the SO4 cells as measured using 2',5',-dichlorofluorescein as substrate. The oxygen radical production induced DNA damage as determined by formation of 8-hydroxydeoxyguanosine. No increase in the formation of oxygen radicals was observed in R-SO4 cells. Concentrations of the intracellular antioxidant, glutathione, and the key enzyme for its synthesis, gamma-glutamylcysteine synthetase, were 150% increased in R-SO4 cells in comparison with that of SO4 cells. Moreover, glutathione ester decreased the formation of 8-hydroxydeoxyguanosine. These results suggested that apoptosis mediated by CD95 in ATL cells is related to the production of oxygen radical species and cellular antioxidant systems, especially, glutathione synthesis.

Apoptosis↗

Intratumoral blood flow analysis in endometrial cancer: does it differ among individual tumor characteristics?

To evaluate whether intratumoral blood flow analysis in endometrial cancer provides individual tumor characteristics, 36 patients with endometrial cancer (5 in stage IA, 14 in stage IB, 5 in stage IC, 4 in stage II, and 8 in stage III) underwent transvaginal color and pulsed Doppler ultrasound before surgery. Histologically, there were 18 patients with well-differentiated adenocarcinoma, 8 with moderate differentiated adenocarcinoma, 4 with poorly differentiated adenocarcinoma, 4 with adenoacanthoma, and 2 with carcinosarcoma. Intratumoral blood flow was recorded, and peak systolic velocity (PSV) and resistance index (RI) were calculated. Endometrial thickness (ET) was also measured. There were no significant differences among PSV and RI values for each stage. There were also no significant differences among PSV and RI values for each histological diagnosis. ET in stages IA, IB, and II was significantly thinner than that in stage III (P < 0.05). Moreover, ET in stage IA was significantly thinner than that in stage IC (P < 0.05). There were significant differences in ET for some histological diagnoses. These results suggest that intratumoral blood flow analysis in endometrial cancer could not predict the tumor staging and histological diagnosis. However, in view of the small number of patients, these observations must be considered preliminary.

Adenocarcinoma↗

Regression of hypertrophy after myocardial infarction is produced by the chronic blockade of angiotensin type 1 receptor in rats.

The efficacy of angiotensin converting enzyme (ACE) inhibitors is well known to prevent the formation of angiotensin II (Ang II) by these agents. The objective of the present study was to evaluate the hemodynamic, biochemical, and morphological responses to Ang II receptor blockade with E-4177, 3-[(2'-carboxybiphenyl-4-yl) methyl]-2-cyclopropyl-7-methyl 3H-imidazol[4,5-b] pyridine, in rats with a healing myocardial infarction that had been induced by the surgical occlusion of the left main coronary artery. The left ventricular weight increased 8 and 12 weeks after infarction in comparison to that in sham-operated rats. Among the rats with experimental infarction, treatment with E-4177 significantly decreased the left ventricular weight. Although the infarct size was not affected by E-4177, its administration ameliorated the elevated end-diastolic pressure and reduced the systolic pressure. The effects of this agent on the levels of Ang II type 1 (AT1) receptor mRNA and ACe mRNA were evaluated in the non-infarcted myocardium by reverse transcriptase polymerase chain reaction and binding assays. Treatment with E-4177 reduced both the elevated AT1 mRNA and the number of Ang II receptors, but not the ACE mRNA or ACE activity. While the receptor affinity remained unchanged with this agent, the collagen concentration was decreased. On the other hand, the depressed Na+/Ca2+ exchange activity was restored in the non-infarcted myocardium at 8 and 12 weeks after injury to the level seen in the sham-operated rats. These findings suggest that the AT1 receptor antagonist, E-4177, has a beneficial effect on the hemodynamics in spite of the lack of any improvement in the infarct size. These observations may be partly attributed to the prevention of angiotensin II formation during the period of post-infarction healing.

Angiotensin II↗

The role of Ca2+ release from sarcoplasmic reticulum in the regulation of sinoatrial node automaticity.

The role of Ca2+ release channels in the sarcoplasmic reticulum in modulating physiological automaticity of the sinoatrial (SA) node was studied by recording transmembrane action potentials and membrane ionic currents in small preparations of the rabbit SA node. Ryanodine, which modifies the conductance and gating behavior of the Ca2+ release channels, was used to block Ca2+ release from the sarcoplasmic reticulum. Superfusion of 1-mM ryanodine decreased the spontaneous firing frequency as well as the maximal rate of depolarization of the SA, and these reductions reached a steady state within approximately 5 min. The action potential recordings revealed that the latter part of diastolic depolarization was depressed and that the take-off potential became less negative. This suggested that the negative chronotropic effect of ryanodine resulted from the blockade of physiological Ca2+ release from the sarcoplasmic reticulum. In voltage clamp experiments, using double-microelectrode techniques, ryanodine did not markedly reduce the Ca2+ current (ICa) but decreased the delayed rectifying K+ current (IK), the steady-state inward current (Iss), and the hyperpolarization-activated inward current (Ih). These observations suggest that, even when the function of C2+ channels in the cell membrane is normally maintained, depression of Ca2+ release channels in the sarcoplasmic reticulum would prevent sufficient elevation of the Ca2+ concentration in SA node cells for the activation of various ionic currents, and, thus adversely affect the physiological automaticity of this primary cardiac pacemaker.

Action Potentials↗

Comparative study of 201Tl-scintigraphic image and myocardial pathologic findings in patients with dilated cardiomyopathy.

The objective of the present study was to characterize the production of 201Tl myocardial perfusion defects, the relation between the 201Tl multiple small defects and the myocardial damage indicated by myocardial fibrosis shown histopathologically in patients with dilated cardiomyopathy (DCM). Rest 201Tl scintigraphy was performed in thirty-seven patients with myocardial tissue fibrosis by endomyocardial biopsy, and without stenosis of the coronary artery. 201Tl myocardial SPECT images were visually classified into 4 grades according to the severity of inhomogeneous perfusion defects (IPD), 0: none, 1: slight, 2: moderate, 3: severe. 201Tl uptake, defect regions (DR), and coefficient of variation % (CV%) were also quantified by Bull's eye quantification in nineteen patients. During cardiac catheterization, three biopsy specimens were obtained from the lateral wall to the apical region of the left ventricle and the amount of fibrosis was assessed by means of light microscopic morphometry. The myocardial fibrosis was also classified into 4 grades by a point-counting method. Autopsy study was also assessed in six patients. 201Tl perfusion defects were observed in 35 (94.6%) patients, of whom 29 (78.4%) showed inhomogeneous perfusion defects. Twenty-four (64.9%) showed Stage 0 and 201Tl findings, and 21 (62.2%) had myocardial fibrosis in stage 1. Clinically, the correlation between the grades of the IPD, % 201Tl uptake, DR and CV% of myocardial uptake, which were calculated semiquantitatively by Bull's eye image, and the histological grades of fibrosis were also good (IPD vs. fibrosis: r = 0.7014; % 201Tl uptake vs. fibrosis: r = -0.6542; DR vs. fibrosis: r = 0.7027; CV% vs. fibrosis: r = 0.6985). The 201Tl SPECT findings were in close agreement with the severity of myocardial fibrosis confirmed by autopsy, but the grading of the IPD was not related to the ejection fraction or left ventricular diameter. It showed a higher rate of inhomogeneous 201Tl myocardial perfusion defects (78.4%) in patients with DCM. This result may contribute to the clinical evaluation of DCM or differentiation from other diseases. Furthermore, the grading of 201Tl inhomogeneous perfusion defects related to the myocardial fibrosis of left ventricular myocardium may contribute to speculation of the myocardial degenerative stage in clinical settings.

Adult↗

Sequence of alterations in subcellular organelles during the development of heart dysfunction in diabetes.

Although changes in different subcellular organelles such as myofibrils, sarcoplasmic reticulum (SR), mitochondria and sarcolemma (SL), as well as in heart function have been reported to occur in chronic diabetes, their inter-relationships and functional significance are poorly understood. In order to gain information on this aspect, diabetes in rats was induced by an intravenous injection of streptozotocin and animals were assessed hemodynamically at 15-27 days. Ventricular tissue from several diabetic animals was pooled, subcellular organelles were isolated and their biochemical activities determined. Significant depressions in cardiac contractile and relaxation were observed to be associated with decreases in myofibrillar Ca(2+)-stimulated ATPase and SR Ca(2+)-pump activities at 21 days from the induction of diabetes. Likewise, the SL Na+-Ca2+ exchange and Ca(2+)-channel density were decreased at 21 days but the affinity of SL Ca(2+)-channels was increased in the diabetic heart. The SL Ca(2+)-pump and Na+-K+ ATPase activities were depressed at 18 and 24 days, respectively. Both alpha- and beta- adrenoceptor densities in SL were decreased at 27 days whereas no changes in mitochondrial function were observed at these early stages of diabetes. The SL low affinity Ca(2+)-binding was decreased while the low affinity Ca(2+)-ATPase activity was increased at 18 days following the induction of diabetes. These results indicate that SL defects precede those in SR, myofibrils or mitochondria and suggest that abnormalities in Ca(2+)-handling as well as interaction of Ca2+ with myofilaments in cardiomyocytes may lead to the development of heart dysfunction in chronic diabetes.

Adenosine Triphosphatases↗

Effect of dehydroepiandrosterone sulfate on maternal cardiac function in term pregnancy.

To search for possible effect of dehydroepiandrosterone sulfate (DHAS) on maternal cardiac function in term pregnancy, impedance cardiographic assessments were made on 15 normal full-term pregnant women before and 5, 10, 15, 20, 25, and 30 minutes after the administration of a 200 mg intravenous dose of DHAS in 20 mL of 5% dextrose. The cardiac output, stroke volume, heart rate, and mean arterial pressure were recorded. Maternal cardiac output increased from baseline by 20% (p < 0.05) after 15 minutes and the mean increase in stroke volume was 25% (p < 0.05) after 15 minutes. No change was found in heart rate or mean arterial blood pressure. DHAS induces a significant increase in both maternal stroke volume and cardiac output without change in heart rate or mean arterial pressure, which suggests a possible increase in cardiac contractility in term pregnancy.

Blood Pressure↗

Mathematical modeling of fetal foot growth: use of the Rossavik growth model.

Growth of the fetal foot has been monitored by foot length (FL), from 12 to 41 weeks menstrual age in 173 normal Japanese fetuses. Growth curve for this parameter has been determined using a Rossavik growth model [p = c(t)k+s(t)]. R2 value of 98.0% was obtained for FL. Variability analysis indicated some progressive increase in variability with fetal age for this parameter. Variability data were used with the growth curve model to determine standard curve for this parameter. This standard curve provides a superior means for evaluating the normal fetal foot growth in the fetus and for assessing menstrual age in utero.

Embryonic and Fetal Development↗

Intrauterine sonographic assessments of embryonal liver length.

Our purpose was to evaluate embryonal liver length measurement using intrauterine sonography with a specially developed 20 MHz flexible catheter-based high-resolution real-time miniature (2.4 mm outer diameter) ultrasound transducer in early first-trimester pregnancy. A total of 36 women about to undergo therapeutic abortion at 7-9.9 weeks gestational age and one abnormal pregnancy with fetal hydrops at 9 weeks were studied. The normal range of embryonal liver length for each day of pregnancy was determined. A relationship between embryonal liver length and crown-rump length measurements is described. A linear relationship was found between the menstrual age and embryonal liver length (R2 = 93.3%), and a normal range of embryonal liver length for estimating the growth of the embryonal liver during early first trimester pregnancy was generated. A normogram of menstrual age as predicted by embryonal liver length was also generated. Embryonal liver length was curvilinearly correlated with crown-rump length (R2 = 92.3%). Embryonal liver length value (6.4 mm) in a case of fetal hydrops at 9 weeks was above the normal range. These results may provide an additional measurement for the estimation of gestational age in the early first trimester of pregnancy. In this limited series one embryonal liver enlargement was demonstrated and, thus, there is a potential for its use in the detection of embryonal congestive heart failure. The value and potential applications of this new embryonal parameter are discussed.

Crown-Rump Length↗

Attenuation by prolonged nitric oxide synthase inhibition of the enhancement of fibrinolysis caused by environmental stress in the rat.

1. Nitric oxide (NO) suppresses platelet aggregation and plasminogen activator inhibitor (PAI) release from platelets, playing physiological and/or pathological roles in the haemostatic system. We investigated the effect of NG-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, on the disseminated intravascular coagulation (DIC)-like phenomena in rats under environmental stress, induced by prolonged fluctuation in air temperature, known as SART (specific alternation of rhythm in temperature) stress. 2. Exposure of rats to SART stress for 7 days caused mild DIC-like symptoms such as thrombocytopenia, hypofibrinogenemia, decreased factor VIII: coagulant activity and shortened euglobulin clot lysis time (ECLT). The enhanced fibrinolysis was accompanied by a marked decrease in the activity of plasma PAI. 3. L-NAME, but not its D-enantiomer, when administered orally at 0.3-10 mg kg-1, twice a day for 7-day exposure to stress, inhibited the stress-induced decrease in fibrinogen levels in a dose-dependent manner, whereas it failed to alter platelet count, factor VIII:coagulant activity and plasma protein levels in stressed rats. All these parameters in unstressed rats were resistant to L-NAME at 10 mg kg-1. 4. Repeated treatment with 10 mg kg-1 of L-NAME blocked the shortening of ECLT and the decrease in PAI activity following stress exposure, although it was without effect in unstressed rats. 5. The inhibitory effects of L-NAME at 10 mg kg-1 on the stress-induced alterations in fibrinogen levels and in ECLT were significantly reduced by coadministered L-arginine at 1000 mg kg-1. 6. These findings demonstrate that repeated administration of L-NAME attenuates the enhanced fibrinolysis, without aggravating thrombocytopenia, in SART-stressed rats. Endogenous NO appears to contribute to the stress-induced development of fibrinolysis by suppressing, plasma PAI activity, most probably as a result of inhibition of the PAI release from platelets.

Animals↗

Physicochemical characterization of bisphosphonic carboxyfluorescein for osteotropic drug delivery.

Disodium (fluorescein-6-carbonyloxy)acetoaminomethylene bisphosphonate (CF-BP), a prodrug of 6-carboxy-fluorescein, is efficiently absorbed by the skeleton where it hydrolyses to carboxyfluorescein. An osteotropic drug-delivery system based on this bisphosphonic prodrug has been developed as a novel method for site-specific and controlled delivery of drugs to the bone. In this study the physicochemical properties of the prodrug have been characterized by investigating the affinity of CF-BP for hydroxyapatite and the hydrolysis of the compound to carboxyfluorescein. In the binding study, CF-BP bound very rapidly to hydroxyapatite without degradation and carboxyfluorescein was subsequently gradually released by hydrolysis of bound CF-BP. Hydrolysis of CF-BP in buffer solutions followed pseudo-first-order kinetics, and quantitative regeneration of carboxyfluorescein was observed. In addition, regeneration of carboxyfluorescein from CF-BP was accelerated in the presence of fresh rat plasma. These results suggest that CF-BP has the physicochemical properties required for site-specific and controlled delivery of carboxyfluorescein to bones.

Animals↗

A modular family 19 chitinase found in the prokaryotic organism Streptomyces griseus HUT 6037.

The specificity of chitinase C-1 of Streptomyces griseus HUT 6037 for the hydrolysis of the beta-1,4-glycosidic linkages in partially acetylated chitosan is different from that of other microbial chitinases. In order to study the primary structure of this unique chitinase, the chiC gene specifying chitinase C-1 was cloned and its nucleotide sequence was determined. The gene encodes a polypeptide of 294 amino acids with a calculated size of 31.4 kDa. Comparison of the amino acid sequence of the deduced polypeptide with that of other proteins revealed a C-terminal catalytic domain displaying considerable sequence similarity to the catalytic domain of plant class I, II, and IV chitinases which form glycosyl hydrolase family 19. The N-terminal domain of the deduced polypeptide exhibits sequence similarity to substrate-binding domains of several microbial chitinases and cellulases but not to the chitin-binding domains of plant chitinases. The previously purified chitinase C-1 from S. griseus is suggested to be generated by proteolytic removal of the N-terminal chitin-binding domain and corresponds to the catalytic domain of the chitinase encoded by the chiC gene. High-performance liquid chromatography analysis of the hydrolysis products from N-acetyl chitotetraose revealed that chitinase C-1 catalyzes hydrolysis of the glycosidic bond with inversion of the anomeric configuration, in agreement with the previously reported inverting mechanism of plant class I chitinases. This is the first report of a family 19 chitinase found in an organism other than higher plants.

Amino Acid Sequence↗

Congenital psoriasiform erythrokeratodermia with cleidocranial dysplasia, urogenital anomalies and atresia ani.

We describe two siblings with unique psoriasiform erythrokeratodermia associated with cleidocranial dysplasia, urogenital anomalies and atresia ani. The skin lesions were characterized by demarcated psoriasiform erythema with scaling. A skin biopsy revealed small abscesses containing polymorphonuclear leukocytes in the parakeratotic horny layer, elongation of the rete ridges and dermal papillae, and other findings consistent with psoriasis. A reverse-transcription polymerase chain reaction analysis disclosed increased expression of transforming growth factor alpha in the affected skin lesion of one of the siblings as well as in the skin of a patient with psoriasis. It is suggested that these cases are a variant of a congenital form of psoriasiform erythrokeratodermia.

Adolescent↗

Interleukin-1 receptor antagonist in cord blood: effects of labor and fetal distress.

OBJECTIVE: To evaluate the effect of labor pains or fetal distress on concentrations of interleukin-1 receptor antagonist (IL-1ra) in cord blood. METHODS: Umbilical cord interleukin-1 beta (IL-1 beta) and IL-1ra were measured in 24 normal appropriately grown newborns delivered vaginally (VD group), 10 normal appropriately grown newborns delivered by elective cesarean section (ECS group), and 5 appropriately grown newborns with fetal distress (FD group). Umbilical cord arterial blood pH and PO2 were also measured. RESULTS: Umbilical artery blood pH and PO2 in the VD group were not significantly different from those in the ECS group. Umbilical artery blood pH and PO2 in the FD group were significantly lower than those in the VD group (p < 0.05). Umbilical artery blood pH in the FD group was significantly lower than that in the ECS group (p < 0.05), but no significant difference for umbilical artery blood PO2 was found between the FD and ECS groups. IL-1 beta levels were undetectable in the three groups of neonates. There were no significant differences for concentrations of IL-1ra in cord blood among the groups. CONCLUSION: These results suggest that the labor pain or fetal distress does not affect concentrations of IL-1ra in cord blood.

Female↗

Mathematical modeling of fetal organ growth using the Rossavik growth model. V. Cerebellum.

Growth of the fetal cerebellum was monitored by transverse cerebellar diameter (CD) from 14 to 39 weeks menstrual age in 125 Japanese fetuses. The growth curve for this parameter was determine using a Rossavik growth model [p = c(t)k & (t)]. An R2 value of 95.5% was obtained for CD. Variability analysis indicated a progressive increase in variability with fetal age for this parameter. Variability data were used with the growth curve model to determine a standard curve for this parameter. This standard curve provides a superior means to evaluate normal fetal cerebellar growth in the fetus and to identify cerebellar abnormalities in utero.

Cerebellum↗

Cord blood cytokines and soluble adhesion molecules in vaginal and cesarean delivered neonates.

OBJECTIVE: Our purpose was to evaluate the effect of labor pain on the concentrations of cytokines and soluble adhesion molecules in cord blood. METHODS: Umbilical cord interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), granulocyte elastase (GEL), intercellular adhesion molecule-1 (ICAM-1), and endothelial lymphocyte adhesion molecule-1 (ELAM-1) were measured in 21 normal appropriately grown newborns delivered vaginally (VD group), and 20 normal appropriately grown newborns delivered by elective cesarean section (ECS group). Umbilical cord arterial blood pH and PO2 were also measured. RESULTS: Umbilical artery blood pH and PO2 in the VD group were not significantly different from those in the ECS group. There were no significant differences for concentrations of IL-6, IL-8, TNF-alpha, GEL, ICAM-1, and ELAM-1 in cord blood between VD and ECS groups. CONCLUSION: These results suggests that labor pains do not affect the concentrations of cytokines and soluble adhesion molecules in cord blood.

Adult↗