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Biomedical subjects

N Matsuda

Publications and source records attributed to N Matsuda.

At least 37 records · Page 2Linked to original sources

Regional cardiac sympathetic reinnervation in transplanted human hearts detected by 123I-MIBG SPECT imaging.

The purpose of this study was to assess the regional cardiac sympathetic reinnervation late (> or = 1 year) after heart transplantation (HTX) by means of 123I-MIBG (MIBG) scintigraphy. Eight patients with a pretransplantation diagnosis of idiopathic dilated cardiomyopathy underwent MIBG scintigraphy more than one year after HTX. The presence or absence of regional MIBG uptake was evaluated in each SPECT image, and global MIBG uptake was semi-quantitatively assessed by the heart to mediastinum ratio (H/M). Five of 8 patients had visible MIBG uptake in both planar and SPECT images (PU group), whereas 3 of 8 patients had no uptake, 2 of them after a period of 2 years, and one of them as long as 5 years after HTX, respectively (NU group). Positive regional MIBG uptake involved the basal anterior region in all 5 patients, the basal septal region in 4 patients, the basal lateral region in 3 patients and the basal posterior region in 1 patient. The H/M value was 1.24+/-0.10 in the PU group and 1.09+/-0.03 in the NU group. In conclusion, MIBG SPECT can detect regional sympathetic reinnervation, indicating that basal septal and lateral regions next to the basal anterior are more likely to be reinnervated, but reinnervation is much less likely to occur in the midventricular and apical regions.

3-Iodobenzylguanidine↗

Plasma brain natriuretic peptide as a parameter to assess efficacy of continuous intravenous infusion of prostacyclin (epoprostenol) to treat severe primary pulmonary hypertension: a case report.

Continuous intravenous infusion of prostacyclin (epoprostenol) as a treatment for primary pulmonary hypertension (PPH) definitely improves the patient's quality of life, but few accurate parameters have been found to evaluate the efficacy of the treatment. We observed a patient with severe PPH whose plasma brain natriuretic peptide (BNP) level changed significantly as her condition and symptoms changed. Plasma BNP may be considered as one of the parameters for assessing the efficacy of prostacyclin treatment.

Adolescent↗

Differential gene transcriptional regulation of Gi isoforms and Gs protein expression in diabetic rat hearts.

Many cardiac diseases can be associated with alterations in the function and quantity of G proteins. We examined the gene expressions and protein levels of Gi-1alpha, Gi-2alpha, Gi-3alpha and G(s alpha) in ventricular myocardial preparations from rats 4-6 weeks after induction of diabetes with streptozotocin in comparison with those from age-matched control rats. Diabetic rat myocardium exhibited reductions in the protein levels of Gi-2alpha and Gi-3alpha by 22+/-2% and 57+/-2%, respectively. In diabetes, 22% and 53% reductions in myocardial mRNA levels of Gi-2alpha and Gi-3alpha were observed. Although a faint protein signal of Gi-1alpha was detectable, no apparent expression of mRNA for Gi-1alpha was found in either control or diabetic myocardium. The reduced protein and mRNA levels of Gi-2alpha and Gi-3alpha were prevented by insulin therapy. No change was found in the protein and mRNA levels of G(s alpha) in diabetic myocardium. In conclusion, diabetes leads to a differential regulation of protein expressions of G(i alpha) isoforms and G(s alpha) in ventricular myocardium. The reduced expression of Gi-2alpha and Gi-3alpha proteins can be explained, at least in part, by the decreases in the transcriptional levels.

Animals↗

Modes of interaction between the Arabidopsis Rab protein, Ara4, and its putative regulator molecules revealed by a yeast expression system.

Ara4, a member of the Rab/Ypt GTPase family derived from Arabidopsis thaliana, causes severe growth inhibition when expressed in several yeast ypt mutants. Mutational analysis of ARA4 indicated that the Ara4 protein titrates at least three factors in yeast, including the GDP dissociation inhibitor (GDI). The coexpression of AtGDI1 (Arabidopsis GDI) suppressed the growth defect caused by Ara4 in yeast ypt1, suggesting that Ara4 and AtGDI1 interact in yeast to compensate for the titration of yeast GDI. We screened an Arabidopsis cDNA library for other suppressors that may also interact with Ara4 physiologically. A novel suppressor, SAY1, encoded a hydrophilic protein with two putative coiled-coil regions, which showed partial similarity to the yeast Vps27 protein. To understand the structural requirements of Ara4 for interacting with these molecules, we examined whether AtGDI1 and SAY1 could suppress the growth defect of ypt1 caused by various mutant versions of ARA4. The results indicated that the interaction between Ara4 and AtGDI1 depends on the conserved C-terminal Cys-motif and Thr44 in the effector domain of Ara4. In contrast, neither of these motifs is necessary for the interaction between Say1 and Ara4. This approach provides a powerful method to dissect complex interactions between a GTPase and its regulators.

Amino Acid Sequence↗

Overproduction of spinach betaine aldehyde dehydrogenase in Escherichia coli. Structural and functional properties of wild-type, mutants and E. coli enzymes.

Betaine aldehyde dehydrogenase (BADH) catalyzes the last step in the synthesis of the osmoprotectant glycine betaine from choline. Although betaine aldehyde has been thought to be a specific substrate for BADH, recent studies have shown that human and sugar beet BADHs also catalyze the oxidation of omega-aminoaldehydes. To characterize the kinetic and stability properties of spinach BADH, five kinds of expression vectors encoding full length, mature, E103Q, E103K, and chimera BADHs were constructed. These enzymes together with Escherichia coli BADH were expressed in E. coli and purified. The affinities for betaine aldehyde were similar in the spinach and E. coli BADHs, whereas those for omega-aminoaldehydes were higher in spinach BADH than in E. coli BADH. A chimera BADH in which part of the Rossmann type fold in the spinach BADH was replaced with that of E. coli BADH, showed properties which resembled spinach BADH more than E. coli BADH. The spinach E103K mutant was almost inactive, whereas the E103Q mutant showed a similar activity for the oxidation of betaine aldehyde to that of wild type BADH, but a lower affinity for omega-aminoaldehydes. All spinach BADHs were dimers whereas E. coli BADH was a tetramer. E. coli BADH was more stable at high temperature than spinach BADHs. The E103Q mutant was most labile to high temperature. These properties are discussed in relation to the structure of spinach BADH.

Aldehyde Oxidoreductases↗

Comparative study of quality of life between the Chinese and Japanese adolescent populations.

Researchers from Japan, China and Singapore have initiated a collaborative project, with the aim of comparing adolescent quality of life (QOL) internationally. This study presents the primary results of the investigation conducted in Beijing, China, and Kobe, Japan. The 70-item Quality of Life Questionnaire for Adolescents (QOLQA) was developed and evaluated in Japan and China. In total, 1114 Japanese and 613 Chinese junior high school students, aged 12-15 years, completed the questionnaire. Chinese students scored significantly higher than the Japanese students in overall QOL scores and in most domains. For both groups, subjects had highest score in the independence domain and lowest in psychological domain. In terms of overall QOL score, Chinese male students ranked first, followed by Chinese girls, Japanese boys, and Japanese girls. In the Japanese group, a continuing decrease of QOL scores with age was observed without exception, but no such tendency was present in their Chinese counterparts. No parallel relationship was observed between the higher level of economic development and better quality of life. The results also suggest that mental health promotion should be a priority in improving overall quality of life of adolescents both in Japan and China.

Adolescent↗

Prognostic significance of tumor grade for renal cell carcinoma.

BACKGROUND: The natural history and prognosis of renal cell carcinoma cannot be predicted. Based on the Japanese classification system, the value of nuclear grade were assessed as a possible prognostic factor for renal cell carcinomas. METHODS: In this retrospective study of 116 patients with renal cell carcinoma, radical nephrectomy was performed. Survival rates were calculated using the Kaplan-Meier method and multivariate analysis was performed using Cox's proportional hazard model. RESULTS: Distribution by stage and grade in the population of renal cell carcinomas was as follows: pT1 in 13 cases (11.3%), pT2 in 65 cases (56.5%), pT3 in 36 cases (31.3%) and pT4 in one case (0.9%) and grade 1, 28 (24.1%), grade 2, 69 (59.5%) and grade 3, 16 (13.8%). Three cases could not be determined because of pre-operative embolization of the renal cell carcinomas. Nuclear grade was correlated with stage (P=0.0002), the presence of perirenal fat involvement (P=0.003) and metastases (P=0.007). A significant difference in survival was found between grades 1 and 3 (P=0.0001) and grades 2 and 3 (P=0.0001), respectively. Survival was significantly correlated with sex (P=0.0125), tumor size (P=0.0001), the presence of lymph node metastasis (P=0.0001), renal vein involvement (P=0.0001), perirenal fat involvement (P=0.002) or distant metastasis (P=0.0001). The multivariate analysis showed that the occurrence of tumor grade (P=0.0006) or distant metastasis were independent prognostic values. CONCLUSION: The observations lead us to conclude that the nuclear grade according to the Japanese classification system appears to be of reliable prognostic value for renal cell carcinomas.

Adult↗

Regulation of coronary myoplasmic Ca(2+)-myosin light chain phosphorylation pathway and vasomotor tone: hyperpolarizing versus depolarizing cardioplegia.

BACKGROUND: This study was designed to compare the effects of hyperpolarizing versus depolarizing cardioplegic solutions on the coronary vasomotor regulation, specifically focusing on coronary myoplasmic Ca2+-myosin light chain (MLC) phosphorylation pathway and beta-adrenergic signal transduction. METHODS: With the use of an in vitro cardioplegic model, rat coronary microvessels loaded with fura-2 were subjected to simulated cold (20 degrees C) cardioplegia and reperfused with Krebs solution for 60 minutes at 37 degrees C. Cardioplegia consisted of either (1) Krebs solution alone (control), (2) Krebs plus adenosine triphosphate-sensitive potassium channel opener (100 micromol/L pinacidil [PCO-CP]), (3) hyperkalemic cardioplegia (K(+) = 25 mmol/L [K-CP]), or (4) K-CP plus magnesium (Mg(2+) = 25 mmol/L; [K/Mg-CP]). RESULTS: At the endpoint of the cardioplegic period, K-CP resulted in a significant increase both in [Ca(2+)](i) and in MLC phosphorylation compared with control (both P <.05). In contrast, PCO-CP did not make any significant difference in these indices compared with control. After reperfusion, the relaxation responses to isoproterenol and forskolin after K-CP were significantly reduced (both P <.05 vs control) but were preserved after PCO-CP. K/Mg-CP provided comparable effects to PCO-CP. CONCLUSIONS: These results suggest that neither an activation of the coronary myoplasmic Ca(2+)-MLC phosphorylation pathway nor beta-adrenergic desensitization seen after exposure to depolarizing cardioplegia occurs with exposure to hyperpolarizing cardioplegia and magnesium-supplemented depolarizing hyperkalemic cardioplegia.

Animals↗

Impairment of cardiac beta-adrenoceptor cellular signaling by decreased expression of G(s alpha) in septic rabbits.

BACKGROUND: Abnormalities in the beta-adrenergic control of cardiac function play a role in the pathogenesis of several disease states. Because circulatory failure in patients with septic shock is known to be less responsive to catecholamines, we investigated whether the beta-adrenoceptor-linked signal transduction mechanisms are altered in the heart of a septic animal model METHODS: Rabbits were rendered endotoxemic by an intravenous injection of 100 microg/kg Escherichia coli lipopolysaccharide. Three and 6 h later, the myocardial tissues were used for the experiments. RESULTS: The positive inotropic response to isoproterenol was significantly impaired in papillary muscles isolated from septic rabbits compared with those from controls. The impaired inotropic responsiveness to isoproterenol was not prevented by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine, indicating no involvement of nitric oxide overproduction. Adenylate cyclase activity stimulated with isoproterenol and 5'-guanylyl imidodiphosphate was markedly reduced in septic myocardium. The contractile and adenylate cyclase responses to colforsin daropate, a direct adenylate cyclase activator, were unaffected by sepsis. Radioligand binding experiments with (-)[125I]iodocyanopindolol revealed no significant alteration in myocardial beta-adrenoceptor density or affinity in sepsis. Determination of cardiac G(s alpha) level by Western blotting showed a reduction of approximately 50% in sepsis. The relative content of G(s alpha) messenger RNA in septic myocardium also was reduced from the control level by about 50%, as determined by Northern blot analysis. Little change was found in protein and messenger RNA levels of G(s alpha) in septic myocardium. CONCLUSIONS: Impairment of myocardial functional responsiveness to beta-adrenoceptor stimulation appears in the early stage of sepsis. The impaired response to beta-adrenoceptor stimulation in the heart in this pathologic state may result in part from a decreased level of G(s alpha) protein which occurs at the level of gene expression.

Adenylyl Cyclases↗

Effects of pinacidil on coronary Ca(2+)-myosin phosphorylation in cold potassium cardioplegia model.

The effects of the potassium (K(+)) channel opener pinacidil (Pin) on the coronary smooth muscle Ca(2+)-myosin light chain (MLC) phosphorylation pathway under hypothermic K(+) cardioplegia were determined by use of an in vitro microvessel model. Rat coronary arterioles (100-260 microm in diameter) were subjected to 60 min of simulated hypothermic (20 degrees C) K(+) cardioplegic solutions (K(+) = 25 mM). We first characterized the time course of changes in intracellular Ca(2+) concentration, MLC phosphorylation, and diameter and observed that the K(+) cardioplegia-related vasoconstriction was associated with an activation of the Ca(2+)-MLC phosphorylation pathway. Supplementation with Pin effectively suppressed the Ca(2+) accumulation and MLC phosphorylation in a dose-dependent manner and subsequently maintained a small decrease in vasomotor tone. The ATP-sensitive K(+) (K(ATP))-channel blocker glibenclamide, but not the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine methyl ester, significantly inhibited the effect of Pin. K(+) cardioplegia augments the coronary Ca(2+)-MLC pathway and results in vasoconstriction. Pin effectively prevents the activation of this pathway and maintains adequate vasorelaxation during K(+) cardioplegia through a K(ATP)-channel mechanism not coupled with the endothelium-derived NO signaling cascade.

Animals↗

Evidence for involvement of the PKC-alpha isoform in myogenic contractions of the coronary microcirculation.

The role of protein kinase C (PKC) isoforms in myogenic tone of the ferret coronary microcirculation was investigated by measuring fura 2 Ca(2+) signals, PKC immunoblots, contractile responses, and confocal microscopy of PKC translocation. Phorbol ester-evoked contractions were completely abolished in the absence of extracellular Ca(2+) but involved a Ca(2+) sensitization relative to KCl contractions. Immunoblotting using isoform-specific antibodies showed the presence of PKC-alpha and -iota and traces of PKC-epsilon and -mu in the ferret coronary microcirculation. PKC-beta was not detectable. When intraluminal pressure (40 to 60 and 80 mmHg) was increased, ferret coronary arterioles showed a transient increase in fura 2 Ca(2+) signals, whereas the myogenic tone remained sustained. The increase in Ca(2+) and tone was sustained at 100 mmHg. Isolated ferret coronary arterioles were fixed and immunostained for PKC-alpha at 40 and 100 mmHg intraluminal pressure. PKC translocation was determined by confocal microscopy. Increased PKC translocation was observed when vessels were exposed to 100 mmHg relative to that at resting pressure (40 mmHg). These results suggest a link between the Ca(2+) sensitization that occurs during the myogenic contraction and activation of the alpha-isoform of PKC.

Animals↗

Overexpression of PRA2, a Rab/Ypt-family small GTPase from Pea Pisum sativum, aggravates the growth defect of yeast ypt mutants.

A large number of Rab/Ypt-family small GTPases have been identified from higher plants. While some of them can complement yeast ypt mutants, the expression of Arabidopsis Ara4 protein aggravated the growth defect of a subset of ypt mutants, probably because of the titration of common regulator(s) of yeast Ypt proteins [Ueda, T. et al. (1996) Plant Cell, 8: 2079-20911. PRA2 from pea Pisum sativum encodes an interesting Rab GTPase whose expression is regulated by light [Yoshida, K. et al. (1993) Proc. Natl. Acad. Sci. USA, 90: 6636-6640]. We examined whether PRA2 complements any of the yeast ypt mutants and found again that PRA2 does not complement but rather confers the growth defect to some of the ypt mutants. No growth defect was observed when PRA2 was expressed in the wild-type yeast cells. Unlike the case of Ara4, neither Arabidopsis nor yeast GDI remedied the growth defect by Pra2, indicating that the mechanism of the exacerbation is different. Mutational analysis of PRA2 suggests that the growth inhibition can be ascribed to unidentified factor(s) which prefers the GTP-bound form of Pra2. This yeast system will be useful for identifying such putative regulatory factor(s) from yeast and plants and analyzing their interactions with Pra2.

Adaptor Proteins, Signal Transducing↗

Differential activation of ERK 1/2 and JNK in normal human fibroblast-like cells in response to UVC radiation under different oxygen tensions.

The mechanisms by which mitogen-activated protein kinases (MAPK) respond to the input of UV-induced signal transduction pathways and the resulting biological functions are not well understood. We investigated whether the level of oxygen tension of culture was responsible for the differential activation of MAPK and different cellular outcomes in UVC-irradiated cells. The intracellular oxidative level of normal human fibroblast-like cells in a normal atmosphere (normoxic, 20% O2) was increased within 30 min after UVC irradiation. When cells were cultured at lower oxygen tension in the presence of an antioxidant N-acetyl-L-cysteine (NAC) or under physiologically hypoxic (5% O2) conditions, the elevation of the oxidative level by UV-irradiation was significantly reduced. Among MAPK, extracellular-signal related kinase (ERK) 1/2 was activated by UV regardless of the oxidative level, while c-Jun N-terminal kinase (JNK) activation was inhibited in NAC-treated and in hypoxic cultures. In addition, in cultures at lower oxygen tension, there was less apoptosis and cell survival was enhanced. These results suggest that UV-induced oxidative stress was responsible for intracellular signaling through the JNK pathway. Furthermore, the balance between ERK1/2 and JNK activities after UV irradiation under different oxygen tensions possibly modified cellular outcome in response to UV.

Apoptosis↗

Predominant contribution of the G protein-mediated mechanism to NaF-induced vascular contractions in diabetic rats: association with an increased level of G(qalpha) expression.

The purpose of this study was to determine the mechanism responsible for alterations in NaF-induced contractions of blood vessels from streptozotocin-induced diabetic rats. In the presence of AlCl(3), NaF (>/=7.5 mM) produced significantly greater contractions in diabetic aorta and mesenteric artery compared with age-matched controls. Pretreatment with 1 microM nifedipine eliminated the enhanced contractile responses of diabetic vessels to NaF, resulting in no difference in the magnitude of NaF-induced contractions between control and diabetic vessels. In the presence of 100 microM deferoxamine, an Al(3+) chelator, NaF-induced contractions of diabetic vessels were markedly attenuated, whereas only the responses to lower concentrations of NaF were reduced in control vessels. No significant difference was found in the peak amplitude of transient contractions induced by 10 microM cyclopiazonic acid between control and diabetic vessels. The addition of 10 microM okadaic acid produced attenuated contractions in diabetic vessels. These findings indicate no involvement of the inhibitory effects of NaF on endoplasmic reticular Ca(2+)-pump ATPase and protein phosphatases in the genesis of the enhanced responsiveness of diabetic vessels to NaF. Western blot analysis showed a 2.5-fold increase in the expression of G(qalpha) in diabetic aortic membranes. In contrast, the G(ialpha) level was modestly decreased and the G(salpha) and G(betagamma) levels were unchanged in diabetes. The present results suggest that enhanced vascular contractions to NaF in diabetes is attributed predominantly to a G protein-mediated Ca(2+) channel activation that results from markedly increased G(qalpha) expression in vascular tissues under this pathological state.

Aluminum Chloride↗

[Equilibration period for PaO2 following alteration of FIO2 in mechanically ventilated patients].

To determine arterial oxygen tension (PaO2) in mechanically ventilated patients, we repeatedly measured arterial blood gas (ABG) to examine changes in PaO2 until equilibration following alteration of fractional concentrations of oxygen in inspired gas (FIO2). Forty anesthetized patients with normal arterial oxygenation were randomly assigned to one of four groups. Group 1 (n = 10): Arterial blood samples were drawn every one minute during a 15-min period of equilibration after change of FIO2 from 1.0 to 0.21. Then FIO2 was returned to 1.0 and the similar sampling was repeated. Group 2 (n = 10): The protocol was same as in Group 1 except for FIO2 targeted for 0.8 and 0.4. Group 3 (n = 10): Blood sampling was every two minutes during a 14-min period and repeated while FIO2 was altered as in Group 1. Group 4 (n = 10): The protocol was same as in Group 3 except for the target FIO2 similar to Group 2. PaO2 was stabilized in 4 min at earliest and in 6 min at latest after change of FIO2 in every settings of this study. In mechanically ventilated patients with normal arterial oxygenation, PaO2 could be stabilized after a 6-min period of equilibration following alteration of FIO2.

Blood Gas Analysis↗

[Hypercapnea after minitracheotomy].

Minitracheotomy is a useful procedure for the respiratory management of patients with sputum retention observed frequently in chronic lung disease and postoperative respiratory failure. However, we experienced a case of hypercapnea after minitracheotomy. An 83-year-old woman was scheduled for gastrectomy. She had respiratory failure of Hugh-Jones 5 with fibroid lungs and the infection with atypical Mycobacterium and MRSA. Her sputum was adhesive and showed persistent increase during pre- and intra-operative periods. After the operation, minitracheotomy was carried out against the sputum retention by using Portex Mini-Trach II kit. Hypercapnea, however, was observed in spite of no evidence of the surgical complications such as bleeding or inadequate care for sputum from the inserted tube. Bronchofiberscope revealed adhesive sputum stuck to the space between the inserted tube and the trachea. In this case, hypercapnea was improved by opening the top of the inserted tube and frequent care for sputum. In cases with a large amount of adhesive sputum, sputum retention may easily occur not only at the peripheral bronchial branch but also between the inserted tube and the trachea and it can cause hypercapnea which may be overlooked.

Aged↗

[Efficacy of continuous intravenous drip infusion of disopyramide in hypertrophic obstructive cardiomyopathy during cardiogenic shock: a case report].

A 54-year-old woman was admitted to our hospital complaining of dyspnea due to hypertrophic obstructive cardiomyopathy. On admission, she was treated with 4 antiarrhythmic drugs and 2 beta-blockers. After 4 of these 6 drugs were withdrawn, the left ventricular outflow pressure gradient markedly increased and then she fell into cardiogenic shock. Therefore, disopyramide(600 mg/day) was administered by continuous intravenous drip infusion to reduce the left ventricular outflow pressure gradient. After intravenous administration of disopyramide, the left ventricular outflow pressure gradient markedly decreased from 100 to 16 mmHg and the cardiogenic shock could be improved. Continuous intravenous drip infusion of disopyramide is effective for the treatment of cardiogenic shock due to severe left ventricular outflow obstruction in patients with hypertrophic obstructive cardiomyopathy.

Anti-Arrhythmia Agents↗

[Exploratory analysis of elevated C-reactive protein without leukocytosis from the clinical laboratory database].

We studied the characteristics of admitted patients who showed discrepancy between C-reactive protein(CRP) and white blood cell count(WBC). We extracted those patients from our laboratory information system by two criteria: WBC is less than 9500/microliter and either(1) CRP is more than 5.0 mg/dl, or(2) the pair of CRP and WBC is out of 95% confidence ellipse. We found 346 and 90 cases by the two criteria, respectively. They consisted of a variety of diseases, prevalent were such as pneumonia, rheumatoid arthritis, malignant lymphoma, post-operative state and so on by either criterion. There was predominance of elderly patients as a whole. The analysis of individual time courses revealed that WBC did not change in parallel with CRP in patients with rheumatoid arthritis and malignant lymphoma, while they paralleled in those with infectious diseases and post-operation states. The elevation of WBC in some patients might have been overlooked since WBC was not always to be ordered together with CRP. We need a prospective study to closely analyze serial relationship between CRP and WBC for factors leading to the discovery.

Aged↗