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Biomedical subjects

H Ohuchi

Publications and source records attributed to H Ohuchi.

At least 19 recordsLinked to original sources

Sonic hedgehog facilitates dopamine differentiation in the presence of a mesencephalic glial cell line.

The aim of this study was to establish a cellular system to investigate the requirement for cell surface and diffusible molecules in the differentiation of fetal mesencephalic cells toward the dopamine lineage. Toward this end, we immortalized rat embryonic day 14 (E14) mesencephalon with a regulatable retroviral vector encoding v-myc. The stably transduced cells were pooled and designated as VME14 cells. VME14 cells proliferated rapidly, stopped proliferating, extended processes, and expressed GFAP after suppression of the v-myc expression with tetracycline, suggesting that VME14 cells differentiated into glial cells. Dissociated cells derived from the E11 rat mesencephalon gave rise to only a small number of tyrosine hydroxylase (TH)-positive neurons. However, when grown on a monolayer of the differentiated VME14 cells, a significantly higher number of cells differentiated into TH-positive neurons. VME14 cells were transduced with the secreted N-terminal cleavage product of the Sonic hedgehog gene (SHH-N), an inducer of mesencephalic dopaminergic neurons. This monoclonal, SHH-N-overexpressing cell line further enhanced dopaminergic differentiation of E11 rat mesencephalon cells. Thus, SHH-N and signals derived from fetal mesencephalic glia act cooperatively to facilitate dopaminergic differentiation. These fetal mesencephalon-derived cell lines will provide tools for the study of signals involved in dopaminergic differentiation.

Animals↗

Influence of ventricular morphology on aerobic exercise capacity in patients after the Fontan operation.

OBJECTIVES: This study investigated the influences of ventricular morphology, hemodynamics and clinical findings on exercise capacity in patients after the Fontan operation. BACKGROUND: Determinants of exercise capacity after the Fontan operation remain unclear. METHODS: Peak oxygen uptake (PVo2) was determined in 105 patients by exercise test and compared to hemodynamics and clinical findings. Patients were divided into three groups based on ventricular morphology: those with a right ventricle (group RV), a biventricle (group BV) and a left ventricle (group LV). RESULTS: Ten patients with atrioventricular valve regurgitation (AVVR) or hypoxia exhibited a low PVo2. After excluding these patients, although PVo2 did not correlate with hemodynamics, except ventricular ejection fraction (p < 0.02), it correlated with age at the Fontan operation and exercise test (p < 0.002). The PVo2 was higher in group LV (63+/-9%) than in groups RV (55+/-9%) and BV (55+/-12%) (p < 0.01), while an inverse correlation between PVo2 and age at operation was demonstrated only in group RV (p < 0.05). Groups RV or BV and age at exercise test were associated with a lower PVo2, whereas group LV was an independent predictor of a higher PVo2 (p < 0.01). During 4.2 years of follow-up, a decrease in peak heart rate was related to a decrease in PVo2 (p < 0.05). The PVo2 decreased in group RV (p < 0.01). CONCLUSIONS: In addition to AVVR, hypoxia, and heart rate response, ventricular morphology is related to exercise capacity. Early Fontan operation may be beneficial in terms of exercise capacity, especially in the group RV patients.

Adolescent↗

Cloning and expression of the chick p63 gene.

We have isolated a chick cDNA for p63, a member of the p53 transcription factor family. This cDNA encodes a protein of 582 amino acids for an alpha isoform in the C-terminal region, while lacking the N-terminal transactivation domain. The chick p63 gene is first expressed in the prospective cutaneous ectoderm at stage 6 and later in the developing epithelia. The p63 expression is intense in specialized epithelial structures, such as apical ectodermal ridge of the limb bud, epithelia of branchial arches and feather buds. Furthermore, we have found that the transcripts are detected in the interdigital epithelium, intersomite epithelium, and epaxial dermamyotome.

Amino Acid Sequence↗

Differential expression of two BMP antagonists, gremlin and Follistatin, during development of the chick feather bud.

Expression of four BMP antagonist genes, noggin, chordin, gremlin and Follistatin, was examined during chick feather development. Although expression of noggin and chordin was not detected, gremlin and Follistatin were expressed differentially in feather buds. The differential expression patterns of gremlin and Follistatin change dynamically from the nascent inter-feather bud region to the posterior domain of the feather bud.

Animals↗

Coagulation profile, hepatic function, and hemodynamics following Fontan-type operations.

We analyzed retrospectively the relationship between coagulation profile, and either hepatic function or hemodynamics, in patients who had undergone a Fontan-type procedure, comparing them, first, with a control group of 12 patients without significant hemodynamic abnormality, and, second, with a group of 14 patients who had not undergone a Fontan procedure, but whose mean right atrial pressure exceeded 8 mmHg. Follow-up catheterization had been performed in all 30 patients submitted to the Fontan-type operation. Prothrombin time, and factor XIII, were significantly lower in those who had undergone the Fontan procedure than in the other groups. Those submitted to the Fontan operation also had lower levels of protein C than controls, and their levels of plasminogen were lower than the patients with high right atrial pressure. Both aspartate aminotransferase and alanine aminotransferase were higher in those undergoing the Fontan procedure than in the other groups, while gamma-glutamyltranspeptidase in these patients was higher than in the control group. Mean right atrial pressure was highest in those undergoing the Fontan procedure, while cardiac index was lowest. Prothrombin time was correlated to some extent with aspartate aminotransferase, mean right atrial pressure, and cardiac index. Protein C correlated with both aspartate aminotransferase and mean right atrial pressure, while factor XIII correlated with alanine aminotransferase, mean right atrial pressure, and cardiac index. Aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltranspeptidase, parameters of hepatic function, correlated significantly with mean right atrial pressure. In those who had undergone the Fontan procedure, decreased synthesis of pro-and anti-coagulant factors is a risk factor for both thrombosis and bleeding. Abnormal hemodynamics, in the absence of a right sided pumping chamber, may predispose to subclinical hepatic dysfunction, leading to selective disturbances of protein synthesis.

Adolescent↗

[Clinical outcome and analysis of radical prostatectomy in clinical stage B and C prostate cancer].

Between 1989 and 1999, 40 patients treated with radical prostatectomy for clinical stage B and C prostate cancer were analyzed. Prostate-specific antigen (PSA) failure after radical prostatectomy occurred in four patients, and one of them died of clinical recurrence of prostate cancer. Cause-specific survival at 5 years was 91.7% and PSA failure-free rate at 5 years was 76.8%. Staging accuracy of CT and MRI image was not satisfactory. In 41.7% patients, extracapsular extension can not be determined. Preoperative serum PSA levels of pathologically organ-confined disease (OCD) patients were significantly lower than those of pathologically non-OCD patients. Further analysis indicated that preoperative serum PSA levels of greater than 20.1 ng/ml are useful predictors for pathologically non-OCD.

Aged↗

[Study of neoadjuvant chemotherapy for invasive bladder cancer with MEC (methotrexate, epirubicin, cisplatin) therapy].

Eighteen patients with locally invasive bladder cancer were treated with 1 or 2 cycles of neoadjuvant chemotherapy consisting of methotrexate, epirubicin and cisplatin (MEC). All patients underwent radical cystectomy and pelvic lymph node dissection. Down-staging was observed in twelve (complete pathological response in 3 and partial pathological response in 9) patients (response rate were 67%). Four of the 18 patients died of disease and all of them had not achieved down-staging. Multivariate analysis revealed nodal status to be the only independent predictor. With regard to side effects, gastrointestinal symptoms and myelo-suppression were observed in almost all patients. Thrombocytopenia was observed in 13 patients (72%) including 7 patients who showed symptoms over grade 3. Gastro-intestinal symptoms and leukocytopenia disappeared with granisetron and granulocyte colony stimulating factor. There were no treatment-related deaths in this study. These results indicate that MEC therapy was safely performed and showed a high response rate in patients with locally invasive bladder cancer.

Aged↗

[Diagnosis of prostate capsular invasion by pelvic magnetic resonance imaging and serum level of prostate specific antigen].

Transrectal ultrasonography (TRUS), computed tomography (CT), and magnetic resonance imaging (MRI) are employed to diagnose the clinical stage of prostate cancer. However, several cases are diagnosed as pathological stage pT3 after total prostatectomy. We investigated the accuracy of the evaluation of pathologic capsular penetration by preoperative pelvic MRI and preoperative serum PSA level and capsular penetration. The diagnostic accuracy of capsular penetration by MRI was 63.3%. On the other hand, the diagnostic accuracy of capsular penetration by preoperative PSA was 89.7% when its cut off value was 17 ng/ml. We conclude that preoperative serum PSA level could be more useful to diagnose accurately stage of prostate cancer than pelvic MRI.

Aged↗

[High pressure occlusion of leukocyte depletion arterial line filter in patients with cardio-pulmonary bypass surgery].

Cardio-pulmonary bypass (CPB) leads the activation of neutrophil, which may cause reperfusion organ dysfunction. Utility of using the leukocyte depletion arterial filter to pretend postoperative complications has been reported. The other side, the risk of the leukocyte depletion filter occlusion with high-pressures of CPB arterial line (high-pressure occlusion) has been noted. We used the leukocyte deletion filter (LG-6, Pall), and experienced two cases of high-pressure occlusion in 421 CPB surgery with LG-6 (0.48%). No high-pressure occlusion was occurred with 1,508 patients used the standard arterial line filter in it period (0%, p = 0.007). In the both cases of high-pressure occlusion, monitored arterial line pressure increased to over 340 mmHg within 10 minutes after CPB installation. The filters were changed to standard type, then no more filter trouble was occurred. In the second case, we inspected the occluded LG-6. Light microscopic survey showed eosin stained small spherical cells (HE) and negative for fibrin (PTAH). Electromicroscopy revealed that spherical cells (1-2 microns) adherated to structure of the filter. No fibrin was detected with Gel electrophoresis. Because of the pathologic analysis, the cells, which might cause the filter occlusion, were platelet. In addition, no fibrin exist suggests that the coagulation system did not relate to the high-pressure occlusion. In conclusion, we experienced two high-pressure occlusion cases of the leukocyte depletion arterial filter with CPB surgery (0.48%); the filter occlusion may be caused by the initial thrombus formation by platelet.

Aged↗

Abnormal cardiac autonomic nervous activity after right ventricular outflow tract reconstruction.

BACKGROUND: There are few studies of cardiac autonomic nervous activity (CANA) in patients with congenital heart disease. Methods and Results-We evaluated CANA in 54 patients after closure of an atrial/ventricular septal defect (group A), 54 patients after successful right ventricular outflow tract reconstruction (RVOTR) (group B1), 35 RVOTR patients with residual stenosis (group B2), and 47 controls. Cardiac parasympathetic nervous activity (PSNA) was estimated by heart rate (HR) change after cholinergic blockade, HR variability, and arterial baroreflex sensitivity (BRS). Cardiac sympathetic nervous activity was estimated by the heart-to-mediastinum (123)I-metaiodobenzylguanidine activity ratio (H/M) and HR increase after isoproterenol infusion (ss). HR response (DeltaHR) and peak oxygen uptake (VO(2)) were measured by exercise test. There was no difference in ss among study groups. Group A exhibited mildly impaired PSNA, which recovered 1 year after surgery, and no change in H/M. Impaired PSNA and low H/M were found in groups B1 and B2 compared with controls (P<0.001), although the PSNA tended to recover 1 year after re-RVOTR. In group B1, PSNA and ss were related to DeltaHR, and BRS correlated inversely with the number of surgical procedures and age at RVOTR and positively correlated with the follow-up period, whereas DeltaHR correlated with peak VO(2) (P<0.01 to 0.001). CONCLUSIONS: After RVOTR, postsynaptic ss-sensitivity is maintained and is important in DeltaHR during exercise, as is PSNA, although ventricular sympathetic denervation is common. Impaired PSNA immediately after RVOTR improves with improved DeltaHR and results in future amelioration of aerobic capacity, whereas ventricular sympathetic reinnervation is uncertain.

Adolescent↗

FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development.

FGF receptor 2 isoform IIIb (FGFR2b), originally discovered as a receptor for FGF7, is known to be an important receptor in vertebrate morphogenesis, because FGFR2b null mice exhibit agenesis or dysgenesis of various organs, which undergo budding and branching morphogenesis. Since FGF7 null mice do not exhibit marked defects in organogenesis, it has been considered that other FGF(s) than FGF7 might function as a major ligand for FGFR2b during organogenesis. One of the candidate ligands is FGF10, because FGF10 binds to FGFR2b with high affinity and the formation of the limb and lung is arrested in FGF10 null mice as found in FGFR2b-deficient mice. Previous analyses of FGF10 null mice revealed that FGF10 is required for limb and lung development. To elucidate the role of FGF10 in wide-range organogenesis, we further analyzed the phenotypes of the FGF10 knockout mice. We found diverse phenotypes closely related to those for FGFR2b-deficient mice, which includes the absence of thyroid, pituitary, and salivary glands, while minor defects were observed in the formation of teeth, kidneys, hair follicles, and digestive organs. These results suggest that FGF10 acts as a major ligand for FGFR2b in mouse multi-organ development.

Animals↗

Ventilatory response to exercise in patients with major aortopulmonary collateral arteries after definitive surgery.

Patients with pulmonary atresia and major aortopulmonary collateral arteries (MAPCAs) may be at risk for both ventilatory impairment and abnormal pulmonary circulation after definitive surgery. We measured the ventilatory response to exercise in 16 patients with MAPCAs after definitive surgery (group A) and compared the results with those in 16 patients with tetralogy of Fallot with pulmonary atresia and without MAPCAs after definitive operation (group B), with 24 patients with tetralogy of Fallot after one-stage repair without previous palliation (group C), and with 48 healthy subjects (group D). Pulmonary function and treadmill exercise tests were performed. Arterial blood gases were also analyzed and the dead space to tidal volume ratio calculated. In group A, the vital capacity, diffusion capacity, and peak oxygen uptake were lowest (p <0.001), whereas the ventilatory equivalent for carbon dioxide was highest and its value at peak exercise correlated with age at time of surgery (r = 0.73, p <0.002). The arterial oxygen tension decreased progressively in group A and its value at peak exercise inversely correlated with the mean pulmonary artery pressure in all patients (r = -0.75, p <0.001). The arterial carbon dioxide tension decreased significantly at peak exercise in controls but showed no change in group A. The dead space to tidal volume ratio decreased during exercise in patients without MAPCAs and in controls but increased in group A, and the dead space to tidal volume ratio at peak exercise was inversely correlated with vital capacity in all patients (r = -0.77, p <0.001). Diffusion capacity independently predicted arterial carbon dioxide tension and dead space ventilation during exercise. Marked restrictive ventilatory impairment with low diffusion capacity along with a pulmonary obstructive change contributed to the abnormal pulmonary gas exchange during exercise in group A. Earlier repair of MAPCAs may prevent the progression of the impaired ventilatory response to exercise in these patients.

Adolescent↗

Clinical effects of ventricular assist system in end-stage cardiac failure. Advantages of left ventricular blood drainage for recovery from cardiac dysfunction.

OBJECTIVES: Heart transplantation is extremely limited currently in Japan. As a consequence ventricular assist system implantation is employed the patient falls into end-stage cardiogenic shock. This preliminary report describes our initial clinical experience with use of 2 kinds of ventricular assist system for 13 Japanese patients. METHODS: 7 patients were supported by a left ventricular assist system with blood drainage from the left atrium (LA drainage Group) using a Toyobo ventricular assist system, while another 6 patients were supported by a left ventricular assist system with blood drainage from the left ventricle (LV drainage Group) using the Toyobo ventricular assist system (1 patient) or TCI-LVAS (5 patients). RESULTS: The average duration of ventricular assist system support in the LV drainage Group was 112 days including two on-going patients (now at 39 days and 241 days) and in the LA drainage Group was 49 days. The average left ventricular ejection fraction at 3 weeks after ventricular assist system implantation was improved from 12.3 to 54% using the TCI-LVAS and from 14 to 33% using the Toyobo ventricular assist system with drainage from the left ventricle. However, this was decreased from 20 to 10% using the Toyobo ventricular assist system with drainage from the left atrium. The ventricular assist system was explanted in 4 patients (31%) with recovery of cardiac dysfunction and 3 were long survivors. The 2 on-going patients are awaiting heart transplantation. Thus the current survival rate overall is 38%. The survival rate (67%) is excellent in the LV drainage Group including 2 long survivors after explantation. CONCLUSION: Ventricular assist system support with drainage from the left ventricle seems to be more advantageous for cardiac functional recovery than from the left atrium for end-stage heart failure.

Adult↗

Development and clinical application of minimally invasive cardiac surgery using percutaneous cardiopulmonary support.

OBJECTIVES: Optimal cardiopulmonary support during minimally invasive cardiac surgery remains controversial. We developed cardiopulmonary bypass for minimally invasive cardiac surgery using percutaneous peripheral cannulation. METHODS: Subjects were 34 patients (age: 58 +/- 13 years; range: 17-73) undergoing minimally invasive cardiac surgery using percutaneous cardiopulmonary support between June 1997 and March 1999. Procedures included atrial septal defect closure (n = 14), partial atrioventricular septal defect closure (n = 1), mitral valve replacement (n = 8), mitral valve repair (n = 3), aortic valve replacement (n = 6), coronary artery bypass grafting (n = 1), and right atrial myxoma extirpation (n = 1). Bicaval venous drainage from the right internal jugular vein and the femoral vein and arterial return to the femoral artery were instituted by percutaneous cannulation. Venous drainage was implemented by negative pressure (-20 to -40 mmHg) and arterial return was by conventional roller pump. All procedures were conducted through a skin incision 8 +/- 1 cm, from 6 to 10 cm and partial sternotomy. Aortic cross clamping and cardioplegic solution were administered in the surgical field. RESULTS: The operation lasted 224 +/- 45 min., cardiopulmonary bypass 104 +/- 32 min., and aortic clamping 77 +/- 23 min.. No deaths occurred. One patient with residual atrial septal defect required reoperation through the same skin incision. Only 1 patient required homologous blood transfusion. The average postoperative hospital stay was 15 +/- 5 days. CONCLUSIONS: Minimally invasive cardiac surgery using percutaneous cardiopulmonary support is safe and an excellent option for selected patients affected by single valve lesion, simple cardiac anomalies, and coronary artery bypass grafting.

Adolescent↗

Involvement of fibroblast growth factor (FGF)18-FGF8 signaling in specification of left-right asymmetry and brain and limb development of the chick embryo.

To elucidate roles of fibroblast growth factors (FGF)18 during vertebrate development, we examined expression patterns of Fgf18 in chick embryos and observed effects of FGF18 protein on the Hensen's node, isthmus, and limb buds. Fgf18 is expressed on the right side of the node before the expression of Fgf8 starts. FGF18 protein can induce expression of Fgf8 on the left side of the node, indicating involvement of both FGFs in specification of left-right asymmetry. In the developing brain, Fgf18 is expressed in the isthmus, following the Fgf8 expression. Since Fgf18 is induced ectopically during formation of the second midbrain by FGF8 protein, both FGFs also elaborate midbrain development. In the limb bud, Fgf18 is expressed in the mesenchyme and ectopic application of FGF18 protein inhibits bone growth in the limb. FGF18 is thus likely an endogenous ligand of FGF receptor 3, whose mutation causes bone dysplasia in humans. These results demonstrate that the FGF18-FGF8 signaling is involved in various organizing activities and the signaling hierarchies between FGF18 and FGF8 seem to change during patterning of different structures.

Amino Acid Sequence↗