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Biomedical subjects

Takashi Miura

Publications and source records attributed to Takashi Miura.

At least 19 recordsLinked to original sources
PubMed2007

Hemodilutional anemia impairs neurologic outcome after cardiopulmonary bypass in a piglet model.

OBJECTIVES: The effect of hemodilution on neurologic outcome after cardiopulmonary bypass remains unclear. We studied the influences of hematocrit on cerebral oxygenation and neuropathologic outcome in a piglet model. METHODS: Eleven piglets (9.3 +/- 1.1 kg) were randomized into 2 groups. Five piglets (group H) received a total blood prime resulting in a high hematocrit (33.0% +/- 2.3%), and 6 piglets (group L) received a crystalloid prime resulting in a low hematocrit (14.0% +/- 3.2%). Both groups underwent 90 minutes of moderate hypothermic cardiopulmonary bypass (28 degrees C) with alpha-stat strategy. Cerebral oxygenation was monitored by near-infrared spectroscopy. Group L received a blood transfusion immediately after cardiopulmonary bypass to reach the postoperative target hematocrit of 30%. The brain was fixed in situ 6 hours after weaning from cardiopulmonary bypass, and a histologic score for neurologic injury was assessed. RESULTS: There were no significant differences in arterial blood gas analyses throughout the experiment between the groups. Mean arterial pressure, mixed venous oxygen saturation, and heart rate were significantly higher in group H compared with group L during hypothermia. Oxyhemoglobin and total hemoglobin signals detected by near-infrared spectroscopy were significantly lower in group L (analysis of variance, P < .0001), although the tissue oxygenation index was not different during cardiopulmonary bypass. Group L showed a poorer histologic score compared with group H (P = .0071). CONCLUSIONS: Excessive hemodilution, such as a hematocrit of less than 15%, may be associated with a high incidence of neurologic injury. Further studies are required to determine the safety limits of hematocrit during pediatric cardiopulmonary bypass.

Anemia↗
PubMed2006

Mathematical analysis of a free-boundary model for lung branching morphogenesis.

Lung branching morphogenesis has been widely studied in the field of developmental biology. Lung airway trees consist of relatively regular-sized distal branches, but how this regular branched pattern is formed is not well understood. In the present study, we undertake a detailed mathematical analysis of the model proposed in (Hartmann & Miura (2006), which numerically captures branching morphogenesis of the simplest possible experimental system in vitro. We investigate analytically the stability of 1D travelling waves with respect to periodic perturbations in two dimensions. This linear stability analysis leads to the so-called dispersion relations, predicting that a certain representative length dominates in this model. As the analytical analysis is restricted to travelling waves, we generalize the linear analysis to any 1D solution by numerical simulations. Both results predict how the representative lengths will change by experimentally changing specific parameters. Finally, we discuss the importance of the analytical results from a biological point of view and propose an experimental scheme for a quantitative comparison between experiments and theory.

Algorithms↗
PubMed2006

Tissue preferential expression of estrogen receptor gene in the marine snail, Thais clavigera.

Sex steroid hormones have been widely detected in molluscs, and experiments have shown the importance of sex steroids in sex determination, gonadal tissue maturation and gametogenesis. Nevertheless, the signaling pathways of sex steroids in invertebrates have not yet been elucidated. In order to gain insights into the mechanism of sex steroid signaling in molluscs, we have, therefore, tried to isolate molluscan estrogen receptors from the prosobranch mollusc Thais clavigera. Cerebral ganglia of T. clavigera (Mollusca, Gastropoda, Prosobranchia) were subjected to RNA extraction, and degenerate primers for amino acid sequences conserved in vertebrate estrogen receptors were designed. PCR amplification using cerebral RNA and degenerate primers followed by 5'- and 3'-RACE identified the cDNA encoding T. clavigera estrogen receptor 1 (tcER1). The deduced amino acid sequence showed 93% identity in the DNA-binding domain and 72% identity in the ligand binding domain when compared to Aplysia estrogen receptor. Reporter gene assay revealed that tcER1 is constitutively active and unresponsive to estrogen. Quantitative analysis of the tcER1 mRNA level demonstrated the preferential expression in the ovary. Furthermore, cerebral ganglia expressed tcER1 at a high level in the spring followed by subsequent enlargement of the ovary in later seasons. These results suggest importance of tcER1 in the seasonal development of reproductive organs in T. clavigera.

Amino Acid Sequence↗
PubMed2006

Modelling in vitro lung branching morphogenesis during development.

It has been shown experimentally that lung epithelial explants have an ability to undergo branching morphogenesis without mesenchyme. However, the mechanisms of this phenomenon remain to be elucidated. In the present study, we construct a mathematical model that can reproduce the dynamics of in vitro branching morphogenesis. We show that the system is essentially governed by three variables--c(0) which is the initial fibroblast growth factor (FGF) concentration, D which is the diffusion coefficient of FGF, and beta which describes the mechanical strength of the cytoskeleton. It is confirmed by numerical simulations that this model can reproduce the experimentally obtained patterns qualitatively. Finally, we experimentally verify two predictions from the model: effects of very high FGF concentration and effects of small mechanical contributions of the cytoskeleton. The theoretical predictions match well with the experimental results.

Animals↗
PubMed2006

Re-operation for tetralogy of Fallot with single right coronary artery.

A 7-year-old girl with tetralogy of Fallot in association with a single right coronary artery, was successfully re-operated on for right ventricular outflow tract obstruction. To identify the course of the abnormal coronary arteries during the re-operation, a probe was directly inserted into the coronary arteries after aortotomy. Ventriculotomy was successfully performed under the guide of the probe, without damaging the coronary arteries. Double outflow technique was applied for the relief of the right ventricular outflow tract obstruction.

Child↗
PubMed2006

[High-dose chemotherapy with peripheral blood stem cell auto transplantation for an intractable case of mediastinal seminoma].

HDC with PBSCT is effective for some intractable cases with malignant neoplasma. We encountered an intractable case of mediastinal seminoma treated by HDC with PBSCT. The patient was a 25-year-old man with mediastinal seminoma. He had undergone chemo-radiotherapy several times and salvage surgery for the mediastinal tumor and chest wall recurrence since September 2001. He was referred to our clinic for management of recurrent seminoma in the chest wall in January 2004. In our clinic, chemo-radiotherapy consisting of cisplatin and etoposide was performed. The tumor size decreased transiently, but re-growth was observed 2 months after chemo-radiotherapy. We then performed HDC with PBSCT twice without any lethal complication. Now, the patient is well and disease-free 1 year after HDC with PBSCT.

Adult↗
PubMed2006

Thymidine phosphorylase levels and dihydropyrimidine dehydrogenase levels in non-small cell lung cancer tissues.

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are the major catabolic enzymes of 5-FU. In this study, we analyzed the concentration of TP and DPD in non-small cell lung cancer tissue by enzyme-linked immunosorbent assay. We measured the TP and DPD levels in 25 adenocarcinoma tissues and 25 squamous cell carcinoma tissues. The mean TP concentration in non-small cell lung cancer tissue was statistically higher than that of normal lung tissue as was the mean DPD concentration. The ratio of the TP level to DPD level in tumor tissue was higher in squamous cell carcinoma than in adenocarcinoma. No significant difference could be detected between the TP level, DPD level, or TP/DPD level and the tumor size or lymph node metastasis. In conclusion, chemotherapy with 5-FU may be more effective in squamous cell lung cancer patients than lung adenocarcinoma patients from the result of the ratio of TP to DPD.

Adenocarcinoma↗
PubMed2005

Mixed-mode pattern in Doublefoot mutant mouse limb--Turing reaction-diffusion model on a growing domain during limb development.

It has been suggested that the Turing reaction-diffusion model on a growing domain is applicable during limb development, but experimental evidence for this hypothesis has been lacking. In the present study, we found that in Doublefoot mutant mice, which have supernumerary digits due to overexpansion of the limb bud, thin digits exist in the proximal part of the hand or foot, which sometimes become normal abruptly at the distal part. We found that exactly the same behaviour can be reproduced by numerical simulation of the simplest possible Turing reaction-diffusion model on a growing domain. We analytically showed that this pattern is related to the saturation of activator kinetics in the model. Furthermore, we showed that a number of experimentally observed phenomena in this system can be explained within the context of a Turing reaction-diffusion model. Finally, we make some experimentally testable predictions.

Animals↗
PubMed2005

Copper reduction by the octapeptide repeat region of prion protein: pH dependence and implications in cellular copper uptake.

The physiological function of the prion protein (PrP) remains enigmatic despite its established involvement in the pathogenesis of spongiform encephalopathies. PrP is a glycolipid-anchored membrane protein, which constitutively recycles between the cell surface and an endosomal compartment. The N-terminal region of PrP contains a four tandem repeat (OP4) of the octapeptide PHGGGWGQ (OP) that binds and reduces Cu(II) ions. We have examined the kinetic properties of the OP4-mediated Cu(II) reduction and found that OP4 exhibits the highest reduction activity around pH 6.5, close to the pH in early endosomes. All four OP units and at least one tryptophan side chain are essential for Cu(II) reduction. The reaction is described by an uncompetitive substrate inhibition mechanism involving a 1:1 Cu(II)-OP4 active intermediate. Structural analysis by Raman spectroscopy has revealed that the Cu(II) ion is coordinated by four histidine Ntau atoms in the active intermediate and the feasibility of formation of this intermediate correlates with the Cu(II) reduction over a pH range from 5.0 to 8.2. Molecular mechanics calculations suggest that two tryptophan residues of OP4 are located near the Cu(II) site, being consistent with the importance of redox-active tryptophan in the Cu(II) reduction. PrP has been proposed to capture Cu(II) ions in the extracellular space and release them in the endosome. The results of this study strongly suggest that PrP also plays a role in the reduction of captured Cu(II) ions prior to their transfer to Cu(I)-specific intracellular copper trafficking proteins.

Amino Acid Sequence↗
PubMed2005

Disruption of actin cytoskeleton and anchorage-dependent cell spreading induces apoptotic death of mouse neural crest cells cultured in vitro.

In vertebrate embryos, neural crest cells emigrate out of the neural tube and contribute to the formation of a variety of neural and nonneural tissues. Some neural crest cells undergo apoptotic death during migration, but its biological significance and the underlying mechanism are not well understood. We carried out an in vitro study to examine how the morphology and survival of cranial neural crest (CNC) cells of the mouse embryo are affected when their actin cytoskeleton or anchorage-dependent cell spreading is perturbed. Disruption of actin fiber organization by cytochalasin D (1 microg/ml) and inhibition of cell attachment by matrix metalloproteinase-2 (MMP-2; 2.0 units/ml) were followed by morphologic changes and apoptotic death of cultured CNC cells. When the actin cytoskeleton was disrupted by cytochalasin D, the morphologic changes of cultured CNC cells preceded DNA fragmentation. These results indicate that the maintenance of cytoskeleton and anchorage-dependent cell spreading are required for survival of CNC cells. The spatially and temporally regulated expression of proteinases may be essential for the differentiation and migration of neural crest cells.

Actins↗
PubMed2005

Spontaneous hemothorax in patients with von Recklinghausen's disease.

Spontaneous massive intrathoracic bleeding is rare except for the rupture of aortic aneurysm or pleural adhesions in association with pneumothorax. We encountered two cases of critical massive hemothorax in patients with von Recklinghausen's disease (type I neurofibromatosis). Case 1; a 59-year-old female suddenly experienced severe back pain followed by syncope and shock. The hemothorax was caused by a bleeding of diffuse type neurofibroma of the parietal pleura and she underwent thoracotomy and surgical ligation of the bleeding vessels. Case 2; a 46-year-old male suddenly suffered back pain and fainted while driving. An intercostal aneurysmal rupture caused a spontaneous hemothorax and he underwent chest tube drainage followed by endovascular coil embolization. We reviewed 23 cases reported in the literature, including our two cases. Spontaneous hemothorax in patients with von Recklinghausen's disease is a life-threatening syndrome and may require emergency surgical or endovascular embolization.

Acute Disease↗
PubMed2005

Successful treatment of an adult patient with pulmonary abscess secondary to congenital cystic adenomatoid malformation.

We report a case of a 29 year old male who at age 25, developed a pulmonary abscess in the left lower lobe. A left lower lobectomy was performed following two recurrences on antibiotic treatment. The result of histopathological examination confirmed congenital cystic adenomatoid malformation (CCAM), a congenital disease characterized by multiple cysts resulting from adenomatous hyperplasia of the bronchial epithelia. In many cases, respiratory distress occurs during the neonatal period, and in about 80-85% of patients, CCAM is diagnosed before the age of two years due to respiratory infection. CCAM which was diagnosed in adulthood is very rare.

Adolescent↗
PubMed2005

Homeobox B3, FoxA1 and FoxA2 interactions in epithelial lung cell differentiation of the multipotent M3E3/C3 cell line.

HOM/C homeobox (Hox) and forkhead box (Fox) factors are reported to be expressed in the foregut endoderm and are subsequently detected in a spatio-temporal pattern during lung development. Some of these factors were reported to influence the expression of lung marker proteins or to modulate lung development. To clarify the molecular mechanisms for generating functional lung cells from progenitor cell populations, we introduced the forkhead box factors, FoxA1 and FoxA2, and the homeobox factor, HoxB3, into the differentiation process in a multipotent hamster lung epithelial M3E3/C3 cell line. Ectopic expression of FoxA2 promoted differentiation to Clara-like cells with up-regulation of the expression of the lung marker proteins, Clara cell-specific 10-kDa protein and surfactant protein-B. In contrast, FoxA1 repressed the differentiation. HoxB3 transfection induced FoxA2 expression transiently at the pre-differentiation stage. The endogenous HoxB3 expression level decreased at later stages of Clara-like cell differentiation, and the attenuation was enhanced by FoxA2 transfection. HoxB3 is a putative upstream regulator that enhances FoxA2 expression at the pre-differentiation stage. In addition, we found that the expression of HoxA4, HoxA5, and HoxC9 increased differentially during Clara-like cell differentiation. These results suggest that HoxB3 may be a putative positive regulator of FoxA2 expression at the pre-differentiation stage, and those interactions of Fox factors and Hox factors could participate in Clara cell differentiation.

Animals↗
PubMed2005

[A case of pulmonary langerhans cell histiocytosis presenting disappearance of coalescing air wall cysts after smoking cessation].

A 17-year-old adolescent was admitted to Oita University Hospital with non-productive cough and exertional dyspnea. She had been smoking approximately 10 cigarettes per day for two years. When the patient was three years old, she underwent surgical removal of skull tumor of Langerhans cell histiocytosis. Initial chest CT scans showed coalescing thick-walled air cysts surrounded by micronodules in both lungs, most predominantly in the middle and upper lung fields. Bronchoalveolar lavage fluid contained 2.3% of CD1a-positive cells and video-assisted thoracoscopic lung biopsy disclosed granulomatous lesions consisting of histiocytic cells containing S-100 protein but without CD68 antigen allowing a diagnosis of pulmonary Langerhans cell histiocytosis. She stopped smoking, resulting in spontaneous resolution of the coalescing air cysts which were replaced by funicular scarring within two years. In case of extra-pulmonary Langerhans cell histiocytosis in children, the close relationship between cigarette smoking and pulmonary involvement should be informed to the parents to prevent the patient starting smoking in the future.

Adolescent↗
PubMed2004

Multiple calcifying fibrous tumors of the pleura.

Calcifying fibrous tumor (CFT) is a rare lesion characterized histologically by hypocellular hyalinized collagenous tissue with psammomatous and/or dystrophic calcifications and patchy lymphoplasmacytic infiltrates. CFT usually occurs in the somatic soft tissue of children and young adults but is rarely found in the pleura. We describe here an unusual case of multiple small CFTs in the right mediastinal pleura of a 54-year-old man who had a history of renal cell carcinoma. Suspecting pulmonary and pleural metastases, we performed wedge resection of the right middle lobe and local excision of two nodules in the right pleura. Light microscopy revealed metastatic lesions of renal cell carcinoma in the resected wedge. The pleural nodules were well circumscribed and composed of hypocellular, dense, hyalinized, collagenous tissue with scant lymphoplasmacytic infiltration and characteristic psammoma bodies. Immunohistochemical staining revealed that most spindle cells were positive for vimentin, CD34 and factor XIIIa, and negative for epithelial membrane antigen, keratin, smooth-muscle actin, desmin, S-100 protein and anaplastic lymphoma kinase. We made a histological diagnosis of CFT of the pleura, and the patient remains well 6 months after the wedge resection.

Calcinosis↗
PubMed2004

Delayed bronchial stenosis after blunt chest trauma with right aortic arch.

We report a case of delayed bronchial stenosis after blunt chest trauma with right aortic arch. A 21-year-old male passenger was involved in a traffic accident. He was brought to an emergency hospital with severe chest pain and dyspnea, and diagnosed with multiple rib fractures, right hemopneumothorax and chylothorax. He was treated with chest tube drainage and the symptoms subsided. About 9 weeks later, he complained of exertional dyspnea and was referred to our hospital. Bronchoscopy demonstrated circumferential stenosis of the right main bronchus approximately 1 cm distal to the carina. Thoracic computed tomography and magnetic resonance imaging revealed the right aortic arch. Successful resection of the bronchial stenotic lesion was performed followed by end-to-end anastomosis through midsternotomy due to the associated right aortic arch. Postoperative bronchoscopy revealed that the site of the anastomosis was patent and his symptoms were relieved.

Adult↗
PubMed2004

Speed of pattern appearance in reaction-diffusion models: implications in the pattern formation of limb bud mesenchyme cells.

It has been postulated that fibroblast growth factor (FGF) treatment of cultured limb bud mesenchyme cells reinforces the lateral inhibitory effect, but the cells also show accelerated pattern appearance. In the present study, we analyze how a small change in a specific parameter affects the speed of pattern appearance in a Turing reaction-diffusion system using linear stability analysis. It is shown that the sign of the change in appearance speed is qualitatively decided if the system is under the diffusion-driven instability condition, and this is confirmed by numerical simulations. Numerical simulations also show that a small change in parameter value induced easily detectable differences in the appearance speed of patterns. Analysis of the Gierer-Meinhardt model revealed that a change in a single parameter can explain two effects of FGF on limb mesenchyme cells-reinforcement of lateral inhibition and earlier appearance of pattern. These qualitative properties and easy detectability make this feature a promising tool to elucidate the underlying mechanisms of biological pattern formation where the quantitative parameters are difficult to obtain.

Animals↗