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Biomedical subjects

Yuji Miyamoto

Publications and source records attributed to Yuji Miyamoto.

At least 19 recordsLinked to original sources

The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage.

The tumor suppressor p53 plays a crucial role in the cellular response to DNA damage by transcriptional activation of numerous downstream genes. Although a considerable number of p53 target genes have been reported, the precise mechanism of p53-regulated tumor suppression still remains to be elucidated. Here, we report a novel role of the DFNA5 gene in p53-mediated etoposide-induced cell death. The DFNA5 gene has been previously reported to be responsible for autosomal-dominant, nonsyndromic hearing impairment. The expression of the DFNA5 gene was strongly induced by exogenous and endogenous p53. The chromatin immunoprecipitation assay indicated that a potential p53-binding sequence is located in intron 1 of the DFNA5 gene. Furthermore, the reporter gene assay revealed that the sequence displays p53-dependent transcriptional activity. The ectopic expression of DFNA5 enhanced etoposide-induced cell death in the presence of p53; however, it was inhibited in the absence of p53. Finally, the expression of DFNA5 mRNA was remarkably induced by gamma-ray irradiation in the colon of p53(+/+) mice but not in that of p53(-/-) mice. These results suggest that DFNA5 plays a role in the p53-regulated cellular response to genotoxic stress probably by cooperating with p53.

Animals↗

Ruptured giant aneurysm of the ascending aorta caused by chronic aortic dissection.

A 55-year-old man developed acute chest pain and dyspnea. Computed tomography demonstrated a rupture of a giant aneurysm of the ascending aorta. The lesion was 14 cm in diameter--the largest ever reported-and resulted from chronic aortic dissection. The patient did not have aortic insufficiency or aortic dissection around the coronary ostium. Graft replacement of the ascending aorta was performed successfully under deep hypothermia with right hemisphere perfusion.

Aortic Dissection↗

Effect of high-frequency jet ventilation on oxygenation during one-lung ventilation in patients undergoing thoracic aneurysm surgery.

PURPOSE: To evaluate the effect of high-frequency jet ventilation (HFJV) and continuous positive airway pressure (CPAP) on oxygenation and the shunt fraction (Qs/Qt) during one-lung ventilation (OLV). METHODS: Twenty-five patients who were undergoing resection of a descending aortic aneurysm were studied. Arterial oxygenation, Qs/Qt, and hemodynamics were evaluated just before the initiation of OLV (T1), 15 min after OLV (T2), and 15 min (T3) and 30 min (T4) after the application of HFJV or CPAP to the nondependent lung. RESULTS: There were no significant changes in the mean arterial blood pressure (MAP), heart rate (HR), central venous pressure (CVP), or mixed venous partial pressure of oxygen throughout this study. The arterial partial pressure of oxygen (Pa(O2)) values after the application of HFJV or CPAP increased significantly, from 173.8 +/- 39.6 mmHg (T2) to 344.1 +/- 87.9 mmHg (T3) and 359.9 +/- 82.4 mmHg (T4) in the HFJV group (P < 0.05), and from 153 +/- 38.5 mmHg (T2) to 243 +/- 48.5 mmHg (T3) and 249.7 +/- 55.0 mmHg (T4) in the CPAP group (P < 0.05). The shunt fraction decreased significantly after the initiation of HFJV or CPAP, from 38.7% +/- 8.9% (T2) to 27.0% +/- 8.0% (T3) and 25.9% +/- 8.7% (T4) in the HFJV group (P < 0.05), and from 44.6% +/- 8.6% (T2) to 34.3% +/- 10.2% (T3) and 32.6% +/- 8.5% (T4) in the CPAP group (P < 0.05). The arterial saturation of oxygen (Sa(O) (2)) increased significantly after the application of either HFJV or CPAP (P < 0.05). CONCLUSIONS: Both HFJV and CPAP can improve oxygenation during OLV.

Adult↗

Large vessel - sternum adhesion after cardiac surgery; a risk-factor analysis.

PURPOSE: To study the clinical results of resternotomy in patients with dense and direct adhesion between the large vessels and the sternum, and define the morphologic features of the adhesion. METHODS: Between 2000 and 2003, 67 patients with a history of cardiac surgery underwent median resternotomy. We studied each patient's profile and the measurements taken from preoperative computed tomography scans. We then conducted multivariate logistic regression analysis to determine the predictive morphologic features of adhesion between the large vessels and the sternum in these 67 patients. RESULTS: Twenty (29.9%) of the 67 patients had direct adhesion between the large vessels and the sternum. Sternal re-entry was performed without injury to the large vessels in 18 (90%) but the aorta was injured in 2 (10%) patients, resulting in catastrophic hemodynamic disorder and operative death in one. Multivariate logistic regression analysis revealed that an extracardiac conduit and a high occupying rate of the aorta and pulmonary artery in the mediastinal space were significant morphologic factors. CONCLUSION: The morphologic features of large vessels to sternal dense adhesion as possible risk factors for injury to the large vessels are the presence of an extracardiac conduit and a large ascending aorta or pulmonary artery in relation to the mediastinal space.

Adult↗

Unusually high serum levels of lactate dehydrogenase without perivalvular leakage following double valve replacement: predictor of tetany attack after thyroidectomy.

A 57-year-old woman who complained of exertional dyspnea was diagnosed as having severe aortic valve stenosis and mitral valve regurgitation. The patient underwent double valve replacement with a mechanical prosthesis. Postoperative laboratory data showed unusually high serum lactate dehydrogenase (LDH) levels, even though no perivalvular leakage was detected by echocardiography. Tetany occurred suddenly owing to hypoparathyroidism, which seemed to be a late complication after thyroidectomy. After calcium administration, the symptoms dramatically diminished, as did the serum LDH levels. Hypoparathyroidism should be doubted if serum LDH levels increase higher than the normal range following valve replacement without obvious perivalvular leakage.

Aortic Valve Stenosis↗

Identification of Mycobacterium species by comparative analysis of the dnaA gene.

For the establishment of a diagnostic tool for mycobacterial species, a part of the dnaA gene was amplified and sequenced from clinically relevant 27 mycobacterial species as well as 49 clinical isolates. Sequence variability in the amplified segment of the dnaA gene allowed the differentiation of all species except for Mycobacterium tuberculosis, Mycobacterium africanum and Mycobacterium microti, which had identical sequences. Partial sequences of dnaA from clinical isolates belonging to three frequently isolated species revealed a very high intraspecies similarity, with a range of 96.0-100%. Based on the dnaA sequences, a species-specific primer set for Mycobacterium kansasii and Mycobacterium gastri was successfully designed for a simple loop-mediated isothermal amplification method. These results demonstrate that the variable sequences in the dnaA gene were species specific and were sufficient for the development of an accurate and rapid diagnosis of Mycobacterium species.

Animals↗

Identification and characterization of the genes involved in glycosylation pathways of mycobacterial glycopeptidolipid biosynthesis.

Glycopeptidolipids (GPLs) are major components present on the outer layers of the cell walls of several nontuberculous mycobacteria. GPLs are antigenic molecules and have variant oligosaccharides in mycobacteria such as Mycobacterium avium. In this study, we identified four genes (gtf1, gtf2, gtf3, and gtf4) in the genome of Mycobacterium smegmatis. These genes were independently inactivated by homologous recombination in M. smegmatis, and the structures of GPLs from each gene disruptant were analyzed. Thin-layer chromatography, gas chromatography-mass spectrometry, and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analyses revealed that the mutants Deltagtf1 and Deltagtf2 accumulated the fatty acyl-tetrapeptide core having O-methyl-rhamnose and 6-deoxy-talose as sugar residues, respectively. The mutant Deltagtf4 possessed the same GPLs as the wild type, whereas the mutant Deltagtf3 lacked two minor GPLs, consisting of 3-O-methyl-rhamnose attached to O-methyl-rhamnose of the fatty acyl-tetrapeptide core. These results indicate that the gtf1 and gtf2 genes are responsible for the early glycosylation steps of GPL biosynthesis and the gtf3 gene is involved in transferring a rhamnose residue not to 6-deoxy-talose but to an O-methyl-rhamnose residue. Moreover, a complementation experiment showed that M. avium gtfA and gtfB, which are deduced glycosyltransferase genes of GPL biosynthesis, restore complete GPL production in the mutants Deltagtf1 and Deltagtf2, respectively. Our findings propose that both M. smegmatis and M. avium have the common glycosylation pathway in the early steps of GPL biosynthesis but differ at the later stages.

Bacterial Proteins↗

Graft replacement and muscle wrap for infected aneurysm of thoracic aorta.

A 68-year-old man was admitted with high fever and enlargement of the distal aortic arch on chest radiography. Computed tomography showed a huge proximal descending thoracic aortic aneurysm. Graft replacement of the proximal descending thoracic aorta was performed on an emergency basis, and a pectoralis major muscle flap was wrapped around the graft. Salmonella enteritidis was detected in the resected tissue. The patient recovered well, with no signs of infection.

Aged↗

Preparation and pharmaceutical evaluation of liposomes entrapping salicylic acid/gamma-cyclodextrin conjugate.

To evaluate the potential use of a drug/cyclodextrin (CyD) conjugate for efficient entrapment in liposomes and prolonged residence of a drug in tissues, we synthesized a salicylic acid (SA) conjugate bound covalently with gamma-cyclodextrin (SA/gamma-CyD conjugate), a model drug/CyD conjugate, and then liposomes entrapping the conjugate (conjugate-in-liposome) were prepared by a freezing-thawing method. The chemical and physicochemical properties of the SA/gamma-CyD conjugate in solution and solid state were investigated and then the physicochemical properties of conjugate-in-liposome, in vitro cellular uptake/release and in vivo disposition of SA/gamma-CyD conjugate after intravenous administration of aqueous suspension containing conjugate-in-liposome in rats, were evaluated, comparing with those of the liposome-entrapped SA alone (SA-in-liposome) or the liposome-entrapped noncovalent SA/gamma-CyD complex (complex-in-liposome). As a result, it was found that the conjugate was amorphous powder and the release of SA from the conjugate in phosphate-buffered saline (PBS) was tolerated to chemical and enzymatic degradation. Meanwhile, the particle sizes and stability of these liposomes were almost identical, and the entrapment ratio of SA/gamma-CyD conjugate in liposomes was higher than those of SA alone and SA/gamma-CyD complex. The cellular uptake of these liposomes was almost equivalent, but the release of SA/gamma-CyD conjugate from RAW264.7 cells was markedly slower, compared with that of SA from cells following cellular uptake of the SA-in-liposome and complex-in-liposome. The disposition of SA or SA/gamma-CyD conjugate following intravenous administration of aqueous suspensions containing each liposome system in rats was comparable, but the residence time of the conjugate in tissues significantly prolonged, compared with that of the SA-in-liposome and complex-in-liposome systems. These results suggest the potential use of SA/gamma-CyD conjugate for efficient entrapment in liposomes as well as of liposomes containing SA/gamma-CyD conjugates for prolonged residence of drugs in tissues.

Animals↗

[Partial response of liver metastasis from colon cancer following intermittent oral administration of TS-1 after intra-hepatic arterial single injection of CDDP, doxorubicin and 5-FU].

An intrahepatic arterial injection of CDDP, doxorubicin and 5-FU, followed by 17 courses of oral TS-1 administration (80 mg/day x 14 days, q=28 days), induced a partial response for 9 months after 18 months of stable disease in a 76-year-old male with asynchronous liver metastasis due to ascending colon cancer. TS-1 showed an excellent anticancer effect against colorectal metastatic liver cancers for a long time without loss of QOL or safety.

Administration, Oral↗

Therapeutic angiogenesis induced by injecting hepatocyte growth factor in ischemic canine hearts.

PURPOSE: Therapeutic angiogenesis, induced by the direct injection of angiogenic growth factors or by transmyocardial laser revascularization (TMLR), has shown great potential as a new therapeutic strategy for end-stage coronary artery disease. However, no significant differences in angiogenic effects of TMLR and vascular endothelial growth factor (VEGF) have been reported. We compared the effects of the intramyocardial injection of hepatocyte growth factor (HGF), a novel angiogenic factor, with those of TMLR, by evaluating the improvement in regional blood flow and regional function in a canine heart model of chronic ischemia. METHODS: To create a model of chronic ischemia, we ligated the left anterior descending artery (LAD) in 15 beagles. We divided the dogs into three groups according to the treatment given 1 month after ligation. Four dogs were given an intracardial injection of human recombinant HGF (H group), six dogs were given TMLR (T group), and five dogs were used as a control (C group). We compared the degree of improvement in regional blood flow and regional function 1 month after the treatment. RESULTS: The regional myocardial blood flow and function were significantly better in the H group than in the T or C groups (P < 0.05). Histologically, there were significantly more von Willebrand factor-positive cells in the LAD region in the H group than in the T or C groups. CONCLUSION: The intramural injection of recombinant human HGF resulted in therapeutic angiogenesis with an intrinsic contractile state, and it may have greater advantages than TMLR for the treatment of chronic ischemic heart disease.

Animals↗

Successful mitral valve replacement in a patient with Ehlers-Danlos syndrome type VI.

A 40-year-old patient with Ehlers-Danlos syndrome type VI (ocular type) had mitral regurgitation due to mitral valve prolapse. Because the patient's tissue was fragile, we replaced the mitral valve with a reinforced prosthetic valve to prevent paravalvular leakage. The excised mitral leaflet showed significant myxomatous change and decrease in collagen fibers. We believe this is the first report of cardiac surgery in a patient with Ehlers-Danlos syndrome type VI.

Adult↗

The effect of gene transfer with hepatocyte growth factor for pulmonary vascular hypoplasia in neonatal porcine model.

BACKGROUND: Severe degree of pulmonary vascular hypoplasia remains a major limitation in congenital heart surgery. Considering the potential effect of gene transfer with hepatocyte growth factor to induce the angiogenesis in the lung, we assessed the effects of hepatocyte growth factor gene transfer in neonatal porcine lung with pulmonary vascular hypoplasia to achieve treatment for severe pulmonary vascular hypoplasia. METHODS: The model of pulmonary vascular hypoplasia was introduced with left pulmonary artery banding in piglet lung. After 7 days of pulmonary artery banding, piglets were transfected selectively to the left lung via the left pulmonary artery with a hemagglutinating virus of Japan E vector bearing the cDNA encoding human hepatocyte growth factor (H group) or control vector (C group). RESULTS: Seven days after the transfection, selective angiography of the left pulmonary artery showed the progression of left pulmonary vascular hypoplasia of the left lung in the C group but a significant attenuation of left pulmonary vascular hypoplasia in the H group. A right pulmonary artery occlusion test showed a marked increase in right ventricular systolic pressure in the C group, but this was significantly attenuated in the H group (C: 22.0 +/- 2.9, H: 13.0 +/- 2.7 mm Hg; P < .05). Histologic examination revealed that hepatocyte growth factor gene transfection increased the pulmonary vasculature in the left lung. CONCLUSIONS: Our results demonstrated that gene transfer of hepatocyte growth factor via the pulmonary artery showed the angiogenic effects in porcine model of pulmonary vascular hypoplasia after pulmonary artery banding.

Angiography↗

Mechanical ventricular assist system required for sustained severe cardiac dysfunction secondary to peripartum cardiomyopathy.

A 29-year old woman developed severe congestive heart failure in the first week after an uneventful full-term delivery. Despite intense medical treatment over the next 6 months, her heart failure symptoms gradually worsened and she eventually developed cardiogenic shock. She successfully underwent the implantation of a left ventricular assist system, but because there was no sign of recovery of ventricular function, she was placed on the waiting list for heart transplantation. After 143 days of support, she suffered from brain hemorrhage, and eventually died after a total of 321 days of left ventricular support. Postmortem examination of the myocardium showed sustained diffuse fibrosis and no inflammatory reaction. This case implies that with severe peripartum cardiomyopathy heart transplantation should be considered without delay even if a mechanical assist system is available.

Adult↗

[Current advances in leprosy research activities].

Due to the advent of multi-drug therapy (MDT) recommended by the WHO, for the treatment of leprosy, presently, leprosy is regarded as a "curable disease". The number of new cases in Japan is relatively very low, due to which the disease is likely to be neglected, but on scientific grounds, there is a necessity to perform in depth studies. Leprosy caused by M. leprae is still unclear on various aspects including transmission, immunology, nerve damage etc. Here we introduce the recent advances in the field of basic leprosy research.

Animals↗

Aggregation of mycobacteria caused by disruption of fibronectin-attachment protein-encoding gene.

The fibronectin-attachment protein (FAP) is conserved among several species of mycobacteria. Although this protein is associated with attachment and internalization of bacteria to host cells via fibronectin, the physiological role of the protein still remains unclear. To investigate this point, we generated FAP gene disruptant in Mycobacterium smegmatis. The gene disruption, verified by Southern blot and PCR analysis, induced changes on the bacteria, which are associated with strong aggregation and alteration of cell surface properties. Increased hydrophobicity and Congo red accumulation was observed in the FAP gene disruptant. In addition, the complementation experiment demonstrated that the corresponding gene restored wild type morphology in the disruptant. These results indicate that the FAP affects the cell surface properties, and its deletion lead to enhanced aggregation of the M. smegmatis.

Adhesins, Bacterial↗