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Biomedical subjects

Jun Amano

Publications and source records attributed to Jun Amano.

At least 19 recordsLinked to original sources
PubMed2006

Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancer.

DNA hypermethylated gene promoter sequences are extremely promising cancer markers. Their use for risk assessment, early diagnosis, or prognosis depends on the timing of this gene change during tumor progression. We studied this for the proapoptotic gene ASC/TMS1 in lung cancer and used the findings to develop a sputum marker. ASC/TMS1 protein levels are reduced in all lung cancer types (30 of 40; 75%) but not in 10 preinvasive lesions. Hypermethylation of ASC/TMS1 is also associated with invasive cancers (41 of 152 or 27.0% of all lung cancer types) with variation in incidence between histopathologic types including 32.1% (26 of 81) of adenocarcinomas, 13.2% (7 of 53) of squamous cell carcinomas, 38.5% (5 of 13) of large-cell carcinomas, and 60% (3 of 5) of small-cell lung cancers. The hypermethylation is particularly correlated with late tumor stages being present in only 14% of stage I but 60% of later-stage tumors. The incidence of ASC/TMS1 hypermethylation in sputum DNA fully mimics the tissue findings being present in only 2% (2 of 85) of high-risk, cancer-free smokers, 15% (3 of 18) of patients with stage I non-small-cell lung cancer (NSCLC), but 41% of patients with stage III NSCLC (18 of 44), including 56% (10 of 18) of those with adenocarcinoma. Importantly, sputum is positive for this marker in 24% (10 of 42) of very high risk, clinically cancer-free individuals previously resected for stage I NSCLC. Thus, hypermethylation of ASC/TMS1 is a marker for late-stage lung cancer and, in sputum, could predict prognosis in patients resected for early-stage disease.

Adenocarcinoma↗
PubMed2006

Giant intraatrial septal aneurysm originating from a branch of the left coronary artery.

We present the case of a 38-year-old woman who had a large intraatrial aneurysm occupied by old thrombosis. The aneurysm was successfully removed, and the atrium was repaired. Pathohistological findings indicated that the inflow artery of the aneurysm had an anomalous origin from the left main coronary artery, and its pathogenesis was unknown. It is occasionally difficult to distinguish a large coronary aneurysm from a mediastinal tumor because this aneurysm is a rare entity, even more so in an atrial septum. A giant coronary aneurysm should be considered an alternative diagnosis in the event of a mediastinal mass. Surgery is recommended for a large coronary aneurysm.

Adult↗
PubMed2006

Genetically engineered Bifidobacterium longum for tumor-targeting enzyme-prodrug therapy of autochthonous mammary tumors in rats.

A fundamental obstacle in systemic therapy for cancer patients is the specific targeting of therapy directly to solid tumors. A strain of the domestic bacterium Bifidobacterium longum, which is non-pathogenic and anaerobic, showed selective localization to and proliferation within solid tumors after systemic application. Here, we propose a novel approach to cancer gene therapy in which anaerobic and non-pathogenic bacteria of the genus B. longum are used to achieve tumor-specific gene delivery and enzyme-prodrug therapy. We constructed a plasmid, pBLES100-S-eCD, which included eCD. Transfected B. longum produced CD in hypoxic tumors and achieved tumor site-specific conversion of 5-FC to 5-FU. Furthermore, we demonstrated antitumor efficacy in rat bearing autochthonous mammary tumors injected with the transfected B. longum directly or intravenously. This method was confirmed to be effective for enzyme-prodrug therapy not only by intratumoral injection but also by systemic administration. To estimate the toxicity of this bacterial vector, the systemic immunogenicity was evaluated by ASA reaction and the anaphylactic activity of IgG was evaluated by PCA reaction in guinea pigs. In the ASA reaction, no anaphylaxis symptoms were observed in any immunized guinea pigs injected with transfected B. longum. In the PCA reaction, B. longum/S-eCD specific-PCA-induced antibody was not detected. Thus, we proposed that anaerobic bacteria of the genus B. longum were an attractive and safe tumor-targeting vector and transfected B. longum was a potential anticancer agent that could effectively and specifically treat solid tumors.

Animals↗
PubMed2006

Therapeutic angiogenesis by bone marrow implantation for critical hand ischemia in patients with peripheral arterial disease: a pilot study.

OBJECTIVE: Implantation of bone marrow mononuclear cells (BM-MNCs), including endothelial progenitor cells, into ischemic lower limbs has been shown to improve symptoms in patients with peripheral arterial diseases (PAD). This study investigated whether BM-MNC implantation (BMI) is also effective for the ischemic hands of these patients. METHODS: Seven PAD patients with hand ischemia were enrolled: six patients had thromboangiitis obliterans and one had collagen disease. All seven had symptoms involving either resting pain or non-healing ischemic ulcers of the hand. Approximately 600 mL of MNCs were separated from BM and concentrated to a final volume of 40-50 mL, which were injected into ischemic hands. Ischemic status was evaluated by measuring the digital/brachial pressure index (DBI), visual analog pain scale, and the healing of ulcers before and 6 months after BMI. RESULTS: The mean number of implanted MNCs, CD34-positive cells, and CD34,133-positive cells was 3.67 +/- 0.53 x 10(9), 4.94 +/- 2.45 x 10(7), and 2.52 +/- 1.57 x 10(7), respectively. Mean DBI in those patients was 0.15 +/- 0.30 before BMI and significantly increased to 0.67 +/- 0.19 at 6 months after BMI (p = 0.004). All patients also showed improvement of pain scale and ischemic ulcers. There was no significant correlation between the number of implanted cells and improvement in the degree of DBI or the pain scale. CONCLUSION: Autologous BMI could be a promising and safe method of therapeutic angiogenesis for critical hand ischemia in PAD patients.

Adult↗
PubMed2006

Rupture of a large cell neuroendocrine carcinoma, causing early local recurrence.

We present a case of large cell neuroendocrine carcinoma (LCNEC) requiring an urgent operation due to a rupture-induced shock. Primary lung cancers rarely rupture. This event could have spread malignant cells. Our patient died of pleural dissemination at day 81 after the operation. We had difficulty diagnosing the lesion before rupture despite various examinations including biopsy. In cases of a large, growing, cavitating mass, we should consider the possibility of malignant tumor, and a surgical approach to prevent rupture. A ruptured malignant tumor may also be treated by adjuvant therapy rather than resection.

Carcinoma, Neuroendocrine↗
PubMed2006

A subtotal sternectomy successfully reconstructed with composix mesh.

Sternal tumors are uncommon, which often require extended resections with reconstructions. Various techniques have been used, including a choice of prostheses and the use of musculocutaneous flaps for reconstructions. A 74-year-old male presented with a metastatic sternal tumor. He underwent a subtotal sternectomy with partial resection of bilateral clavicles and ribs. A sternal reconstruction was performed with Composix mesh and pectoralis major (PM) muscle flaps. This prosthesis was thought to be very suitable due to the ease of handling, good stability, and prevention of adhesion. In comparison to conventional prostheses, these points could be advantageous.

Adenocarcinoma↗
PubMed2005

Successful surgical treatment for acute aortic dissection in pregnancy with Marfan's syndrome.

A 34-year-old pregnant woman with Marfan's syndrome in the 34th week of gestation was diagnosed with acute DeBakey type I aortic dissection. Immediately after cesarean section, she underwent emergent operation of combined total aortic arch and aortic root replacement using cardiopulmonary bypass, deep hypothermia and antegrade cerebral perfusion. Both maternal and fetal outcomes were good and uneventful. Pregnancy increases the risk of aortic dissection especially for patients with Marfan's syndrome. Moreover it should be noted that cardiac surgery using cardiopulmonary bypass and deep hypothermia generally results in fetal loss. If fetal maturity can be confirmed as in our case, cesarean section should be done before cardiovascular surgery. We describe here a case of successful operation for mother and infant at the 34th week of gestation.

Aortic Dissection↗
PubMed2005

Cardiac rupture after catheter ablation procedure.

We describe a patient in whom cardiac tamponade developed owing to left ventricular rupture after a catheter ablation procedure. Rapid surgical exploration and use of cardiopulmonary bypass facilitated safe repair of the injury site and survival of the patient without complications.

Cardiac Surgical Procedures↗
PubMed2005

Surgery for acute type A aortic dissection in pregnant patients with Marfan syndrome.

OBJECTIVE: Acute type A aortic dissection during pregnancy can be fatal to both the mother and the fetus. The goal of the present study was to characterize the prevalence, treatment and outcomes of this dangerous condition in an effort to determine optimal management. METHODS: A retrospective study was conducted using data from four Marfan patients with acute type A aortic dissection during pregnancy at our institution between 1991 and 2003. RESULTS: The mean gestational period at the time of operative repair was 31 weeks, with a range of 26-34 weeks, and the aortic root diameter ranged from 35 to 85 mm. Two of the four patients underwent a combined operation with cesarean section followed by aortic repair. One patient underwent operative aortic repair following spontaneous delivery. The final patient underwent aortic repair with the fetus remaining in situ. Median sternotomy and cardiopulmonary bypass were established via the femoral artery with direct right atria drainage and left atrial venting in all patients. Composite graft replacement combined with re-implantation of the coronary artery and aortic valve replacement were performed in three patients, and aortic valve replacement with coronary artery bypass grafting of the right coronary artery was performed in one patient. Three of four patients underwent aortic arch repair utilizing antegrade cerebral perfusion and deep hypothermia with total circulatory arrest. The patient that underwent operative correction with the fetus remaining in situ experienced fetal demise with miscarriage just after cardiac surgery, and the patient died 4 days later secondary to disseminated intravascular coagulation and multi-organ failure. The remaining three cases recovered uneventfully, and the mothers and babies were discharged in good condition. CONCLUSIONS: Based on these data, we advocate cesarean section with concomitant aortic repair for patients with Marfan syndrome and acute type A aortic dissection during pregnancy. Minimization of deep hypothermic circulatory arrest time is also recommended for cases in which the fetus remains in situ.

Adult↗
PubMed2005

Stimulation of P19CL6 with multiple reagents induces pulsating particles in vivo.

OBJECTIVE: Injection of stem cells into ischaemic areas of the heart is expected to be an effective method for myocardial regeneration. The embryogenic carcinoma (EC) cell line P19CL6 is known to differentiate into cardiomyocytes when cultured with dimethyl sulfoxide (DMSO) and is expected to be a promising source for regenerative therapy in cardiac disease. To establish a high-yield method of cardiomyocyte differentiation, P19CL6 cells were double-stimulated with 5-azacytidine. Double stimulation-induced cardiomyocytes were also transplanted into ectopic sites in mice and their function evaluated. METHODS AND RESULTS: To induce differentiation under adherent conditions, P19CL6 cells were incubated in growth medium with 10 microM 5-azacytidine for 24 h. After 5-azacytidine treatment, P19CL6 cells were incubated with 1% DMSO for nine days until they began to pulsate. Prior to transplantation, cells were treated again with 5-azacytidine. Differentiated cells were injected into the greater omentum, para-aorta region of the retroperitoneum and peri-femoral artery of adult BALB/c nude mice. Nine days after transplantation, irregularly pulsating tissues at a rate slower than the host heart were observed in the transplanted sites. Light microscopy showed formation of cardiac muscle tissues originating from P19CL6 cells. Differentiated cardiomyocytes were positive for cardiac troponin I, cadherin and alpha-smooth muscle actin, and the expressions of Csx/Nkx2.5 and GATA4 mRNAs were up-regulated. Electron microscopy demonstrated components specific to cardiomyocytes, such as Z-bands, desmosomes, fasciae adherens, myofibrils and mitochondria, which confirmed successful heterotopic cardiac muscle differentiation from P19CL6 cells. CONCLUSION: This study demonstrated high-yield cardiac muscle differentiation of P19CL6 by 5-azacytidine and DMSO double stimulation and successful formation of cardiac muscle-like tissue by ectopic transplantation of cardiomyocytes derived from P19CL6 into the retroperitoneal area as well as into the peripheral vessel area.

Adaptor Proteins, Signal Transducing↗
PubMed2005

A critical increase in right-to-left shunt after acute myocardial infarction in a 68-year-old male with tetralogy of Fallot.

A male patient with tetralogy of Fallot accompanied by aortic regurgitation had maintained sufficient exercise capacity for a number of decades with the status of acyanotic tetralogy of Fallot. When he was 67 years old, he suffered a posterior wall acute myocardial infarction and direct percutaneous coronary angioplasty successfully revascularised the target lesion in the left circumflex artery. However, a few months after the onset of the myocardial infarction, his shortness of breath became clinically significant and was associated with increased right-to-left shunt and increased right ventricular end-diastolic pressure, as well as hypoxia. At 68 years old, therefore, total corrective repair of the tetralogy with replacement of the aortic and pulmonary valves was performed. The patient was asymptomatic after the successful operation. This report suggests that coronary artery disease can be one of the potential factors in inducing critical hemodynamic changes in aging patients with congenital heart disease, especially those who have a shunt between the right and left chambers. The unique clinical course is described with some discussion of the repair of tetralogy in adults.

Aged↗
PubMed2005

A case of unilateral gravid macromastia in 23-year-old Japanese woman associated with elevated serum CA19-9.

We report a rare case of gravid macromastia (GM) treated after delivery. A 23-year-old woman with left breast enlargement was referred to our hospital. Laboratory investigations revealed an elevated serum CA19-9 level of 200.3 U/ml. Gravid macromastia was diagnosed by clinical examination (US, MRI) and 11G mammotome biopsy. Tumorectomy of the left breast and mammoplasty were performed. The mass had proliferated to the exclusion of normal gland. Histological examination revealed abundant proliferation of stromal loose connective tissue and interposed fat cells surrounding normal and lactating lobules. The epithelial cells were positive for CA19-9 on immunohistochemical staining. Serum CA19-9 decreased to normal levels 3 months after operation. GM is exceedingly rare and occurs in less than 0.001-0.003% of all pregnant women. Once established, the condition is likely to continue to successive pregnancies. This benign tumor is sometimes difficult to distinguish from malignant tumors since it shows few histological characteristics and grows rapidly. Attention is necessary to diagnose tumors of the breast during pregnancy.

Adult↗
PubMed2004

Suppression of acute and chronic rejection by hepatocyte growth factor in a murine model of cardiac transplantation: induction of tolerance and prevention of cardiac allograft vasculopathy.

BACKGROUND: Although treatment with immunosuppressive agents has contributed to overcoming acute rejection and improving the midterm survival of transplanted hearts, cardiac allograft vasculopathy (CAV) has remained the main cause of primary graft failure. Recent approaches have shown that hepatocyte growth factor (HGF) exhibits cardiotrophic functions. We therefore addressed whether HGF would regulate acute and chronic rejection in cardiac transplantation. METHODS AND RESULTS: We used a murine heterotopic cardiac transplantation model between fully incompatible strains and administered 500 microg x kg(-1) x d(-1) HGF during the initial 14 days after transplantation. The HGF-treated allografts showed significantly prolonged survival (42.3+/-4.1 days, P<0.001) compared with the controls (11.1+/-0.6 days), with tolerance induction in 47.4%. Histopathologically, the number of infiltrating cells was significantly decreased and myocardial necrosis was less prominent with a reduction of apoptosis in the allografts by HGF treatment during acute rejection. In the long-term surviving allografts, HGF significantly inhibited the development of CAV and interstitial fibrosis. With respect to intragraft cytokine mRNA expression, HGF treatment reduced the early expression of interferon-gamma and enhanced the expression of transforming growth factor-beta1 during the acute phase and of interleukin-10 continuously through the acute phase to the chronic phase. CONCLUSIONS: Our findings demonstrate that HGF can prolong the survival of allografts by its cardioprotective and immunomodulative potencies. Thus, HGF administration may constitute a new therapeutic approach to preventing cardiac graft failure that has not been overcome by conventional immunosuppressive agents.

Acute Disease↗
PubMed2004

Successful repair of aberrant right subclavian artery aneurysm combined with bicuspid aortic valve through a median sternotomy.

We report a case of a successfully repaired aberrant right subclavian artery aneurysm combined with bicuspid aortic valve using a multibranched vascular prosthesis. Approaching solely through a median sternotomy under cardiopulmonary bypass, hypothermic circulatory arrest, and selective cerebral perfusion, we performed a successful single-stage correction by aortic valve replacement, resection of aneurysm, and reconstruction of the right subclavian artery.

Aged↗
PubMed2003

Effects of expiratory pressure on nitric oxide in exhaled breath. Is exhaled nitric oxide really unaffected by pressure?

The measurements of exhaled nitric oxide (ENO) concentrations in several previous reports have been quite disparate but the cause of this variability is unclear. In the present study, we have attempted to elucidate the effects of expiratory pressure upon ENO values by taking measurements at pressures ranging from 2 to 10 cmH2O in control subjects and in both smokers and asthmatics. Differences in ENO concentrations (delta pNO) were then estimated and the concentration levels were found to increase with elevated expiratory pressure levels in both the control volunteers and in the asthmatics (under 2 and 3 L/min flow rates). These results indicate that changes in expiratory pressure indeed affect ENO concentrations. The measurement of ENO concentrations in human patients must therefore be undertaken using standard procedures that must incorporate expiratory pressure levels in order to properly interpret ENO values.

Adolescent↗
PubMed2003

Serine protease inhibitors modulate smoke-induced chemokine release from human lung fibroblasts.

Smoking is associated with lung inflammation and a protease-antiprotease imbalance. We previously reported that cigarette smoke extract (CSE) stimulates human lung fibroblasts to release chemotactic cytokines. We hypothesized that serine protease inhibitors might modulate lung fibroblast release of chemotactic cytokines in response to CSE. To test this hypothesis, serine protease inhibitors (FK706, alpha1-antitrypsin, methoxysuccinyl-Ala-Ala-Pro-Val chloromethyl ketone, or Nalpha-p-tosyl-L-lysine chloromethyl ketone) were evaluated for their capacity to attenuate the release of neutrophil chemotactic activity (NCA) and monocyte chemotactic activity (MCA) from human fetal lung fibroblasts by the blind-well chemotactic chamber. Metalloproteinases and cysteine proteinases were not examined in this study. Similarly, the release and gene expression of chemokines and nuclear factor-kappaB (NF-kappaB) activation were measured by means of enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. Release of NCA, MCA, chemotactic chemokines including interleukin-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and granulocyte-macrophage colony-stimulating factor, and the expression of interleukin-8 and monocyte chemoattractant protein-1 mRNA were attenuated by FK706. Furthermore, FK706 suppressed NF-kappaB activation. These data suggest that serine protease inhibitors attenuate the CSE-induced release of NCA and MCA from human fetal lung fibroblasts and that the inhibitory action of antiproteases might depend on NF-kappaB signaling pathway.

Benzoates↗
PubMed2003

Peroxynitrite enhances interleukin-10 reduction in the release of neutrophil chemotactic activity.

Peroxynitrite, formed by nitric oxide and superoxide, has been shown to nitrate and reduce the function of proinflammatory proteins such as interleukin (IL)-8, monocyte chemoattractant protein-1, and eotaxin, but in contrast, to enhance the function of the anti-inflammatory cytokine IL-10 in reducing IL-1 release from blood monocytes. However, the effect of nitrated IL-10 on release of proinflammatory cytokines from lung epithelial cells is unknown. We hypothesized that peroxynitrite would enhance the capacity of human IL-10 to reduce inflammatory mediators released by epithelial cells. To test this hypothesis, recombinant human IL-10 was evaluated for its capacity to attenuate the release of neutrophil chemotactic activity and IL-8 from a human epithelial cell line in response to IL-1 beta and tumor necrosis factor-alpha. Neutrophil chemotactic activity and IL-8 in lung epithelial culture supernatant fluids were significantly lower after culture with nitrated human IL-10 compared with non-nitrated human IL-10 controls (P < 0.05). Consistent with these results, nitrated human IL-10 attenuated IL-8 mRNA expression more than non-nitrated human IL-10 controls (P < 0.05). These data demonstrate that peroxynitrite exposed human IL-10 has enhanced anti-inflammatory activity and suggest that nitration may play a critical role in the regulation of inflammation within the lower respiratory tract.

Anti-Inflammatory Agents↗