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Biomedical subjects

Shinichiro Miyoshi

Publications and source records attributed to Shinichiro Miyoshi.

At least 19 recordsLinked to original sources

Pulmonary artery dissection complicating lung transplantation for primary pulmonary hypertension.

We report a case of pulmonary artery (PA) dissection complicating lung transplantation. A 30-year-old man with primary pulmonary hypertension underwent bilateral single lung transplantation. Thirty hours postoperatively he had signs of obstruction of the right main pulmonary artery develop due to dissection demonstrated on transesophageal echocardiography and pulmonary arteriography. Surgical repair of the dissection with reanastomosis of the pulmonary artery was successfully carried out, and the patient subsequently improved to a favorable condition. Pulmonary hypertension is a risk factor of pulmonary artery dissection; our case suggested that underlying chronic pulmonary hypertension might have led to this rare and life-threatening anastomotic problem after lung transplantation.

Adult↗

Attenuation of lung injury in allograft rejection using NF-kappaB decoy transfection-novel strategy for use in lung transplantation.

OBJECTIVE: Increased production of nitric oxide (NO) is known to be a marker of lung allograft rejection and lung injury. NO production is up-regulated directly or indirectly by nuclear factor-kappa B (NF-kappaB), a transcriptional factor of inflammatory cytokines and iNOS. We attempted to determine whether transfection of an NF-kappaB decoy into allografts could reduce NO production and ameliorate acute lung injury during allograft rejection. METHODS: Left lung transplantation was performed in pairs of Brown Norway (RT1n) and Lewis (RT1) rats. In Group NF (n=6), the allografts were flushed with 20 ml of PBS solution containing a hemagglutinating virus of Japan (HVJ) liposome-ODN complex as an NF-kappaB decoy and preserved for 60 min at 4 degrees C. A scramble decoy was used in the positive control (Group S, n=5) and simple PBS solution in the negative control (Group C, n=5). Five days after transplantation without use of immuno-suppressants, exhaled NO, gas exchange, and graft histological rejection score were determined. RESULTS: The exhaled NO level was significantly reduced in Group NF as compared with Group S (445+/-162 vs 1305+/-123 ppb, P<0.02), while improvements in PaO2 (197+/-28 vs. 60+/-18 mmHg, P<0.02) and rejection score (1.8+/-0.3 vs. 2.5+/-0.4) were also observed. There were no differences in these parameters between Groups S and C. CONCLUSIONS: Inhibition of NF-kappaB activation in the allograft by ODN decoy transfection into the donor lung ameliorated lung injury during acute allograft rejection. Our results imply a possible therapeutic target for the inflammation process in lung transplantation clinical settings.

Acute Disease↗

Application of HVJ-liposome mediated gene transfer in lung transplantation-distribution and transfection efficiency in the lung.

OBJECTIVE: A novel hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer system has been shown to have benefits of a high efficiency of transfection and low immunogenicity. The aims of this study were to determine the effect of re-transfection of the HVJ-liposome system via the airway, and to quantify the distribution of gene expression between transtracheal and transplantation approaches. METHODS: Beta-galactosidase (beta-gal) plasmid DNA was introduced into lung tissues using the HVJ-liposome method. Two groups of Sprague-Dawley (SD) rats received intratracheal instillation of 10 microg of the beta-gal gene, once on Day 0 in 1 group (Group Tb-1, n=4) and 3 times on Days 0-2 in another (Group Tb-3, n=4). In a third group of SD rats (Group Tx, n=5), an orthotopic left lung transplantation was performed after the donor lung was flushed with an HVJ-liposome complex solution and preserved for 1h. Gene expression and distribution in lung tissue was then quantified by counting the X-gal stained cells. RESULTS: Both the transtracheal and transplantation approaches resulted in low levels of transfection in the vascular endothelial cells (0.2+/-0.1 and 4.0+/-1.8%), respectively, but a moderate degree of transfection to the airway (11.0+/-7.1 and 28.0+/-20.7%) and alveolar cells (3.0+/-1.8 and 6.0+/-3.6%). Three repetitive injections via the airway increased gene expression in airway epithelial cells of 41.0+/-12.0% compared with the single administration of 11.0+/-4.3%. CONCLUSIONS: Our results suggest that the repeated transtracheal gene transfection using HVJ-liposome may have benefits for treatment of problems after lung transplantation. In addition, gene transfer using a flushing solution during harvest may provide an opportunity for gene manipulation in the setting of lung transplantation.

Animals↗

Surgical resection for lung cancer with infiltration of the thoracic aorta.

OBJECTIVE: The purpose of this study was to evaluate the results of a combined resection of the thoracic aorta and primary lung cancer. METHODS: Sixteen patients underwent thoracic aorta resection along with a left pneumonectomy (n = 6), left upper lobectomy (n = 9), or partial lung resection (n = 1), of whom 10 also received preoperative induction therapy. Cardiopulmonary bypass was used in 10 patients, and a passive shunt between the ascending aorta and the descending aorta was used in 4 patients. RESULTS: Six postoperative major complications occurred in 5 patients, including postoperative bleeding (n = 3), intraoperative bleeding (n = 1), chylothorax (n = 1), and respiratory failure (n = 1). The postoperative morbidity rate was 31%, and the mortality rate was 12.5% (2/16). Furthermore, 4 patients died of systemic tumor relapse, and 1 patient died of intrapleural recurrence. Nine patients were alive after a median follow-up of 54 months (range, 12-199 months). The median survival time of patients with postoperative pathologic N0 disease was 31 months, whereas it was 10 months for those with pathologic N2 or N3 disease. Five-year survivals were 70% for patients with N0 disease and 16.7% for patients with N2 or N3 disease ( P = .0070). CONCLUSIONS: Although pulmonary resection with the involved aorta might cause high surgical morbidity and mortality rates, encouraging long-term survivals were obtained in patients without mediastinal nodal involvement.

Adenocarcinoma↗

Limited mediastinal lymph node dissection for non-small cell lung cancer according to intraoperative histologic examinations.

BACKGROUND: Although radioisotopic procedures are commonly used to detect sentinel lymph nodes in breast cancer surgery, these procedures are often problematic and not necessarily suitable for lung cancer surgery. METHODS: Our previous study revealed that the mediastinal sentinel lymph node, defined as the regional mediastinal lymph node, consisted of nodes 2, 3, or 4 in right upper lobe cancers; 3, 7, or 8 in right lower lobe cancers; 4, 5, or 7 in left upper lobe cancers; and 4, 7, or 8 in left lower lobe cancers. On the basis of these findings, we pathologically investigated one representative lymph node at each of the 3 levels dissected during surgical intervention in 69 patients with non-small cell lung cancer from September 1993 through December 2002. Fifty-eight patients with lung cancer underwent lobectomies with limited mediastinal lymph node dissection according to this strategy. RESULTS: Mediastinal lymph node recurrence was observed in only one patient during 41 +/- 25 months (maximum, 98 months) of follow-up. The cancer-specific 5-year survivals were 96.6% in patients with pathologic stage IA disease (n = 31) and 67.4% in patients with stage IB disease (n = 16). CONCLUSION: These results suggested that limited mediastinal lymph node dissection is applicable to patients with non-small cell lung cancer whose regional mediastinal lymph nodes are not metastatic.

Adult↗

Reduced expression of Dicer associated with poor prognosis in lung cancer patients.

Emerging evidence suggests that microRNA, which are well-conserved, abundant and small regulatory RNA, may be involved in the pathogenesis of human cancers. We recently reported that expression of let-7 was frequently reduced in lung cancers, and that reduced let-7 expression was significantly associated with shorter patient survival. Two members of the double-stranded RNA-specific endonuclease family, Dicer and Drosha, convert precursor forms of microRNA into their mature forms using a stepwise process. In the present study, we examined expression levels of these genes in 67 non-small cell lung cancer cases, and found for the first time that Dicer expression levels were reduced in a fraction of lung cancers with a significant prognostic impact on the survival of surgically treated cases. It should be noted that multivariate COX regression analysis showed that the prognostic impact of Dicer (P=0.001) appears to be independent of disease stage (P=0.001), while logistic regression analysis demonstrated that the higher incidence of reduced Dicer expression in poorly differentiated tumors remained significant even after correction for other parameters (P=0.02). Given the fundamental and multiple biological roles of Dicer in various cellular processes, our results suggest the involvement of reduced Dicer expression in the development of lung cancers, thus warranting further investigations of the underlying mechanisms, which can be expected to enhance understanding of the molecular pathogenesis of this fatal cancer.

Adult↗

A valve replacement technique for heavily calcified mitral valve and annulus.

Severe mitral annular calcification is frequently encountered in patients with chronic renal failure requiring dialysis. The procedures are described for the implantation of mitral prostheses in two dialysis patients with mitral stenosis who exhibited heavily calcified mitral annuli. In both cases the calcifications extended around the entire mitral annulus as well as the valve leaflets, papillary muscle, atrial wall and ventricular myocardium, making it impossible to secure prosthetic valves to the mitral annuli. Before implantation, the calcification was partially debrided ultrasonically, and an 'atrioventricular channel' created. A mechanical valve with a polyester fabric collar was fixed on the atrial side of the calcified annulus using double sutures and gelatin-resorcin-formol glue. Perivalvular leakage, obstruction of valve opening or tortuous movements of prosthetic valve ring were not observed, and neither patient developed heart failure after surgery. This technique represents a potentially useful approach in the surgical treatment of patients with severely calcified mitral annuli.

Calcinosis↗

Physiologic aspects in human lung transplantation.

Heart-lung transplantation (HLT), followed by single lung transplantation (SLT) and subsequently bilateral lung transplantation (BLT) have been developed as treatments for patients with end-stage pulmonary diseases. Initially, SLT was limited to idiopathic pulmonary fibrosis (IPF) cases and thought to be contraindicated not only for infectious diseases, but also for non-infectious diseases, including pulmonary emphysema (PE) and primary pulmonary hypertension (PPH), based on physiologic points of view. However, SLT is now widely performed for those non-infectious diseases and most of the recipients return to a normal active life. It is quite possible that BLT is superior to SLT in terms of pulmonary function, and it has been reported that BLT is better for PE and PPH patients in regards to perioperative course, postoperative exercise capacity, and long-term survival. For those situations and because of the present scarcity of donor organs, SLT must be utilized for selected non-infectious diseases for which it is safe and effective. When a single lung is replaced for IPF, PE, and PPH recipients, different physiologic situations are produced postoperatively, the understanding of which is extremely important to achieve good results, not only in the perioperative but also in the long term.

Graft Rejection↗

A surgical case of concomitant aneurysms of the brachiocephalic and coronary arteries.

Brachiocephalic artery aneurysm with concomitant coronary artery aneurysm is rare. We describe a case of a patient with a history of prosthetic graft placement following resection of an abdominal aortic aneurysm and was subsequently found to have a brachiocephalic artery aneurysm. After surgical correction of the brachiocephalic aneurysm, postoperative coronary arteriography demonstrated coronary artery aneurysms, and the patient subsequently underwent coronary artery bypass grafting (CABG).

Aneurysm↗

Benefits of home parenteral nutrition before lung transplantation: report of a case.

A 54-year-old woman, who was severely malnourished and awaiting lung transplantation for chronic respiratory failure, was given nutritional support by home parenteral nutrition (HPN). The patient's emaciated state was further compromised by the fact that she had undergone a distal gastrectomy 4 years earlier. We decided that HPN was indicated because her oral intake was so poor and drinking enteral formula reduced her appetite. After 1 year of HPN, her body weight increased and her nutritional, anthropometric, and biochemical values were well maintained by the time of transplantation. Moreover, her progress after lung transplantation was remarkably good, indicating the effectiveness of nutritional support by HPN during the protracted waiting period.

Chronic Disease↗

Induction concurrent chemoradiation therapy for invading apical non-small cell lung cancer.

OBJECTIVE: Although non-small cell lung cancer (NSCLC) involving the superior sulcus has been generally treated with radiation therapy (RT) followed by surgery, local recurrence is still a big problem to be solved. We investigated a role of induction therapy, especially induction concurrent chemoradiation therapy (CRT), on the surgical results of this type of NSCLC. METHOD: We retrospectively reviewed 30 patients with NSCLC invading the apex of the chest wall who underwent surgery from 1987 to 1996. Ten patients (57 +/- 8 years) received surgery alone, 9 (55 +/- 13 years) received RT (42 +/- 7 Gy) followed by surgery and 11 (51 +/- 9 years) received cisplatin based chemotherapy and RT (47 +/- 5 Gy) as an induction therapy. RESULTS: Two and 4-year survival rates were 30% and 20% in patients with surgery alone, 22% and 11% in patients with induction RT, and 73% and 53% in patients with induction CRT, respectively. The survival was significantly better in patients with induction CRT than those with induction RT or surgery alone. Univariate analysis demonstrated that curability (yes versus no: p = 0.027) and induction therapy (surgery alone and RT versus CRT: p = 0.0173) were significant prognostic factors. Multivariate analysis revealed that only induction therapy (p = 0.0238) was a significant prognostic factor. CONCLUSIONS: Induction CRT seems to improve the survival in patients with NSCLC invading the apex of the chest wall compared with induction RT or surgery alone.

Antineoplastic Combined Chemotherapy Protocols↗

Different secretion patterns of two molecular forms of cardiac adrenomedullin in pressure- and volume-overloaded human heart failure.

BACKGROUND: In the final step of production of adrenomedullin (AM), an inactive intermediate form of glycine-extended AM (AM-glycine) is converted to the active mature form of adrenomedullin (AM-mature) by enzymatic amidation. Recent studies have revealed that AM-mature and AM-glycine circulate in human plasma. In this study, we investigated the differences of the concentrations of cardiac AM between pressure-overloaded (PO) heart failure (HF) and volume-overloaded (VO)-HF in humans. METHODS AND RESULTS: We measured AM-mature and AM-glycine by immunoradiometric assays in pericardial fluid and plasma in 38 patients who underwent valve replacement surgery (PO-HF: aortic stenosis, n=14; VO-HF: aortic or mitral regurgitation, n=24). Stable coronary artery disease with normal left ventricular function served as the control (n=24). Plasma AM-mature (VO-HF: +59%, PO-HF: +65%, P<.05) and AM-glycine (VO-HF: +43%, PO-HF: +50%, P<0.05) were similarly higher in the 2 HF groups than in the control group. Interestingly, pericardial fluid AM-mature was markedly higher than that in plasma (control: +789%, VO-HF: +1050%, PO-HF: +1745%, all P<.001). Pericardial fluid AM-mature was higher in VO-HF (+106%, P<.01) than in controls and they were further increased in PO-HF (+243%, P<.05). Pericardial fluid molecular forms of AM correlated with left ventricular systolic pressure, but not with left ventricular end-diastolic volume index in PO-HF. In contrast, they correlated with left ventricular end-diastolic volume index, but not with left ventricular systolic pressure in VO-HF. CONCLUSION: These results suggest that cardiac AM is differently regulated from plasma AM and that cardiac AM production is upregulated in both types of HF in response to each different stimulus.

Adrenomedullin↗

Intrathoracic neurogenic tumors--50 years' experience in a Japanese institution.

OBJECTIVE: Intrathoracic neurogenic tumors are relatively uncommon, and there have been few reports regarding their entire clinical characteristics in the Asian population. OBJECTIVES: We retrospectively reviewed our Japanese institutional experience of intrathoracic neurogenic tumors, with emphasis on the clinical spectrum. METHODS: We analyzed the records of 146 patients with intrathoracic neurogenic tumors who were treated over the past 50 years. There were 60 pediatric and 86 adult patients (74 males and 72 females). RESULTS: There were 51 ganglioneuromas, 37 schwannomas, 30 neurofibromas, 18 neuroblstomas, 5 gangliobastomas, and 5 others, of which 136 cases were located in the posterior mediastinum, 9 in the chest wall, and 1 in the lung parenchyma. Neurogenic tumors were most commonly seen as a pediatric mediastinal tumor (46.2%), as compared to 11.2% in the adult population (P<0.001). Eighty-four percent of adult patients and 60% of pediatric patients were asymptomatic. In thirteen patients (8.9%), the tumor showed an intraspinal extension, the so-called dumbbell-type. Overall, 20.5% of the neoplasms were malignant, occurring predominantly in the first 5 years of life. Complete resection was performed in 95.7% cases for benign tumors and 63.3% for malignant tumors, including a laminectomy for six cases of the dumbbell-type. There were no operative deaths and minimal morbidity. CONCLUSIONS: Age seemed to be the most important clinical parameter for distinguishing between histological type and rate of malignancy for neurogenic tumors. Recognition of this clinical spectrum will lead to the immediate and appropriate surgical intervention.

Adolescent↗

Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA levels in tumor tissues and the efficacy of 5-fluorouracil in patients with non-small-cell lung cancer.

We examined 116 stage I-IIIA non-small-cell lung cancer (NSCLC) patients for intra-tumoral expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) using TaqMan reverse transcription polymerase chain reaction (RT-PCR) assay to clarify the correlation between gene expression and the efficacy of 5-fluorouracil (5-FU) in patients with NSCLC. Patients who were administered 5-FU alone after surgery comprised the 5-FU group (n = 30), and those who underwent only surgery comprised the control group (n = 86). When dichotomized at the mean TS and DPD mRNA level, patients with low-DPD tumors who were administered 5-FU had a significantly better prognosis than those who did not receive adjuvant treatment (p = 0.041). In addition, in the 5-FU group, 10 patients with both low-TS and low-DPD tumors have not had any relapse, whereas 8 of the 20 patients with either high-TS or high-DPD tumors developed distant metastasis after surgery. Based on these results, the quantitation of TS and DPD mRNA levels may predict the efficacy of 5-FU after surgery for patient with NSCLC.

Aged↗

[A case of bronchostenosis in the allograft after lung transplantation in pulmonary lymphangioleiomyomatosis].

Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease characterized by hamartomatous proliferation of abnormal smooth muscle cells in the lungs. Recently, severe LAM has been listed as an indicated disease for lung transplantation. A 34-yr-old woman with severe pulmonary cystic changes in a chest CT scan was diagnosed as having an isolated form of pulmonary LAM without genetic disorders. Despite intensive progesterone treatment, her pulmonary functions deteriorated rapidly. In January 2001, a left single-lung transplantation was performed from a cadaveric donor. The total operating time was 8 hours and 47 minutes. Total ischemic time was 5 hours and 59 minutes, which was within the permitted time limit. Except for right pneumothorax, the postoperative course was fairly good without any sign of rejection or infection in the allograft. For about two months after transplantation, bronchostenosis occurred in the left lower lobe bronchus, and necessitated a stent placement. During the following three months, stenosis of the bronchi in the anastomotic and peripheral sites occurred repeatedly, which also necessitated stent placement or balloon dilations on each occasion. Despite all the intensive treatment, the bronchostenosis of the peripheral sites still remains and improvement of her pulmonary functions has been poor. Moreover, a recent chest CT scan revealed a progression of the disease in the native lung. Consequently, we registered her as a candidate for transplantation of the right lung. Bronchostenosis should be kept in mind as a complication of lung transplantation.

Adult↗