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Hiroshi Date

Publications and source records attributed to Hiroshi Date.

At least 37 records · Page 2Linked to original sources
PubMed2006

Bilateral native lung-sparing lobar transplantation in a canine model.

OBJECTIVE: Bilateral living-donor lobar lung transplantation has become an accepted approach in response to the cadaveric lung donor shortage. Because only one lobe is implanted in each chest cavity, this procedure is usually confined to patients of small size. The purpose of this study was to develop a technique of bilateral native lung-sparing lobar transplantation that can be applied to large adult patients. METHODS: Bilateral native lung-sparing lobar transplantation was performed in 12 pairs of dogs. In donor animals the right middle, lower, and cardiac lobes were separated as a right graft, and the left lower lobe was separated as a left graft. In recipient animals these 2 grafts were implanted in the natural anatomic position with sparing native right upper, left upper, and middle lobes. In an acute study (n = 6), transplanted graft function was assessed for 3 hours after ligation of the pulmonary artery branches to the native spared lobes. In a chronic study (n = 6) the immunosuppressed recipients were observed for 3 weeks to assess the quality of bronchial healing and long-term pulmonary function. RESULTS: Morphologic adaptation of the 2 grafts was found to be excellent. All 6 animals in the acute study showed excellent pulmonary function. Five of 6 animals in the chronic study survived for 3 weeks, with excellent pulmonary function and satisfactory bronchial healing. CONCLUSION: Bilateral native lung-sparing lobar transplantation was technically possible and associated with excellent pulmonary function and good bronchial healing in a canine experimental model.

Animals↗
PubMed2006

Carvedilol inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. Inhibition of proliferation of pulmonary artery smooth muscle cells (PASMCs) may be an effective treatment of patients with idiopathic pulmonary arterial hypertension. Recent studies have shown that carvedilol, an alpha- and beta-blocker with antioxidant and calcium channel blocking properties, inhibits the proliferation of cultured normal human pulmonary artery smooth muscle cells. In this study, we tested the hypothesis that carvedilol has antiproliferative effects on pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Pulmonary artery smooth muscle cells from six idiopathic pulmonary arterial hypertension patients who had undergone lung transplantation were cultured. To determine cell proliferation, H-thymidine incorporation was measured. Platelet-derived growth factor-induced proliferation of IPAH-PASMCs was significantly greater than that of normal control pulmonary artery smooth muscle cells. Carvedilol (0.1 microM to 10 microM) inhibited the proliferation of idiopathic pulmonary arterial hypertension-pulmonary artery smooth muscle cells in a concentration-dependent manner. Prazosin (an alpha-blocker) and N-acetyl L cysteine (an antioxidant agent) (0.1 microM to 10 microM) did not inhibit their proliferation, but the high concentration of propranolol (a beta-blocker) and nifedipine (a calcium channel blocker) (10 microM) inhibited the proliferation. The combination of propranolol and nifedipine inhibited the proliferation but only at a high concentration (10 microM) combination. Cell cycle analysis revealed that carvedilol (10 microM) significantly decreased the number of cells in S and G2/M phases. These results indicate that carvedilol inhibits the exaggerated proliferation of pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension partially via its beta-blocking [corrected] and calcium channel blocking effects in vitro.

Adolescent↗
PubMed2005

A canine experimental study to assess the potential of unilateral double lobar lung transplantation.

OBJECTIVE: We recently reported a technique of unilateral double lobar lung transplantation (UDLLT) in a canine model that was associated with satisfactory early pulmonary function. The purpose of the present experimental study was to assess the quality of bronchial healing, complication rates, survival rates and long-term pulmonary function of this new transplantation technique. METHODS: Unilateral double lobar lung transplantation was performed in 14 weight-matched pairs of dogs. In recipient animals, two grafts obtained from donor animals were implanted in the right hemithorax after right pneumonectomy. One graft (left graft) was implanted as a right upper lobe in an upside-down position and the other (right graft) was implanted in the natural anatomic position. The immunosuppressed recipients were observed for 3 weeks. Transplanted graft function was assessed under left main pulmonary artery occlusion at 1 and 3 weeks after transplantation. RESULTS: All animals survived the operation. Pulmonary artery kinking (3/14, 21%) and pulmonary venous thrombus (4/14, 29%) were exclusively observed in the graft implanted in the upside-down position. These complications decreased as the number of transplantations increased. Two of the first seven (29%) and five of the last seven recipient dogs (71%) survived for 3 weeks with excellent pulmonary function and good bronchial healing. CONCLUSIONS: This procedure was associated with a high complication incidence in the non-anatomically positioned graft. However, a precise surgical technique could decrease these complications. This technically demanding procedure provided excellent pulmonary function and good bronchial healing.

Animals↗
PubMed2005

Prednisolone inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. There is no therapy that specifically inhibits SMC proliferation. Recent studies reported that prednisolone (PSL) inhibits the postangioplasty proliferation of SMCs in atherosclerotic arteries. In this study, we tested the hypothesis that PSL has antiproliferative effects on pulmonary artery SMCs of patients with IPAH. METHODS AND RESULTS: Pulmonary artery SMCs were harvested from the pulmonary arteries of 6 patients with IPAH who underwent lung transplantation. Control SMCs were obtained from 5 patients with bronchogenic carcinoma who underwent lung lobectomy. After incubation in the presence of platelet-derived growth factor (PDGF), PSL was added at different concentrations and cell proliferation was assessed by 3H-thymidine incorporation. PSL (2x10(-4) and 2x10(-3) mol/L) significantly inhibited PDGF-stimulated proliferation (P<0.05) of SMCs from patients with IPAH but did not affect cell viability of SMCs, as confirmed by trypan blue staining. In cell cycle analysis using a microscope-based multiparameter laser scanning cytometer, PSL inhibited the progression of SMCs from G(0)/G1 to the S phase. This inhibition was associated with increased p27 expression level. PSL (2x10(-4) mol/L) also inhibited PDGF-induced SMC migration. CONCLUSIONS: Our results indicate that PSL has an antiproliferative effect on cultured SMCs of pulmonary arteries from patients with IPAH and suggest that PSL may be potentially useful therapeutically in patients with IPAH.

Becaplermin↗
PubMed2005

The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers.

PURPOSE: Recent studies reported that clinical responsiveness to gefitinib was associated with somatic mutation of epidermal growth factor receptor (EGFR) gene in non-small cell lung cancers (NSCLC). Here, we investigated the relationship between EGFR mutation and clinicopathologic features. EXPERIMENTAL DESIGN: EGFR mutational status of 120 NSCLCs was determined mainly in EGFR exons 18 to 21 by direct sequence and correlated with clinicopathologic parameters. RESULTS: EGFR mutations were present in 38 cases (32%) and the majority of mutations were in-frame deletions of exon 19 (19 cases) and a missense mutation in exon 21 (18 cases). EGFR mutations were frequently associated with adenocarcinoma (P < 0.0001), never smoker (P < 0.0001), and female gender (P = 0.0001). Of interest, increasing smoke exposure was inversely related to the rate of EGFR mutation (P < 0.0001). Multivariate analysis showed that smoking and histology were independent variables. Furthermore, gender difference was observed for the mutational location (P = 0.01) dominance of exon 19 for males and exon 21 for females. Twenty-one cases were treated with gefitinib and found that EGFR mutation was significantly related to gefitinib responsiveness (P = 0.002). In addition, median survival times of patients with and without EGFR mutations treated with gefitinib were 25.1 and 14.0 months, respectively. Patients with EGFR mutations had approximately 2-fold survival advantage; however, the difference was not significant. CONCLUSIONS: We show that EGFR mutations were significantly related to histology and smoke exposure and were a strong predictive factor for gefitinib responsiveness in NSCLC.

Adult↗
PubMed2005

Aberrant promoter methylation of human DAB2 interactive protein (hDAB2IP) gene in lung cancers.

The human DOC-2/DAB2 interactive protein gene (hDAB2IP) is a novel member of the Ras GTPase-activating gene family that is known to act as a tumor suppressor gene and is inactivated by methylation in prostate and breast cancers. We established previously a methylation-specific PCR (MSP) for the promoter region (m2a and m2b regions) of hDAB2IP and examined hDAB2IP methylation status in breast cancers. We analyzed the methylation and expression status of hDAB2IP in lung cancers. The methylation status of hDAB2IP was examined in lung cancer cell lines using bisulfite sequencing and MSP. Expression was examined using conventional and real-time RT-PCR, and methylation was found to be inversely correlated with expression, confirming that the MSP can also be used to examine hDAB2IP methylation status in lung cancers. Aberrant methylation was detected at the m2a region in 19 of 47 lung cancer cell lines (40%) and 26 of 70 primary tumors (37%) and at the m2b in 16 lines (34%) and 25 of 70 tumors (36%). Gene expression was restored in methylated cell lines supplemented with 5-aza-2'-deoxycytidine, confirming that methylation was responsible for downregulation. We also examined the relationship between hDAB2IP methylation and clinico-pathological features of the lung cancers and found that hDAB2IP methylation was associated with advanced disease stage. Our results demonstrate that hDAB2IP methylation is frequently present in lung cancers and plays a key role in hDAB2IP silencing. hDAB2IP methylation could be used as a biomarker for disease stage, reflecting the degree of clinico-pathological malignancy of lung cancer.

Aged↗
PubMed2005

Hemodynamic effects of pumpless extracorporeal membrane oxygenation (ECMO) support for chronically pressure-overloaded right heart failure in a canine experimental model.

PURPOSE: This study was done to evaluate the hemodynamic effects of a pumpless implantable extracorporeal membrane oxygenation (ECMO) circuit between the right ventricle (RV) and left atrium (LA) in a chronic canine model with an RV pressure overload. METHOD: We created a model of right-sided heart failure by pulmonary artery banding in ten dogs for a duration of more than 3 months. After demonstrating that the RV pressure increased, a bypass circuit was created between the RV and LA with an in-line oxygenator. Both the hemodynamics and gas exchange were measured. RESULTS: The effects of a pulmonary bypass in nine dogs were studied. Approximately half of the RV output was passively shunted through the bypass circuit, and a marked reduction in the RV pressure and recovery from right heart failure were observed. After a complete ligation of the main pulmonary artery, five of the nine dogs survived more than 6 h. The RV pressure did not change significantly, but the cardiac output and blood pressure gradually decreased. The blood gas state was sufficiently maintained throughout the experiment. CONCLUSION: The present study indicates the hemodynamic benefit of a partial pumpless ECMO system in dogs with chronically pressure-overloaded right heart failure; however, the experimental preparation of the total pumpless ECMO circuit proved to be unstable.

Animals↗
PubMed2005

Transintestinal oxygenation with perfluorocarbon: investigation of perfusion rate.

OBJECTIVE: Perfluorocarbons are structurally similar to hydrocarbons but with the hydrogen atoms replaced by fluorine. In general, perfluorocarbons have an excellent oxygen and carbon dioxide carrying capacity. We studied the suitability of oxygenated perfluorocarbon as an agent for transintestinal oxygenation and measured its perfusion rates under different conditions. SUBJECTS AND METHODS: We used FC-77 (Sumitomo 3M, Tokyo, Japan) perfluorocarbon and a rat hypoventilation model (room air, 20 breaths/min, a tidal volume of 10 ml/kg). Oxygenated FC-77 was perfused through the small intestine for 4 hours. Rats were allocated to 3 experimental groups according to the perfusion rate and a control group: Group 1 (n=6), 10 ml/min; Group 2 (n=6), 2.5 ml/min; Group 3 (n=6), 0.75 ml/min; Group 4 (n=6) served as a control (hypoventilation only). Arterial blood samples were drawn every 30 minutes. Standard blood gas analysis was performed. RESULTS: After four hours of perfusion, the PaO2 levels in Groups 1 to 3 were significantly better than Group 4 (p<0.01, Group 1: 141.7 +/- 18.0 mmHg, Group 2: 145.2 +/- 25.1 mmHg, Group 3: 120.5 +/- 21.2 mmHg, Group 4: 67.4 +/- 7.2 mmHg). PaCO2 levels in Groups 1 and 2 were significantly better than Groups 3 and 4 (p<0.01, Group 1: 42.6 +/- 7.2 mmHg, Group 2: 52.1 +/- 7.7 mmHg, Group 3: 78.2 +/- 22.8 mmHg, Group 4: 75.3 +/- 10.3 mmHg). CONCLUSION: In the present settings, 8 ml/kg/min was adequate for oxygenation and CO2 clearance. This approach promises to become another modality for respiratory assistance.

Animals↗
PubMed2005

Non-small cell lung cancer coexisting with pulmonary aspergilloma.

A 77-year-old male with a long-standing history of smoking and working in mines was referred to our department for the evaluation of an enlarging subpleural mass in the right upper lobe. Both transbronchial and computed tomography-guided biopsies of the mass were non-diagnostic. A partial resection of the right S2 mass under video-assisted thoracic surgery (VATS) confirmed the diagnosis of primary non-small cell lung cancer. VATS right upper lobectomy (ND2a) was then performed for complete resection. Histological examination revealed that the mass composed of adenocarcinoma and the dilated bronchioles contained Aspergillus, the fungal component. Here we report a rare case of non-small cell lung cancer coexisting with pulmonary aspergillosis. The morphologic coexistence pattern of the two pathologies was believed to be the colonization of saprophytic Aspergillus in the bullous air spaces, obstructed by or contained within the tumor, according to the progression of the lung cancer.

Adenocarcinoma↗
PubMed2005

Living-donor lobar lung transplantation for bronchiolitis obliterans after bone marrow transplantation.

We report a successful case of living-donor lobar lung transplantation (LDLLT) for severe bronchiolitis obliterans (BO) after bone marrow transplantation (BMT). The patient is a 29-year-old woman who underwent BMT because of aplastic anemia in 1995. In 1996, BO developed in the patient because of chronic graft-versus-host disease. In May 2000, a LDLLT was performed. Pulmonary function tests showed improvement of both vital capacity and forced expiratory volume in 1 second. At present, 91 months after BMT and 38 months after lung transplantation, the patient is in good health. LDLLT may offer a therapeutic option for the treatment of BO after BMT.

Adult↗
PubMed2005

Equivalence of flow velocities through bilateral pulmonary vein anastomoses in bilateral living-donor lobar lung transplantation.

BACKGROUND: Intraoperative transesophageal echocardiography (TEE) during lung transplantation is useful for monitoring cardiac condition and pulmonary vascular anastomoses to detect vascular complications, but the parameters for evaluation by TEE during lung transplantation have not been established. METHODS: We performed intraoperative TEE on 17 patients during living-donor lobar lung transplantation (LDLLT) and investigated the usefulness of measurement of peak flow velocities through bilateral pulmonary vein (PV) anastomoses and evaluation of the equivalence. RESULTS: The peak flow velocities through bilateral PV anastomoses were almost equivalent in 14 patients without complications and were not equivalent in 3 patients with complications such as vascular stenosis and peripheral atelectasis. CONCLUSIONS: The flow velocities through the bilateral PV anastomoses are shown to be nearly equivalent during bilateral LDLLT, and the equivalence may be one factor for predicting the success of LDLLT.

Adolescent↗
PubMed2005

Effects of postmortem heparinization in canine lung transplantation with non-heart-beating donors.

OBJECTIVE: Microthrombus formation appears to be one of the major detrimental factors in lung transplantation from non-heart-beating donors. The purpose of this study was to evaluate the effects of postmortem heparinization by closed-chest cardiac massage in a canine model of left single-lung allotransplantation from non-heart-beating donors. METHODS: Left lung transplantation was performed in 18 weight-matched pairs of mongrel dogs. Donors were killed with an intravenous injection of potassium chloride and left at room temperature for 2 hours. The cadaveric donors were assigned randomly to one of the three groups. In group 1 (n = 6), no heparin was given as a control. In group 2 (n = 6), heparin sodium (1000 U/kg) was administered intravenously before cardiac arrest. In group 3 (n = 6), heparin sodium (1000 U/kg) was administered intravenously 10 minutes after death, then closed-chest cardiac massage was performed for 2 minutes. After 2 hours of cardiac arrest, donor lungs were flushed with low-potassium dextran-glucose solution and preserved for 60 minutes. After left lung transplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 3 hours. Univariate and multivariate repeated analyses were used for statistics. RESULTS: Both groups 2 and 3 had significantly better gas exchange and lower pulmonary vascular resistance than group 1. Changes in thrombin-antithrombin III complex concentration during the warm ischemia indicated that postmortem heparinization suppressed clotting activation in the donor. CONCLUSIONS: Postmortem heparinization by cardiac massage is beneficial in lung transplantation from non-heart beating donors by preventing microthrombus formation.

Animals↗
PubMed2005

Risk of alveolar hemorrhage in patients with primary pulmonary hypertension--anticoagulation and epoprostenol therapy.

BACKGROUND: Anticoagulation therapy and continuous intravenous infusion of epoprostenol are the standard treatment for primary pulmonary hypertension (PPH). Because epoprostenol has an antiplatelet effect, concomitant use of an anticoagulant could increase the likelihood of hemorrhagic complications. METHODS AND RESULTS: In the present study, 31 consecutive patients with PPH (10 men, 21 women, mean +/- SD age, 28.5+/-10.1 years) treated with anticoagulation and epoprostenol between April 1999 and December 2003 were retrospectively evaluated. Clinical and hematological data at the time of the bleeding episode were retrieved from the medical records. Nine patients (22.6%) experienced 11 bleeding episodes: 9 episodes (81.8%) were alveolar hemorrhage and 2 patients were in severe respiratory distress. The mean dose of epoprostenol at the time of the first bleeding episode was 89.0 +/-40.5 ng.kg(-1).min(-1) (range, 28.1-164.0). More of the patients who did not have a bleeding episode remain alive than did patients with bleeding episodes (59% vs 33%) nor did they require lung transplantation. CONCLUSIONS: A considerable number of patients with PPH who received combined anticoagulant and high-dose epoprostenol therapy developed alveolar hemorrhage, which can be fatal.

Adolescent↗
PubMed2005

A new treatment strategy for advanced idiopathic interstitial pneumonia: living-donor lobar lung transplantation.

BACKGROUND: Among patients awaiting cadaveric lung transplantation, patients with idiopathic interstitial pneumonia (IIP) have been demonstrated to have the highest mortality rate. Contraindications to cadaveric lung transplantation include current high-dose systemic corticosteroid therapy because it may increase airway complications and various types of infection. STUDY OBJECTIVES: To analyze the effect of living-donor lobar lung transplantation (LDLLT) for patients with advanced IIP including those receiving high-dose systemic corticosteroids. DESIGN: Retrospective analysis. SETTING: Okayama University Hospital and Okayama Medical Center. PATIENTS: We report on the first nine patients (seven female and two male; age range, 13 to 55 years) with advanced IIP receiving LDLLT. All nine patients had a very limited life expectancy, and eight patients were dependent on systemic corticosteroid therapy as high as 50 mg/d of prednisone. LDLLT was performed under cardiopulmonary bypass using two lower lobes donated by two healthy relatives. RESULTS: There were no airway complications in the 18 bronchial anastomoses. There was one early death (11%) due to severe acute rejection. Eight patients (89%) are currently alive with a follow-up period of 10 to 48 months. Their vital capacity reached 2.03 +/- 0.20 L (mean +/- SEM), 71.4% of predicted at 1 year. All 18 donors have returned to their previous lifestyles. Excised lungs were pathologically diagnosed as usual interstitial pneumonia (UIP) in six cases and fibrotic nonspecific interstitial pneumonia (NSIP) in three cases. CONCLUSIONS: These early follow-up data support the option of LDLLT in patients with advanced IIP, including UIP and fibrotic NSIP, who would die soon otherwise. Current high-dose systemic corticosteroid therapy is not a contraindication in LDLLT.

Adolescent↗