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Biomedical subjects

Hiroshi Date

Publications and source records attributed to Hiroshi Date.

At least 55 records · Page 3Linked to original sources

[Clinical status of lung transplantation].

The first successful living-donor lobar lung transplant (LDLLT) in Japan was performed at Okayama University in October, 1998 after a long period of waiting for the legalization of the thoracic organ transplantation. By May, 2005, a further 67 lung transplants have been performed; 45 from living donors and 22 from cadaveric donors. Although the number of lung transplants is still small, survival in Japan, at 76.9% after 5 years, is better than the world average. Because the number of available cadaveric donors for lung transplantation is limited at less than 5 per year, LDLLT is a realistic option for properly selected candidates.

Humans↗

Relation of epidermal growth factor receptor, phosphorylated-Akt, and hypoxia-inducible factor-1alpha in non-small cell lung cancers.

The role of the epidermal growth factor receptor (EGFR)/Posphorylated-Akt (P-Akt) signaling axis in regulating hypoxia-inducible factor-1alpha (HIF-1alpha) expression in vivo is not well understood and is of potential clinical importance since the extent of hypoxia in the tumor environment is thought to be an important determination of resistance to chemotherapy and radiotherapy. We performed the immunohistochemical studies in 80 patients with non-small cell lung cancers to evaluate EGFR, P-Akt, and HIF-1alpha expression. Significant correlation between P-Akt and HIF-1alpha (P=0.0006) and marginal correlation between EGFR and P-Akt (P=0.066) were found. P-Akt was shown to be a poor prognostic factor as to patients with lymph node involvement (P=0.031).

Aged↗

Characterization of the bone morphogenetic protein (BMP) system in human pulmonary arterial smooth muscle cells isolated from a sporadic case of primary pulmonary hypertension: roles of BMP type IB receptor (activin receptor-like kinase-6) in the mitotic action.

The functional involvement of bone morphogenetic protein (BMP) system in primary pulmonary hypertension (PPH) remains unclear. Here we demonstrate a crucial role of the BMP type IB receptor, activin receptor-like kinase (ALK)-6 for pulmonary arterial smooth muscle cell (pphPASMC) mitosis isolated from a sporadic PPH patient bearing no mutations in BMPR2 gene. A striking increase in the levels of ALK-6 mRNA was revealed in pphPASMC compared with control PASMCs, in which ALK-6 transcripts were hardly detectable. BMP-2 and -7 stimulated the mitosis of pphPASMCs, which was opposite to their suppressive effects on the mitosis of the control PASMCs. BMP-4 and -6 and activin inhibited pphPASMC mitosis, whereas these did not affect control PASMCs. The presence of BMP signaling machinery in pphPASMCs was elucidated based on the analysis on Id-1 transcription and Smad-reporter genes. Overexpression of a dominant-negative ALK-6 construct revealed that ALK-6 plays a key role in the mitosis as well as intracellular BMP signaling of pphPASMCs. Gene silencing of ALK-6 using small interfering RNA also reduced DNA synthesis as well as Id-1 transcription in pphPASMCs regardless of BMP-2 stimulation. Although Id-1 response was not stimulated by BMP-2 in control PASMCs, the gene delivery of wild-type ALK-6 caused significant increase in the Id-1 transcripts in response to BMP-2. Additionally, inhibitors of ERK and p38 MAPK pathways suppressed pphPASMC mitosis induced by BMP-2, implying that the mitotic action is in part MAPK dependent. Thus, the BMP system is strongly involved in pphPASMC mitosis through ALK-6, which possibly leads to activation of Smad and MAPK, resulting in the progression of vascular remodeling of pulmonary arteries in PPH.

Adolescent↗

Intermittent pneumatic compression is effective in preventing symptomatic pulmonary embolism after thoracic surgery.

PURPOSE: Postoperative pulmonary embolism (PE) remains a fatal complication even in thoracic surgery. We have used intermittent pneumatic compression for the prophylaxis of postoperative PE since 1998, and herein examined its effectiveness. METHODS: Seven hundred and six patients, whose medical records showed use/no use of pneumatic compression for prophylaxis of PE, underwent general thoracic surgery in our department from December 1995 to December 2000. Their clinical records were reviewed, and variables were compared between patients who experienced clinically apparent PE and patients who did not have PE. RESULTS: Three hundred and forty-four patients did not receive any prophylactic treatment, and 7 of these (2.0%) experienced postoperative PE. Three hundred and sixty-two patients received prophylactic pneumatic compression and none of these developed PE. There was a statistical correlation between the occurrence of PE and the application of pneumatic compression (Chi(2)-test, P = 0.006). Six of the seven patients with PE were operated on in the right decubitus position, and the operative position and the prevalence of PE was also significantly correlated (Chi(2)-test, P = 0.024). Other factors, such as age, sex, operative time, duration until patients became fully ambulatory, body mass index, and character of the disease, did not have significant correlation with the occurrence of PE. CONCLUSIONS: Pneumatic compression was found to effectively prevent postoperative PE. The right decubitus position is considered to be a risk factor for the development of postoperative PE in thoracic surgery.

Aged↗

Lung transplantation in Japan.

The first successful living-donor lobar lung transplant (LDLLT) in Japan was performed at Okayama University in October 1998 after a long period of waiting for the legalization of thoracic organ transplantation. By May 2003, a further 41 lung transplants had been performed; 28 from living donors and 13 from cadaveric donors. The indications for a lung transplant are very specialized in Japan, the most common being primary pulmonary hypertension. Although the number of lung transplants is still small, survival in Japan, at 72% after 4 years, is better than the world average. Because the number of available cadaveric donors for lung transplantation is limited, at less than 5 per year, LDLLT is a realistic option for properly selected candidates.

History, 20th Century↗

Allowable warm ischemic time to tracheal extraction for allotransplantation of cryopreserved trachea.

OBJECTIVE: The allowable warm ischemic time from circulatory arrest to tracheal extraction for allotransplantation of cryopreserved tracheal grafts from cadaveric donors was examined in adult mongrel dogs. SUBJECTS AND METHODS: The animals were divided into 4 groups (n = 28) according to the warm ischemic time of less than 1 hour, 3 hours, 6 hours, and 12 hours, after transplantation, and comparisons were made. The grafts were cryopreserved for at least 2 months and were evaluated by extraction from the recipients generally 2 months after transplantation. RESULTS: All the grafts with a warm ischemic time of less than 1 hour were viable and did not show stenosis. This group did not differ significantly from the groups with a warm ischemic time of 3 and 6 hours in terms of viability. However, all of the grafts with a warm ischemic time of 12 hours showed stenosis, and there was a significantly lower viability rate. Histological examination of the grafts showed that warm ischemia caused necrosis of the tracheal cartilage. CONCLUSION: Based on these results, it was concluded that 6 hours was the maximum allowable warm ischemic time for cryopreserved tracheal transplantation, and that necrosis of the tracheal cartilage due to warm ischemia reduced the viability of the grafts.

Animals↗

Effect of a kink in unilateral pulmonary artery anastomosis on velocities of blood flow through bilateral pulmonary vein anastomoses in living-donor lobar lung transplantation.

Intraoperative transesophageal echocardiography is generally performed to detect vascular complications during lung transplantation. We report a case with a kink in pulmonary artery (PA) anastomosis suggested by an abnormal flow profile of pulmonary vein (PV) anastomoses during living-donor lobar lung transplantation. During the transplantation, velocity of blood flow through the right PV anastomosis showed abnormal elevation. Then, the patient's PA pressure elevated abnormally and a kink in the left PA anastomosis was found. Careful monitoring of PV anastomoses may enable detection of not only an abnormality of PV anastomoses but also that of PA anastomoses, especially in living-donor lobar lung transplantation.

Adult↗

Differences between flow profiles of pulmonary vein anastomoses affected by peripheral atelectasis in cadaveric and bilateral living-donor lobar lung transplantations.

We report two cases of peripheral atelectasis during cadaveric and living-donor lobar lung transplantation, which had different effects on the flow profile of pulmonary vein (PV) anastomoses. In the patient who underwent living-donor lobar lung transplantation, we detected the increase in the velocity of blood flow through the left PV anastomosis by intraoperative transesophageal echocardiography. Then peripheral atelectasis occurred in the transplanted left lung lobe. On the other hand, in the patient who underwent cadaveric bilateral lung transplantation, peripheral atelectasis occurred, but no changes in velocities of blood flow through PV anastomoses were detected by intraoperative transesophageal echocardiography. This difference may have been caused by the difference in sizes of pulmonary beds of transplanted grafts. These findings indicate the necessity of careful monitoring of PV anastomoses, especially in cases of living-donor lobar lung transplantation.

Adult↗

How to predict forced vital capacity after living-donor lobar-lung transplantation.

BACKGROUND: Living-donor lobar-lung transplantation (LDLLT) has evolved from a rarely performed experimental procedure to an accepted therapy for selected patients who are unlikely to survive the long wait for cadaveric lungs. However, a convincing study has not been performed that shows the effects of small grafts and of pre-operative variables in predicting functional outcome of recipients after LDLLT. METHODS: From October 1998 to March 2002, 2 male and 11 female patients underwent LDLLT. Mean age was 27.3 years (range, 8-53 years). Diagnoses included primary pulmonary hypertension (n = 5), idiopathic interstitial pneumonia (n = 2), bronchiolitis obliterans (n = 2), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1), and cystic fibrosis (n = 1). Donors included 12 men and 14 women with a mean age of 40 years. Given that the right lower lobe consists of 5 segments, the left lower lobe of 4, and the whole lung of 19, we estimated the graft forced vital capacity (FVC) based on the donor's measured FVC and compared this with the recipient's FVC measured after LDLLT. RESULTS: Currently, all patients are alive, with a mean follow-up of 22.2 months (range, 10-51 months). The recipients' FVC measured at 6 months (1,813 +/- 86 ml) correlated well with the graft FVC (1,803 +/- 70 ml), estimated based on the donors' measured FVC (r = 0.802, p = 0.00098). CONCLUSIONS: Recipient FVC after LDLLT can be predicted by measuring donor FVC before surgery regardless of the diagnosis of the recipient.

Adolescent↗

The technique of unilateral double lobar lung transplantation in a canine model.

OBJECTIVE: Bilateral living-donor lobar lung transplantation has become an accepted alternative to cadaveric lung transplantation. Because only one lobe is implanted in each chest cavity, this procedure seems to be best suited for children and small adults. The purpose of this study was to develop a technique of unilateral double lobar lung transplantation that can be applied to large adult patients. METHODS: Unilateral double lobar lung transplantation was performed in 6 weight-matched 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 right hemithorax after right pneumonectomy. The left graft was implanted as a right upper lobe, having been rotated 180 degrees along the vertical axis and then 180 degrees along the horizontal axis. The right graft was implanted in the natural anatomic position. Function of the transplanted grafts was assessed for 3 hours after ligation of the left main pulmonary artery while the animals were ventilated with 100% oxygen. RESULTS: Morphologic adaptation of the 2 grafts in the right hemithorax was found to be excellent. All 6 animals survived the assessment period with excellent pulmonary function. At the end of the 3-hour assessment period, the arterial oxygen tension was 519 +/- 31 mm Hg, and the mean pulmonary artery pressure was 30.5 +/- 1.7 mm Hg. CONCLUSIONS: Unilateral double lobar lung transplantation was technically possible and associated with satisfactory early pulmonary function in a canine experimental model.

Animals↗

Improved survival after living-donor lobar lung transplantation.

OBJECTIVE: Survival after living-donor lobar lung transplantation has been reported to be similar to that after cadaveric lung transplantation. The purpose of this study was to summarize our 5-year experience of living-donor lobar lung transplantation for critically ill patients. METHODS: Between October 1998 and April 2004, we performed living-donor lobar lung transplantation in 30 critically ill patients with various lung diseases, including 5 (17%) patients on a ventilator. Mean age was 30.4 years (range, 8-55 years). Postoperative management included slow weaning from a ventilator, relatively low-dose immunosuppressants, and careful rejection monitoring on the basis of radiographic and clinical findings without transbronchial lung biopsy. RESULTS: The average duration of mechanical ventilation was 15.4 days, intensive care unit stay was 23.5 days, and hospital stay was 64.6 days. Clinically judged acute rejection occurred at an average rate of 1.5 episodes per patient, but infection occurred in only one patient during the first month. In spite of the complicated postoperative course, all patients were discharged without oxygen inhalation. Four patients had unilateral bronchiolitis obliterans syndrome, but the decrease in their forced expiratory volume in 1 second values stopped within 9 months. All 30 recipients are currently alive, with a follow-up period of 1 to 66 months. All donors have returned to their previous lifestyles. CONCLUSIONS: Living-donor lobar lung transplantation can be applied to both pediatric and adult patients with very limited life expectancies. It might provide better survival than conventional cadaveric lung transplantation.

Adolescent↗

SYT-SSX fusion genes in synovial sarcoma of the thorax.

Synovial sarcoma (SS) is characterized by a chromosomal translocation resulting in the expression of an SYT-SSX chimeric transcript, usually SYT-SSX1 or SYT-SSX2. Synovial sarcoma typically originates in the limbs, and its location in the thorax is rare. Synovial sarcomas are usually classified into three histologic subtypes: biphasic, monophasic and poorly differentiated tumors. The detection of the characteristic chimeric transcript often contributes to a histopathological diagnosis, especially when the tumor arises in an unusual location. Previous studies have shown that SYT-SSX1 is the most common SYT-SSX fusion transcript in biphasic synovial sarcomas of the limbs. Here, we report two cases of synovial sarcoma originating in the thorax. The presence of SYT-SSX2 chimeric transcripts was confirmed by reverse transcript polymerase chain reaction (RT-PCR) and a direct sequencing analysis in both cases. The tumor in case 1 originated from the pericardium, which is an exceedingly rare site for primary synovial sarcoma; only three other cases of synovial sarcoma originating in the pericardium have been previously reported. Case 2 exhibited a biphasic synovial sarcoma of the mediastinum containing an SYT-SSX2 fusion transcript, which is a rare fusion type in biphasic synovial sarcomas of the limbs. We reviewed previous reports of thoracic synovial sarcomas containing an analysis of the SYT-SSX fusion transcript and found that case 2 in the present study was the first description of a biphasic synovial sarcoma of the thorax with an SYT-SSX2 fusion transcript. However, the number of reported cases was not sufficient to conclude that SYT-SSX2 fusion in biphasic synovial sarcoma of the thorax is, indeed, rare. Further genetic analysis is needed to fully understand the biological and clinical features of synovial sarcoma originating in the thorax.

Adolescent↗

Suppressed erythropoiesis after ABO-minor-mismatched living-donor lobar lung transplantation.

Anti-A and/or anti-B antibodies synthesized by lymphoid tissues contained in ABO-mismatched solid organ grafts have been reported to cause hemolytic anemia, but not suppressed red blood cell production. A case of living-donor lobar lung transplantation is presented in which suppression of erythropoiesis was associated with ABO mismatched organ transplantation.

ABO Blood-Group System↗

Anastomosis of an anomalous segmental vein with the azygos vein in living-donor lobar lung transplantation.

We report the case of a living-donor lobar lung transplantation in which we found an abnormal segmental vein in the right lower lobe of the donor lung. The abnormal vein was anastomosed to the azygos vein of the recipient so that lung edema and congestion could be avoided. This alternative technique is effective in living-donor lobar lung transplantation when the superior segmental vein in the right lower lobe of the donor drains into the superior vein.

Anastomosis, Surgical↗

Failure of disopyramide to improve right ventricular outflow tract obstruction after living-donor lobar lung transplantation.

Right ventricular (RV) outflow tract obstruction (RVOTO) is an uncommon complication of lung transplantation in patients with pulmonary hypertension (PH) and both medical management and surgical intervention are required. A 28-year-old female with primary PH was referred and because she did not respond to medical treatment, living-donor lobar lung transplantation was performed. The operation was successful, but dyspnea and exercise intolerance developed during rehabilitation and transthoracic echocardiography revealed RVOTO. Intravenous disopyramide during cardiac catheterization reduced the pressure gradient from 35 mmHg to 16 mmHg without decreasing RV systolic pressure. However, electrical and hemodynamic parameters were adversely affected by disopyramide and thus, after cardiac catheterization, administration of fluid and a low dose of atenolol was started, and her symptoms improved. Transthoracic echocardiography showed improvement in the RVOTO. This case suggests that disopyramide should be avoided for patients with RVOTO following lung transplantation and that other negative inotropic agents, such as beta-blockers, are more effective for relief of RVOTO.

Adult↗

Functional evaluation of lung by Xe-133 lung ventilation scintigraphy before and after lung volume reduction surgery (LVRS) in patients with pulmonary emphysema.

We evaluated the respiratory functions of patients with pulmonary emphysema who underwent lung volume reduction surgery (LVRS) by the mean transit time (MTT) with Xe-133 lung ventilation scintigraphy, forced expiration volume in 1 sec (FEV1.0), residual volume (RV), distance walked in 6 min (6-min walk), and the Hugh-Jones classification (H-J classification) before and after LVRS. In 69 patients with pulmonary emphysema (62 men, 7 women; age range, 47-75 years; mean age, 65.4 years +/- 6.1, preoperative H-J classification, III (two were II)-V) who underwent LVRS, all preoperative and postoperative parameters (MTT 3 weeks after LVRS and the others 3 months after LVRS) were judged statistically by the Wilcoxon signed-ranks test and Odds ratio. Every postoperative parameter was improved with a significant difference (P < 0.05) compared to preoperative parameters. MTT at 3 weeks after LVRS was not associated with %FEV1.0 and the H-J classification at 3 months after LVRS, but was associated with RV and a 6-min walk at 3 months after LVRS. MTT was useful for the clinical evalution of aerobic capability after LVRS.

Aged↗

DNA methylation of multiple genes and clinicopathological relationship of non-small cell lung cancers.

Aberrant methylation of 5' CpG islands is thought to play an important role in the inactivation of tumor suppressor genes in several types of cancers. In non-small cell lung cancer (NSCLC), several genes are known to be frequently methylated and the correlation of their methylation with clinical features has been studied. We determined the methylation of p16, CDH13 and RAR-beta which were reported to be methylated frequently in NSCLCs and HPP-1 which was known to be methylated in other types of cancers. The correlation between methylation and clinicopathological features were examined. The frequencies of methylation in NSCLCs were 20% for p16, 37% for CDH13, 34% for RAR-beta, and 13% for HPP1. The methylation of p16 is correlated with smoking history and methylation of HPP1 was significantly more frequent in adenocarcinomas than in squamous cell carcinomas. This is the first description of aberrant methylation of the HPP1 gene in lung cancers and our data support the previous reports on methylation in NSCLCs and association with smoking.

Adenocarcinoma↗