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Biomedical subjects

Hiroshi Date

Publications and source records attributed to Hiroshi Date.

69 records · Page 4Linked to original sources
PubMed2004

Aberrant methylation of p57KIP2 gene in lung and breast cancers and malignant mesotheliomas.

The p57KIP2 gene belongs to the Cip/Kip family of CDK inhibitors and has been demonstrated to be a tumor suppressor gene, being inactivated in various types of human cancers. We analyzed the methylation and expression status of p57KIP2 in lung and breast cancers, and in malignant mesotheliomas (MMs). The promoter region of p57KIP2 was determined by methylation-specific PCR (MSP) in samples of lung and breast cancer, and of MM. The expression of the gene in the cell lines was determined by RT-PCR and correlated with the methylation status. Aberrant methylation was detected by MSP in 9 of 27 (33%) and 25 of 78 (32%) lung cancer cell lines and tumors, respectively, 11 of 18 (61%) and 17 of 38 (45%) breast cancer cell lines and tumors, respectively, and 1 of 25 (4%) MM tumors. DNA methylation was detected but rarely in the corresponding non-malignant tissues. In addition, the gene expression was restored in the methylated cell lines following 5-aza-2'-deoxycytidine treatment, confirming that the methylation was indeed responsible for the gene down-regulation. We also examined the relationship between the p57KIP2 methylation status and the clinicopathological features of the primary tumors, and found that there was no relationship between the p57KIP2 methylation status and any of the examined clinicopathological features. In summary, our results demonstrate that p57KIP2 methylation associated with the gene down-regulation is frequently present in lung and breast cancers and plays an important role at the molecular level in the pathogenesis of these cancers.

Adenocarcinoma↗
PubMed2003

Bronchogenic cyst with high serum carcinoembryonic antigen.

A 64-year-old woman had a large subcarinal cyst accompanied by high serum carcinoembryonic antigen (CEA) of 55.7 ng/ml removed thoracoscopically. The pathological diagnosis was benign bronchogenic cyst. Immunohistochemical findings clearly showed CEA in the stratified columnar epithelial lining of the cyst. Serum CEA returned to the normal range within 40 days of surgical resection.

Bronchogenic Cyst↗
PubMed2003

Living-donor lobar lung transplantation for various lung diseases.

OBJECTIVE: We report on our early experience in living-donor lobar lung transplantation for patients with various lung diseases including restrictive, obstructive, septic, and hypertensive lung diseases. METHODS: From October 1998 to March 2002, living-donor lobar lung transplantation was performed in 14 patients with end-stage lung diseases. There were 11 female patients and 3 male patients, with ages ranging from 8 to 53 years, including 4 children and 10 adults. Diagnoses included primary pulmonary hypertension (n = 6), idiopathic interstitial pneumonia (n = 2), bronchiolitis obliterans (n = 2), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1), and cystic fibrosis (n = 1). Bilateral living-donor lobar lung transplantation was performed in 13 patients and right single living-donor lobar lung transplantation was performed for a 10-year-old boy with primary pulmonary hypertension. RESULTS: All the 14 patients are currently alive with a follow-up period of 4 to 45 months. Although their forced vital capacity (1327 +/- 78 mL, 50.2% of predicted) was limited at discharge, arterial oxygen tension on room air (98.5 +/- 1.8 mm Hg) and systolic pulmonary artery pressure (24.8 +/- 1.6 mm Hg) were excellent. Forced vital capacity improved gradually and reached 1894 +/- 99 mL, 67.4% of predicted, at 1 year. All donors have returned to their previous lifestyles. CONCLUSIONS: Living-donor lobar lung transplantation can be applied to restrictive, obstructive, septic, and hypertensive lung diseases. This type of procedure can be an alternative to conventional cadaveric lung transplantation for both pediatric and adult patients who would die soon otherwise.

Adolescent↗
PubMed2003

Improved lung function by means of retrograde flush in canine lung transplantation with non-heart-beating donors.

OBJECTIVE: Use of lungs from non-heart-beating donors would increase the pulmonary donor pool. The aim of this study was to evaluate the effects of retrograde flush in canine lung transplantation from non-heart-beating donors. METHODS: Left lung transplantation was performed in 12 weight-matched pairs of dogs. Donors were killed without heparinization, left at room temperature for 2 hours, and then randomized into 2 groups. In group AF (n = 6) lung retrieval was performed after flushing the lung block with low potassium dextran glucose (50 mL/kg) solution through the pulmonary artery. In group AF+RF (n = 6) additional retrograde flushing (low potassium dextran glucose, 25 mL/kg) was performed through the left atrium before retrieval. Flushed solution was sampled at intervals to measure hemoglobin concentrations. The lungs were preserved at 4 degrees C for 2 hours, and the left lung was implanted to the recipient being subjected to a total ischemic time of 5 hours. After left lung transplantation, the right pulmonary artery and main bronchus were ligated. Lung function, including arterial blood gas and pulmonary hemodynamics, was measured for 3 hours. For lung function study, statistical analyses were performed by using 1-way analysis of variance with repeated measures. RESULTS: Group AF+RF had significantly better gas exchange and lower wet/dry weight ratio of the transplanted lung than group AF. Changes of hemoglobin concentration in the flushed solution indicated that additional retrograde flush could remove residual microthrombi after antegrade flush. CONCLUSIONS: This study supports the theory that additional retrograde flush improves lung function after lung transplantation by removing residual pulmonary microthrombi in the lungs of non-heart-beating donors.

Animals↗
PubMed2003

Successful treatment of limited disease-small cell lung cancer with multimodality treatment consisting of concurrent chemoradiotherapy, high-dose chemotherapy with autologous peripheral blood stem cell transplantation and surgical resection.

A 65-year-old man with limited disease-small cell lung cancer was treated with concurrent chemoradiotherapy which resulted in a partial response. He further received high-dose chemotherapy with autologous peripheral blood stem cell transplantation. Development of non-small cell carcinoma was, however, suspected at a site of the residual nodule in cytological examination using bronchoscopy. He then underwent lobectomy, which revealed that the nodule was composed of necrotic tissue. He has been alive without recurrence for seven years. This multimodality treatment appeared to be effective for this patient. However, further investigation is necessary to clarify the role of multimodality treatment.

Aged↗
PubMed2002

Abnormal auditory neural networks in patients with right hemispheric infarction, chronic dizziness, and moyamoya disease: a magnetoencephalogram study.

The purpose of this study was to determine whether the auditory cortex is sensitive to cortical insults and to determine the specificity of the insults in three clinical situations with different cortical involvement. Auditory-evoked magnetic fields of ten normal subjects, 8 patients with right hemispheric infarction, 11 with chronic dizziness, and 2 with moyamoya disease were measured. To analyze the abnormality of auditory neural networks, the magnitude ratio and the angle difference (Deltatheta) between response vectors, which were determined from maximum current arrows corresponding to the N100m peak for contralateral and ipsilateral stimuli were used. A normal range of the parameters was defined so that abnormal values could be determined. Of the three parameters, Deltatheta was the most sensitive: 4 patients with right hemispheric infarction, 4 with chronic dizziness, and 1 with moyamoya disease had abnormal Deltatheta. The electrical activity in the patients with such abnormal Deltathetas had a circular current pattern. These findings suggest that right infarction lesions sometime affect the left auditory neural network, dizziness is caused by abnormal neural networks between the vestibular cortical area and the auditory cortex or by an imbalance between left and right auditory-cortex activities, and moyamoya-disease patients have almost normal auditory-electrical activity.

Acoustic Stimulation↗
PubMed2002

Experimental study on size matching in a canine living-donor lobar lung transplant model.

OBJECTIVE: In an effort to address the donor-shortage issue, living-donor lobar lung transplants have been performed with satisfactory results. The use of small grafts is potentially problematic because it could cause high pulmonary artery pressure, resulting in lung edema. The purpose of this study was to evaluate the effect of small grafts on early pulmonary function and to identify the predictor for acceptable size discrepancy. METHODS: Seventeen pairs of mongrel dogs with various donor-recipient sizes were used. Body weight, height, chest circumference, and lung weight were measured as size parameters. Right middle, lower, and cardiac lobes were implanted as a right lung of the recipient and the left lower lobe was implanted as a left lung without use of cardiopulmonary bypass. Pulmonary function of the recipient was measured for 6 hours after reperfusion. RESULTS: A significant negative correlation was found between donor/recipient body-weight ratio and mean pulmonary artery pressure at 1 hour (r = -0.594, P =.025). A significant correlation was found between donor/recipient body-weight ratio and PaO(2) at 6 hours (r = 0.704; P =.007). There was no significant correlation between the other 3 size parameters and postoperative pulmonary function. All 8 recipients with a donor/recipient body-weight ratio of 1.2 or greater survived the 6-hour assessment period, and their PaO(2) exceeded 500 mm Hg at 6 hours. CONCLUSIONS: Donor/recipient weight ratio is an important predictor of early pulmonary function in a canine living-donor lobar lung transplant model.

Animals↗
PubMed2002

Recovery of cardiac function after living-donor lung transplantation in a patient with primary pulmonary hypertension.

Legislation for brain death and organ transplantation was passed in Japan in 1997, but there is still a great shortage of brain-death donors. Primary pulmonary hypertension (PPH) is a progressive disease that is usually followed by death within 5 years of diagnosis. Continuous infusion of prostacyclin is effective, but some patients will ultimately require heart-lung or lung transplantation. The first case of bilateral living-donor lobar lung transplantation (LDLLT) for PPH in Japan is reported. The recipient was a 19-year-old woman who was diagnosed as PPH at the age of 14 years and began intravenous prostacyclin therapy. Initially her symptoms improved, but she returned to New York Heart Association class IV in 2000. In January 2001, she underwent bilateral LDLLT. Postoperative echocardiography showed that the right ventricular diameter had decreased and septal wall motion had normalized, resulting in a round-shaped left ventricle. Right heart catheterization demonstrated that cardiac output and pulmonary arterial pressure had normalized. The right ventricular ejection fraction improved from 15% to 77%. The patient was discharged from hospital after 60 days postoperatively. LDLLT will become one of the options in Japan for end-stage PPH.

Adult↗
PubMedDate not supplied

Humoral immune responses during acute rejection in rat lung transplantation.

The detailed responses of humoral immunity during acute rejection remain obscure in lung transplantation (LTx). In order to clarify the reactions of alloantibodies (allo-Abs) during acute rejection, we demonstrated the time-course of changes in anti-donor Ab reaction in the peripheral blood and deposition in the grafts using a rat LTx model. Lewis (LEW) rats served as recipients for Brown Norway (BN) lung allografts (MHC fully incompatible combination). The left lung was transplanted orthotopically using a cuff technique. Syngeneic transplants (LEW to LEW) served as control. No immunosuppression therapy was administered in this model. We evaluated the alloreactivity against donor in rat recipients by detecting allo-Abs with a flow cytometric cross-match (FCXM) technique. Recipient serum samples were incubated with donor lymphocytes and stained with anti-rat immunoglobulin (Ig), to determine the titers of circulating allo-Abs in the peripheral blood with a three-color FCXM technique. We also examined the deposition of anti-donor Abs (IgG and IgM) in the grafts with an immunofluorescent method. All allografts were completely rejected and lost their aeration within 6 days after LTx. Strong allo-Abs responses of both IgG and IgM were observed in the peripheral blood during acute rejection. The level of IgM allo-Abs had already significantly increased on day 2 at the time of mild rejection; however, IgG Abs did not elevate until day 6, when the grade of rejection was severe. Circulating IgM levels started decreasing on day 8, whereas IgG Abs continued elevating. On the other hand, no evident deposition of allo-Abs in the grafts was observed until day 6. We have shown in this study that circulating IgM allo-Abs was detected at the time of mild allograft rejection, interestingly, before evident deposition in the graft. It might be suggested that allograft rejection progressed without antibody deposition until severe rejection.

Animals↗
PubMedDate not supplied

Tandem high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation for recurrent soft tissue sarcoma.

BACKGROUND: Patients with recurrent soft tissue sarcoma (STS) are seldom curable, with 5-year survival rates of less than 10% in all large series. The role of high-dose chemotherapy (HDC) with hematopoietic stem cell support in this disease has not been established. CASE REPORT: We report on two patients with recurrent STS who were treated with tandem HDC supported by autologous peripheral blood stem cell transplantation (PBSCT). One patient with malignant fibrous histiocytoma recurred with multiple lung metastases. This patient achieved a partial response after two cycles of induction chemotherapy consisting of ifosfamide and epirubicin. During four cycles of induction chemotherapy, peripheral blood stem cells (PBSCs) were harvested. Tandem high-dose ICE regimen (ifosfamide 3 g/m2 on days-7 to -3, carboplatin 400 mg/m2 on days-7, -5 and 3, etoposide 500 mg/m2 on days-7, -5 and 3) supported by autologous PBSCT gave rise to further regression of the tumors. Another patient with malignant hemangiopericytoma was treated by tandem high-dose ICE regimen supported by autologous PBSCT after the 3rd removal of abdominal tumors. Relapse-free intervals until the 1st, 2nd and 3rd relapses were 40, 19 and 22 months, respectively. Tandem high-dose ICE regimen might delay the relapse. CONCLUSION: These observations suggest that a tandem high-dose ICE regimen with autologous PBSCT is feasible with some clinical efficacy in the control of refractory STS.

Adult↗
PubMedDate not supplied

Long-term effect of gefitinib (ZD1839) on squamous cell carcinoma of the lung.

This case report describes the effects of long-term treatment with the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib ('Iressa', ZD1839) on a patient with squamous cell carcinoma of the lung. Gefitinib is an orally active agent that blocks signal transduction pathways implicated in the proliferation and survival of cancer cells and host-dependent processes that promote tumor growth. A 62-year-old Japanese man with a history of heavy smoking was diagnosed with squamous cell carcinoma of the lung, clinical stage IIIB (T4N3M0), in August 2000. He received two cycles of cisplatin-based chemotherapy and subsequently underwent left upper lobectomy followed by thoracic radiotherapy. After these treatments, he underwent partial lobectomy and pneumonectomy because of disease recurrence. In June 2002, he started treatment with gefitinib 250 mg/day orally because of mediastinal lymph node recurrence and an elevated serum cytokeratin 19 fragment (CYFRA) level. As a result, the mediastinal lymph node markedly regressed and the serum CYFRA level became normalized. Although he experienced recurrence three times during the 18 months prior to treatment with gefitinib, recurrence has not been experienced in the 13 months since the start of gefitinib treatment, while tolerability has been acceptable.

Antigens, Neoplasm↗