Biomedical subjects

Shinichiro Miyoshi

Publications and source records attributed to Shinichiro Miyoshi.

34 records · Page 2Linked to original sources

PubMed2003

New prognostic indicator for non-small-cell lung cancer, quantitation of thymidylate synthase by real-time reverse transcription polymerase chain reaction.

Thymidylate synthase (TS) is an enzyme that catalyzes an important DNA biosynthesis process. The gene expression of TS has not been reported in non-small-cell lung cancer (NSCLC) patients. To clarify the correlation between TS mRNA levels and clinicopathological features of NSCLC, we examined 70 Stage I and II NSCLC patients for intra-tumoral expression of TS using TaqMan reverse transcription polymerase chain reaction (RT-PCR) assay and immunohistochemistry methods. We also investigated the TS promoter 28 bp polymorphism in 48 cancer tissues using PCR amplification of genomic DNA. Lung cancer tissue showed higher TS mRNA levels than normal lung tissue (Mann-Whitney U-tests; p = 0.0020). Further, TS mRNA expression was correlated with immunohistochemical TS expression (p = 0.029). We obtained 2 different DNA fragments, which indicated triple-repeat (3R) and double-repeat (2R) type alleles. Cancer tissues with the 3R/3R genotype showed significantly higher TS mRNA levels as compared to those with other genotypes (p = 0.0019). The TS genotype was also correlated with immunohistochemical TS expression (chi(2) test; p = 0.0079). The disease-free survival of the low TS mRNA level group was significantly better than those with high TS mRNA levels (log-rank test; p = 0.010), however, there were no significant differences found by immunohistochemical evaluation (p = 0.34) or TS genotype analysis (p = 0.11). A multivariate analysis revealed that high TS mRNA levels independently contributed to disease-free survival. The quantitation of TS mRNA levels is clinically more sensitive and useful for determining the prognosis of Stage I and II NSCLC patients than an immunohistochemical evaluation.

Aged↗

PubMed2003

Primary germ cell tumors in the mediastinum: a 50-year experience at a single Japanese institution.

BACKGROUND: Primary germ cell tumors (GCT) of the mediastinum share similar clinical and biologic characteristics, which are different from their testicular counterpart. The purpose of the current study was to review the authors' institutional experience of mediastinal GCT, emphasizing the clinical spectrum, time trends of treatment, and recent advances in therapeutic modalities for malignant GCT. METHODS: Between 1951 and 2000, 129 patients (70 males and 59 females) underwent surgical treatment for GCT, which accounted for 16.0% of the mediastinal tumors during the same period. There were 95 patients with mature teratomas, 13 patients with seminomas, and 21 patients with nonseminomatous germ cell tumors (NSGCT) with median ages of 26.4 years, 27.6 years, and 28.5 years, respectively. RESULTS: Adult patients with mature teratomas were less symptomatic (33.3%) than pediatric patients (52.4%). All patients with mature teratoma were cured by resection alone. Eight of the 13 patients (61.5%) with seminoma were symptomatic and 10 of 13 patients (83.3%) survived after surgery and radiation with/without chemotherapy. Nineteen of 21 patients (90.5%) with NSGCT had dyspnea, chest pain, and superior vena cava syndrome. Before 1985, patients received radical resection and/or chemoradiotherapy. However, all patients died due to disease progression, with a median survival period of 7.6 months. After 1986, six of eight patients received cisplatin-based chemotherapy, including three who received additional high-dose chemotherapy with a supporting peripheral blood stem cell transplantation until tumor markers normalized. Five patients who underwent salvage resection are currently disease free with a median survival period of 58.3 months. CONCLUSIONS: The institutional experience indicates the benign nature of mediastinal mature teratomas and the excellent prognosis for patients with seminomas after resection. An improved survival advantage was ensured with cisplatin-based preoperative chemotherapy in patients with NSGCT.

Adolescent↗

PubMed2003

Clinical spectrum of primary mediastinal tumors: a comparison of adult and pediatric populations at a single Japanese institution.

BACKGROUND AND OBJECTIVES: The purpose of this study was to review our Japanese institutional experience of mediastinal tumors and to compare differences in the clinical spectrum between adults and children. METHODS: We retrospectively reviewed the records of 806 patients (676 adults and 130 children) between 1951 and 2000 at our institution. RESULTS: There were 244 thymomas (36%), 106 germ cell tumors (16%), 95 congenital cysts (14%), 82 lymphomas (12%), 76 neurogenic tumors (11%), and 24 thyroid tumors (4%) in adult patients. There were 60 neurogenic tumors (46%), 24 germ cell tumor (19%), 17 lymphoma (13%), 10 congenital cysts (8%), and 5 thymomas (4%) in the pediatric patients. There was a significant higher incidence of neurogenic tumors and a lower incidence of thymomas and thyroid tumors in children than adults. The most common location was the anterior compartment (68%) in adults and the posterior compartment in children (52%). The prevalence of malignancy in pediatric patients was lower than adults (37% vs. 47%; P < 0.05). Symptoms due to compression or direct invasion into adjacent structures may have caused the higher incidence of dyspnea or respiratory distress in the pediatric group compared to the adults (15.4% vs. 4.0%; P < 0.001). There were fewer incidences of facial edema in children compared to adults (2.6% vs. 10.7%; P < 0.02). Emergent operations were required more often in the pediatric group than the adult group. CONCLUSIONS: We demonstrated definite differences in histologic distribution, location, and symptomatology in mediastinal tumors between adult and pediatric populations, which should be considered in the evaluation and planning of a therapeutic modality for mediastinal tumors.

Adolescent↗

PubMed2003

Intrapleural administration of a large amount of diluted fibrin glue for intractable pneumothorax. A clinical study based on 57 cases: including 2 unsuccessful cases.

OBJECTIVE: Pleurodesis using chemical agents has been applied to high-risk patients with pneumothorax. This treatment, however, is sometimes unsuccessful in patients with intractable pneumothorax. We have developed intrapleural administration of diluted fibrin glue as an effective treatment for such patients. METHODS: Fibrin glue was diluted 4-fold with saline and/or contrast media. Pleurodesis with a large amount of the diluted fibrin glue was performed in 55 high risk patients (57 cases, bil.2 patients) with intractable pneumothorax. RESULTS: The air leaks were stopped by administration of the glue in all except 2 patients. During the follow-up period, a recurrence rate of 10.5% was observed. These recurrent pneumothoraces were successfully treated using the same procedure with no further recurrence. Pyrexia (12.3%) and chest discomfort (8.8%) were observed as side effects, and there was no occurrence of severe chest pain or thoracic empyema. CONCLUSIONS: These results suggested that intrapleural administration of a large amount of diluted fibrin glue was an effective treatment for intractable pneumothoraces in high-risk patients.

Aged↗

PubMed2003

Needlescopic operation for partial lung resection.

Needlescopic operation using instruments with a diameter of 2 mm has not been applied to partial lung resection because of the difficulty in grasping the lung firmly or the possibility of injuring the lung easily with 2-mm forceps. We have developed a technique using a mini-loop retractor and successfully performed partial lung resection in 35 patients with pneumothorax, small lung tumor, or interstitial pneumonia.

Humans↗

PubMed2003

The immunologic role of thymectomy in the treatment of myasthenia gravis: implication of thymus-associated B-lymphocyte subset in reduction of the anti-acetylcholine receptor antibody titer.

BACKGROUND AND PURPOSE: Thymectomy is generally accepted as the major option of treatment for myasthenia gravis. To elucidate the biological role of thymectomy in the treatment of myasthenia gravis, the immunologic characteristics of the thymus was studied in association with the postoperative kinetics of the anti-acetylcholine receptor antibody titer. MATERIALS AND METHODS: Thirty-four patients with nonthymomatous myasthenia gravis who had positive anti-acetylcholine receptor antibody titer and undergoing extended thymectomy were subjected to the study. Reduction of anti-acetylcholine receptor antibody titer was evaluated in terms of the proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy to that before the operation. The numbers of B lymphocytes (CD19(+) cells) and the germinal center B lymphocytes (CD19(+)CD38(high) cells) present in 1 g of the thymic tissue were calculated by flow cytometry. RESULTS: The proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy ranged from 27.5% to 150%. The numbers of B lymphocytes and the germinal center B lymphocytes in 1 g of the thymic tissue ranged from 0.19 x 10(6)/g to 162.8 x 10(6)/g and from 0.09 x 10(6)/g to 33.4 x 10(6)/g, respectively. The proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy had a significant inverted correlation with the number of B lymphocytes (P =.002) as well as that of the germinal center B lymphocytes (P =.007). CONCLUSION: Effectiveness of thymectomy was dependent on predominance of B lymphocytes and the germinal center B lymphocytes in the thymus, suggesting that one of the biological roles of thymectomy in the treatment of myasthenia gravis is removing the thymus-associated germinal centers.

ADP-ribosyl Cyclase↗

PubMed2003

Clinicopathological investigation of 20 cases of primary tracheal cancer.

OBJECTIVE: Primary tracheal cancer is considered to be relatively rare. Its epidemiology, therapeutic strategy and prognosis are not well understood. METHODS: We retrospectively investigated the clinicopathological aspects of 20 patients with primary tracheal cancer. RESULTS: Patients included 11 men and nine women with a mean age of 57.3 years. There were 12 squamous cell carcinomas and eight adenoid cystic carcinomas. Four patients received only palliative therapy. Sixteen patients underwent surgical treatment such as segmental tracheal, laryngotracheal, or carinal resection. One patient with squamous cell carcinoma died of postoperative mediastinitis. Although resected specimens from five patients had tumor positive margins, only one of those patients died after local recurrence and only three patients had postoperative treatment. The 5-year survival rate for patients who underwent surgery was 72.3%. CONCLUSIONS: Surgical treatment is the first choice therapeutic modality for primary tracheal cancer in consideration of its prognosis. While performing the operation, safety of the anastomosis should take precedence over completeness of resection.

Adult↗

PubMed2003

Clinical spectrum of mediastinal cysts.

OBJECTIVES: Congenital cysts of the mediastinum are an uncommon but important diagnostic group, representing 12 to 30% of all mediastinal masses. The purpose of this study was to review our institutional experience with congenital cysts of the mediastinum, emphasizing the clinical spectrum of the disease. DESIGN: Retrospective study. OBJECTIVES: University hospital unit of general thoracic surgery. METHODS: We retrospectively reviewed the records of 105 patients with cysts of the mediastinum (50 male and 55 female patients) who comprised 13.0% of mediastinal masses over the past 50 years. RESULTS: There were 10 pediatric patients (< 15 years old) and 95 adult patients. The prevalence of cysts in the adult populations was higher than that in children (14.1% vs 7.7%, p < 0.05). There were 47 bronchogenic cysts, 30 thymic cysts, 12 pericardial cysts, 7 pleural cysts, 4 esophageal duplications, 2 meningoceles, 1 thoracic duct cyst, and 2 others. MRI has become a useful tool for providing supplemental data in combination with CT. Overall, 38 patients (36.2%) with mediastinal cysts were symptomatic, including 39.2% with bronchogenic/esophageal cysts, 40% with thymic cysts, and 15.8% with pericardial/pleural cysts. One hundred patients had complete resection of their masses, 3 patients with pericardial diverticulum received a thoracoscopic fenestration without mortality, and 2 patients refused surgery. CONCLUSION: Early recognition of these relatively rare lesions would lead to immediate and appropriate surgical intervention. Early surgical intervention is also important because definitive histologic diagnosis can only be established by means of surgical extirpation.

Adult↗

PubMed2003

Left common carotid artery cannulation for type A aortic dissections.

We used left common carotid artery cannulation for repair of type A aortic dissection in 2 patients for whom both femoral artery and axillary artery cannulation were thought to be more dangerous, due to dissection of the brachiocephalic trunk and left subclavian artery in association with abdominal stenosis. Before performing end-to-side anastomosis, we attached a small partial clamp to the left common carotid artery, thereby maintaining adequate cerebral blood flow during perfusion. To date, neither of our patients has experienced neurologic complications related to this procedure. We believe that left common carotid artery cannulation for type A dissections is useful when dissection of the brachiocephalic trunk and left subclavian artery is found in association with abdominal or femoral artery stenosis. To the best of our knowledge, these 2 cases are the 1st described in the medical literature.

Aortic Dissection↗

PubMed2002

Overexpression of the Wilms' tumor gene WT1 in de novo lung cancers.

Expression of the Wilms' tumor gene WT1 in de novo lung cancer was examined using quantitative real-time RT-PCR and immunohistochemistry. Overexpression of the WT1 gene was detected by RT-PCR in 54/56 (96%) de novo non-small cell lung cancers examined and confirmed by detection of WT1 protein with an anti-WT1 antibody. Overexpression of the WT1 gene was also demonstrated in 5/6 (83%) de novo small cell lung cancers by immunohistochemistry. Furthermore, when the WT1 gene was examined for mutations by direct sequencing of genomic DNA in 7 lung cancers, no mutations were found. These results suggest that the nonmutated, wild-type WT1 gene plays an important role in tumorigenesis of de novo lung cancers and may provide us with the rationale for new therapeutic strategies for lung cancer targeting the WT1 gene and its products.

Aged↗

PubMed2002

Prognostic significance of p27KIP1 expression in resected non-small cell lung cancers: analysis in combination with expressions of p16INK4A, pRB, and p53.

BACKGROUND AND OBJECTIVES: Whether a prognostic role for expression of the tumor suppressor gene (TSG) products exists in resected non-small call lung cancers (NSCLCs) remains controversial. Our study was performed to determine the value of TSGs expressions for patients survival in NSCLCs. METHODS: We examined 108 resected NSCLCs for the expression of TSG products, p27(KIP1), p16(INK4A), pRB, and p53 that govern cell cycle transition by immunohistochemistry and compared them with patient clinical characteristics and prognoses. RESULTS: Abnormal expressions of p27(KIP1), p16(INK4A), pRB, and p53 were found in 61 (57%), 53 (49%), 42 (39%), and 48 (44%), respectively, of the 108 NSCLCs. Univariate analysis showed abnormal expression of p27(KIP1) to be a strong indicator for poor patient survival, not only in the total cohort (P = 0.0024), but also in subgroups with T1-T2 (P = 0.016), N0 (P = 0.047), and squamous cell carcinomas (P = 0.026), but not according to the expression of p16(INK4A), pRB, or p53. In the Cox regression analysis, p27(KIP1) expression was found to be an independent prognostic factor (P = 0.0148) and associated with pathological stage (P = 0.0278). CONCLUSIONS: Our results suggest that abnormal p27(KIP1) expression may be a useful indicator to predict postoperative prognosis, especially in patients with early stage NSCLCs, as compared to other TSG products examined.

Adenocarcinoma↗

PubMed2002

Oncological significance of WHO histological thymoma classification. A clinical study based on 286 patients.

OBJECTIVES: The clinical significance of thymoma histology remains controversial because of the numerous histological classifications of thymic epithelial tumors. Universal classification of such tumors was achieved by the World Health Organization (WHO) in 1999. We studied the prognostic significance of this classification. METHODS: We studied clinical features and postoperative survival in cases of thymoma, but not thymic carcinoma, based on WHO histological classification in 286 patients undergoing surgery between 1958 and 2001. RESULTS: Tumors were 19 type A, 79 type AB, 59 type B1, 102 type B2, and 27 type B3. The proportion of invasive tumors increased by type--from A to AB, B1, B2, and B3. The great vessels were involved more frequently in type B2 and B3 tumors than in type A, AB, and B1 tumors. The 20-year survival was 100% in type A, 87% in type AB, 91% in type B1, 65% in type B2, and 38% in type B3 tumors. Multivariate analysis showed Masaoka staging and WHO histological classification to be significant independent prognostic factors, while age, gender, myasthenia gravis association, resection completeness and great vessel involvement were not. In stage III patients, 13 of 45 patients with type B2 and B3 tumor died of their tumors, while no tumor deaths occurred in 11 patients with type A, AB, and B1 tumors. CONCLUSION: WHO histological classification realistically reflects the oncological behavior of thymoma.

Adolescent↗

PubMed2002

A study on CD45 isoform expression during T-cell development and selection events in the human thymus.

CD45 molecules are known to appear as various isoforms generated by alternative splicing of variable exons 4, 5, and 6, but the detailed profile of CD45 isoform expression during thymocyte development has not been revealed. We examined the CD45 isoforms expressed in the various human thymocytes' subsets defined by CD3, CD4, and CD8 expressions using RT-PCR and 4-color flow cytometry. RT-PCR study revealed that RABC, RAB, RBC, RB, and R0 isoforms were expressed in thymocytes while any of RAC, RA, or RC isoforms were not detected. RABC, RAB and RBC isoforms were expressed at CD3(-)CD4(-)CD8(-) and CD3(+)CD4(+)CD8(-) stages, but were barely detectable at CD3(-)CD4(+)CD8(+) stage. RB isoform was consistently expressed at a relatively high level at all stages. R0 isoform was expressed at a low level at CD3(-)CD4(-)CD8(-) and CD3(-)CD4(+)CD8(-) stages but upregulated at CD3(+)CD4(+)CD8(+) and CD3(+)CD4(+)CD8(-) stages. In combination with the results obtained by 4-color flow cytometric study, CD45 isoform expression on human thymocytes were determined to be RABC(+)RAB(+/-)RBC(+)RB(+)R0(+/-) at CD3(-)CD4(-)CD8(-) stage, RABC(-)RAB(-)RBC(-)RB(+)R0(+) at CD3(-)CD4(+)CD8(-) and CD3(-)CD4(+)CD8(+) stages, RABC(+/-)RAB(+)RBC(+)RB(++)R0(++) at CD3(+)CD4(+)CD8(+) stage, and RABC(+)RAB(+)RBC(+)RB(++)R0(+) at CD3(+)CD4(+)CD8(-) stage. Bcl-2 expression was upregulated between CD3(-)CD4(+)CD8(+)CD45R0(+) and CD3(+)CD4(+)CD8(+)CD45R0(+) stages. Expression of CD45R0 epitope was upregulated between CD3(-)CD4(+)CD8(+)CD69(-) and CD3(+)CD4(+)CD8(+)CD69(+) stages while CD45RA epitope expression was unchanged. Thus, when thymocytes are positively selected, CD45R0 isoform expression seems to be upregulated while CD45RABC isoform expression stays at a very low level. In summary, various isoforms of CD45 were shown to be tightly regulated during thymocyte development and through the selection process.

Antigens, CD↗

PubMed2002

Hepatocyte growth factor stimulates proliferation of respiratory epithelial cells during postpneumonectomy compensatory lung growth in mice.

Although it is known that the lung undergoes compensatory growth after pulmonary resection, mechanisms by which lung cells exhibit compensatory proliferation are not well defined. We investigated the involvement of hepatocyte growth factor (HGF) in postpneumonectomy compensatory lung regeneration in mice, because HGF has mitogenic and morphogenic actions on lung epithelial cells. Following left pneumonectomy, alveolar and airway epithelial cells underwent compensatory DNA synthesis, reaching maximal levels 5 d after the surgery. Before changes in DNA synthesis in lung epithelial cells, expression of HGF mRNA and protein levels in the remaining lung, liver, and kidney were changed in response to left pneumonectomy, and these changes were associated with postoperative increases in plasma HGF levels. c-Met/HGF receptor expression was localized predominantly in alveolar type II and airway epithelial cells, whereas c-Met/HGF receptor mRNA expressions were transiently upregulated before the peak in lung DNA synthesis. Neutralization of endogenous HGF by an antibody in pneumonectomized mice suppressed the compensatory DNA synthesis in lung epithelial cells, whereas administration of recombinant HGF to pneumonectomized mice stimulated DNA synthesis in lung epithelial cells. These results strongly suggest that HGF has a role as a pulmotrophic factor in postpneumonectomy compensatory lung regeneration.

Animals↗

PubMed2002

New electroablation technique following the first-line stapling method for thoracoscopic treatment of primary spontaneous pneumothorax.

STUDY OBJECTIVES: A new tip for the electroablation of pneumocysts was examined clinically as a second-line method for stapled resection of pneumocysts during video-assisted thoracoscopic surgery (VATS). DESIGN: A trial to assess feasibility. SETTINGS: National referral hospitals. PATIENTS: One hundred seven patients were studied, of whom 99 patients were eligible for the study (85 men and 14 women; age range, 15 to 69 years; median age, 23 years), who had undergone VATS for primary spontaneous pneumothorax between July 1996 and June 1998. Apical pneumocysts were resected employing staplers, and residual pneumocysts, if present, were electroablated employing a new tip for the electrosurgery unit (ball shape, 8 mm in diameter, and made of stainless steel). MEASUREMENTS AND RESULTS: Thirty-three patients (33%) underwent electroablation only for small (< 2 cm in diameter) pneumocysts (group S), and 11 patients (11%) underwent electroablation for large (>/= 2 cm in diameter) pneumocysts (group L). The remaining 55 patients (56%) did not undergo electroablation because there were no residual pneumocysts (group N). There were no complications during surgery. The duration of the operation was significantly shorter (about 20 min on average) for group N, but there was no significant difference in the amount of blood loss, the number of applied staples, the duration of drainage, and the duration of hospital stay. Group S achieved a 100% relapse-free rate (33 of 33 patients), group L achieved a 64% relapse-free rate (7 of 11 patients), and group N achieved an 89% relapse-free rate (49 of 55 patients) [group S vs group N, p = 0.08; group L vs group N, p = 0.001; and group S vs group L, p = 0.002]. CONCLUSION: Electroablation with the M-tip is feasible as a second-line method for the treatment of small pneumocysts following the stapling technique during VATS.

Adolescent↗

PubMed2002

[NSIP group III treated with the first cadaveric single lung transplantation in Japan].

A 43-year-old woman developed dyspnea on effort in January 1996. She was treated with various antibiotics but developed dyspnea and pretibial edema. She was referred to our hospital and admitted on February 20, 1996. On the basis of the clinical course and radiological findings, she was diagnosed as having idiopathic pulmonary fibrosis with right-side heart failure. After high-dose steroid therapy (methylprednisolone, 1,000 mg/day for 3 days) and the administration of a diuretic, oral prednisolone therapy was initiated. Her condition gradually recovered. To obtain a definite diagnosis, an open lung biopsy was recommended but the patient refused the procedure. She was discharged from the hospital and placed on home oxygen therapy. After her informed consent was obtained, she became a candidate recipient for the nationwide Central Lung Transplant Evaluation Committee on August 7, 1998. Her name was then listed in the Japan Organ Transplant Network. The patient was admitted to our hospital in October 1998 because of respiratory failure. She underwent left lung transplantation at Osaka University Hospital on March 29, 2000. After the lung transplantation, she was discharged and is presently doing well without the need for supplementary oxygen. A differential diagnosis of the removed lung as nonspecific interstitial pneumonia (NSIP) group III or UIP was required. We finally diagnosed NSIP group III because of the temporal uniformity and diffuse distribution of the fibrosis. In this report, we also describe the background of the clinical diagnosis, the indications for lung transplantation and the clinical course before and after transplantation.

Adult↗