Search PubMed⌕ Search

Biomedical subjects

Teruhisa Kazui

Publications and source records attributed to Teruhisa Kazui.

At least 55 records · Page 3Linked to original sources

Adenovirus-mediated gene transfer of interferon alpha inhibits hepatitis C virus replication in hepatocytes.

Recently we reported that on-site interferon (IFN)-alpha production in the liver using an adenovirus vector can achieve a substantial confinement of IFN-alpha in the target organ and can improve liver fibrosis in a rat liver cirrhosis model. However, the major therapeutic effect of IFN for hepatitis C virus (HCV)-associated liver diseases is its antiviral effect on HCV. As a prelude to the in vivo HCV infection experiment using a primate animal model, here we examined the antiviral effect of IFN-alpha gene transfer into HCV-positive hepatocytes in vitro. The non-neoplastic human hepatocyte cell line PH5CH8 was inoculated with HCV-positive serum. Successful in vitro HCV replication and thus the validity of this model was confirmed by a strong selection for HCV variants determined by sequence analysis of the hypervariable region and an increase of HCV RNA estimated by real time TaqMan RT-PCR. One day after the inoculation of HCV, PH5CH8 cells were infected with adenoviral vectors encoding human IFN-alpha cDNA. HCV completely disappeared 9 days after the adenoviral infection, which is linked to the increase of 2('),5(')-oligoadenylate synthetase activity, suggesting that IFN-alpha produced by gene transfer effectively inhibits HCV replication in hepatocytes. This study supports the development of IFN-alpha gene therapy for HCV-associated liver diseases.

2',5'-Oligoadenylate Synthetase↗

Solitary fibrous tumor of the pleura with hemothorax at the thoracic apex.

A 31-year-old man was referred to our hospital with a diagnosis of a left lung mass and substantial pleural effusion. 1,300 mL of blood was drained. Chest computed tomography (CT) and magnetic resonance imaging (MRI) revealed a hypervascular, round shaped mass, 9 cm in diameter occupying the left thoracic apex. The mass was broad-based, arising from the area of antero-lateral parietal pleura at the level of the thoracic apex and the first rib. The tumor was successfully resected via median sternotomy and left first intercostal thoracotomy without either claviculectomy or claviculotomy. For the complex surgical access and the tumor's hypervascularity, a careful operative procedure was needed to avoid massive bleeding. The tumor was diagnosed microscopically and immunohistochemically as a solitary fibrous tumor of the pleura and did not meet the criteria for malignancy.

Adult↗

Evaluation of HER-2 status in breast carcinoma by fluorescence in situ hybridization and immunohistochemistry.

BACKGROUND: Evaluation of HER-2 status is essential for selecting appropriate candidates for treatment with trastuzumab, a recombinant humanized monoclonal antibody active against human epidermal growth factor receptor-2 (HER-2) protein. METHODS: To standardize a HER-2 diagnostic system for breast cancer tissue, we compared immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) results. We studied specimens from 110 patients with invasive ductal breast cancer who underwent operation. IHC analysis was performed using HercepTestTM (Dako A/S), and results assessed according to the HercepTestTM criteria. FISH was performed using a PathVysionTM HER-2 DNA probe kit (Vysis Inc.), with specimens considered HER-2 positive if the ratio of the total HER-2 signals to chromosome 17 centromere (CEP17) signals was greater than 2. RESULTS: FISH results were indefinite in 3 patients and positive in 24 patients (22%). IHC scores were 0 in 27 patients (25%), 1+ in 53 patients (48%), 2+ in 10 patients (9%), and 3+ in 20 patients (18%). All 20 patients with a score of 3+ by IHC were positive by FISH, with only 1 (10%) of 10 patients with an IHC score of 2+ positive by FISH. CONCLUSIONS: Our results indicated that an IHC score of 3+ is equivalent to FISH-positivity for HER-2 diagnosis, while patients with an IHC score of 2+ should undergo FISH testing.

Adult↗

Pulmonary resection with chest wall removal and reconstruction for invasive pulmonary mucormycosis during antileukemia chemotherapy.

A 54-year-old woman undergoing chemotherapy for acute myeloid leukemia developed invasive pulmonary mucormycosis in the right upper lobe at the neutropenic nadir. Amphotericin B therapy became ineffective after an abscess formed in the affected lung, and insufficient infection control compelled us to interrupt chemotherapy. The lesion was suspected of invading the anterior chest wall. After right upper lobectomy combined with the anterior chest wall resection, the chest wall defect was reconstructed using autologous free rib grafts. Successful control of the fungal infection by resection enabled us to restart chemotherapy with concomitant use of Amphotericin B. In selected cases of leukemia-associated pulmonary mucormycosis refractory to Amphotericin B therapy, aggressive surgical intervention may facilitate anti-leukemia chemotherapy and prolong survival.

Female↗

CTLA4Ig-gene transfection inhibits obliterative airway disease in rats.

BACKGROUND: Obliterative airway disease (OAD) is a major cause of long-term morbidity following lung transplantation. Its pathologic characteristics are small-airway inflammation and occlusion by fibrous tissue. However, the pathogenesis is uncertain and therapy is ineffective. This study presents the effects of CTLA4Ig-gene therapy on OAD in heterotopically transplanted rat tracheal allografts. METHODS: Dark Agouti (DA, RT1a) allografts and Lewis (LEW, RT1l) isografts were transplanted into Lewis recipients. The tracheal graft was transplanted heterotopically into the subcutaneous pocket into the back. Adenoviral vectors (1.0x10(9) pfu) containing the CTLA4Ig-gene (AdCTLA4Ig) or the LacZ-gene (AdLacZ) were injected into the tail vein immediately after grafting. Grafts were harvested and examined after more than 35 days for mononuclear cell infiltration development and lumen occlusion with fibrosis. RESULTS: Fully allogenic DA tracheas, treated with AdCTLA4Ig had significantly lower pathologic scores and infiltrating scores than the control allografts. The pathologic findings of the grafts, treated with AdCTLA4Ig, were very similar to those of the syngeneic grafts. The animals experienced no adverse events during follow-up. No evidence of vector-mediated tissue damage was seen in any graft. CONCLUSIONS: Adenoviral vectors containing the CTLA4Ig-gene markedly inhibited the obliteration of the airway lumen. OAD may be associated with T-cell responses against graft tissue and alloimmune injury.

Abatacept↗

Late reoperation for proximal aortic and arch complications after previous composite graft replacement in Marfan patients.

BACKGROUND: Marfan patients who received composite graft replacement for proximal aortic disease frequently require late reoperation. The initial surgical technique for this lesion remains controversial. METHODS: Fourteen Marfan patients who received composite graft replacement for annuloaortic ectasia with or without aortic dissection required late reoperation thorough re-median sternotomy. The techniques used for an initial composite graft replacement were the original Bentall procedure in 11 patients, the Cabrol procedure in 2, and coronary button technique in 1. Reoperation was indicated for prosthesis-related complications in 10 patients, distal aortic lesion in 13, or for both lesions in 8. Reoperations were performed, on average, 8.4 years after an initial operation. Reoperative procedures included re-composite graft replacement in 1 patient, total arch replacement in 5, and re-composite graft replacement with total arch replacement in 8. RESULTS: There were two in-hospital deaths (14.3%). Although pseudoaneurysms of the coronary artery or distal aorta occurred in the original Bentall or Cabrol procedures, true aneurysms of the coronary artery were noted even in the coronary button technique. Six patients required a total of eight subsequent descending or thoracoabdominal aortic replacements for an aneurysmal formation of a distal false lumen. CONCLUSIONS: The coronary button technique, with a small side hole for coronary anastomosis, is the procedure of choice for annuloaortic ectasia because it reduces the risk of coronary artery-related complications. Concomitant total arch replacement may be recommended for annuloaortic ectasia with DeBakey type I aortic dissection in selected patients to avoid the risk of reoperation on the aortic arch.

Adult↗

Brain protection using antegrade selective cerebral perfusion: a multicenter study.

BACKGROUND: To evaluate the results of antegrade selective cerebral perfusion as a method of brain protection during surgery of the thoracic aorta and to determine predictors of hospital mortality and adverse neurologic outcome. METHODS: Between October 1995 and March 2002, 588 patients underwent aortic surgery with the aid of antegrade selective cerebral perfusion. There were 334 men (56.8%); the mean age was 63.7 +/- 11.8 years. One hundred sixty-two patients (27.6%) underwent urgent operation. The separated graft technique was employed to reimplant the arch vessels in 230 patients (65.3%) of the 352 requiring aortic arch replacement. Associated procedures were performed in 254 patients (43.2%). One hundred twelve patients underwent elephant trunk procedure. The mean cerebral perfusion time was 67 +/- 37 minutes. RESULTS: The overall hospital mortality rate was 8.7%. A logistic regression analysis revealed urgent operation, recent central neurologic event, tamponade, unplanned coronary artery revascularization and pump time to be independent predictors of hospital mortality (p < 0.05). The permanent neurologic dysfunction rate was 3.8%. A logistic regression analysis showed tamponade to be independent predictor of permanent neurologic dysfunction (p < 0.05). The transient neurologic dysfunction rate was 5.6%. Recent central neurologic event, tamponade, coronary disease, and aortic valve replacement were indicated as independent predictors of transient neurologic dysfunction by logistic regression (p < 0.05). CONCLUSIONS: In our experience the utilization of antegrade selective cerebral perfusion resulted in encouraging results in terms of hospital mortality and brain complications. Neither the extent of the replacement nor the duration of the cerebral perfusion had an impact on hospital mortality and neurologic outcome.

Aorta, Thoracic↗

Mechanical properties of various z-stent designs: an endovascular stent-grafting perspective.

PURPOSE: To comparatively assess the mechani-cal behavior of various clinically relevant Z-stent designs. METHODS: A total of 16 Z-stents of original, biliary, spiral, and double-skirted designs (n=4 for each) were constructed using similar specifications for all. Stents were then evaluated for stiffness, snap opening force (SOF), flexibility, and displacement force using a novel tensiometer. Differences among the stents were determined using statistical methods. Stents explanted from dog aorta after a mean follow-up of 13 months were examined under a scanning electron microscope for surface defects. RESULTS: Forces required for about 50% reduction in diameter were 1.88 +/- 0.16 N, 3.81 +/- 0.21 N, 2.76 +/- 0.22 N, and 3.35 +/- 0.19 N for original, biliary, spiral, and skirted designs, respectively. Differences among the four designs were statistically significant at almost all points of measurement (P < 0.0001). Biliary and skirted designs showed higher SOF values in the early measurements. Stents explanted from dog aorta after a mean duration of 13 months showed no obvious corrosion or breakage in the wire struts. CONCLUSIONS: Significant differences exist among the various Z-stent designs in terms of their mechanical properties. Understanding them should help to select the appropriate stent for a given lesion. 316L stainless steel shows a favorable long-term tissue interaction.

Angioplasty↗

Surgical local resection for early gastric cancer.

In Japan, endoscopic mucosal resection remains a familiar treatment of early gastric cancers even though long-term results of surgical local resection (SLR) including a laparoscopic or open approach have been unclear. We reviewed our SLR experiences. Laparoscopic wedge resection (LWR), laparoscopic intragastric surgery (LIS), and open local resection (OLR) were performed in 11, 7, and 11 patients, respectively. Four LIS patients were converted to open surgery. Histologically, resected specimens demonstrated that larger-sized materials were obtained in OLR and LWR. Five patients overall showed submucosal invasion; 1 patient underwent reoperation (gastrectomy). Long-term results showed no primary-lesion related death; 2 patients died of other diseases. However, 2 LWR patients showed new lesions in the remnant stomach at 29 months and 7 years later. Both patients underwent subsequent gastrectomy. In conclusion, SLR is safe and curative for properly selected cancer patients. Precise preoperative diagnosis and careful remnant stomach survey is important.

Adenocarcinoma↗

Association of allelic loss at 8p22 with poor prognosis among breast cancer cases treated with high-dose adjuvant chemotherapy.

To identify specific allelic losses that might correlate with postoperative mortality of breast cancer patients treated with high-dose adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil, we examined tumors from a cohort of 150 such patients, who were followed clinically for 5 years postoperatively, for allelic losses (loss of heterozygosity, LOH) among 18 microsatellite markers throughout the genome. Patients whose tumors had lost an allele at 8p22 had significantly higher risks of mortality than those whose tumors retained both alleles at those loci. At 8p22, the 5-year mortality rate was 31% among patients with losses vs. 8% with retention (P=0.0354). No other region showed correlation between LOH and prognosis. The data indicate that LOH at 8p22 is a significant predictor of postoperative mortality for breast cancer patients who received high-dose postoperative adjuvant chemotherapy. Thus, LOH at 8p22 can serve as a negative prognostic indicator to guide postoperative management of patients.

Adult↗

Enhanced secretion of tissue plasminogen activator by simultaneous use of retinoic acid and ascorbic acid from tissue cultured gastroepiploic artery.

Tissue-type plasminogen activator (tPA) is a key enzyme in the fibrinolysis system and the regulation of its expression has been extensively studied in cultured vascular endothelial cells. Many kinds of supplements including growth factors are needed, however, to keep endothelial cells viable, which leads the culture condition far from the physiological milieu. Using a new device of amorphous calcium phosphate coated culture plate, we succeeded in culturing ring-cut gastroepiploic artery in a basic medium of RPMI 1640 containing 10% fetal calf serum. The overall normal vessel architecture and the antigenicity of von Willebrand factor, tPA and plasminogen activator inhibitor type 1 (PAI-1) were retained for at least 9 days. tPA was constantly secreted into the conditioned medium at least up to day 12. Employing this organ culture technique, we analyzed the effects of two well-known profibrinolytic vitamins of retinoic acid (Vit. A) and ascorbic acid (Vit. C) on the release of tPA and PAI-1. The cultured artery responded well and the tPA secretion was enhanced by factors of 1.5 fold by Vit. A, 1.7 fold by Vit C and 3.2 fold by their combination, whereas none of these stimuli increased PAI-1 secretion. These results suggested that the cultured ring-cut artery retained functional endothelial cells for at least 9 days and was suitable in analyzing the regulatory mechanism of protein synthesis and secretion from the vascular wall. Using this method, vitamins A and C were shown to lead the intravascular condition to a profibrinolytic state.

Ascorbic Acid↗

Total aortic arch replacement for thoracic aneurysm involving an isolated left vertebral artery.

We conducted 4 total aortic arch replacements in patients with an isolated left vertebral artery. In all 4, surgery was done using 4-branched arch grafts with moderately hypothermic selective cerebral perfusion and systemic circulatory arrest. All reconstructed isolated left vertebral arteries anastomosed to the native left subclavian artery or to the graft branch for this artery showed good patency. None of our patients had cerebral complications and all were discharged in good condition.

Aged↗

Aortic root replacement using a homograft for recurrent valve endocarditis.

Prosthetic valve endocarditis is a relatively rare condition associated with high mortality. Endocarditis affecting 2 successive mechanical valves at the aortic position has not, to the best of our knowledge, been described. We reported such a patient whose condition was further complicated by mitral regurgitation, pulmonary hypertension, worsening heart failure, and cardiac conduction abnormalities. Considering the failure of 2 previous mechanical valves, we conducted a homograft replacement of the aortic root with coronary reattachment. Mitral regurgitation was treated by annuloplasty. The patient's early postoperative course was uneventful and he was doing well 16 months after surgery. We discuss the overall treatment strategy for recurrent prosthetic valve endocarditis and potential homograft advantages.

Adult↗

Aortic arch resection under temporary bypass grafting for advanced thymic cancer.

Extensive surgery for malignant disease requiring cardiopulmonary bypass may cause postoperative immunosuppression. We conducted resection of the aortic arch and total arch replacement under temporary bypass grafting in a patient with advanced thymic cancer invading the aortic arch. No major postoperative complications such as brain damage or paraplegia occurred. Temporary bypass grafting is thus applicable in extensive surgery for malignant disease invading the aortic arch.

Aorta, Thoracic↗

Total and subtotal aortic replacement for extensive aortic dissection in patients with or without Marfan's syndrome.

OBJECTIVES: Extensive aortic dissection with multiple entries often found in Marfan's syndrome patients ultimately requires replacement of the whole aorta. We present a surgical strategy and results for total and subtotal aortic replacement. METHODS: Subjects were 18 patients, including 14 Marfan's patients undergoing total (n = 13) or subtotal (excluding aortic arch) aortic replacement (n = 5), for DeBakey type I aortic dissection (n = 13) and DeBakey type IIIb aortic dissection with annuloaortic ectasia (n = 5) between February 1991 and April 2001. Mean age was 39.9 +/- 0.8 years--34.9 +/- 6.6 years in Marfan's patients vs. 57.7 +/- 4.7 years in non-Marfan patients. All operations were staged, with the mean number required per patient 3.1 +/- 0.8. RESULTS: Early mortality was 0% and late mortality 11% (2 of 18). Paraplegia or paraparesis occurring in 11%. Except for these patients, all current survivors enjoy good quality of life. CONCLUSIONS: Total and subtotal aortic replacement for extensive aortic dissection may decrease mortality due to rupture or associated disease.

Adult↗

Surgical outcome of acute type A aortic dissection: analysis of risk factors.

BACKGROUND: The aim of this study was to assess the risk factors for the early and late outcome of the surgical treatment of acute type A aortic dissection. METHODS: From 1983 to 2000, a total of 130 patients underwent operation for acute type A aortic dissection. Extent of distal aortic resection included ascending aorta in 19 patients (15%), hemiarch in 29 (22%), and total arch in 82 (63%). In all, 31 preoperative and perioperative variables were analyzed using univariate and multiple logistic regression models for independent predictors of in-hospital mortality and risk of late reoperation. After excluding in-hospital deaths, risk factors for late death were analyzed by Cox proportional hazard analysis. RESULTS: In-hospital mortality was 19.2% (25 of 130 patients). Multivariable analysis indicated that renal/mesenteric ischemia and shock were independent predictors of in-hospital death. At 10 years, the actuarial survival rate including in-hospital mortality was 70.9% +/- 4.7%, and the reoperation event-free rate was 73.5% +/- 5.7%. Aortic valve resuspension was an independent predictor of proximal aortic reoperation, whereas nonresection of intimal tear and younger age were independent predictors for distal aortic reoperation. Chronic obstructive pulmonary disease was the only independent predictor for late death. CONCLUSIONS: Patients' preoperative dissection-related complications and comorbidities significantly affect early and late survival rates after surgical treatment of acute type A aortic dissection.

Acute Disease↗

Reconstruction of diaphragm using autologous fascia lata: an experimental study in dogs.

BACKGROUND: We investigated whether fascia lata is an appropriate material for reconstruction of the diaphragm. METHODS: A diaphragmatic defect (2 cm by 5 cm) was reconstructed with a patch of autologous fascia lata in the experimental group (n = 12) and with expanded polytetrafluoroethylene in the control group (n = 12). Maximal tensile strength at the sutured region was measured serially. RESULTS: The maximal tensile strength at the sutured region reconstructed with the fascia lata was 1.14 +/- 0.50 kgf 15 days and 2.04 +/- 0.94 kgf 30 days after operation. The values were higher than those of expanded polytetrafluoroethylene (p < 0.0001). These values of fascia lata were close to the original maximal tensile strength of the muscular region of the diaphragm (1.52 to 1.66 kgf). CONCLUSIONS: Reconstruction of diaphragm using autologous fascia lata is safe, easy, and inexpensive, and provides smooth wound healing. The only disadvantage is the necessity of a femoral incision for harvest; nevertheless, it may be worthwhile to use fascia lata in clinical trials to further assess its suitability as a reconstruction material.

Animals↗