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Biomedical subjects

T Koyanagi

Publications and source records attributed to T Koyanagi.

At least 37 records · Page 2Linked to original sources

Impact of nephron-sparing surgery on quality of life in patients with localized renal cell carcinoma.

OBJECTIVES: The aim of the study is to evaluate the impact of nephron-sparing surgery on postoperative quality of life (QOL) in patients with localized renal cell carcinoma, compared with radical nephrectomy. METHODS: From 1986 to 1996, a total of 66 patients with localized small renal cell carcinoma <4 cm in diameter and a functioning contralateral renal unit underwent radical nephrectomy (n = 51) or nephron-sparing surgery (n = 15). Of these, 50 patients evaluated various dimensions of QOL using standardized self-rating questionnaires, EORTC QLQ-C30. RESULTS: There is no significant difference in 5-year overall survival between the nephron-sparing surgery group and the radical nephrectomy group. With regard to postoperative QOL, patients who underwent nephron-sparing surgery showed a significantly higher score on physical function than patients treated with radical nephrectomy (p<0.05). Nephron-sparing surgery was additionally superior to radical nephrectomy in terms of fatigue, sleep disturbance, pain and constipation. CONCLUSION: Selected patients with localized, small, unilateral renal cell carcinoma and a normal contralateral kidney will benefit from nephron-sparing surgery.

Adult↗

The selenoorganic compound ebselen suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats.

Ebselen (2-phenyl-1,2-benzoisoselenazol-3[2H]-one) is a selenoorganic compound containing selenium that has various pharmacological effects, including anti-inflammatory and antioxidant activity. Kupffer cells, residual hepatic macrophages, play an important role in the development of liver injury by producing free radicals and cytokines. The aim of this study is to evaluate whether ebselen suppresses macrophage-associated liver injury in rats. In vivo, we examined the effects of ebselen on liver injury, induced by Propionibacterium acnes and lipopolysaccharide (P. acnes-LPS), in rats where hepatic macrophages are considered to be primarily involved in injury development. Ebselen administration reduced the incidence of death following hepatic failure by P. acnes-LPS (82% vs. 20%, p<0.05). Serum levels of alanine aminotransferase, at 5 h after LPS administration, were significantly lower in the ebselen-treated group than in the control group (202.4+/-100.3 IU/l vs. 558.4+/-146.4 IU/l, p<0.05). Histological evidence of injury, such as necrosis, hemorrhage, and degeneration, was also suppressed by ebselen. Further, to assess the mechanisms involved, we investigated the production of cytokines and superoxide anions produced by activated hepatic macrophages in vivo. Serum levels of TNF alpha, interleukin-18 (IL-18)/IFN gamma-inducing factor (IGIF), and interferon gamma (IFN gamma) at 1 h after LPS administration were significantly lower in the ebselen-treated group. Formazan depositions, which were generated by the perfusion of the liver with nitroblue tetrazolium, were also observed less frequently in the ebselen treated group, suggesting a suppression in the release of superoxide anion from activated hepatic macrophages. In addition, we examined the effects of ebselen on cytokine production and mRNA expression, in vitro, using rat primary Kupffer cell culture. Ebselen also inhibited TNF alpha production and mRNA expression in vitro. These data imply that ebselen suppresses liver injury by inhibiting the production and/or release of proinflammatory cytokines and superoxide from activated hepatic macrophages. These data also suggest that ebselen is potent in the prevention of hepatic injury, such as endotoxemia, where hepatic macrophage activation has been implicated.

Alanine Transaminase↗

[The feasibility of a limited operation for primary lung cancer].

We reviewed 33 patients who underwent a limited operation for primary lung cancer between 1980 and 1998. These cases were divided into three groups; a poor risk group consisting of 18 patients who had a high risk such as pulmonary or cardiac dysfunction and who underwent partial resection of a lung, a reduction group consisting of 9 patients who had advanced lung cancer or uncontrolled cancer of an organ other than the lung and who underwent partial resection, and an active limited operation group consisting of 6 patients who underwent segmentectomy with lymphoadenectomy for the treatment of early lung cancer. The 1 and 3-year survival rates in the poor risk group, reduction group and active limited operation group were 73.9, 60.0, 100%, and 63.4, 0.0, 100%, respectively. The results of limited operations performed for poor risk cases were satisfactory in terms of both functional state and prognosis. Limited operations performed to reduce tumor in advanced lung cancer cases did not improve the prognosis. Although an active limited operation for a case of early lung cancer remains controversial with respect to indication, it is thought that this operation is not inferior to a standard radical operation (lobotomy with mediastinal lymphoadenectomy) in selective cases in which the maximum tumor diameter is 2 cm or less. The indication for a limited operation must be further examined from aspects of tumor size, tumor histology and the other factors of the tumor.

Adenocarcinoma↗

Clinical and endocrinological features of adrenocorticotropic hormone- independent bilateral macronodular adrenocortical hyperplasia.

PURPOSE: We report clinical findings in 5 patients with adrenocorticotropic hormone independent bilateral macronodular adrenocortical hyperplasia. MATERIALS AND METHODS: In 4 males and 1 female 32 to 61 years old (median age 50) we evaluated clinical symptoms, endocrinological and radiological characteristics, treatment modality and postoperative clinical course. RESULTS: All cases presented with some features of Cushing's syndrome. Endocrinological examination revealed autonomous adrenal cortisol production with suppressed adrenocorticotropic hormone and a loss in the diurnal circadian rhythm of plasma cortisol. Abdominal computerized tomography showed bilateral enlargement of the adrenal glands with multiple nodules. 131Iodine labeled adosterol scintigraphy demonstrated remarkable bilateral uptake by the adrenal glands. The pituitary gland appeared normal on magnetic resonance imaging. Open unilateral complete adrenalectomy and contralateral partial adrenalectomy were performed in patient 1, open bilateral complete adrenalectomy was done in patients 2 and 3, and 2 and 1-stage laparoscopic bilateral complete adrenalectomy was performed in patients 4 and 5. Single removed adrenal glands weighed 32 to 108 gm. (median 60). The histological diagnosis was macronodular adrenocortical hyperplasia in all cases. Postoperative followup was 3 to 90 months. Clinical symptoms of Cushing's syndrome disappeared or improved after surgery in all cases. CONCLUSIONS: Although adrenocorticotropic hormone independent bilateral macronodular adrenocortical hyperplasia is a rare form of Cushing's syndrome, physicians are advised to consider it when diagnosing and treating cases of Cushing's syndrome with enlarged bilateral adrenal glands. Bilateral complete adrenalectomy is currently recommended as the treatment of choice.

Adrenal Glands↗

Saccular aneurysm of pulmonary autograft after the Ross procedure.

The Ross procedure, which includes removal of the malformed aortic valve and replacement of a pulmonary autograft in the aortic position, has increased the number of available treatment options. Recently, dilatation of the autograft pulmonary root after the Ross procedure has been reported as a complication. We report a patient with bicuspid aortic valve malformations and aortic annulus dilatation, who had a saccular-form, true-type, aneurysm in the pulmonary autograft seven months after the Ross procedure. These changes have not been described so far as complication. Pathologically, marked mucoid degeneration was noted in the tunica media of the aneurysm, as well as in the original aortic root. These findings may suggest similar pathological characteristics between the aorta and pulmonary arteries. Hence, the surgical risks accompanying vascular characteristics in patients with congenital aortic valve malformations should be considered.

Adult↗

Use of an implanted marker and real-time tracking of the marker for the positioning of prostate and bladder cancers.

PURPOSE: A real-time tracking radiotherapy was investigated to assess its usefulness in precise localization and verification of prostate and bladder cancers. METHODS AND MATERIALS: The real-time tracking radiation therapy (RTRT) system consists of implantation of a 2.0-mm gold marker into a clinical target volume (CTV), three-dimensional radiation treatment planning (3DRTP) system, and the use of two sets of diagnostic x-ray television systems in the linear accelerator room, image processing units, and an image display unit. The position of the patient can be corrected by adjusting the actual marker position to the planned marker position, which has been transferred from the 3DRTP and superimposed on the fluoroscopic image on the display unit of the RTRT system. The position of the markers can be visualized during irradiation and after treatment delivery to verify the accuracy of the localization. Ten patients with prostate cancer and 5 patients with bladder cancer were examined using this system for the treatment setup on 91 occasions. RESULTS: After manual setup using skin markers, the median of absolute value of discrepancies between the actual position of the marker and the planned position of the marker for prostate cancer was 3.4 (0.1-8.9) mm, 4.1 (0.2-18.1) mm, and 2.3 (0.0-10.6) mm for the lateral, anteroposterior, and craniocaudal directions, respectively. The 3D median distance between the actual and planned positions of the marker was 6.9 (1.1-18.2) mm for prostate cancer and 6.9 (1.7-18.6) mm for bladder cancer. After relocation using RTRT, the 3D distance between the actual and planned position of the marker was 0.9 +/- 0.9 mm. Median 3D distances between actual positions after treatment delivery and planned positions were 1.6 (0.0-6.3) mm and 2.0 (0.5-8.0) mm during daily radiotherapy for the marker in patients with prostate cancer and bladder cancer, respectively. CONCLUSION: We believe the new positioning system can reduce uncertainty due to setup error and internal organ motion, although further improvement is needed for the system to account for the rotational and elastic changes of the affected tissues.

Humans↗

Suppressive effects of dominant negative ras mutant N116Y on transformed phenotypes of human bladder cancer cells.

To investigate the suppressive effect of dominant negative H-ras mutant N116Y on transformed phenotypes, we established two N116Y ras mutant stable transfectant clones (C5, C13) of human bladder cancer cell line, UMUC-2. These N116Y ras mutant transfectants, especially the C5 cells, showed a dramatic change of cellular morphology and significantly reduced growth in soft agar compared to their control. Furthermore, phosphorylation of the Jun NH2-terminal kinase (JNK) was significantly decreased in these transfectants compared to the control. These results suggest that the N116Y-induced suppression of transformed phenotypes in UMUC-2 cells is associated with inhibition of JNK phosphorylation.

Cell Transformation, Neoplastic↗

Clinical effects of ventricular assist system in end-stage cardiac failure. Advantages of left ventricular blood drainage for recovery from cardiac dysfunction.

OBJECTIVES: Heart transplantation is extremely limited currently in Japan. As a consequence ventricular assist system implantation is employed the patient falls into end-stage cardiogenic shock. This preliminary report describes our initial clinical experience with use of 2 kinds of ventricular assist system for 13 Japanese patients. METHODS: 7 patients were supported by a left ventricular assist system with blood drainage from the left atrium (LA drainage Group) using a Toyobo ventricular assist system, while another 6 patients were supported by a left ventricular assist system with blood drainage from the left ventricle (LV drainage Group) using the Toyobo ventricular assist system (1 patient) or TCI-LVAS (5 patients). RESULTS: The average duration of ventricular assist system support in the LV drainage Group was 112 days including two on-going patients (now at 39 days and 241 days) and in the LA drainage Group was 49 days. The average left ventricular ejection fraction at 3 weeks after ventricular assist system implantation was improved from 12.3 to 54% using the TCI-LVAS and from 14 to 33% using the Toyobo ventricular assist system with drainage from the left ventricle. However, this was decreased from 20 to 10% using the Toyobo ventricular assist system with drainage from the left atrium. The ventricular assist system was explanted in 4 patients (31%) with recovery of cardiac dysfunction and 3 were long survivors. The 2 on-going patients are awaiting heart transplantation. Thus the current survival rate overall is 38%. The survival rate (67%) is excellent in the LV drainage Group including 2 long survivors after explantation. CONCLUSION: Ventricular assist system support with drainage from the left ventricle seems to be more advantageous for cardiac functional recovery than from the left atrium for end-stage heart failure.

Adult↗

Clinical experience of milrinone as a pharmacological bridge to heart transplantation.

A 19-year-old man with idiopathic dilated cardiomyopathy developed cardiogenic shock. A HeartMate left ventricular assist device was inserted as an emergency procedure, but removed after 189 days due to sepsis related to the device. Intravenous milrinone was administered because of recurrence of heart failure, and as a result the symptoms disappeared and the urinary output increased. Echocardiography showed improvement in the left ventricular ejection fraction. Subsequently, the patient successfully underwent heart transplantation. Milrinone was effective as a pharmacological bridge to heart transplantation in this patient with terminal and critical heart failure after removal of a left ventricular assist device.

Adult↗

Abortive alloantigen presentation by donor dendritic cells leads to donor-specific tolerance: a study with a preoperative CTLA4lg inoculation.

Donor dendritic cells (DCs) within allografts initiate the induction of an allospecific T cell response, while an abortive alloantigen presentation by DCs may induce allospecific unresponsiveness. We thus investigated the tolerogenic effect of donor DCs that were made incompetent in alloantigen presentation by treatment of CTLA4Ig. When we treated rats with donor DCs (2 x 10(6)/rat i.v.) on the preoperative day, nine rejected allografts in an accelerated manner (5.0 +/- 2.2 vs. 8.2 +/- 1.6 days in the control group). Preoperative inoculation of DCs pulsed with CTLA4Ig, a procedure which suppresses an allogeneic mixed lymphocyte reaction (MLR), also provoked an accelerated rejection (5.6 +/- 1.7 days). When DCs and CTLA4Ig (500 microg/rat i.p. on days -9, -7 and -5) were concomitantly inoculated, allograft survival was significantly prolonged (>38.7 +/- 40.0 days); a preoperative CTLA4Ig inoculation alone failed to do so (7.5 +/- 1.2 days). Long-term graft survivors tolerated skin grafts from the donor but not from those from a third party. These results indicate that abortive alloantigen presentation by donor DCs, upon which an accessory signal pathway is suppressed by CTLA4Ig, leads to prolonged graft survival and donor-specific tolerance.

Abatacept↗

Redo without transfusion in a patient with idiopathic thrombocytopenic purpura.

Mitral valve replacement was able to be carried out at redo operation requiring neither allogeneic platelet nor blood transfusion in a patient with idiopathic thrombocytopenic purpura, by means of preoperative high-dose intravenous gamma-globulin, autologous blood predonation, use of a centrifugal pump, heparin-coated extracorporeal circuits, and simultaneous splenectomy.

Extracorporeal Circulation↗

An improved intravesical model using human bladder cancer cell lines to optimize gene and other therapies.

Orthotopic implantation of human bladder cancer cells into immunodeficient mice is an important tool for studying the biology and effects of therapy. Nevertheless, the incidence of tumor implantation and growth by transurethral instillation of the human bladder cancer cells into murine bladders has been low or not reproducible. However, using a modified intravesical technique and the human bladder cancer cell lines, KU-7 and UM-UC-2, we have been able to obtain a high and reproducible incidence of superficial bladder tumors. Furthermore, intravesical administration of the LacZ adenovirus vector resulted in significant beta-galactosidase expression in these bladder tumors as well as the normal urothelium, which was associated with the removal of the glycosoaminoglycan layer. Because this modified technique produces a high incidence of superficial human tumor growth and allows the efficacy of gene transfer to be evaluated, it should be a useful model for the study of intravesical gene therapy for human bladder cancer.

Adenoviridae↗

Enterocolitis with pathogenic Escherichia coli infection in renal transplant recipients: case reports.

PURPOSE: We report three cases of enterocolitis associated with pathogenic Escherichia coli infection in renal transplant recipients. METHODS/RESULTS: Patients presented with abdominal pain and diarrhea at 1, 3 and 7 years after living-related renal transplantation. Pathogens of enterocolitis were identified by stool culture as verotoxin-2-producing O157:H7 E. coli, non-verotoxin-producing E. coli 06 and 0125. All patients were basically treated with fluid replacement with additional fosfomycin administration in the patient with O157:H7 E. coli infection. Immunosuppressive drugs were kept at maintenance doses throughout the treatment. CONCLUSION: All patients recovered uneventfully within 10 days after the onset of enterocolitis without severe complications.

Adult↗

Significance of the Grb2 and son of sevenless (Sos) proteins in human bladder cancer cell lines.

The epidermal growth factor (EGF) receptor has been suggested to have an important role in tumor initiation and progression of human bladder cancers. Grb2 protein, which is the downstream effector of the EGF receptor, acts as an adaptor protein between the EGF receptor and the Ras guanine-nucleotide exchange factor, son of sevenless (Sos) protein. Sos protein regulates the action of Ras protein by promoting the exchange of GDP for GTP. However, the significance of Grb2 and Sos proteins, which is related to EGF-triggered Ras activation, has not been elucidated in human bladder cancer. The aim of the present study is to clarify the significance of these proteins in human bladder cancer cell lines. In the present study, we used four human bladder cancer cell lines (T24, KU-7, UMUC-2, UMUC-6) and two kinds of cultured normal urothelial cells (HMKU-1, HMKU-2) isolated from patients with no malignancy. We examined the expression of EGF receptor, Grb2, and Sos proteins in these cells by Western blot analysis. Furthermore, the bladder cancer cell lines were subjected to sequence analysis to identify a point mutation in the c-H-ras gene at codon 12. There was no marked difference in the expression of the EGF receptor between human bladder cancer cell lines and cultured normal urothelial cells. On the other hand, expression of Grb2 and Sos proteins was substantially increased in all human bladder cancer cell lines examined in comparison with cultured normal urothelial cells, whether codon 12 of H-ras was mutated or not. These results suggest that the amplification of both Grb2 and SOS proteins plays an important role in the carcinogenesis of human bladder cancer.

Adaptor Proteins, Signal Transducing↗