Induction of transplantation tolerance by perioperative injection of "quasi-self" chimeric class I MHC antigen combined with a short cyclosporine course.
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Biomedical subjects
Publications and source records attributed to T Hamashima.
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The urethral polyps in children are different from those in adults because the polyps usually originate at the proximal vermontanum, and are covered with transitional epithelium. A case of posterior urethral polyp in a child is reported herein. In this case, 5 years of age, the polyp was thought to be the cause of urinary tract infection (UTI) and histological findings revealed fibrous non-prostatic tissue. Transurethral resection of polyp was performed successfully.
Submucosonography to stage tumors of the esophagus and stomach is well reported. Here we report our experience with a modified procedure to evaluate the stage of bladder tumor cystoscopically and compare the results of staging by other methods. The evaluation was carried out on accuracy 10 patients (10 bladder tumors). A water soluble contrast medium (CM: lohexol 33 mg/ml) was injected into the submucosa of the bladder cystoscopically. Usually the injected point was one centimeter to the urethral margin of the tumor and up to three points were selected. Within 30 minutes after the injection, the lateral and frontal X-ray pictures were taken. The accuracies of staging by submucosonography were compared with the results of other methods, i.g., ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI). By submucosonography, three categories depending on the diffusion of CM were classified as follows. Type I: (diffuse type) without disturbance of diffusion. Type II: (borderline type) between type I and III. Type III: (defect type) local disturbance of diffusion. Overall accuracies of each were 70.0% (submucosonography), 62.5% (US), 44.4% (CT), 66.7% (MRI) respectively. The accuracies of submucosonography were high in stage Ta, above stage T2 and low in stage T1.
The synergistic effects of inoculation with donor lymphocytes via portal vein (PV) in combination with FK506 or monoclonal anti-T lymphocyte antibody (OX19) on cardiac allograft survival were investigated in rat heart transplant model (Lewis engrafted BN heart). The recipients were divided into the six groups. A) Control B) FK506 group C) PV group D) FK506+PV group E) OX19 group F) OX19+PV group. The recipients of PV group and FK506 group displayed a prolongation of cardiac allograft survival [MST: 11.2 +/- 1.0 and 12.4 +/- 1.0 days] compared with control group [MST: 7.3 +/- 0.3 days]. However, MST of FK506+PV group was 10.6 +/- 0.8 days, showing no synergistic effect of FK506 with PV administration. Significant prolongation of the graft survivals was not observed between OX19 group and OX19+PV group [MST: 17.2 +/- 2.1 and 15.0 +/- 1.2 days]. Serum from PV-treated hosts on day 7 after transplantation had suppressor effect (92.7%) on the MLR of Lewis responder cells toward donor BN cells. On the other hand, suppressor effect of serum from FK506+PV group was significantly reduced (5.8%) compared with PV alone. These results indicate that FK506 might inhibit the generation of suppressor factor which was induced in the serum after administration of donor lymphocytes, and that generation of suppressor factor might be dependent on T cell.
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All patients with renal transplants are very much concerned about their chance of long-term graft function. Chronic rejection is the most common cause of decline in function and graft failure, and after the first post-transplant year, 3-4% of recipients lose their graft every year. However, the cause, time of onset and mechanism of decline in graft function are not clear. Also unclear is whether clinical and laboratory parameters may predict patients who are at risk of developing chronic rejection. The aim of this study was to find the marker which may determine long-term graft survival in the azathioprine era and in the cyclosporine era.
Cytokine production by graft-infiltrating cells (GIC) of helper T cell (Th) subtypes were investigated in rat kidney allograft compared to those infiltrating the spleen, those in peripheral blood, and in regional lymph nodes. The relative proportion of OX-22 positive cells (Th type 1) and the W3/25-positive cells (Th) of GIC was 49.4 +/- 2.1% on day 3 and 52.7 +/- 2.2% on day 6, whereas those in spleen cells was 80.3 +/- 4.1% (p less than 0.05) and 95.5 +/- 2.5% (p less than 0.01), respectively. GIC produced more B cell-stimulating factor 2 (BSF-2, 106.3 +/- 8.2 U/ml) when compared to spleen cells (15.9 +/- 4.6 U/ml; p less than 0.01), peripheral blood mononuclear cells (4.2 +/- 1.0 U/ml; p less than 0.01) or lymph node cells (24.9 +/- 4.0 U/ml; p less than 0.01) upon stimulation with donor BN lymphocytes in vitro. However, GIC produced less interleukin 2 (IL-2, less than 1.0 U/ml) and IL-3 (less than 1.0 U/ml) than produced by spleen cells (5.1 +/- 0.9 U/ml, p less than 0.05, and 10.5 +/- 2.3 U/ml, p less than 0.01, respectively) or lymph node cells (4.5 +/- 0.4 U/ml, p less than 0.01; 23.5 +/- 3.1 U/ml, p less than 0.01, respectively). These results demonstrate that the subtype of Th cells which produce BSF-2 migrates selectively to allografts.
To assess the role of amniotic fluid (AMF) in the maintenance of pregnancy, immunosuppressive effects of AMF were studied in vivo, and the mechanisms of suppressor activity were analyzed immunologically in vitro in the rat. Female Lewis (LEW, RT-1l) rats mated with Brown-Norway (BN, RT-1n) rats for 14 days were sacrificed and cell-free AMF was obtained. AMF was diafiltered with PBS (PH 7.2) and reconstituted to 2 OD units measured at 280 nm. Untreated LEW hosts rejected BN renal grafts at 7.8 +/- 0.2 days (n = 10). Five days of intravenous inoculation of AMF into LEW hosts remarkably enhanced BN graft survivals (MST = 20.3 +/- 4.4 days, n = 12) compared with controls (P less than 0.01), and slightly prolonged third-party DA (RT-1a) graft survivals (MST = 9.4 +/- 0.8 days, n = 7) compared with control LEW hosts engrafted with a DA kidney (MST = 7.6 +/- 0.2 days, n = 6). Five days of intravenous inoculation of pregnant sera into LEW hosts had no effect on BN graft survival. The AMF suppressed the proliferative response of LEW lymphocytes against not only irradiated BN stimulator cells but also irradiated third-party DA stimulators. The AMF also suppressed allokiller T cell generation of normal LEW lymphocytes against BN cells by 70.1% and 51.3%, and against DA cells by 64.9% and 38.9% at concentrations of 25% and 12.5%, respectively (P less than 0.01). To dissect the immunosuppressive activity of AMF, the effect of AMF on cytokine production and interleukin 2 (IL-2) receptor expression of concanavalin A-stimulated lymphocytes were investigated. AMF suppressed interferon and IL-2 production. Interestingly, however, AMF did not suppress interleukin 3 (IL-3) and interleukin 6 (IL-6) production, as well as IL-2 receptor expression. These results demonstrated that rat AMF displayed a strong immunosuppression in vivo as well as in vitro, and that AMF might play an important role in the maintenance of pregnancy.
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We analyzed the incidence of anal disease in patients with nonbacterial prostatitis (NBP) or with prostatitis-like syndrome (PLS), and evaluated the clinical efficacy. The complicated rate of anal disease in these patients was 29.7% (31.8% for NBP and 28.1% for PLS), and the overall incidence of active anal disease was 15.4% (16.2% for NBP and 14.8% for PLS), it yielded a significantly higher complicated rate than other urological disease (p less than 0.01). The most common type of anal disease was hemorrhoids, especially piles. The clinical cure rate for anal disease in NBP patients was 71.4%, and in PLS patients was 58.2%. The high incidence of hemorrhoids (especially piles) was in these patients by clinico-statistical observation suggests that the development of anal disease may be etiologically correlated with NBP and PLS. Furthermore, we noted that Kampo treatment (Keisibukuryogan) was useful in the treatment of prostatitis complicated by anal disease, especially when combined with anti-hemorrhoidal suppositories against active anal disease in PLS patients (p less than 0.05).
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The effects of perioperative portal venous (P.V.) administration of donor lymphocytes on skin allograft survival were investigated in rat skin transplant model. Heterotopic skin transplantations were performed form Brown-Norway (BN, RT-1n) to Lewis (LEW, RT-1(1] male rats. P.V. administration of donor BN lymphocytes (1 x 10(8] resulted in significant prolongation of BN skin graft survival (MST = 13.4 +/- 3.9 days, p less than 0.05) compared with I.V. administration of same number of donor lymphocytes (8.6 +/- 1.2 days) or with PV administration of third party DA (RT-1a) rat's lymphocytes (7.4 +/- 0.8 days) or with untreated controls (9.0 +/- 1.4 days). These results suggested that this effect was antigen specific. P.V. administration of donor lymphocytes prevented recipient which received BN skin graft form developing delayed-type hypersensitivity responses to donor antigen. Serum from LEW recipients which induced unresponsiveness by PV administration with donor BN lymphocytes had significant antigen specific suppressor effect (77.0 +/- 5%) on the MLR proliferative reaction of LEW responder cells toward donor BN cells, but not third party DA stimulation. Moreover, this immunological unresponsiveness was transferable by the serum in kidney transplant model. These results indicate that PV administration of donor lymphocytes induces recipient's unresponsiveness to donor alloantigen in rat skin transplant model, and this effect is transferable by the suppressor factor in the serum.
Bladder tumor antigen (BTA) is a tumor marker isolated from the urine of individuals with TCC of the bladder. This antigen can be detected by the Tu-MARK BTA test, a simple and rapid slide latex agglutination test performed on freshly voided urine. Sensitivity and specificity of BTA were calculated, and the correlation with pathological grade, histological stage, and urinary findings were statistically evaluated (chi 2-test) in 110 patients (72 male, 38 female; age: 16-91, mean age 54.4) examined between September, 1989 and April, 1990 including 46 TCC of the bladder (primary 28, secondary 18; grade 1:10, grade 2:27, grade 3:9, pTis: 2, pTa: 2, pT1: 23, pT2: 5, pT3: 4, pT4: 2), and 64 benign diseases. Sensitivity was 45.6%, specificity was 60.9%. In bladder tumor cases a correlation was seen between BTA and stage (p less than 0.02), and between BTA and grade (P less than 0.05). The positive ratio was higher in T1-T4 (55.9%) than in Tis.Ta (p less than 0.02). A high positive ratio of BTA was seen in bladder tumor cases with hematuria (70%, p less than 0.01) and pyuria (86.7%, p less than 0.01). This method is easy and rapid and the values are highly correlated with stage. Therefore, it should be useful for not only screening but followup of bladder tumor. Furthermore, BTA in combination with urine cytology is a more useful way for diagnosing TCC of the bladder.