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T Hamashima

Publications and source records attributed to T Hamashima.

At least 55 records · Page 3Linked to original sources
PubMed1990

The effects of perioperative portal venous inoculation with donor lymphocytes on renal allograft survival in the rat. I. Specific prolongation of donor grafts and suppressor factor in the serum.

In order to investigate the in vivo functional role of the liver in the immune responses in organ transplantation, effects of perioperative portal venous p.v. administration of donor lymphocytes on renal allograft survival were tested in the rat kidney transplant model. Donor lymphocytes were prepared from BN (BN, RT-1n) or third-party DA (RT1a) rat spleens and lymph nodes and injected p.v. or intravenously to Lewis (LEW, RT-1l) hosts on the day of transplantation (day 0). Untreated LEW hosts rejected BN renal grafts at 7.8 +/- 0.6 days (n = 10). Intravenous administration of 1 x 10(8) BN cells to LEW hosts on day 0 caused a slight, but not significant, prolongation of renal allograft survival (MST = 9.5 +/- 3.0 days, n = 13, NS), whereas portal venous inoculation of 1 x 10(8) BN cells on day 0 remarkably prolonged renal graft survival to 22.2 +/- 5.3 (n = 10, P less than 0.01). The prolongation of graft survival was antigen-specific; the administration of 1 x 10(8) DA cells p.v. to LEW hosts did not prolong the survival of BN renal grafts (MST = 7.4 +/- 0.8, n = 5). Spleen cells from p.v. treated LEW hosts 10 days after transplantation had no suppressor effect on the one-way MLC reaction of normal LEW responder cells toward donor BN or third-party DA stimulators. On the other hand, when serum from p.v.-treated LEW hosts was added to MLC at a concentration of 3 per cent of total volume, it suppressed the MLC reaction toward donor BN cells by 71.6 per cent, but not toward third-party DA stimulators (-8.5 per cent suppression, NS). Histological examination of p.v.-treated LEW hosts at 10 days after transplantation revealed that the liver had normal lobular architecture without expansion of portal tracts and infiltration of inflammatory cells. On the other hand, the transplanted kidney demonstrated a moderate mononuclear cell infiltration around the artery without an interstitial hemorrhage. Moreover, adoptive transfer of the serum from p.v.-treated LEW rats into the virgin secondary LEW hosts significantly prolonged the graft survival of BN kidneys from 7.8 days to 18.9 +/- 5.5 days (P less than 0.01), but not third-party DA graft survivals (MST = 7.5 +/- 0.6 days), indicating that an antigen-specific tolerogenic factor was released into the circulation through the process of allogeneic cells in the liver.

Animals↗
PubMed1990

The effects of perioperative portal venous inoculation with donor lymphocytes on renal allograft survival in the rat. II. Phenotypic and functional analyses of graft-infiltrating cells.

Phenotype, donor-specific cytolytic activity, and helper activity to release cytokines of cells infiltrating within renal allografts of hosts rendered unresponsive by perioperative administration of donor lymphocytes via the portal vein (p.v.) were investigated in order to analyze the mechanism of prolongation of allograft survival. Graft-infiltrating cells (GIC) were obtained from Lewis (LEW, RT-1l) hosts inoculated perioperatively with 1 x 10(8) donor Brown-Norway (BN, RT-1n) lymphocytes p.v., a group that displays prolonged renal allograft survival (MST: 22.2 +/- 5.3 days, n = 10) compared with an uninoculated control group (MST: 7.8 +/- 0.6 days, n = 10, P less than 0.01). The percentages of cytotoxic/suppressor T cells (OX-8+) and Ia-positive cells (OX-6+) in GIC (23.1 +/- 4.4% and 9.0 +/- 2.0%, respectively) and in spleen cells (7.5 +/- 2.6% and 8.5 +/- 1.1%, respectively) from p.v.-inoculated LEW hosts on day 6 postgrafting were significantly lower than those of uninoculated control recipients (GIC: OX-8; 39.4 +/- 8.2%, OX-6; 23.0 +/- 1.9%. SP cell: OX-8; 21.6 +/- 9.9%, OX-6; 12.7 +/- 0.4%, P less than 0.05). Cytolytic activity of GIC from tolerant hosts on day 6 postgrafting toward donor blastoid lymphocytes was significantly decreased (19.0 +/- 1.2% at E/T = 50), compared with that from control allografts during ongoing rejection (51.5 +/- 5.3%, P less than 0.01). The amounts of in vitro cytokine production of GIC from tolerant hosts after mitogen stimulation were remarkably decreased (IL-2: 8.7 +/- 1.4 U/ml, IL-3: 15.4 +/- 0.6 U/ml, and BSF-2: 24.6 +/- 3.5 U/ml) than those of uninoculated control hosts during ongoing rejection (IL-2: 19.6 +/- 2.9 U/ml, IL-3: 22.2 +/- 2.7 U/ml, and BSF-2: 67.5 +/- 13.2 U/ml, P less than 0.05). These results demonstrated that activation of both Tc cells and Th cells was inhibited in the spleen and in situ in renal allografts following administration of donor lymphocytes through the portal vein.

Animals↗
PubMed1990

[The effect of combination therapy of cyclosporine with steroid on the production of gamma-interferon and interleukin-1 in kidney transplant recipients].

The present study examined the effects of CsA administered with steroid in vivo on the capacity of kidney transplant recipient mononuclear cells to generate cytokines and their gene expression at the level of messenger RNA (mRNA). Peripheral blood mononuclear cells (PBMC) from CsA-Prednisolone (Pred) treated recipients displayed 66.9% inhibition (54.3 + 12.4 IU/ml, n = 42, p less than 0.01) of gamma-IFN production compared with normal individuals (134.6 + 18.6 IU/ml, n = 23). Azathioprine (Az)-Pred treated recipients displayed significantly less inhibition of gamma-IFN generation (96.0 + 16.1 IU/ml, n = 22, p less than 0.05) than CsA treated patients. Macrophages (m phi) from CsA-Pred treated recipients displayed 60.0% inhibition (5.1 + 0.7 U/ml, n = 20, p less than 21). These result were confirmed by the experiments using cDNA probe for gamma-IFN or IL-1 (alpha, beta). High levels of gamma-IFN mRNA in PHA-stimulated PBL or IL-1 (beta) mRNA in LPS-stimulated m phi were present in normal individuals, but not in CsA treated recipients as judged by hybridization to a cloned human gamma-IFN or IL-1 (beta) cDNA probe. These studies demonstrated that combination therapy of CsA with steroid inhibits both gamma-IFN and IL-1 gene expression at the level of mRNA at physiological concentration.

Cyclosporins↗
PubMed1990

[Phenotype and function of cells infiltrating rat renal allograft].

Phenotype and function of graft infiltrating cells (GIC) from rat renal allografts were investigated in comparison with those of spleen (SP) cells, peripheral blood mononuclear cells (PBMC), and regional lymph node (LN) cells of the recipient. Relative proportions of all T cell, suppressor/cytotoxic T cell, helper T cell, and antigen-activated cell displayed significant increases in GIC during ongoing rejection assessed by flow cytometry. Cytolytic activity (using 51Cr release assay) of GIC on day 3 was much higher (20.2%) than those of SP (6.0%), PBMC (3.8%), and LN (3.2%) on BN target cells and this activity gradually increased during ongoing rejection up to 53.1% (GIC), on day 6. In vitro production of cytokines (IL-2, IL-3, gamma-IFN, and BSF-2) from these groups of cells were investigated. GIC demonstrated the most remarkable increases of cytokine production from day 3 to day 6. Especially, GIC on day 6 produced higher amount of BSF-2 compared with SP cells, PBMC and LN cells. These results demonstrated that alloactivated Th cells as well as Tc cells accumulated within the allografts and that the subtype of Th cells which produce BSF-2 preferentially assembled to the allograft.

Animals↗
PubMed1990

[Examination by densitometer on visualization of non-ionic contrast medium (iohexol) in excretory urography. 1. Visualization by bolus injection].

The visualization of non-ionic contrast medium (Omnipaque 300) in the excretory urography by bolus injection was examined with regard to the normal sided urinary tract in patients with urolithiasis using a densitometer and further compared with that of ionic contrast medium (60% Urografin). In relation to the photographing method, both contrast media showed an increasing frequency of high opaque site in the order of Tomo, A-P and P-A images, which tended to shift from the upper to the lower urinary tract. In relation to the site of determination, both agents showed a good image in the upper urinary tract by the each photographings, while P-A image was better than A-P image in the lower urinary tract, suggesting their high usefulness for the imaging diagnosis. The visualization in relation to the contrast medium used was better in Omnipaque 300 groups than in 60% Urografin group with a significant difference (P less than 0.05-0.01) in the calyx and pelvis of the kidney by the each photographings, suggesting a high usefulness of non-ionic contrast medium. A densitometer seemed to be a useful means for evaluation and examination of the visualization with excellent objectivity as compared with conventional macroscopic methods.

Absorptiometry, Photon↗
PubMed1990

[Examination by densitometer on visualization of non-ionic contrast medium (iohexol) in excretory urography. 2. Changes in visualization by DIP].

Changes in the visualization of non-ionic contrast medium (Omnipaque 300) in the urography by DIP were monitored for the normal sided urinary tract in patients with urolithiasis using a densitometer. In addition, changes of the visualization in relation to the dose of contrast medium used was examined and compared with that of ionic contrast medium (60% Urografin). The optimum photographing time was 15 minutes in the upper urinary tract (nephrogram, calyx, pelvis, upper ureter) and 20 minutes in the lower urinary tract (lower ureter, urinary bladder). Visualization of high usefulness appeared to be obtainable for the imaging diagnosis by DIP in subjects with normal renal function even when the photographing was completed 20 minutes after infusion of contrast medium. In relation to the doses of contrast medium used, no difference was observed in the variation pattern but a better imaging was obtained in the 100 ml group than 50 ml group with a significant difference (P less than 0.01) in the 15-20 minute images of the calyx and pelvis of the kidney and urinary bladder in particular, this suggested the high usefulness of 100 ml dosing for the imaging diagnosis. In the visualization of ionic contrast medium, some difference was observed in the variation pattern and the visualization was better in Ominpaque 300 groups than in 60% Urografin group with a significant difference (P less than 0.01) in the 15-20 minute images of the calyx and pelvis of the kidney and urinary bladder. This suggested the high usefulness of non-ionic contrast medium.

Absorptiometry, Photon↗
PubMed1989

Cyclosporine-associated microangiopathic hemolytic anemia in a renal transplant recipient.

A case of microangiopathic hemolytic anemia (MHA) associated with the immunosuppressive agent, cyclosporine, is reported herein. The patient manifested anemia with red blood cell fragmentation, hypertension, thrombocytopenia, elevation of serum LDH levels and glomerular capillary thromboses within a few days of his transplantation. Extensive treatments with urokinase and heparin proved ineffective and graftectomy was performed 7 days after his transplantation. Immunofluorescent staining failed to show immunoglobulin (IgG or IgM) or complement (C3) deposition within the glomeruli, which discriminated MHA from acute humoral-vascular rejection.

Adult↗
PubMed1989

Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. I. Inhibition of expression of alloantigen-activated suppressor cells, as well as induction of alloreactivity.

The effect of FK506 on in vitro human lymphocyte responses was assessed in comparison with cyclosporine. FK506 suppressed, in a dose-dependent fashion, the lymphocyte response to stimulation with PHA and with alloantigens in primary mixed lymphocyte reactions at a 70-100-fold lower concentration than CsA--namely, 50% inhibition (IC50) was obtained with 8.6 nM FK506 and with 750 nM CsA in the PHA response, and with 0.21 nM FK506 and with 20 nM CsA in MLR. Allocytolytic T lymphocyte induction was also inhibited by FK506, whereas the ability of CTL to lyse targets was not affected by the agent, indicating that FK506 did not affect the recognition and binding of alloantigen by CTL. FK506 inhibited, in a dose-dependent fashion, both IL-2 receptor and transferrin receptor expression on the alloactivated lymphocytes--whereas this agent inhibited only incompletely both expression of both receptors on lymphocytes stimulated with PHA. Lymphocytes from primary MLR cultured in the presence of FK506 were tested for suppressor cell activity on day 8 of culture. FK506 did not allow for the expression of alloantigen-activated suppressor cells when used in a dose sufficient to inhibit CTL generation.

Adult↗
PubMed1989

Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. II. Inhibition of the production of IL-2 and gamma-IFN, but not B cell-stimulating factor 2.

The mechanism whereby FK506 inhibits immune responses was assessed in in vitro human studies. FK506 inhibited in a dose-dependent manner both interleukin 2 and gamma-interferon secretion of PBMC stimulated with PHA. Complete inhibition was obtained at the concentration of 0.25 nM of FK506 for IL-2 and 1 nM of FK506 for gamma-IFN production. Inhibition of 50% (IC50) was detected with 0.06 nM for IL-2 and 0.25 nM for gamma-IFN production. On the other hand, FK506 could not inhibit the B cell-stimulating factor 2 (BSF-2) production of PBMC, indicating the possibility that FK506 might spare the B cell function. Cloned T cells and cloned B cells, once activated, were scarcely affected by the agent; neither IL-2-driven proliferation of cloned T cells nor BSF-2-driven proliferation of cloned B cells was inhibited by FK506 at any concentration.

Adult↗
PubMed1989

[Effects of portal venous administration with allogenic cells on renal allograft survival in the rat].

The effects of administration of donor lymphocytes via portal vein (PV) on capacity of alloreactivity and renal allograft survival were investigated in comparison with those of intra-venous (IV) administration in the rats. Orthotopic renal transplantations were performed from Brown-Norway (BN, RT-In) to Lewis (LEW, RT-11) male rats. Donor lymphocytes were prepared from BN or third party DA(RT-1a) rat spleens and lymph nodes and injected via PV or IV to LEW rats on the day of transplantation (day 0). Untreated LEW hosts rejected BN grafts at 7.8 +/- 0.6 days (n = 10). IV administration of 1 x 10(8) BN cells to LEW rats caused a slight prolongation of BN graft survival to 10.4 +/- 3.1 days (n = 9, p less than 0.05), whereas PV inoculation of the same number of BN cells further prolonged graft survival to 28.9 +/- 9.2 days (n = 9, p less than 0.01). This effect was antigen specific; the administration of 1 x 10(8) third party DA cells via PV to LEW rats did not prolong survival of BN graft (MST = 7.4 +/- 0.8, n = 6). Serum from tolerant recipients had significant antigen specific suppressor effect (70.6%) on the MLR proliferative reaction of LEW responder cells toward donor BN cells, but not third party DA cells. Spleen cells from these recipients did not show any suppressive effect. These results demonstrate that PV administration of donor lymphoid cells to recipients results in rapidly inducible and long-lasting immunologic tolerance specific to donor alloantigen, and that this tolerance is mediated by serum factor induced in hosts, but not by suppressor cells.

Animals↗