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Biomedical subjects

N Yoshimura

Publications and source records attributed to N Yoshimura.

At least 487 records · Page 27Linked to original sources

[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↗

[Evaluation of experimental proliferative vitreoretinopathy in rabbits].

We established an effective animal experimental model for proliferative vitreoretinopathy (PVR) by intravitreally injecting cultured cells in order to investigate therapies for PVR, including intravitreal drugs, radiation and hyperthermia. After making posterior vitreal separation by injecting SF6 gas into the rabbit's vitreous body, cultured cells were intravitreally injected. Fundus changes were followed up for 4 weeks and PVR stage was recorded according to the classification described by Hida et al. The cultured cells injected were rabbit dermal fibroblasts (5 x 10(4) and 10 x 10(4) and human retinal pigment epithelial (RPE) cells (5 x 10(4]. A total of 37% of animals reached STAGE 5-7 (traction retinal detachment) in 4 weeks in 41 eyes injected with 5 x 10(4) rabbit fibroblasts and were 86% in 14 eyes injected with 10 x 10(4) rabbit fibroblasts. The 10 eyes injected with human RPE cells showed STAGE 2 or less in 4 weeks. Consequently, we selected the experimental PVR model using injecting of 10 x 10(4) rabbit fibroblasts as the most effective method.

Animals↗

[A case of Marfan syndrome with recurrent bilateral pneumothorax and anuloaortic ectasia].

A 17-year-old male patient with Marfan syndrome was admitted due to recurrent bilateral pneumothorax which had recurred totally 11 times during the past 3 years. For the treatment of obstinately continuing right pneumothorax resection of bullae in combination with pleuropexy using OK 432 was effective. Two months thereafter Bentall operation with a composite graft consisting of a woven Dacron tube and a Björk-Shiley 27 mm aortic valve prosthesis was performed for his anuloartic ectasia. Left pneumothorax recurred 2 weeks after Bentall operation. But it was treated successfully with OK 432 injection into the left pleural cavity. Now, he is doing well as a student.

Aged↗

Combination therapy of cyclosporine with steroid inhibits gamma-interferon and interleukin-1 gene expression at the level of mRNA synthesis in vivo.

The present study examined the effect of cyclosporine (CsA) administered with steroid in vivo on the capacity of peripheral blood mononuclear cells (PBMC) from kidney transplant recipients to generate cytokines and their gene expression at the level of messenger RNA (mRNA). 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-interferon (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 0.01) of interleukin-1 (IL-1) production compared with normal individuals (13.0 +/- 2.9 U/ml; N = 21). These results were confirmed by the experiments using cDNA probe for gamma-IFN or IL-1 (alpha, beta). High levels of gamma-IFN mRNA in phytohemagglutinin (PHA)-stimulated PBMC or IL-1(beta) mRNA in lipopolysaccharide (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 concentrations.

Cyclosporins↗

The successful outcome of second kidney transplantation and its contributing factors.

Fourteen out of 301 patients who underwent allogeneic kidney transplantations, between April, 1970 and December, 1987, received second kidney allografts, including 4 living and 10 cadaveric grafts. The survival of the second grafts transplanted in those 14 recipients was superior to that of the first grafts transplanted in the other 287 recipients. Furthermore, the survival of the second grafts from 4 years onwards was significantly higher than that of the first grafts, in spite of a higher population of cadaveric grafts used in the second transplantation than in the first. Although it was impossible to determine the main factor which induced the improved survival of the second grafts when compared with that of the first, a combination of beneficial factors, such as a high rate of living related transplantation resulting in long-term graft survival of the first transplantation, the administration of immunosuppressive drugs during the period of re-hemodialysis and blood transfusion prior to the second transplantation, was considered to be the reason why successful second graft survival was achieved.

Cyclosporins↗

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↗

A case of endoscopic injection sclerotherapy for a bleeding duodenal varix.

A case of bleeding duodenal varix which was treated successfully with endoscopic injection sclerotherapy (EIS) is reported. The patient developed a hemorrhage from a varix in the descending portion of the duodenum two months after EIS for esophageal varices, and hemostasis was achieved using EIS with an intravericeal injection of 1% polidocanol. The duodenal varix decreased in size after EIS. Two months after EIS, a splenectomy was performed. During a 14-month follow up period after the EIS for the duodenal varix, there was no recurrent bleeding.

Adult↗

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↗

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↗

Characterization and analysis of soluble suppressor factor from early human decidual cells.

To assess the role of decidual cells (DC) in the maintenance of pregnancy, immunosuppressive activity of culture supernatants from human DC were investigated. Dispersed DC suspensions from decidual tissue of early pregnancies were prepared by an enzyme digestion method using collagenase and DNase, and were enriched over 90 per cent without contamination of macrophages and lymphocytes in the fraction, with specific gravity between 1.033 and 1.044 (fraction 2 [Fr2] ) by a Percoll discontinuous density gradient method. The culture supernatants of Fr2 cells suppressed the responses of normal peripheral blood lymphocytes to PHA, MLR, and killer T cell generation at the 50 per cent concentration. To determine the mechanism of the immunosuppressive activity of the culture supernatants, the effect of the supernatants on interleukin-2 and gamma-interferon production, as well as IL-2 receptor expression, on PBL was investigated. The supernatants from 3 x 10(6)/ml of DC cells inhibited not only IL-2 and gamma-INF production, but also IL-2 receptor expression, compared with normal controls. The supernatants also suppressed immunoglobulin (IgG and IgM) production by pokeweed mitogen-stimulated B cells. To purify the suppressor factor from culture supernatants of DC, serum free culture supernatants of 3 x 10(6)/ml of DC, which showed 32 per cent of inhibitory activity on MLR, were applied to gel filtration. Fractions between mw 67,000 and 43,000 suppressed the MLR. These results suggest that DC from decidua of early pregnancy excrete an immunosuppressive factor with a molecular weight between 43,000 and 67,000 daltons.

Centrifugation, Density Gradient↗

[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↗