Shinji Takasu

Induction of antiidiotypic antibodies by donor-specific blood transfusions. Establishment of a human-mouse hybridoma secreting the MLR-inhibiting factor

We describe a patient transfused with 200 ml of donor fresh whole blood three times at 2-week intervals. Three weeks after the last transfusion, transplantation and splenectomy were done at the same time. Splenic cells from this DST pretreated patient were fused with murine myeloma cells (X63-Ag8, 653). With DST pretreatment, various clones were developed in vivo, and finally 69 human immunoglobulin-secreting clones were obtained. Modulation of the alloantigen-specific MLR by supernatants from 69 clones showed various degrees of suppression or augmentation. The hybridoma clone 7 and clone 2, which had been secreting IgG antibody for more than 6 months, showed some degree of suppression in the alloantigen-specific MLR (mean suppression = 63%, 46% respectively). According to the result of MLR, clone 7 antibody was directed against recipient lymphocytes and clone 2 antibody was against donor lymphocytes. Immunoprecipitation was carried out by clone 7-IgG and clone 2-IgG. Clone 7-IgG specifically precipitated 1 molecule from the recipient lymphocyte with a molecular weight of 120 KD, similar to the molecular weight range reported for T cell receptors. Clone 2-IgG precipitated a 20 KD molecule from the donor lymphocyte. The data suggest that DST induces antibodies directed against the blood donor alloantigen-specific receptors on the recipients T lymphocytes--and, at the same time, induces antibodies against donor lymphocyte antigens. These antibodies may be essential to prolongation of kidney allograft survival following DST.

Immunosuppressive mechanism of 15-deoxyspergualin on sinusoidal lining cells in swine liver transplantation: Suppression of MHC class II antigens and interleukin-1 production

To elucidate the precise mechanism of action of 15-deoxyspergualin (DSG) in swine liver transplantation, the expression of MHC class II antigens (Ia) on hepatic sinusoidal lining cells (SLC) and their production of interleukin-1 (IL-1) were examined. In our previous study, we isolated sinusoidal endothelial cells (SEC) and Kupffer cells (KC) by enzymatic digestion and centrifugal elutriation, and demonstrated that both SEC and KC present alloantigens effectively and generated IL-1 in response to allogenic or lipopolysaccharide stimulation. Animals were divided into three groups: group 1, nontransplanted normal controls (n = 3); group 2, no immunosuppressive treatment following liver transplantation (n = 5); group 3, DSG (0.8 mg/kg/day) intravenously for 7 days following liver transplantation (n = 5). At 1 week after transplantation, the three liver grafts in groups 2 and 3 were processed for the study of Ia expression and IL-1 production on SEC and KC. The expression of Ia was detected in 21.5 +/- 4.7% of SEC and 24.3 +/- 11.1% of KC in group 1. In group 3, Ia expression was suppressed compared with group 2, being 3.6 +/- 2.8% versus 22.0 +/- 2.8% for SEC (P less than 0.02) and 15.5 +/- 11.3% versus 24.3 +/- 7.1% for KC. IL-1 production by SEC and KC was respectively 11,483 +/- 3311 cpm and 9077 +/- 2161 cpm in group 1. In group 3, IL-1 production was inhibited compared with that in group 2, being 7190 +/- 883 cpm versus 19,297 +/- 5182 cpm for SEC (P less than 0.05) and 16,130 +/- 3769 cpm versus 25,857 +/- 3963 cpm for KC.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone metabolism on long-term follow-up after total parathyroidectomy with autotransplantation.

二次性副甲状腺機能亢進症による腎性骨異栄養症 (ROD) に対して上皮小体全摘一部自家移植術 (PTX-AT) が行われているが, 術後3年以上の遠隔期における骨代謝, 骨所見に関する報告は少ない. 過去8年で38例に, PTX-ATを施行した. このうち術後3年以上経過した27症例について骨代謝の生化学的指標と, 全身骨X線所見について検討した. 透析歴は120-235か月 (平均181.1±30.7か月), PTX-AT後36-89か月 (平均61.9±11.9か月) を経過していた. C-PTHは術直後より減少し, 術後3年で5ng/ml以下のものは22例で, 残り5例中4例は術後もほとんど減少せず, その後の検査で残存副甲状腺を確認した. 骨新生の指標となるオステオカルシンを, 術後症例 (PTX-AT群) とC-PTH 10ng/ml以上の二次性副甲状腺機能亢進症例 (2°HPT群) で比較検討すると, PTX-AT群 (n=26) は平均106.9±98.7ng/ml, 2°HPT群 (n=27) は平均230.9±157.9ng/mlで, 有意にPTX-AT群が低値を示した (p<0.005). また, PTX-AT群では100ng/ml以下のものは19例でその全例がC-PTH 5ng/ml以下であった. 100ng/ml以上の8例は, 2°HPT群と有意差を認めなかった. さらに, 両群においてオステオカルシンとC-PTHは正の相関が認められた (p=0.05). 全身骨X線所見を1. 手指骨 (Tuft resorption, TR), 2. 頭蓋骨 (Salt and pepper, SP), 3. 腰椎 (Rugger jersey, RJ) の骨吸収像に分けてPTX-AT前後で比較検討した.1) TR (n=23): 悪化例0, 不変例2, 改善例21, 2) SP (n=21): 悪化例0, 不変例1, 改善例20, 3) RJ (n=21): 悪化例1, 不変例10, 改善例10.以上より, PTX-ATにより手指骨, 頭蓋骨は著明に改善するが, 腰椎は半数が不変であり改善傾向が少なかった. また, 術後持続副甲状腺機能亢進症を呈する症例では, 骨所見改善に乏しく, 骨代謝の生化学的指標のC-PTH, オステオカルシンと骨所見は相関するものと考えられた.

Abdominal organ cluster transplantation in pigs and FK

Using a swine abdominal organ cluster transplantation model, we investigated the postoperative function and immunological reactions of a cluster graft and evaluated the immunosuppressive activity of FK506. The animals were divided into two groups. Group I (n = 6) served as controls, while in group II (n = 6) a daily dose of 0.1 mg/kg FK506 was given intramuscularly. Postoperative pancreatitis was the most important factor influencing the early outcome in both groups. In group I, the cause of late death was cachexia due to diabetes mellitus induced by pancreatic rejection. In group II, emaciation despite a well‐functioning graft was the principal cause of late death. Histologically, in group I the grade of rejection in the pancreas was more severe than in the liver, and no sign of rejection was observed in group II. In conclusion, the pancreas suffered more severe rejection than the liver, and FK506 could significantly prevent cluster allograft rejection in this model.

Abdominal organ cluster transplantation in pigs and FK506.

Using a swine abdominal organ cluster transplantation model, we investigated the postoperative function and immunological reactions of a cluster graft and evaluated the immunosuppressive activity of FK506. The animals were divided into two groups. Group I (n = 6) served as controls, while in group II (n = 6) a daily dose of 0.1 mg/kg FK506 was given intramuscularly. Postoperative pancreatitis was the most important factor influencing the early outcome in both groups. In group I, the cause of late death was cachexia due to diabetes mellitus induced by pancreatic rejection. In group II, emaciation despite a well-functioning graft was the principal cause of late death. Histologically, in group I the grade of rejection in the pancreas was more severe than in the liver, and no sign of rejection was observed in group II. In conclusion, the pancreas suffered more severe rejection than the liver, and FK506 could significantly prevent cluster allograft rejection in this model.