Relationship between the Decrease of Cytotoxic Antibody with the Elapse of Time and Hyperacute Rejection in Hyperimmunized Rats

Preformed cytotoxic antibody which causes hyperacute rejection is formed on gestation, blood transfusion and infection. It is an important problem whether or not transplantation is possible in the recipients sensitized like this. We studied the decrease of preformed cytotoxic antibody with the elapse of time in sensitized recipients and its influence on graft survival time, using inbred rats. Inbred ACI rats and Fischer rats were used as experimental models. Hyperimmunized Fischer rat recipients were prepared by skin grafting and spleen lymphoid cell booster. In order to observe the course of decrease or disappearance of the antibody after sensitization, anti T cell warm cytotoxic antibody (CA-TW) was assayed in rat groups which were hyperimmunized one week, one, three and six months before, respectively. The hearts of ACI rats were transplanted to the groups of hyperimmunized Fischer rat recipients to study the relationship between graft survival time and cytotoxic antibody. 1. Controls: The heart of ACI rat transplanted to nontreated Fischer recipient showed graft survival time of 8.1 ± 1.4 days. 2. Group of rats hyperimmunized one week before: The transplanted ACI heart was hyperacutely rejected 0.55 ± 0.38 hr after grafting in all recipients. 3. Group of rats hyperimmunized one month before: The transplanted ACI heart was hyperacutely rejected in five of the 12 recipients. The graft survival time was 17.2 ± 9.2 hr. 4. Group of rats hyperimmunized three months before: Hyperacute rejection was observed in three of the 12 recipients. The graft survival time was 43.0 ± 28.1 hr. 5. Group of rats hyperimmunized six months before: Hyperacute rejection was not observed. The graft survival time of the transplanted heart was 96.0 ± 37.5 hr. The pattern of rejection varied from accelerate to acute rejection. 6. Spontaneous decrease of preformed cytotoxic antibody after hyperimmunization: Fischer rats were hyperimmunized by skin grafting from ACI rat and five booster shots of spleen lymphoid cell. The change of their antibody titer was examined. CA-TW of the groups hyperimmunized three and six months before, respectively were significantly lower than that for the group hyperimmunized one week before the transplantation. 7. Relationship between preformed cytotoxic antibody titer and graft survival time of transplanted heart: There was a negative correlation between CA-TW titer and graft survival time; r = —0.7274. To sum up, cytotoxic antibody generated by hyperimmunization was decreased with the passage of time. It was thought that the decrease of CA-TW closely related to graft survival time. It was revealed that hyperacute rejection no longer occurred after a lapse of six months after sensitization and that the graft was taken for more than 90 hr and then rejected either by accelerate or by acute rejection

Studies on the Control of Hyperacute Rejection in Hyperimmunized Rat: Combination of Donor Specific Blood Transfusion (DST) and Immunosuppressive Drugs

In order to decrease preformed cytotoxic antibodies, which are the main cause of hyper-acute rejection, donor specific blood transfusion (hereafter designated as DST) was performed. Immunosuppressants were administered at the same time to examine whether the combined treatment with DST can inhibit rapid reproduction of antibodies in the serum of a sensitized recipient. Hyper immunized Fischer rat recipients were used as experimental models. Blood of ACI rat was transfused to the recipients as DST. Beta-methosone and Anti-lymphocyte serum (hereafter designated as ALS) were given as immuno suppressive drugs combined with DST. The heart of ACI rat was transplanted to the hyperimmunized Fischer recipent treated as described above. The cardiac graft survival time was observed and the change in cytotoxic antibody titer of the recipient was determined with the elapse of time. Performed cytotoxic antibodies formed by hyperimmunization were adsorbed or diminished, by DST, and the heart graft survivied for about 54 hr in the group treated with DST, while it was hyperacutely rejected after about 0.4 hr in controls. However, DST was effective only when it was performed once. Transfusion after that acted as a booster, inducing reproduction of anti T-cell warm cytotoxic antibody (CA-TW). Therefore repeated transfusion was thought to be contraindication. Beta-methasone or ALS were administered after adsorption of antibodies by DST in order to prevent antibodies from being rapidly formed again in the serum of a sensitized recipient. The suppressive effect was greatest in the group treated with combination of DST and ALS, and the heart graft survivied for 94 hr. In this group, the pattern of rejection was not hyperacute rejection but acute to accerelated one. It wa revealed that hyperacute rejection can be depressed to some extent

ラット心移植における hyperacute rejection モデルの作製

Using genetically homogeneous inbred ACI and Fischer rats, the author has conducted active immunization with the skin and lymphoid cells from ACI rat to Fischer rat and succeeded in making an experimental model that unfailingly causes hyperacute rejection, which has heretofore been considered to be extremely difficult. Semipermanent survival was gained with syngenetic graft. With allograft, acute rejection of the cardiac graft took place in 8.1±1.4 days. On heart transplantation from ACI to Fischer recipients sensitized by skin graft from ACI and two times active immunization with spleen lymphoid cells from ACI, accelerate rejection occurred in 60.8±32.7 hr. On transplantation of ACI heart in Fischer recipients subjected to skin graft and five times or more hyperimmunization with spleen lymphoid cells, hyperacute rejection of the cardiac graft occurred in all cases in 2.2 ± 3.5 hr. As regards active immunization and anti-T cell warm cytotoxic antibody formation, skin graft followed by five times active immunization gave a titer of 2^8.11 ±1.5 and the antibody formation reached a plateau. Anti-T cell warm cytotoxic antibody and survival time of the cardiac graft showed the following correlation. log10 (y) = －0.054x+2.113　　(x<3.622) log10 (y) = －0.4742x+3.4778　(x>3.622) C = 3.622 was recognized. The anti-T cell warm cytotoxic antibodies were found to be decreased with a　significant difference (P<0.01) after hyperacute rejection

腎移植臨床例における T.G 陽性細胞の変動 : 合併症との関連性を中心に

The changes in lymphocyte subpopulations in renal transplant recipients were determined. Prior to immunosuppressive therapy, the subpopulation levels in the recipients were similar to those of healthy adults, but after administration of therapy, the T-cell ratio (%T) decreased, while the IgG-Fc receptor-bearing T-cell ratio (%T.G) increased. However, review of these changes in individual cases showed that among those with the same degree of decrease in %T, the %T.G increased only slightly in some, but markedly in others, thus, indicating that there was not necessarily an inverse correlation between the decrease in %T and increase in %T.G. Further, it is noted that when %T.G was markedly increased, the patient was susceptible to bacterial infection

Mizoribine を用いたヒト腎移植の経験

In addition to steroids and azathioprine, mizoribine was administered to 17 renal transplant recipients. In 9 of the 17, 16 acute rejections occurred. Seven of these 9 recovered without deterioration of graft function, but one lost the function. Mizoribine, which has been elucidated to produce a chronic rejection preventing effect fully when administered concurrently with steroids and azathioprine, proved to give a satisfactory immunosuppressive effect in a dose of 1 mg/kg/day when used simaltaneously with steroids and azathioprine

腎移植後患者の急性拒絶反応に合併した DIC

A kidney transplant recipient with disseminated intravascular coagulation (DIC) accompanied by acute rejection was described. The principal symptome of the patient was massive gross hematuria. She showed thrombocytopenia, marked decrease of fibrinogen and elevation of fibrinogen degradation products (FDP) level. The patient was treated by continuous intravenous heparin infusion (total dose was 85, 800 units), and it was very effective. The symtoms due to DIC were improved on the 9th day after the beginning of heparin therapy

閉塞性黄疸をきたした腹部大動脈瘤の一例

The authors have experienced a very rare case of obstructive jaundice resulting from direct compression of the region of the porta hepatis by an abdominal aneurysm developing below the renal artery, whose life was saved by an operation performed just before rupture of the aneurysm occurred. The case is reported

腎移植における Ureteroneocystostomy の問題点 : Intravesical UreteroneocystostomyとExtravesical Ureteroneocystostomy の比較

The authors have made extensive studies of ureteroneocystostomies, that are intravesical and extravesical methods, and postoperative urological complications on 58 cases of living related renal transplants and 12 cases of cadaveric renal transplants at the Second Department of Surgery, Hiroshima University School of Medicine. Among the 21 cases in whom intravesical ureteroneocystostomy was employed, there was one case of urinary fistula. Among the 49 cases in whom extravesical ureteroneocystostomy was employed, two case of postoperative bleeding, a case of stenosis of the ureter and a case of urinary fistula of the anastomosis were observed. There was one case of graft loss in each method, but no case died. The incidence of complications is low on both methods. But extravesical ureteroneocystostomy does not require a large incision of the vesical wall and is advantageous in having a possibility to conduct the submucosal tunnel visually and a easy doing of anastomosis between the ureter and the vesical mucosa. Then, the procedure of our modified extravesical ureteroneocytostomy was reported