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Biomedical subjects

Y Iwaki

Publications and source records attributed to Y Iwaki.

At least 19 recordsLinked to original sources
PubMed1992

A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies.

Twenty-six adult patients with preformed IgG donor lymphocytotoxic antibodies received primary liver allografts under FK 506 immunosuppression. The effect of the crossmatch-positive state on early graft function and on the immunopathological and histopathological findings was compared with that of 52 crossmatch-negative control recipients. The presensitized (crossmatch-positive) patients had prolongation of early graft dysfunction, underwent more clinically indicated biopsies and had a higher incidence of cellular rejection, both overall (p less than 0.05) and within 10 days of transplantation (p less than 0.01). They also had a higher incidence of graft failure in the first 180 days (p less than 0.01). Hyperacute rejection with necrotizing or neutrophilic arteritis was not seen in the crossmatch-positive grafts. However, histological findings associated with presensitization included platelet margination in central veins and sinusoids in biopsy specimens 60 to 90 min after graft revascularization. Later biopsy specimens had neutrophilic portal venulitis followed by cholangiolar proliferation, acute cholangiolitis and centrilobular hepatocyte swelling that mimicked preservation injury, endothelial activation of arteries with medial changes and relapsing episodes of acute cellular rejection. These clinicopathological observations suggest that lymphocytotoxic antibodies can have a deleterious effect on liver allograft function and survival, even if they do not precipitate immediate or hyperacute rejection.

Adult↗
PubMed1992

Immunopathology of antibodies as effectors of orthotopic liver allograft rejection.

We have come a long way in our understanding of antibodies as effectors of liver graft damage, but we still have much to learn. Animal heterografts provided the first evidence that livers are susceptible to antibody-mediated damage. The pathophysiologic events are similar to those of extrahepatic organ grafts, but the liver is relatively resistant and rapidity of graft destruction is slower, if it occurs at all. Nevertheless, the ABO isoagglutinins can predictably cause human liver allograft failure, often in a quickened, but rarely a hyperacute fashion. The liver is more resistant to lymphocytotoxins, and in many cases will suffer no apparent damage. However, when present, a spectrum of graft pathologic changes can be seen. Early manifestations include hemorrhagic necrosis and lesions mimicking "preservation" injury. Later on, ischemic biliary necrosis and small bile duct loss may be seen. The variability is likely related to a balance between destructive antibody class, specificity, and titers and the ability of the liver to withstand the assault. More precise characterization of lymphocytotoxic antibodies is needed in clinical practice. In addition, antigen distribution in the graft, release of soluble MHC antigens, the role of Kupffer cells and other mechanisms of liver resistance are likely areas of fruitful investigation.

ABO Blood-Group System↗
PubMed1992

The adverse impact on liver transplantation of using positive cytotoxic crossmatch donors.

Because of the liver graft's ability to resist cytotoxic antibody-mediated rejection, it has become dogma that the conventional transplant crossmatch used to avoid hyperacute rejection of other organs is irrelevant to the liver. We examined this hypothesis in a consecutive series of adult primary liver recipients treated with FK506 and low-dose steroids. Twenty-five of 231 (10.8%) patients received a liver from a cytotoxic-positive crossmatch donor (more than 50% of donor T lymphocytes were killed by dithiothreitol-pretreated recipient serum). The outcome was compared with that of 50 negative crossmatch patients who had their transplantations just before and after the crossmatch positive cases. The one-year graft and patient survivals were 56% and 68%, for positive and 82% and 86% for negative crossmatch patients (P = 0.004, P = 0.03, respectively). The difference between patient and first graft survival was accounted for by retransplantation, which was 4 times more frequent in the positive-crossmatch cases. Histologically, failed allografts obtained at the time of retransplantation revealed a spectrum of pathologic findings related to vascular injury. This study showed a higher difficulty of intraoperative blood product management, a degraded prognosis, and a poorer average quality of ultimate graft function when liver transplantation was performed against positive cytotoxic crossmatches. In such patients for whom crossmatch-negative donors may never be found because of the broad extent and intensity of sensitization, special therapeutic strategies perioperatively must be evolved if results are to improve.

Adult↗
PubMed1992

Prolongation of second heart transplants in rats.

Second clinical kidney grafts often survive longer than first grafts. Using a rat cardiac allograft model, we examined the conditions under which survival of a second graft can be longer than first graft survival. In the BUF-to-LEW combination, following rejection of the first transplant, second cardiac allografts from the same donor strain implanted immediately survived longer than the first grafts (P = 0.047). Although the mean survival time of first grafts was 9.0 days, second grafts implanted in the same animals survived 19.5 days. In contrast, when ACI donors were used for the same LEW recipients, the second grafts were rejected in 3 days compared with 6.6 days for first grafts. Donor-specific spleen cell transfusions in these combinations resulted in prolonged survival in the BUF to LEW combination, but had no effect when the donor strain was ACI. Second grafts from BUF had prolonged survival following rejection of the first graft. Thus the histocompatibility difference was a determining factor of whether or not prolongation would be obtained. Another factor was timing of the second transplant. If 7 days were allowed to elapse following rejection of the first graft before implantation of the second, the enhancement effect was lost. Moreover, in the LEW-to-ACI combination in which second grafts were rejected rapidly, removal of the first graft after 7 days (before rejection), resulted in prolonged survival of the second graft. There is, therefore, a window of time before rejection of first grafts and shortly thereafter, when the enhancement effect can be obtained. Passive transfer of serum in the BUF-to-LEW combination resulted in enhancement, but transfer of splenic cells was ineffective. We conclude that graft rejection can result in induction of enhancement during a specific period, after which this effect is lost; and that enhancement can be obtained only in certain strain combinations. This suggests that human patients with heart transplants that reject might benefit from a second graft, even from a donor with a mismatch similar to the first graft.

Animals↗
PubMed1992

[A case of hepatocellular carcinoma responding to intraarterial infusion of epirubicin and mitomycin C].

A 64-year-old male was admitted for treatment of hepatocellular carcinoma. He was diagnosed as having many tumors in the area of S6 and the AFP level was elevated to 878 ng/ml. Initially, intraarterial infusion of Epirubicin only was not effective. After the first course of treatment, tumors increased in size and the AFP level was elevated. Next, intraarterial infusion of Epirubicin and Mitomycin C was performed. After the second course of treatment, the AFP level decreased from 5,006 ng/ml to 754 ng/ml and the tumors had almost completely disappeared on angiography. The tumors continued to decrease in size and thereafter the AFP level decreased to 10 ng/ml and was not elevated. The tumors almost completely disappeared in this case, and the coadministration of Epirubicin and Mitomycin C provided effective.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Histopathologic study of experimental chorioretinopathy induced in pigmented rabbits by intravenous adrenalin injection].

Experimental chorioretinopathy was induced by injecting 0.1% adrenalin intravenously in pigmented rabbit eyes. The fundus of each eye was analyzed with ophthalmoscopy and fluorescein fundus angiography (FFA). Histopathological sections were examined from each of following areas: (a) those with serous retinal detachment and evidence of dye leakage on FFA, (b) those with serous retinal detachment, but no dye leakage on FFA, and (c) those without detachment. In areas with serous detachment and dye leakage on FFA, the choroidal arterioles showed irregularly narrowed cavities, and the lumens of the choriocapillaris were remarkably narrowed. Most of the choroidal venules were enlarged and filled with many blood cells. Some had wide openings in the endothelial intercellular spaces, resulting in leakage of blood components into suprachoroidal space. Bruch's membrane was hypertrophic and some of overlying retinal pigment epithelium (RPE) had disappeared. The residual RPE showed degenerative changes, such as intracellular vacuole formation. Both in areas with detachment but no dye leakage on FFA, and in areas without detachment, similar but milder pathological changes were observed in choroidal arteriole and choriocapillaris. Severe damage, such as RPE defects and wide openings of endothelial intercellular spaces in choroidal venule, were not observed. These results suggest that intravenous adrenalin may affect choroidal venules as well as the choroidal arterioles and choriocapillaris in rabbit eyes, resulting in wide openings of their endothelial intercellular spaces. These histopathological change may lead to RPE damage by the choroidal ischemia and the leakage of blood components, leading to the induction of experimental chorioretinopathy.

Animals↗
PubMed1991

Replacement of donor lymphoid tissue in small-bowel transplants.

The presence of recipient lymphocytes in grafts is thought to equate with rejection. Thus, we wished to follow the fate of lymphocytes after transplant of the small bowel. Three complete small-bowel transplants, two with the liver from the same donor also transplanted, were done successfully. Patients were immunosuppressed with FK 506. 5 to 11% of lymphocytes in the recipients' peripheral blood were of donor origin during the early postoperative period when there were no clinical signs of graft-versus-host disease. However, donor cells were no longer detectable after 12 to 54 days. Serial biopsy specimens of the grafted small bowel showed progressive replacement of lymphocytes in the lamina propria by those of the recipient's HLA phenotype. Lymphoid repopulation was complete after 10 to 12 weeks but the epithelial cells of the intestine remained those of the donor. The patients are on enteral alimentation after 5, 6, and 8 months with histopathologically normal or nearly normal intestines. Re-examination of assumptions about the rejection of intestinal grafts and strategies for its prevention are required following these observations.

Anti-Bacterial Agents↗
PubMed1991

Early events in liver allograft rejection. Delineation of sites of simultaneous intragraft and recipient lymphoid tissue sensitization.

The early events of liver allograft rejection in untreated rats were studied in the DA to BN rejection strain combination and compared with DA and BN liver isograft recipients. In the liver allografts, T-cell infiltration first occurred at 2 days after transplantation and localized to the portal triads and subjacent to the terminal hepatic venules (THV), regions rich in intensely Ia + spindle and dendritic-shaped interstitial cells. Double staining showed distinct 'clustering' between donor Ia-positive dendritic-shaped cells and W3/25+ infiltrating lymphocytes, or to a lesser extent, OX8+ cells. The infiltrating mononuclear cells underwent blastogenesis and proliferated in both the triads and THV regions at 3 and 4 days. Donor Ia-positive cells were also noted in the W3/25+ periarterial lymphatic sheath and marginal zone of the recipient spleen 1 day after transplantation. The number of these cells in the spleen peaked at 3 to 4 days, but were no longer detectable by 10 to 12 days. Mitotic activity became evident in these same regions by days 3 and 4. Paracortical blastogenesis (day 2) and proliferation (days 3 and 4) were also noted in the regional lymph nodes of liver allograft recipients, but no donor Ia+ cells were found in the mesenteric nodes or thymus of the allograft recipients. These results demonstrate that sensitization of the recipient lymphoid tissue to liver allografts can occur both peripherally (intragraft) and centrally (spleen and lymph nodes). Passenger leukocytes (donor dendritic cells) are likely the primary stimulators of the rejection reaction. Still, it is probable that other pathways of sensitization exist.

Animals↗