ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Immunological enhancement of allogeneic heart graft survival by serum from rats tolerized by liver grafting has been studied. Serum taken from long-term-surviving PVG rats carrying orthotopic DA liver transplants (OLT serum) was able to increase the survival time of PVG.RT1aheterotopic heart grafts in PVG recipients. Administration of 1 ml of OLT serum at the time of heart grafting led to permanent survival of the grafts in all animals. The recipients became systemically tolerant of RT1aand several weeks later were able to accept permanently skin grafts from the same donor strain, while rejecting third-party grafts. Enhancement appeared to be mediated initially by IgG antibodies in the OLT serum against class II donor RT1aantigens; significant enhancement was produced by as little as 100 μg of antibody. Recipient alloantibody responses following enhancement were studied and showed selective suppression of the anti-class-I (RT1Aa) antibody levels, while the anti-class-II antibody response was apparently unaffected. The implications of these results for mechanisms of unresponsiveness following enhancement and liver transplantation are discussed.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

In most previous studies of cryopreserved isolated pancreatic islets, a slow cooling rate has been employed. We recently observed that faster cooling (5°C/min) resulted in better functional islet preservation than cooling at 0.5°C/min. We found that a culture period after the collagenase isolation of the islets, but prior to freezing, is crucial for the preservation of the islet B cell function. In the present investigation the function of isolated mouse pancreatic islets cooled in Hanks' solution supplemented with 2 M dimethylsulphoxide was compared with that of nonfrozen, cultured islets prepared from the same donors. The islets were cultured in RPMI 1640 + 10% calf serum for 3 days before freezing, and for 3 days after rapid thawing at 37°C. Islets were cooled at rates of 5, 15, or 25°C/min to 70°C and then plunged into liquid nitrogen. All three groups of cryopreserved islets responded with insulin secretion when challenged with high glucose concentrations in batch-type incubations. In further experiments it was found that glucose-stimulated (pro)insulin biosynthesis in islets frozen at 25°C/min was the same as that in the controls. Similar observations were made with respect to glucose-stimulated insulin release in perifusion experiments. However, a 30% reduction in insulin content was observed in the rapidly frozen islets. There was no difference in the replicatory capacity of the islets cells in vitro, as determined by an autoradiographic technique, between control islets and islets cooled at 5°C or 25°C/min. Intrasplenic implantation of 600–800 cryopreserved syngeneic islets into alloxan-diabetic mice led to complete or partial normalization of the hyperglycemia in seven of nine mice. When splenectomy was performed in five animals the serum glucose concentrations increased promptly. We conclude that relatively rapid cooling rates may be useful for cryopreservation of isolated pancreatic islets.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Posttransplant injection of fractionated donor bone marrow cells results in the prolonged survival of mouse skin allografts. In this investigation, we extended the study to the use of donor bone marrow fractionated by density-gradient centrifugation in a larger animal model, canine renal transplantation. Renal allografts were placed in outbred, histoincompatible dogs treated daily with rabbit or horse antilymphocyte serum (ALS) from days −6 to +7 relative to kidney transplantation on day 0. Fresh, unfractionated donor bone marrow (BM) or a bone marrow fraction (BM Fr3) produced by centrifugation in a discontinuous Percoll density gradient was intravenously infused into recipients on days +13 or +14. Alternatively, frozen/thawed (F/Th) BM or BM Fr3 was infused after storage at −80°C for two weeks. BM Fr3 and unfractionated BM significantly (P<0.005) prolonged for median allograft function time (MFT) beyond the controls treated only with ALS (46 and 35 days vs. 18 days). The longer MFT with BM Fr3 was achieved with 20–40% of the unfractionated BM cell dose. In addition, BM Fr3-treated dogs exhibited a slower rate of loss of kidney function. F/Th BM was as effective as fresh BM in prolonging graft survival. A reduced mixed lymphocyte response to donor and third-party cells and markedly reduced responsiveness to Con A, PHA, and pokeweed mitogens at 30—45 days posttransplant suggested that animals were nonspecifically immunosuppressed during this period. By 60 days poettransplant, in two dogs treated with BM Fr3, the MLR to third-party cells, but not to donor cells, and the responsiveness to mitogens had returned to pre-ALS treatment values. Thus, treatment with ALS combined with fresh or F/Th BM that has been fractionated is an effective method for the prolongation of kidney allografts in dogs. The development of specific, long-term immuno-suppression induced by fractionated bone marrow and success with F/Th BM in this canine renal allograft model suggests that application to human transplantation may be effective with fresh or F/Th BM fractions obtained from living-related or cadaveric donors.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The results of renal transplantation in patients with amyloidosis were studied in 45 patients receiving primary cadaver grafts at a single center between March 1973 and October 1981. A control group of 45 patients with glomerulonephritis receiving primary cadaver grafts during the same period was also studied. These were matched according to the number of A and B locus incompatibilities and the date of transplantation.The 3-year survival of the patients with amyloidosis was statistically significantly inferior (51%) to that of the controls (79%). Age over 40 years was the major factor determining low survival in these patients. Mortality was concentrated in the early posttransplantation period. The 3-year graft survival rate was the same in amyloidotics (38%) and controls (45%); with death of patients not included in graft loss, the corresponding figures were 53% and 49%.Appearance of amyloid in the transplant was established by biopsy in four patients at 11—37 months of follow-up. Renal transplants functioning for more than one year were calculated to incur a minimum risk of 20% of acquiring amyloid.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

We prospectively studied patients with enigmatic nausea and vomiting after allogeneic marrow transplantation to define the causes of this syndrome. Fifty consecutive episodes of persistent vomiting were investigated using physical examination and laboratory tests, endoscopic biopsies and brushings, and clinical follow-up for four weeks. Potential causes of vomiting were identified in 39 of the 50 cases (78%). Fifteen cases had gastrointestinal infections (mainly herpesviruses), 13 had unsuspected acute intestinal graft-versus-host disease (GVHD), 8 had intestinal infection plus acute GVHD, and 3 had other causes (subdural hematomas, bacteremia, and encephalitis). In the remaining 11 cases, no cause of vomiting was found. Endoscopy was necessary for diagnosis in 36 cases and required a combination of methods: routine histology, cytology, viral culture, and immunohistology using monoclonal antibodies to cytomegalovirus (CMV) and herpes simplex virus type 1. Patients with unexplained vomiting or intestinal GVHD had significant improvement of nausea and vomiting over the four-week observation period, but those with CMV did not (P= .01).We conclude that most allogeneic marrow transplant patients with enigmatic nausea and vomiting have gastrointestinal herpesvirus infections, acute GVHD, or both. Untreated CMV infections and persistent GVHD are associated with protracted vomiting in these patients.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

A group of 42 renal transplants performed in the presence of a T-cell-positive crossmatch were analyzed to determine the class and specificity of the donor-reactive cytotoxic antibodies. Dithiothreitol (DTT) was used to reduce IgM antibodies and a monoclonal antibody directed at a monomorphic determinant present on all HLA class I antigens (PA2.6) was used to inhibit cytotoxicity of anti-HLA class I antibodies. Sera from 26 of the positive crossmatches were considered to be autoreactive, and the positive crossmatch proved to be due to IgM and not directed at HLA class I in each case. One year graft survival was 100% in the 5 living-related and 60% in the 21 cadaver donor transplants, of which 10 were regrafts. Of the 42 positive crossmatches, 16 were not due to autoantibody. One was positive in the current serum taken at the time of transplantation, and this graft was rejected hyperacutely, while 15 were positive with peak but not current serum samples. Of the positive crossmatches, 12 were inhibited by PA2.6 demonstrating that they were directed at HLA class I antigens. PA2.6 inhibition could not be shown in 3 and in 1 DTT reduction was technically unsatisfactory. While 4 of the 7 positive crossmatches due to IgM antibodies were successful, the 7 transplants performed with positive crossmatches due to IgG antibodies all failed. DTT reduction and inhibition of cytotoxicity by PA2.6 helps to define positive crossmatches with donor T cells that are not associated with graft failure. Transplantation in the presence of a peak positive T cell crossmatch due to an anti-HLA antibody might only be successful if the antibody in the peak serum is of the IgM class.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

A case of small intestinal allotransplantation is described. Cyclosporine and Solumedrol were used for immunosuppression. A hemolytic episode occurred, caused by anti-A antibodies derived from graft lymphocytes. Sudden severe encephalopathy developed on the ninth postoperative day, followed by intractable hypotension and death. Hepatic and splenic microinfarcts were identified on postmortem examination. Allograft rejection was identified by serial stomal biopsies and correlated with a rise in monocyte procoagulant activity, a potentially useful serologic marker of rejection. The absence of an anatomic circuit for recycling of cyclosporine did not alter serum radioimmunoassay/high-performance liquid chromatography ratios.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Lymphokines produced as a result of allostimulation may play an important role in allograft rejection, mediating changes in cellular infiltration and migration, regional blood flow, and vascular permeability in a manner similar to that of delayed type hypersensitivity reactions. Changes in cellular recruitment (CR), regional blood flow (RBF), and vascular permeabilty (VP) were studied in paired healed subcutaneous urethane sponge grafts inoculated with secondary mixed leukocyte culture supernatant (2° MLC SN), a rich source of a variety of lymphokines secreted in response to allostimulation. Intravenous injection of Indium-111-labeled unsensitized lymphocytes (UL), Rubidium-86-chloride, and Iodine-125-labeled albumin were used to assess CR, RBF, and VP, respectively. An increase in CR (P<0.001), RBF (P<0.05), and VP (P<0.001) could be demonstrated at the site of injection of allogeneically restimulated 2° MLC SN compared with the syngeneically restimulated 2° MLC SN. The quantitative response and the kinetics of CR using 2°MLC SN were similar to previous studies in which specifically sensitized lymphocytes were injected with target cells bearing the sensitizing alloantigen, but the increase in RBF and VP were less. Injection of purified human interleukin 2, serotonin, histamine, and bradykinin had no significant effect on CR. Injection of purified human interleukin 1 resulted in a moderate increase in CR. These results are consistent with previous studies suggesting that the in vivo elaboration of lymphokines during allogeneic cellular interactions leads to an increase in CR, RBF, and VP. The small changes in RBF and VP in these experiments, however, do not account for the greater magnitude of the changes in CR. It is likely that other specific or nonspecific chemoattractants or inhibitors of cell migration also play a significant role in CR in vivo.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

To investigate the phenomenon of different erythrocyte saturation capacities for cyclosporine (CsA) in the blood of different individuals, hemolysates of washed red cells were examined for the presence of a CsA-binding protein. Using gel filtration column chromatog-raphy of hemolysates from patients receiving CsA orally, the majority of erythrocyte-associated CsA eluted as a single peak with Mr15,000–17,000, distinct from hemoglobin and carbonic anhydrase. [3H]CsA added to a hemolysate in vitro eluted similarly. [125I]CsA added to a hemolysate eluted much later in the same position as [3H]CsA mixed with albumin and myoglobin (presumably as free unbound drug). These findings indicate that CsA normally binds to an intraerythrocytic protein similar in molecular size to calf thymus cyclophilin (Mr15,000). By equilibrium dialysis, the purified erythro-cyte proteins calmodulin (Mr16,700) and cytochrome b5(Mr15,000) failed to bind CsA. By equilibrium dialysis, [3H] CsA did bind to column fractions containing the CsA-binding protein, but [125I]CsA did not, suggesting that attachment to CsA occurs at or near a carbon-carbon double bond in an unusual nine-carbon amino acid of CsA. These results have important implications for CsA therapy with regard to distribution space, phar-macokinetics, and a possible protein-receptor mechanism of action.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID