摘要:

SUMMARYElectrolytic lesions were produced in the tuberal hypothalamus and amygdala of male Fischer and female BNLF1rats, and in male Fischer and female BNLF1rats that had received antecedent hypophysectomies. Skin grafts from Lewis rats survived less well on tuberal-lesioned male Fischer rats than similar grafts on sham-operated and amygdala-lesioned male Fischer rats. Lewis skin graft survival was also curtailed in male Fischer rats that had received hypophysectomies followed by tuberal lesions. These differences were not apparent across the male to female (H-Y) BNLF1histocompatibility barrier.We conclude: (1) that tuberal hypothalamic lesions stimulate allograft reactivity in rats, (2) that this response is greater when the immunogenetic disparity between donor and host is greater, and (3) that the mechanism governing this response involves a direct neural pathway which bypasses the hypothalamic-hypophyseal axis.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SUMMARYPatients with hematological malignancies undergoing allogeneic marrow transplantation from HLA-identical siblings were entered into a randomized study to determine whether the prophylactic administration of horse anti-human thymocyte globulin (ATG) would decrease the incidence or severity of graft-versus-host disease (GVHD). Patients were conditioned with high-dose cyclophosphamide and total body irradiation before grafting and received methotrexate after grafting. When marrow engraftment was documented (median 16.5 days after transplantation), patients were randomized either to receive or not to receive horse ATG, 7 mg/kg, i.v., every other day for six doses. Twenty-nine patients received ATG and 27 patients did not. Both groups were comparable with respect to diagnoses, disease status, age, sex, donor-recipient sex match, and supportive care. Administration of ATG was associated with fever and chills in most patients, but was otherwise well tolerated. Patients receiving ATG had no delay in recovery of peripheral granulocyte or platelet counts, did not require increased platelet support, and did not have more infectious complications. No significant difference in either incidence or severity of GVHD was noted between patients receiving and those not receiving prophylactic ATG, although GVHD, if it developed, tended to be less severe among patients receiving ATG. Survival and causes of death were also comparable between groups. Thus, administration of horse ATG after documentation of marrow engraftment in recipients of HLA-identical allogeneic marrow grafts had neither significant toxicity nor beneficial effect.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SUMMARYThe influence of grafting more than one skin transplant simultaneously on one recipient was investigated. When a mixed lymphocyte culture (MLC)-negative skin was transplanted along with an MLC-positive skin, the MLC-negative skin survived for a significantly shorter time than when transplanted alone. This indicated that the MLC-positive skin provided a stimulus that could provide help to reject the MLC-negative skin. This finding might be important clinically. When an MLC-negative transplant is given to a patient, one should not transfuse this patient with MLC-positive leukocyte-rich blood.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SUMMARYTissue levels of adonosine triphosphate (ATP) have been measured in rat kidneys following periods of warm ischaemia: (1) immediately after the ischaemic period and (2) after the kidney had been reperfused with blood for 10 min. ATP levels at the end of the period of ischaemia are similar for ischaemic periods of 10 to 60 min and give no indication of the kidneys subsequent functional ability. The amount of ATP regenerated in 10 min of reperfusion correlates both with the duration of the period of ischaemia and with the subsequent functional ability of the kidney.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SUMMARYThe cause of agonal renal spasm in cadaver kidney donors is not well understood but may be related to renal ischaemia, systemic hypotension, or hypercarbia. In these experiments renal vascular resistance was measured in rats using renal venous cannulation and a pressure transducer to record renal blood flow and arterial blood pressure, respectively. It was found that renal ischaemia produced by clamping the renal pedicle for 1 hr was a weak inducer of renal vascular spasm. On the other hand, 1 hr of hypotension (BP, 50 mm Hg) caused a 46% reduction in renal blood flow when measured after the blood pressure had been restored to 100 mm Hg. Prior administration of phenoxybenzamine helped to diminish the vascular spasm, although renal blood flow remained reduced by 24%. Prehydrating the rats with normal saline successfully abolished the spasm and infusion of dopamine (6 μg/kg/min) in saline actually increased the rate of renal blood flow.Hypercarbia produced by inhaling 10 to 20% CO2caused considerable renal vasospasm in the rats, and blood flow was reduced by 57%. Preadministration of phenoxybenzamine made these rats haemodynamically unstable and resulted in a fall in systemic blood pressure which was unresponsive to blood transfusions. Saline infusion on the other hand helped to prevent the spasm from occurring both during and after the period of hypercarbia.It would appear, therefore, that in rats hypercarbia and hypotension are far more deleterious to renal blood flow than is renal ischaemia alone. Infusions of saline and dopamine were more effective than phenoxybenzamine in preventing vascular spasm under these conditions.Renal vasoconstriction in cadaver kidneys is quite common and may explain why some kidneys with a relatively short ischaemia time function poorly after transplantation. Renal vasospasm with reduction in renal blood flow (RBF) has been shown to occur during the agonal phase in a cadaver kidney donor, although the precise cause has not been determined. After a ventilator “switch off,” the donors' kidneys are exposed to ischaemia, hypotension, and hypercarbia, so we have chosen to study these effects in anaesthetised rats to see what influence they may have individually on RBF. The effect of pretreatment with phenoxybenzamine, dopamine, and saline infusions on RBF was also studied.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SUMMARYPrevention of canine graft-versus-host disease (GVHD) was attempted with in vitro treatment of the marrow graft with absorbed rabbit anti-dog thymocyte globulin (aATG). Cross-reactive antibodies against hemopoietic stem cells were eliminated following absorption with liver and kidney homogenate and spleen cells of newborn dogs. The growth of granulocytic colonies was almost completely inhibited by prior incubation of marrow with crude antithymocyte globulin (ATG) in the presence of complement, but not by incubation with aATG. In vitro treatment of marrow with aATG did not interfere with its ability to reconstitute a lethally irradiated autologous host. Allogeneic transplantations were performed in lethally irradiated DLA heterozygous recipients with marrow of compatible, DLA homozygous littermates.Transplantation of untreated marrow resulted in death from GVHD of five of five recipients. In vitro treatment of marrow with aATG at a concentration of 1:100 (v/v) prevented GVHD and induced stable graft-versus-host tolerance in one dog, delayed GVHD in two dogs, and interfered with hemopoietic engraftment in two dogs. Treatment with aATG at a concentration of 1:200 induced tolerance in three dogs and prolonged survival in two. The four surviving chimeras are alive 240 to 380 days after transplantation without ever having shown symptoms of GVHD. The potential value of in vitro treatment of marrow with aATG in clinical bone marrow transplantation is discussed.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SUMMARYThe antibody-dependent cell-mediated cytotoxicity (ADCC) effector activity and phytohemagglutinin (PHA) response of kidney transplant patients were monitored by a new whole blood microassay that permitted performance of 20 tests using only 1 ml of blood. Eleven patients were followed on as many as 55 different occasions with these tests. The ADCC activity of dialysis patients was essentially the same (78% chromium release as compared with 83% in normal controls). However, patients with kidney transplants undergoing immunosuppression had approximately one-half the chromium release (40%). Daily fluctuation in the chromium release could not be used as a predictor of subsequent rejection. The PHA response was as much as 50-fold less in the immunosuppressed patients. Both values also tended to be slightly higher among patients who were doing well than those who were doing poorly. This may reflect the need for greater immunosuppression in the rejecting patients.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SUMMARYThe results of skin grafts transplanted in immunized and nonimmunized recipients was analysed. Specific sensitization for HLA-A or B determinants shortens graft survival if the recipients were immunized by s.c. injections of leukocytes. When the recipients had been pregnant, no such influence of specific HLA-A or B sensitization could be demonstrated. The variance in mean survival times of grafts exchanged between mixed lymphocyte culture (MLC)-positive donor-recipient combinations was significantly smaller than the variance in mean survival time (MST) of grafts exchanged between MLC-negative combinations. This difference could be the result of the influence of allograft immune-activating determinants of different strength in the MLC-negative donor-recipient combinations. Also the variance in MST of grafts in immunized recipients was significantly larger than the variance in MST of grafts in nonimmunized recipients. Apart from the obvious effect of HLA-A and B sensitization, other less well documented factors must have influenced graft survival. We did not find evidence for a graft enhancing effect of B cell-specific antibodies.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SUMMARYAdapting the Roberts and Hayry sponge allograft model, we have demonstrated the presence of an enriched, specifically cytotoxic population of cells which infiltrate rejecting sponge allografts. The number of cells infiltrating a rejecting sponge allograft peaks on day 14 after transplantation. Utilizing a short-term51chromium cytotoxicity assay, peak antiallogeneic killing was demonstrable on day 14 also. Only T cell killing was apparent for the first 15 days after transplantation. After day 20, specific cytolysis was present which was not sensitive to anti-&thetas; serum and complement. The infiltrating cytotoxic cells are large, specifically cytotoxic, do not proliferate in culture, do not respond to mitogen, and do not respond in mixed lymphocyte culture even to the same alloantigen to which the animal had been sensitized. In contrast, spleens from sponge-bearing animals kill poorly, respond to mitogen, and respond vigorously in mixed lymphocyte culture to specific and nonspecific alloantigens.The following hypotheses are set forth with regard to the cytotoxic lymphocytes. (1) Such cells may be end stage and cannot proliferate. (2) The cytotoxic cells may kill the stimulator cells more rapidly than they can be stimulated to proliferate. (3) The sponge cell population may be enriched for nonspecific supressor cells. (4) The sponge cells may be devoid of helper T cells.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SUMMARYThe minimum length of time required for lymph node lymphocytes to recognize alloantigens in vitro was examined in mixed skin cell-lymphocyte culture reactions. Responding lymphocytes in the mixture were successfully separated from stimulating skin cells by Ficoll-Hypaque gradient sedimentation. Lymphocyte activation by allogeneic skin cells took place within 15 min of contact. The amount of measured stimulation was approximately 30% of that produced by an equal concentration of antigen present continuously in culture. The presence of alloantigen was no longer needed after 24 hr. Several control experiments were made in order to exclude the effects of contamination and culture conditions. Identical results were obtained with allogeneic hepatocytes. These data indicate that the recognition of alloantigen leading to lymphocyte proliferation may occur during the early period of contact.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID