Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have found that murine lymphokine activated killer (LAK) cells have veto and natural suppressor activities in vitro, and prevent graft-versus-host disease (GVHD) in vivo. To determine whether human LAK cells mediate veto and natural suppression we measured their ability to inhibit generation of allospecific cytotoxic T cells (CTL) in mixed lymphocyte culture (MLC). When added to MLCs at low concentrations LAK cells caused veto-type inhibition: stimulator-type LAK cells inhibited generation of CTL but responder or third-party LAK cells did not. At higher concentrations LAK cells caused nonspecific inhibition: all three LAK cell types inhibited generation of CTL. LAK cell veto and natural suppressor activities were largely eliminated by irradiation with 30 Gy and by depletion of CD56+ cells, but increased after depletion of CD3+ cells. LAK cell veto activity is not likely an artifact of cold-target inhibition by the LAK cells themselves or by proliferation of T cells contaminating LAK cell preparations: (1) veto only occurred when LAK cells were added to MLC on days 0 through 2, but not when added on day 5; (2) addition of saturating numbers of labeled targets to fixed numbers of allo-CTL effectors failed to overcome the inhibitory effects of adding stimulator-type LAK cells at the onset of MLC; and (3) CD3-depleted LAK cells showed greater veto activity than threefold greater numbers of control LAK cells. In light of our previous findings in mice, the current results imply that adoptive immunotherapy with LAK cells may be useful in preventing GVHD in human bone marrow transplant recipients.
 ...
PMID:Human lymphokine activated killer (LAK) cells suppress generation of allospecific cytotoxic T cells: implications for use of LAK cells to prevent graft-versus-host disease in allogeneic bone marrow transplantation. 137 Feb 6

We have shown that acute (GVH) reactions produced in the parental-F1 hybrid combination, A/J----(C57BL/6 x A/J)F1 result in the activation of two cytotoxic cell populations: a host-derived Thy-1+/- natural killer (NK) cell with a lytic spectrum confined to YAC-1 targets, and a donor-derived Thy-1+ NK-like cell that has the ability to lyse target cells that are normally insensitive to lysis by NK cells. Cold-target inhibition (CTI) experiments have shown that the greater range of target cell killing seen in the NK-like population is mediated by a single effector cell with a broadened lytic repertoire. Percoll density fractionation studies have revealed that NK and NK-like cells co-fractionate, suggesting that both are large granular lymphocytes. We we have also shown that NK-like cells do not express either Lyt-2 or L3T4 markers. We have also observed that there is a close temporal relationship between elevated levels of interleukin-2 (IL-2) secretion by spleen cell cultures from mice with GVH disease and the subsequent emergence of splenic NK activity in both acute [A/J----(C57BL/6 x A/J)F1] and chronic (A/J----CBA x A/J)F1 GVH reactions. We have also noted that, despite high levels of IL-2 secretion, mice with chronic GVH reactions do not generate NK-like activity. Interferon (IFN) measurements have shown that, although increased IFN activity can be detected in both acute and chronic models, a preponderance of IFN-alpha/beta and some IFN-gamma is produced in the acute reaction, whereas only IFN-gamma can be detected in the chronic model. These results suggest that, although IL-2 may participate in augmenting conventional NK activity, IL-2 by itself does not generate NK-like activity. We suggest that IFN-alpha/beta may be the cytokine that, either alone or in concert with IL-2, triggers the NK-like cell response. The NK-like cell described in our study resembles a phenotypically identical, donor-derived large granular lymphocyte, identified by others, in close proximity to dead or dying epithelial cells in mice with GVH disease [14]. It has been suggested that these cells may mediate tissue injury. If in fact these graft-derived NK-like cells are involved in the pathogenesis of acute GVH disease, our present findings suggest that they must first be activated by an appropriate complement of cytokines that includes IFN-alpha/beta.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Natural killer (NK) cell activity in mice with acute graft-versus-host reactions: characterization of a Thy-1+ NK-like cell with a broadened spectrum of lytic activity in the spleen and lymph nodes. 170 18

T cell depletion of donor bone marrow prevents graft-versus-host disease (GvHD) but increases the risk of rejection. Rabbit bone marrow was T-cell-depleted using the properties of rabbit T cells to form spontaneous rosettes in the cold and by incubation in methylprednisolone (1 mg/ml, 10(6) cells/ml). New Zealand white rabbits were transplanted with Red Burgundy rabbit bone marrow from the opposite sex after conditioning with 12 Gy total body irradiation. Untreated animals die of GvHD at day 23. Three groups were studied: T cell depletion plus ciclosporin (A), T-cell-depleted bone marrow plus irradiated autologous bone marrow plus irradiated donor buffy coat (B), and T-cell-depleted bone marrow plus irradiated autologous bone marrow plus irradiated donor buffy coat plus ciclosporin (C). Buffy coat cells irradiated with 15 Gy were given for 5 days. Such cells do not form colonies in culture; however, they are able to release interleukin-2. In group A, 9 of 15 animals rejected, 6 survived for 45 days (median, range 16-249 days). In group B, all 5 of 5 animals died of rejection (median survival time 14 days, range 13-20 days). In group C, 8 of 10 animals did engraft, 4 died of GvHD (median survival 48 days, range 26-58 days), and 4 are long-term survivors (greater than 6 months to greater than 1 year), 3 as complete chimeras. We conclude that the combination of irradiated donor buffy coat cells, irradiated autologous bone marrow and ciclosporin restores engraftment of T-cell-depleted mismatched bone marrow without losing the benefit of reduced GvHD.
 ...
PMID:Engraftment of T-cell-depleted rabbit bone marrow. 311 31

Cold blood cardioplegia followed by terminal cardioplegia was employed as a method of myocardial protection for acquired valvular disease. Postoperative clinical results of both cardiac iso-enzyme and cardiac function were discussed from the effect of the myocardial protection. In operative procedures of 62 cases, 30 cases underwent mitral valve replacement and other mitral repair, 17 cases aortic valve replacement, 10 cases double valve replacement and 5 cases modified Bentall operation. Iso-enzymes of Creatine-Kinase (CK) and Lactate-Dehydrogenase (LDH) were measured by the constant time-interval. Cardiac function was estimated in acute postoperative phase and late phase. Hospital mortality was 1.5%. The cause of death was thought to be postoperative Graft Versus Host Disease with skin rash and pancytopenia. Cardiac function during acute phase well recovered in 62 cases of which two cases were controlled with intra-aortic balloon pumping. The values of CK-MB were measured during aortic cross-clamp, 30 min, 3 hours, 6 hours and 24 hours after cross-clamp release. Peak CK-MB value was detected 3 hours or 6 hours in almost cases. In contrast, peak LDH-1 value was detected 24 hours after cross-clamp release. Perioperative myocardial infarction was occurred in one case with modified Bentall operation whose CK-MB value was elevated over 150 IU/L at 3rd hour and 24th hour. However, the cardiac radio-isotope data of this case revealed good cardiac function with left ventricular ejection fraction (LVEF) 76% by cardiac pool imaging in spite of small postero-lateral perfusion defect by Thallium 201 scintigram.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Operative results of acquired valvular disease with blood cardioplegia followed by terminal cardioplegia]. 318 95

Patients who have lost such a large portion of their small bowel that they permanently require total parenteral nutrition for survival would greatly benefit by receiving a small-intestinal transplant. Over the past two decades, many experimental studies have delineated the specific problems surrounding small-bowel transplantation and provided strategies for their control. Control of rejection, the most difficult problem, may be achieved with a combination of cyclosporine, azathioprine, prednisone, antithymocyte globulin, and monoclonal antibodies. The threat of graft-versus-host disease originating from the allogeneic lymphatic tissues in the allograft is abolished by in vitro x-irradiation of the cold, nonperfused graft with 1000 rads. Monitoring of the intestinal allograft is possible with the combination of a function test (maltose absorption, glucose absorption, or any other function test) and repeated graft biopsy. Effective short-term preservation of small-bowel segments for up to 18 h is possible by intravascular flushing with a balanced electrolyte solution containing 3% fructose and by subsequent hypothermic storage. Clinical small-bowel transplantation is certainly not an imminent therapeutic tool. However, clinical trials in highly selected patients could be envisioned on the basis of our present understanding of small-bowel transplantation and of transplantation biology in general, and in view of the clinical successes achieved with duodenal grafts transplanted in conjunction with pancreatic grafts.
 ...
PMID:Current status of small-bowel transplantation. 327 69

The 402AX teratocarcinoma is a 129/J-derived mouse major histocompatibility complex (MHC) antigen negative tumor that is induced to express H-2b class I antigens during rejection. Resistance to 402AX by MHC allogeneic and syngeneic mice is immunologically mediated and involves the recognition of tumor-associated antigens (TAA) in the context of induced MHC class I antigens. The current studies were undertaken to define the 402AX TAAs. Reconstitution of irradiated susceptible hosts (129/J) with 402AX-primed resistant spleen cells (C57BL/6) results in acute graft-versus-host disease, suggesting that tumor-primed C57BL/6 splenocytes are reactive to tumor genotype (129/J) minor histocompatibility (Hm) antigens. C57BL/6 anti-129/J effector cells, although not directly cytotoxic for 402AX cells, are specifically cold target inhibited by 402AX cells. Genetically susceptible hosts (C3H.SW) immunized to 129/J Hm antigens by skin grafting become resistant to an i.p. challenge of 402AX cells. These results suggest that 129/J Hm antigens may be the TAAs recognized during genetically controlled rejection of the 402AX teratocarcinoma.
 ...
PMID:Resistance to 402AX teratocarcinoma involves immunity to minor histocompatibility antigens. 330 46

Sixty-seven pairs of HLA matched siblings, each comprising marrow donor and recipient in the Seattle marrow transplant program, were analyzed to establish phenotype for a newly described minor H antigen, W1. The test for phenotype entailed cold target inhibition of cytotoxicity, directed at this antigen and mediated by specifically stimulated T cell lines. There were 58 compatible and six W1 incompatible pairs. The low frequency of W1 mismatch is due to the strong preponderance of W1-positive individuals in the general population. Severe graft-versus-host disease (GVHD), both acute and chronic, was observed among the 58 recipients of marrow from W1 matched donors. These results do not reveal any particular importance for W1 incompatibility in human GVHD and indeed indicate that other systems are involved. Even if some cases are triggered by incompatibility at W1, the maximum frequency with which this could occur would be about 10%, due to the limited polymorphism of this alloantigenic system.
 ...
PMID:Study of a human minor alloantigen in relation to clinical graft-versus-host disease. 333 47

In small-bowel transplantation, the transfer of large numbers of donor lymphocytes with the intestinal allograft may provoke a lethal graft-versus-host reaction. The effectiveness of allograft irradiation in vitro as a method of preventing graft-versus-host disease (GVHD) was studied in a rat model of small-bowel transplantation, with the Lewis----Lewis X Brown Norway F1 hybrid strain combination. Cold harvested small-bowel allografts were irradiated immediately prior to heterotopic or orthotopic transplantation. Animals that had received heterotopic allografts irradiated with 0, 250, or 500 rad all died of GVHD after 14.4 +/- 3.0, 15.0 +/- 1.3, and 14.2 +/- 1.9 days, respectively. None of the animals that had received allografts treated with 1000 rad developed clinical or pathologic evidence of GVHD, however, and all survived for more than 6 months (P less than 0.001). Allograft function was studied in animals that underwent orthotopic transplantation. Recipients of nonirradiated orthotopic allografts all died of GVHD after 14.0 +/- 0.7 days, whereas recipients of allografts irradiated with 1000 rad all survived for more than 5 months (P less than 0.001). After 120 days, weight gain (51.8 +/- 11.7%), serum albumin (3.9 +/- 0.7 g/dl), serum triglycerides (67.0 +/- 24.3 mg/dl), CBC, and differential in these animals were not statistically different from those in either age-matched isograft recipients or normal animals, and when the rats were sacrificed, irradiated allografts showed no changes suggestive of radiation injury. These results indicate that irradiation of small-bowel allografts in vitro prevents development of GVHD, and that this can be achieved at a dose which does not cause injury to or malfunction of the allograft.
 ...
PMID:In vitro allograft irradiation prevents graft-versus-host disease in small-bowel transplantation. 387 77

Antibodies to Merkel cells (MC) are not known to occur in human sera. Using a newly described technic, we looked for the presence of antibodies directed against skin structures in sera from 2,300 patients with various dermatologic and hematologic disorders, as well as graft-versus-host disease (GVHD). Three of these sera (0.1%) were found to react with MC. One monoclonal IgM antibody was present in serum obtained from a patient with chronic cold agglutinin disease, the second from a patient with GVHD, and the third from a patient with pemphigus vulgaris. The present inadequate knowledge about normal MC function and the absence of described symptoms of MC dysfunction preclude analysis of the pathogenic significance of these MC antibodies in human sera.
 ...
PMID:Antibodies to Merkel cells in human sera. Incidence and significance. 620 22

Hematopoietic reconstitution by bone marrow transplantation (BMT) is used as therapy for the treatment of various malignancies and genetic blood disorders. Allogeneic BMT is the most common application of this treatment but is frequently associated with graft-versus-host disease (GVHD). Recent clinical studies have shown that sibling transplant using umbilical cord blood (UCB) is an acceptable alternative to BMT and may involve fewer problems with GVHD. We have investigated the in vitro alloreactive capacity of UCB as it relates to allogeneic transplantation. Initial screening assays demonstrated that UCB T cells were functionally immature. It was not possible to generate significant levels of alloantigen-specific cytotoxic T lymphocytes (CTL) in either primary or secondary mixed lymphocyte cultures. Limiting dilution analyses revealed that cord blood T cells were 10-1000 x less alloreactive in terms of proliferative T cells (PTLp) and cytotoxic T cells (CTLp) compared with adult peripheral blood lymphocytes (PBL). However, UCB was equivalent to adult PBL in terms of natural killer (NK) and lymphokine-activated killer (LAK) cell precursors. Analysis of cells from alloantigen-stimulated MLC revealed that UCB generated primarily CD4+ and CD16+ cells that made little or no IL-4, IL-6, TNF-alpha or IFN-gamma on antigenic stimulation. Cold target inhibition analyses revealed that alloantigen-stimulated cord blood T cells had a fine specificity similar to NK cells. From these in vitro results cord blood would seem to be unlikely to mediate severe GVHD reactions in vivo and should be suitable for allogeneic transplantation.
 ...
PMID:Analysis of the alloreactive capacity of human umbilical cord blood: implications for graft-versus-host disease. 785 29


1 2 3 Next >>