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

Antithymocyte globulin (ATG) is used commonly in patients with severe aplastic anemia and those undergoing renal transplant. Its utility also is being explored in the treatment of myelodysplastic syndrome, conditioning regimens for hematopoietic stem cell transplant, and prophylaxis of graft-versus-host disease. As indications for ATG expand, knowledge regarding its administration and management of associated toxicities is needed. These toxicities range from life-threatening anaphylaxis associated with the infusion to flu-like symptoms that occur one to two weeks after the infusion. Adverse effects are classified according to the severity and system impacted. Mild toxicities respond to comfort measures and include fever, chills, urticarial rash, and vomiting. Moderate toxicities require acute interventions and include fluid-responsive hypotension, nonischemic chest pain, and reversible oxygen desaturation. Severe toxicities require intensive support and include those refractory to earlier intervention. Management of these toxicities usually is limited to fluid resuscitation and noninvasive monitoring. Occurrence of infusion-related toxicities may require premature discontinuation of therapy. Therefore, an educated healthcare team and interdisciplinary clinical management guidelines are important to ensure the safe administration and complete course of ATG.
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PMID:Management of patients receiving antithymocyte globulin for aplastic anemia and myelodysplastic syndrome. 1563 53

Transfusion-associated graft-versus-host disease (TA-GVHD) is a fatal complication of blood transfusion resulting from the contamination of blood products by leukocytes. In order to prevent this disease, gamma or X-ray irradiation of blood components,which can inactivate leukocytes, is currently used. However, the minimal doses needed to destroy lymphocytes promote the leakage of potassium from red blood cells (RBCs), which can induce other side effects, such as hyperpotassemia and cardiac arrest. The reactive oxygen species (ROS) generated by the irradiation of aqueous solutions may accelerate the leakage through oxidation of the RBC membrane. Here we studied the effect of dipyridamole, Trolox, human plasma or mannitol on the leakage of potassium from RBCs following irradiation. RBC preparations (hematocrit; 30%) containing antioxidants were irradiated at 30 Gy and stored at 4 degrees C for 7 d. The leakage of potassium from the RBCs caused by the irradiation was significantly suppressed by dipyridamole (more than 50 microM), Trolox (more than 5 mM) or human plasma (50%). Mannitol (80 mM) is used to inhibit hemolysis as a constituent of MAP solution, which is a solution used for the storage of RBC products in Japan. Here it was clarified that the leakage of potassium from not only irradiated but also non-irradiated RBCs was unexpectedly promoted by mannitol. The amount of mannitol in MAP solution may have to be reconsidered. The osmotic pressure of the RBC preparation increased in a manner dependent on the concentration of mannitol. The elevated osmotic pressure may promote the leakage. In conclusion, although antioxidants have the potential to suppress the leakage of potassium ascribed to the irradiation, the extent of the suppression (10-20%) by dipyridamole (DPM), Trolox or human plasma seems insufficient for the clinical use of these agents as an additive for MAP solution.
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PMID:Leakage of potassium from red blood cells following gamma ray irradiation in the presence of dipyridamole, trolox, human plasma or mannitol. 1599 24

Lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) generation and the concomitant decline in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) were demonstrated in human monocyte-derived dendritic cells (DC). Further, their relation to the maturation of DC, characterized by the production of cytokines, up-regulation of cell surface molecules and allo-stimulatory capacity, was examined. The LPS-induced ROS generation was demonstrated using electron paramagnetic resonance spectroscopy in intact cells, and was also confirmed using laser scanning confocal microscopy. The GSH/GSSG was assesed using a glutathione assay kit. When the DC were treated with alpha-phenyl-tert-butylnitrone, the ROS generation was attenuated, but the declined GSH/GSSG was not attenuated, and only cytokine production was suppressed among the above-mentioned maturation characteristics. When the DC were treated with glutathione monoethyl ester, both the ROS generation and the declined GSH/GSSG were attenuated, and the maturation characteristics were all suppressed. These findings suggest that the LPS-induced ROS generation and the concomitant decline in GSH/GSSG occur in human monocyte-derived DC and that the former is involved in cytokine production, while the latter is involved in the up-regulation of cell surface molecules and allo-stimulatory capacity. Since the cytokine production and the allo-stimulatory capacity of DC play an important role in inflammatory and immune responses, differential regulation of the ROS generation and the declined GSH/GSSG may be useful as therapeutic tools in diseases where both responses become entangled, such as sepsis and graft-versus-host disease.
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PMID:LPS-induced ROS generation and changes in glutathione level and their relation to the maturation of human monocyte-derived dendritic cells. 1628 Jan 35

Pulmonary function (PF) was studied in 69 consecutive patients with hematologic diseases, with a minimum 5-year (range, 5-13 years) follow-up after allogeneic stem cell transplantation from an HLA-matched sibling. Fifty-six patients (81%) received total body irradiation based myeloablative stem cell transplantation (MT) and 13 (19%) underwent nonmyeloablative stem cell transplantation (NST). Thirty-one patients (45%) developed a late decrease in PF from baseline, 25 with a restrictive and 6 with an obstructive pattern PF abnormality. Twelve patients (17%) were symptomatic, 8 with a severe restrictive PF defect, but none required supplemental oxygen. The incidence of developing a late PF abnormality was comparable in MT (24 of 56) and NST (5 of 13; P = .51). In multivariate analysis, chronic graft-versus-host disease (relative risk, 16) and pretransplantation diffusion capacity for carbon monoxide or forced expiratory volume in the first second <80% predicted were independently associated with a late decrease in PF from baseline (relative risk, 7). Our results indicate that late PF abnormality is common after MT and NST. Patients with a low pretransplantation diffusion capacity for carbon monoxide of or forced expiratory volume in the first second who developed chronic graft-versus-host disease were most severely affected. Longer follow-up is needed to determine whether PF will continue to decrease or reach a plateau and whether more patients with PF abnormality will eventually become symptomatic.
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PMID:Chronic GVHD and pretransplantation abnormalities in pulmonary function are the main determinants predicting worsening pulmonary function in long-term survivors after stem cell transplantation. 1716 7

Extensive chronic graft-versus-host disease (ecGVHD) is characterized by fibrosis similar to that of patients with systemic sclerosis (scleroderma). Since stimulatory autoantibodies against the platelet-derived growth factor (PDGF) receptor (PDGFR) have been found in patients with scleroderma and are responsible for the activation of skin fibroblasts, we tested the hypothesis that these autoantibodies are also present in patients affected by ecGVHD. Serum from 39 patients subjected to allogeneic stem cell transplantation for hematologic malignancies (22 with ecGVHD and 17 without cGVHD) and 20 healthy controls was assayed for the presence of stimulatory autoantibodies to the PDGFR by incubating purified IgG with mouse-embryo fibroblasts lacking PDGFR alpha or beta chains or with the same cells expressing PDGFR alpha. Stimulatory antibodies to the PDGFR were found selectively in all patients with ecGVHD but in none of the patients without cGVHD. Higher levels were detected in patients with generalized skin involvement and/or lung fibrosis. Antibodies recognized native PDGFR, induced tyrosine phosphorylation, accumulation of reactive oxygen species (ROS), and stimulated type 1 collagen gene expression through the Ha-Ras-ERK1/2-ROS signaling pathway. The biologic activity of these autoantibodies suggests a role in the development of fibrosis and argues for a common pathogenetic trait in ecGVDH and scleroderma phenotypes.
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PMID:Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. 1736 28

The side-chain effects of metalated and protonated dipeptides, including GGH(+)M(+), GAH(+)M(+), AGH(+)M(+), AAH(+)M(+), GWH(+)M(+), GSH(+)M(+), GTH(+)M(+), GFH(+)M(+), GYH(+)M(+), and GVH(+)M(+) (G = glycine, A = alanine, W = tryptophan, S = serine, T = threonine, F = phenylalanine, and V = valine; M = Li, Na, and K), are theoretically explored in this paper on their positive binding energies (PBEs), which are derived from interactions of M+ with the carboxyl oxygen(s). The B3LYP/6-311++G(**)// B3LYP/6-31G(*) calculations suggest that the PBEs of dipeptides with side chain(s) are much smaller than those with no side chain (GGH(+)M(+)). Generally, larger side chains and smaller M(+) radii would lead to fewer PBEs for the M(+) involved systems. On the basis of the direct dependence of PBE on the electrostatic repulsion between two kinds of cations (H(+) and M(+)) in these dipeptide models, it could be reasonably expected that the side-chain effect on the electrostatic repulsion and consequently on the PBEs could offer one good insight, on a chemical-physical basis, into the origin of regular ordering of the amino acids when they form a filter in the K(+) channel protein (MacKinnon, et al. Science 1998, 280, 106).
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PMID:Dependence of positive binding energies on side chains--a theoretical prediction on the origin of regular ordering for the amino acid residues in the selectivity filter. 1802 Apr 37

The objective of this study was to investigate the function and mechanism of hyperbaric oxygen (HBO) in antagonizing acute graft-versus-host disease (aGVHD) and improving the rate of survival. The lethally irradiated C57BL/6 recipients were injected with bone marrow and lymphocyte of spleen from BALB/c donors and were treated with HBO, cyclosporine A (CsA) and methotrexate (MTX). T lymphocytes and subsets, adhesion molecules and cytokines were detected by flow cytometry, ELISA and RT-PCR respectively. The results showed that the survival rate in HBO group was much higher than that in allogenetic bone marrow transplantation (allo-BMT) group and CsA + MTX group; the numbers of CD3(+), CD4(+), CD8(+), CD4(+)CD11a(+), CD4(+)CD18(+), CD8(+)CD11a(+), CD8(+)CD18(+) lymphocytes in spleen were decreased markedly by HBO and CsA + MTX (p < 0.05); the levels of IL-2 and TNFalpha mRNA and their serum concentrations in HBO group were much lower than those in allo-BMT group but were higher than those in CsA + MTX group; the levels of IL-4 and IL-10 mRNA in HBO group were much higher than those in allo-BMT group and CsA + MTX group. It is concluded that HBO has more remarkable advantage in improving the rate of survival than CsA + MTX, its mechanism of anti-aGVHD is tightly correlated with the transform of T cell and its subsets and the expression of adhesion molecules and cytokines.
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PMID:Effect of hyperbaric oxygen on acute graft-versus-host disease after allogeneic bone marrow transplantation. 1854 42

We reported 5 patients who developed air-leak syndrome (ALS) including pneumothorax, pneumomediastinum and subcutaneous emphysema after allogeneic stem cell transplantation (SCT). The underlying diseases were AML (n=2), ALL (n=1), MDS (n=1), and CML (n=1). All patients received allogeneic SCT from related donors including 2 donors with HLA mismatch. Total body irradiation was performed as a conditioning regimen in all patients. Late-onset noninfectious pulmonary complications (LONIPC) were detected in all patients before the development of ALS. The interval from diagnosis of LONIPC to onset of ALS was 10-360 days (median, 20 days). Four of 5 patients were treated with corticosteroid for chronic graft-versus-host disease and/or LONIPC. To date, three patients have died of respiratory failure. The others are currently alive and one of these surviving patients is receiving home oxygen treatment. Physicians should be aware of this rare complication following LONIPC, because treatment of ALS is difficult in some patients.
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PMID:[Air-leak syndrome in patients with non-infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation]. 1922 28

Late-onset noninfectious pulmonary complications (LONIPCs) are life threatening for allogeneic hematopoietic SCT (allo-HSCT) recipients. However, the impact of LONIPCs on survival has not been properly evaluated and little is known about treatment efficacy. We retrospectively investigated 290 allo-HSCT recipients in our institute and reviewed the clinical aspects of 44 patients who had been diagnosed with LONIPCs. LONIPCs were significantly associated with higher rates of chronic GVHD (P<0001) and nonrelapse mortality (P=0.013), and lower rates of relapse (P=0.009). As a result of these effects, OS was significantly worse in those with LONIPCs (P=0.003). This result differs from a previous report. We then assessed short-term treatment response and final outcome. These results were defined by radiological findings, subjective symptoms, oxygen requirement and survival. Use of inhaled and systemic steroids did not affect either short-term response or final outcomes. However, administration of systemic corticosteroids earlier than at 21 days (median interval of time from onset of symptoms to systemic corticosteroids administration) was associated with a better outcome (P=0.054 for short-term response, and 0.016 for final outcome). Our study indicates that LONIPCs reduce OS, and early intervention with systemic corticosteroids may be effective.
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PMID:Outcome and treatment of late-onset noninfectious pulmonary complications after allogeneic haematopoietic SCT. 2020 71

Plumbagin inhibited activation, proliferation, cytokine production, and graft-versus-host disease in lymphocytes and inhibited growth of tumor cells by suppressing nuclear factor-kappaB (NF-kappaB). Plumbagin was also shown to induce reactive oxygen species (ROS) generation in tumor cells via an unknown mechanism. Present report describes a novel role of cellular redox in modulation of immune responses in normal lymphocytes by plumbagin. Plumbagin depleted glutathione (GSH) levels that led to increase in ROS generation. The decrease in GSH levels was due to direct reaction of plumbagin with GSH as evinced by mass spectrometric and HPLC analysis. Further, addition of plumbagin to cells resulted in decrease in free thiol groups on proteins and increase in glutathionylation of proteins. The suppression of mitogen-induced T-cell proliferation and cytokine (IL-2/IL-4/IL-6/IFN-gamma) production by plumbagin was abrogated by thiol antioxidants but not by non-thiol antioxidants confirming that thiols but not ROS play an important role in biological activity of plumbagin. Plumbagin also abrogated mitogen-induced phosphorylation of ERK, IKK, and degradation of IkappaB-alpha. However, it did not affect phosphorylation of P38, JNK, and AKT. Our results for the first time show that antiproliferative effects of plumbagin are mediated by modulation of cellular redox. These results provide a rationale for application of thiol-depleting agents as anti-inflammatory drugs.
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PMID:Plumbagin inhibits proliferative and inflammatory responses of T cells independent of ROS generation but by modulating intracellular thiols. 2056 4


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