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)

Host versus graft (HVG) syndrome may be induced in parental strain mice by perinatal inoculations of F1 hybrid spleen cells. The principal manifestations of the disease include thrombocytopaenia, intravascular fibrin deposits, intestinal haemorrhage, hepatic infarcts, lymphosplenomegaly and renal disease. Immune complexes have been shown to be the cause of the renal lesions, and have been implicated as the triggers for disseminated intravascular coagulation. In the present studies of RFM mice perinatally inoculated with (T6 x RFM)F1 spleen cells (RFM/(T6 x RFM)F1 mice), quantitative determinations of serum immunoglobulins (Ig) revealed marked elevations of IgG1, IgG2, IgA and IgM. Electrophoretic analyses revealed the polyclonal pattern which typically follows chronic antigenic stimulation. However, IgG1 levels which reached 29 to 72 times control values suggested disruption of homeostatic mechanisms which control circulating Ig levels. Because antibody responses to histocompatibility antigens were present only occasionally, and then in low titre, it seemed unlikely these antigens were the principal causes of hypergammaglobulinaemia and plasmacytosis. Morphological studies indicated that the elevated levels of Ig seen in end-stage HVG syndrome correlated well with marked plasmacytosis, the third morphological finding in a sequence that included the precocious development of germinal centres and subsequent depletion of thymic-dependent (T) lymphocytes. The fact that spleen cells from RFM/(T6 x RFM)F1 mice were severely impaired in their capacity to cause graft versus host disease in related (T6 x RFM)F1 and unrelated C3H mice provided strong evidence that the HVG reaction resulted in T-cell depletion, rather than specific immunoincompetence.
 ...
PMID:Hyperimmunoglobulinaemia, T-cell deficiency and plasmacytosis in RFM mice with host versus graft disease induced by the perinatal inoculations (T6XRFM)F1 spleen cells. 108 3

An investigation has been undertaken of 479 deaths occurring up to the end of 1990 among 883 patients diagnosed with non-Hodgkin's lymphoma from 1974 to 1985 who were included in the population based National Registry of Childhood Tumours. The objectives were to perform a descriptive analysis looking particularly at the deaths not directly due to non-Hodgkin's lymphoma, to determine the frequency of the different causes of death and to study the trends over time. Among the 476 patients with sufficient information for the cause of death to be established, these were: non-Hodgkin's lymphoma, 377 (79%); treatment related (other than second primary tumour), 86 (18%); second primary tumour, 10 (2%); and other, three (1%). The proportion of all deaths not directly due to non-Hodgkin's lymphoma increased from 15% for those diagnosed during 1974-6 to 32% for those diagnosed during 1983-5. Among the 86 treatment related deaths, the more precise causes were bacterial infections, 26 (30%); viral and other infection, 14 (16%); metabolic, 19 (22%); renal, eight (9%); anaesthetic related, seven (8%); respiratory, four (5%); cardiac, three (3%); graft versus host disease, three (3%); and other, two (2%). Treatment related deaths from infection accounted for 27 (6%) of all patients diagnosed in 1974-9, and 13 (3%) in 1980-5. Treatment related deaths not due to infection occurred in 23 (5%) of those diagnosed in 1974-9 and 23 (6%) in 1980-5. Five treatment related deaths, including four anaesthetic related deaths, were identified as avoidable. Some of the deaths from metabolic and renal disease may also have been avoidable. Only 11 deaths have been recorded more than five years after diagnosis, six being due to second primary tumours. As follow up is relatively short for patients diagnosed more recently, further deaths from second malignancies and treatment related cardiovascular problems may well occur. A substantial number of children with non-Hodgkin's lymphoma die to treatment related causes. Deaths from infection have decreased in line with the overall improvement in survival rates. Other treatment related mortality has remained constant. Further improvements in survival for childhood non-Hodgkin's lymphoma will depend on maintaining the fine balance between the therapeutic value of intensive treatment and its potential harmful effects.
 ...
PMID:Causes of death in children diagnosed with non-Hodgkin's lymphoma between 1974 and 1985. 147 92

The induction of a chronic graft-versus-host (cGVH) disease in (Balb/c x A/J)F1 mice by the intravenous injection of either Balb/c or A/J parental lymphoid cells led to the development of two different models of disease. In this paper we compared the clinical aspects and the antigen specificities which recognized the autoantibodies developed by the animals of these two models of cGVH disease. Renal disease, alopecia, and purpura lesions were common in both models, although their frequency and intensity varied between groups. The models were differentiated by two main characteristics. When donor cells were of Balb/c origin, a joint disease similar to rheumatoid arthritis developed in 50% of the animals, and when donor cells were of A/J origin, 25% of the animals developed edema of the front feet, occasionally with loss of the nails, similar to that of scleroderma. Differences among the autoantibodies found in the sera of these two groups of mice were also observed. After the injection of Balb/c lymphoid cells, rheumatoid factors reactive with human and murine IgG were characteristically present (69 and 75%, respectively) and a statistically significant correlation was found between high titers of rheumatoid factor and arthritis (P less than 0.001). Antinuclear antibodies (ANAs) were present in all animals. Anti-dsDNA and anti-histones were positive in 50 and 25%, respectively. Anti-snRNP were detected at a low titer in 35% of the animals. When donor cells were of A/J origin, ANAs were also present in all mice. Anti-dsDNA, anti-histones, and anti-snRNPs antibodies were present in 90, 15, and 65%, respectively. The most outstanding characteristics among anti-snRNPs were the high titers of anti-U1 and anti-U3 detected in 50 and 30%, respectively. Rheumatoid factors reactive with human and murine IgG were positive in 15 and 42% of animals, respectively, but no significant correlation was found between these factors and disease. Our results indicate that the graft-versus-host disease induced in the same F1 strain of mice can be manifested in different forms of connective tissue disease, depending on whether the cells come from one or the other of the parental strains. Furthermore, in this paper the occurrence of rheumatoid factors in mice with cGVH is described for the first time.
 ...
PMID:Different strains of donor parental lymphoid cells induce different models of chronic graft-versus-host disease in murine (Balb/c x A/J)F1 hybrid hosts. 214 68

In spite of intensive endeavours, attempts to identify nephritogenic antigens in cases of immune complex glomerulonephritis have not yielded convincing results. Cationic antigens can have high affinity for the glomerular basement membrane and are prime candidates as nephritogens. They can be expected to play a role in post-infectious and in autoimmune glomerular disease. Histones show great promise in the latter case: we are able to demonstrate (1) a high affinity for the glomerular basement membrane and (2) their ability to promote glomerular deposition of anionic antigens as an additional target. Histones were detectable in glomerular deposits in two murine models of glomerulonephritis: the spontaneous lupus-like disease of NZB/W F1 mice and in graft-versus-host disease. We propose that histones may be responsible for the induction of glomerulonephritis in lupus-like syndromes, as well as other types of autoimmune renal disease. As an analogue, histone-like proteins from micro-organisms may also be responsible for glomerular disease in post-infectious nephritis.
 ...
PMID:The role of cationic proteins in the pathogenesis of immune complex glomerulonephritis. 215 42

Theophylline (Th) augments suppressor T cell activity (STCA). We attempted to test this immunoregulatory effect of TH on survival, renal disease and several immunologic parameters in NZB/W F-1 female mice. The median survival was 274 +/- 50 days for the mice receiving Th and 235 +/- 39 days for the controls (p less than 0.01). Assessment of the extent of renal damage by light microscopy revealed activity scores of 1.86 +/- 2 and 4.71 +/- 2.7 for the Th and control groups, respectively (p less than 0.001). T cell activity of NZB/W F-1 lymphocytes was assessed by the local xenogeneic GVH reaction. The mean GVH reaction volume of the Th group was significantly lower (9.3 +/- 8.8 mm3) as compared to controls (31 +/- 9 mm3) (p less than 0.001). The proportion of Lyt-1 versus Lyt-2 spleen lymphocytes did not change significantly. It is concluded that Th prolongs survival and decreases the extent of renal damage in female NZB/W F-1 mice.
 ...
PMID:Theophylline prolongs survival and decreases renal damage in female NZB/W F-1 mice. 297 91

Cyclosporin A (Sandimmun) has gained wide acceptance by most transplant physicians as the immunosuppressant of choice for preventing rejection of solid organ grafts and graft-versus-host disease. The drug has a specific effect on T-lymphocytes in which it seems to prevent the transcription of genes for several lymphokines. The reduction in IL-2 prevents the clonal expansion of T-lymphocytes and their differentiation into effector T-cells. The reduction in IFN-tau interrupts the feedback mechanism between T-cells and macrophages and the aberrant expression of MHC class II molecules. Through these mechanisms Sandimmun exerts an immunosuppressive and anti-inflammatory effect. Considerable evidence has accumulated to suggest that rheumatoid arthritis (RA) is an auto-immune disease. Activated T-lymphocytes interrelate with macrophages, other inflammatory cells and effector cells in joint tissue, leading to symptoms of inflammation accompanied by joint destruction. Immunosuppressive treatment is already well established in this disease and several trials have already taken place using Sandimmun. A total of 224 patients with RA refractory to conventional disease-modifying drugs have participated in 11 published clinical studies. A review of these studies concludes that Sandimmun is efficacious in controlling inflammatory and functional symptoms, although this improvement is no generally accompanied by reductions in ESR and rheumatoid factor. The frequency of adverse events is comparable to that of other treatments but nephropathy remains the principal factor limiting the use of Sandimmun. Recent evidence suggests that with a strict dosage strategy and good monitoring this problem is controllable and reversible. Further studies are under way to confirm these claims.
 ...
PMID:Sandimmun (cyclosporin A): mode of action and clinical results in rheumatoid arthritis. 307 82

Monoclonal antibodies have proved invaluable in identification and characterization of hemopoietic cell surface macromolecules. We have used a number of these monoclonal antibody probes for immunohistochemical analysis of interstitial cell populations in diseased human kidney tissues and in certain prototypic cutaneous cellular immune reactions. The studies demonstrate that the relative proportions of T-cell subpopulations present in graft rejection (OKT8+ exceeding OKT4+) differ from those observed in drug nephrotoxicity and end-stage kidney disease. In this regard rejection resembles graft versus host disease of skin but not delayed-type hypersensitivity. However, analysis of cell populations in interstitial infiltrates from various forms of chronic renal disease (glomerulonephritis, end-stage renal disease of varied etiologies) failed to demonstrate any unique or characteristic profile. These studies led to the recognition that certain monoclonal antibodies directed against B- and leukemic cell surface antigens also bind to normal renal cells and that nephron development in the human fetus is characterized by differential binding of these probes.
 ...
PMID:Analysis of renal cell populations using monoclonal antibodies. 640 Jan 52

The influence of cyclosporine A (CsA) treatment on the development of glomerulonephritis and glomerulosclerosis was investigated in chronic graft-versus-host disease (GvHD), a murine model for lupus nephritis. The renal disease is characterized by the formation of IgG-containing electron-dense deposits along the glomerular basement membrane (GBM) and in the mesangium, followed by the onset of proteinuria which starts, varying per individual mouse, about six weeks after the induction of the disease. Glomerular mRNA levels for matrix molecules were increased from week 4, preceding mesangial matrix expansion and GBM thickening which occurred from week 6. These initial events finally led to development of glomerulosclerosis, and end-stage renal failure. Groups of mice received three intraperitoneal (i.p.) injections per week with different doses of CsA, and treatment was started 2, 4, or 6 weeks after induction of the disease. Treatment with 10 or 50 mg CsA/kg/week did not influence the development of glomerulonephritis or glomerulosclerosis. Injection of 100 mg CsA/kg/week delayed the onset of proteinuria only when treatment was started in week 2. In week 6 some mice had already developed proteinuria whereas others had not. Treatment with 250 mg CsA/kg/week starting in week 6 abrogated glomerulonephritis and glomerulosclerosis only in those animals which were not yet proteinuric at that time. This, despite comparable increased autoantibody levels against DNA, GBM, and renal tubular epithelium (RTE) in both treated and untreated GvHD mice. Further increase in proteinuria and development of glomerulosclerosis could not be prevented if the mice already had developed proteinuria when CsA treatment was started. Dot blot analysis and in situ hybridization showed significantly decreased mRNA levels for alpha 1(I) and alpha 1(IV) collagen in kidneys of CsA-treated mice as compared to those of untreated mice 12 weeks after induction of the disease, if the highest dose of CsA was administered before the onset of proteinuria. No effect on these whole-kidney mRNA levels was observed in mice which had already developed proteinuria before CsA injections were started. Increased mRNA expression for matrix molecules in this group and in untreated GvHD mice was observed mainly in the interstitium. The kidneys of the treated GvHD mice and those of mice injected with 250 mg CsA/kg/week without induction of GvHD showed no morphological signs of CsA nephrotoxicity. We conclude that treatment with 250 mg CsA/kg/week prevents the development of glomerulonephritis and glomerulosclerosis in this model of lupus nephritis, if started before the onset of proteinuria.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Prevention of glomerulosclerosis by early cyclosporine treatment of experimental lupus nephritis. 770 25

Mice with chronic graft-versus-host disease (GVHD), induced by injection of DBA/2 lymphocytes in (C57BL10*DBA/2) F1 hybrids, develop a syndrome resembling systemic lupus erythematosus (SLE) with immune complex glomerulonephritis. In this model we evaluated the role of interactions between CD11a (LFA-1alpha) and CD54 (intercellular adhesion molecule-1 (ICAM-1)) molecules on leucocytes in the development of renal disease in systemic autoimmunity. Two weeks after induction of GVHD, when anti-nuclear autoantibodies were detected in the circulation and immune complexes had formed in the glomeruli, mice were injected twice per week with rat anti-CD11a and anti-CD54 MoAbs, or with their vehicle PBS, or with control rat IgG. MoAb treatment significantly lowered albuminuria and increased survival compared with control mice with GVHD. In the glomeruli of MoAb-treated mice there was markedly less binding of immunoglobulin and C3, while anti-renal tubular epithelium autoantibodies, but not anti-glomerular basement membrane autoantibodies, were significantly lowered in the circulation 4 weeks after disease induction. In addition, MoAb treatment inhibited the glomerular influx of CD11a+ cells and decreased development of histological abnormalities in the kidneys. Both rat IgG- and MoAb-treated mice developed anti-rat immunoglobulin antibodies. Furthermore, a marked splenomegaly with an increase of the T cell compartment was observed in MoAb-treated mice with GVHD. These results show that CD11a/CD54 interactions are crucial for the full-blown development of lupus nephritis in this model. Treatment aimed at blocking the activity of these molecules profoundly attenuated the development of renal disease in chronic GVHD even if started when first symptoms of SLE (i.e. anti-nuclear autoantibodies in sera and glomerular binding of immunoglobulins) were already detectable.
 ...
PMID:Effective treatment of experimental lupus nephritis by combined administration of anti-CD11a and anti-CD54 antibodies. 915 6

The purpose of this article is to review a set of recently obtained data concerning matrix and matrix adhesion molecules in renal disease. Our goal is not to cover the entire topic, but rather to focus on findings obtained with an experimental model for chronic lupus nephritis, evoked in mice by inducing graft-versus-host disease (GVHD). The overall aim of these studies was to investigate the role of adhesion molecules as targets for autoantibodies, in the recruitment of inflammatory cells, and in the accumulation of matrix in kidney disorders. In addition, we set out to discover how matrix proteins in renal diseases differ from normal matrix molecules both quantitatively, in their increased frequency, and qualitatively, in their intramolecular structure. The advances in understanding and methodology described in this review imply a substantial capability for greater insight into the pathogenesis of kidney disease; for making better use of renal biopsies, such as in applying competitive reverse-transcriptase-polymerase chain reaction (RT-PCR) in RNA analysis for matrix; and in developing more effective treatment strategies for patients with kidney disease.
 ...
PMID:Matrix and adhesion molecules in kidney pathology: recent observations. 935 73


1 2 3 4 5 6 7 Next >>