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)

Cardiac pathologic findings were analyzed in 22 necropsy cases from a series of 29 patients with leukemia, aplastic anemia, or metastatic cancer who had been treated with ablative therapy followed by bone marrow transplantation. Some cardiac alterations were similar to those that occur in patients with hematologic and neoplastic diseases not treated with bone marrow transplantation, and consisted of cardiomegaly, cardiac atrophy, hemorrhage, foci of necrosis due to shock associated with sepsis or hepatic failure, myocardial abscesses secondary to systemic candidiasis or staphylococcal infection, fibrinous pericarditis, and hemosiderosis. Other cardiac alterations were more specifically related to factors associated with transplantation procedure. Six patients exhibited a distinctive interstitial reactive change characterized by the presence of (1) moderate to large numbers of Anitschkow cells, occurring alone or in small cellular aggregates and histiocytes, histiocytic cells with nuclei of the Anitschkow type, lymphoid cells, and plasma cells, and (2) nuclei of the Anitschkow type in cardiac vascular and endocardial smooth muscle, endothelial and Schwann cells, and occasional cardiac muscle cells. This alteration may have been induced by abnormal immune mechanisms, as suggested by the observation that five of the six patients with interstitial change had clinical evidence of graft-versus-host disease. Two patients developed fatal congestive cardiac failure in the early post-transplant period and exhibited myocardial damage with histologic and post-transplant period features indicative of severe acute injury. Findings in these two patients consisted of necrotic muscle cells, which exhibited multiple contraction bands, diastase-resistant PAS staining, and intracellular fibrin deposits; microthrombi, which were composed of fibrin and occasionally of fibrin and platelets; and extravasated erythrocytes and fibrin strands in the interstitium. One of the two patients also exhibited unusual nuclear alterations, which were characterized by replacement of normal chromatin by palely stained fibrous and filamentous material. Clinicopathologic analysis strongly suggested that the fatal cardiotoxicity in both patients resulted primarily from effects of high doses of cyclophosphamide, which were administered as part of a four drug regimen that provided tumor ablation and immunosuppression for bone marrow transplantation. Our findings emphasize the need for less toxic antineoplastic and immunosuppressive therapy for use in bone marrow transplantation procedures.
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PMID:Cardiac pathologic findings in patients treated with bone marrow transplantation. 110 69

Twitcher mouse is a murine model of human globoid cell leukodystrophy (Krabbe disease), which is characterized by a genetic deficiency in galactocerebrosidase (GALC) activity. The nervous system is affected early and severely by demyelination in the white matter. So far, there is no effective treatment for Krabbe disease except bone marrow transplantation (BMT). However, BMT has inherent limitations such as unavailability of donors and graft-versus-host disease. In this study, we injected recombinant adenovirus encoding GALC into the lateral ventricle of twitcher mice at postnatal day 0 (PND 0) and the therapeutic effects were evaluated. Our results showed slight, but significant improvements in motor functions, body weight and twitching and a prolonged life span. In brain, GALC activity was increased to 15% that of normal littermates and psychosine concentration was decreased to 55% that of untreated twitcher mice at PND 15. The number of PAS-positive globoid cells in brain stem was also reduced significantly at PND 35. In contrast, when adenoviruses were injected to the twitcher mice at PND 15, almost no improvements were observed. These results demonstrate that the timing of treatment may be of great importance in Krabbe disease.
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PMID:Intraventricular administration of recombinant adenovirus to neonatal twitcher mouse leads to clinicopathological improvements. 1152 55

Allogeneic mixed chimerism achieved by low-dose total body irradiation (TBI) and anti-CD40L monoclonal antibody (mAb) with donor bone marrow transplantation (BMT) and host T cell depletion overcomes both allo- and autoimmunity. We investigated whether a similar regimen without T cell depletion cured diffuse proliferative glomerulonephritis. Male BXSB mice (H-2b) were injected with 20 x 10(6) BALB/c (H-2d) BM cells. When indicated, 3 Gy TBI on day -1 and anti-CD40LmAb (2 mg) on day 0 of BMT was given. Skin grafting was performed 1 day after BMT. BXSB mice were divided into four groups--I: BMT with TBI and anti-CD40LmAb; II: TBI; III: TBI and anti-CD40LmAb; and IV: no treatment. Chimerism in peripheral blood was analyzed. The kidney was examined histologically. TBI with anti-CD40LmAb and BMT allowed induction of multilineage mixed chimerism and donor-specific tolerance to skin grafts without graft-versus-host disease (GVHD). There was significant decrease in glomerular PAS-positive material deposition score, glomerular cell numbers, IgG, and C3 deposition in chimeric mice. All chimeric mice survived. Allogeneic mixed chimerism induced by a less toxic, nonlymphoablative regimen achieved allograft tolerance and cured glomerulonephritis in BXSB lupus mice.
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PMID:Allogenic mixed chimerism induced by nonlymphoablative regimen including donor BMT with low-dose TBI and anti-CD40L cured proliferative glomerulonephritis in lupus mice. 1791 51