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)

A novel immunosuppressant, succinyl acetone (4,6-dioxoheptanoic acid), was studied in dogs. Results with bolus intravenous injections at doses ranging from 50 to 1600 mg/kg showed dose-dependent alpha and beta half-lives, ranging from 30 to 80 min and 7 to 27 hr, respectively. Results suggested that continuous i.v. infusion was necessary to maintain constant plasma levels. Four dogs were given 9.2 Gy total-body irradiation and autologous marrow transplants along with continuous i.v. infusion of succinyl acetone at 50, 100, 200, or 400 mg/kg/day for 21 days, and all four had rapid, sustained hematopoietic engraftment. However, two of the four dogs receiving 200 and 400 mg succinyl acetone/kg/day, respectively, developed bilateral hind-limb ataxia, with histologically confirmed cerebellar lesions in the dog given the higher dose, thus establishing a potential dose-limiting neurotoxicity. Prevention of graft-versus-host disease was studied in recipients of allogeneic marrow. Dogs were given 9.2 Gy TBI, followed by hematopoietic grafts from unrelated DLA-nonidentical or DLA-haploidentical littermate dogs. Succinyl acetone was given as continuous infusion for 21 days after transplant at doses of 100-300 mg/kg/day. Starting succinyl acetone on the day of marrow infusion in four dogs failed to prevent rapid onset of acute GVHD, and dogs survived no longer than controls. Starting succinyl acetone 3 days before transplant delayed the onset of acute GVHD and prolonged survival significantly compared with that of dogs not given postgrafting immunosuppression (P = 0.008); survival was comparable to that in previously reported dogs given either methotrexate or cyclosporine as postgrafting immunosuppression (P = 0.88 and 0.99, respectively). Seven of the sixteen allogeneic recipients developed evidence of neurotoxicity during succinyl-acetone infusion. Neurological dysfunctions were manifested by hind-limb ataxia and posterior paresis. In conclusion, succinyl acetone significantly delayed the onset of GVHD and prolonged survival of DLA-nonidentical marrow graft recipients but did not induce graft-host tolerance and was associated with dose-limiting neurotoxicity.
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PMID:Pharmacologic, toxicologic, and marrow transplantation studies in dogs given succinyl acetone. 144 Aug 68

The ability to define subpopulations of immunologically competent lymphocytes has permitted an enhanced understanding of the interaction between functionally distinct components of the immune system. T cells can provide help in antibody formation or they may suppress antibody production. Abnormal immunoregulatory mechanisms have been demonstrated in the hyperimmunoglobulin E-recurrent infection syndrome. This disorder is associated with a marked elevation of IgE and specific elevations of IgE antibodies directed toward staphylococcal antigens. Abnormal T cell regulation of immune responses has been demonstrated. Graft-versus-host disease (GVHD) occurs in an immunodeficient patient who has received an infusion of immunocompetent cells. The diagnosis of graft-versus-host (GVH) reaction may be complicated by the protean manifestations of the disorder. The acute form, consisting of a maculopapular rash, fever, and diarrhea, may be confused with acute infection or drug reaction. Chronic GVHD has been incorrectly diagnosed as histiocytosis X, acrodermatitis enteropathica, or scleroderma. Utilizing chromosome markers and/or identification of histocompatibility antigens, the presence of circulating lymphocytes from donor immunocompetent cells (blood transfusion, maternal source) can be documented. The development of sensitive technics for identifying cells can establish a precise diagnosis. Certain immunodeficiency disorders can be identified by biochemical means. Biotin-dependent multiple carboxylase enzyme deficiency is associated with a chronic dermatitis, alopecia, ataxia, and secondary infection of the skin with Candida. The disorder responds promptly to the administration of biotin with correction of dermatologic, neurologic, and immunologic abnormalities.
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PMID:New insight into the causes of immunodeficiency disorders. 638 1

A 32-year-old Japanese male in his second remission of acute lymphoblastic leukemia (ALL) received a matched unrelated donor bone marrow transplant (BMT) from the Japan Marrow Donor Program. On day +83, a bone marrow examination revealed 5.2% leukemic cells. Despite the cessation of cyclosporine, leukemic cells in the bone marrow increased to 18.4% on day +91. Treatment was started with interferon (IFN)-alpha-2b 3 x 10(6) U/body s.c. daily on day +92 and leukemic cells in the bone marrow disappeared completely. The toxicity of IFN-alpha treatment included leukoencephalopathy consisting of somnolence, disorientation, short-term memory loss, lack of coordination and ataxia, myelotoxicity requiring multiple platelet transfusions and exacerbation of graft-versus-host disease (GVHD) of oral cavity, skin and lung. Because of progressive GVHD, IFN-alpha was discontinued on day +124. On day +132, a bone marrow aspirate showed 6.4% leukemic cells. The patient died of progressive ALL on day +178. IFN-alpha may be useful for the treatment of leukemic relapse following BMT, although its toxicity is marked.
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PMID:Interferon-alpha treatment of acute lymphoblastic leukemia relapse after unrelated bone marrow transplantation. 959 46

A 68-year-old female with severe aplastic anemia (SAA) refractory to initial immunosuppressive therapy, including anti-thymocyte globulin (ATG) and cyclosporine, received a reduced-intensity cord blood transplant (CBT) in June 2015. Tacrolimus (TAC) and mycophenolate mofetil were administered for graft-versus-host disease (GVHD) prophylaxis, and she received prolonged TAC and prednisolone to treat chronic GVHD. The patient presented with progressive ataxia 14 months after CBT. A brain magnetic resonance image (MRI, FLAIR) detected a high-intensity lesion in the left cerebellar hemisphere, which suggested infarction. Her consciousness level gradually continued to deteriorate and another brain MRI (T2) revealed that the size of the cerebellar lesion had increased and had involved the pons. A cerebrospinal fluid (CSF) examination showed normal cell count and protein levels; however, polymerase chain reaction (PCR) analysis of CSF was positive for JC virus (JCV). Therefore, she was eventually diagnosed with progressive multifocal leukoencephalopathy (PML) and treated with mefloquine. The symptoms were reduced after 3 months, and JCV in CSF disappeared without new lesions after 6 months. This is an unusual case of PML initially involving the cerebellum, and we report here PML after an immunosuppressive therapy and CBT in the patient with SAA.
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PMID:[Progressive multifocal leukoencephalopathy developing subsequent to cord blood transplantation in a patient with severe aplastic anemia]. 3084 86

Stem cells (SCs) are discovered long back but the idea that SCs possess therapeutic potential came up just a few decades back. In a past decade stem cell therapy is highly emerged and displayed tremendous potential for the treatment of a wide range of diseases and disorders such as blindness and vision impairment, type I diabetes, infertility, HIV, etc. SCs are very susceptible to destruction after transplantation into the host because of the inability to sustain elevated stress conditions inside the damaged tissue/organ. Heat shock proteins (HSPs) are molecular chaperones/stress proteins expressed in response to stress (elevated temperature, harmful chemicals, ischemia, viruses, etc) inside a living cell. HSPs protect the cell from damage by assisting in the proper folding of cellular proteins. This review briefly summarises different types of HSPs, their classification, cellular functions as well as the role of HSPs in regulating SC self-renewal and survival in the transplanted host. Applications of HSP modulated SCs in regenerative medicine and for the treatment of ischemic heart disease, myocardial infarction (MI), osteoarthritis, ischemic stroke, spinocerebellar ataxia type 3 (SCA3), leukemia, hepatic ischemia-reperfusion injury, Graft-versus-host disease (GVHD) and Parkinson's disease (PD) are discussed. In order to provide potential insights in understanding molecular mechanisms related to SCs in vertebrates, correlations between HSPs and SCs in cnidarians and planarians are also reviewed. There is a need to advance research in order to validate the use of HSPs for SC therapy and establish effective treatment strategies.
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PMID:Heat Shock Proteins and their Protective Roles in Stem Cell Biology. 3125 66

Complications involving the central nervous system (CNS) occur in 9-14% of patients following allogeneic hematopoietic stem cell transplantation (HSCT), including stroke-like episodes, demyelination, encephalitis, and nonspecific neurological symptoms. Here we report a case of multiple sclerosis (MS) like relapsing remitting encephalomyelitis following allogeneic HSCT, which did not respond to disease modifying therapies (DMTs) and "domino" autologous HSCT. A 53-year-old male was treated with allogeneic HSCT for lymphoid blast transformation of chronic myeloid leukemia. Ten months later he presented with confusion, slurred speech, left sided facial weakness and ataxia. A magnetic resonance imaging brain scan showed multiple enhancing tumefactive lesions. Neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein (MOG) antibodies were negative. After extensive investigations for infections, autoimmune disorders and recurrence of malignancy, he underwent brain biopsy, which showed a macrophage rich lesion with severe myelin loss but axonal preservation indicating a demyelinating pathology. Although his symptoms improved with corticosteroids, he relapsed five months later. In the absence of any systemic features suggesting graft versus host disease (GvHD), his presentation was thought to be compatible with MS. The illness followed an aggressive course that did not respond to glatiramer acetate and natalizumab. He was therefore treated with "domino" autologous HSCT, which also failed to induce long-term remission. Despite further treatment with ocrelizumab, he died of progressive disease. An autopsy limited to the examination of brain revealed multifocal destructive leukoencephalopathy with severe myelin and axonal loss. Immunohistochemistry showed macrophage located in the perivascular area, with no T or B lymphocytes. The appearance was unusual and not typical for chronic MS plaques. Reported cases of CNS demyelination following allogeneic HSCT are very limited in the literature, especially in relation to histopathological examination. Although the clinical disease course of our patient following allogeneic HSCT resembled an "MS-like" relapsing remitting encephalomyelitis, the autopsy examination did not show any evidence of active inflammation. The impact of DMTs and HSCT on the histological appearance of "MS-like" CNS pathologies is unknown. Therefore, reporting this and similar cases will improve our awareness and understanding of underlying disease mechanisms.
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PMID:A Case of Multiple Sclerosis-Like Relapsing Remitting Encephalomyelitis Following Allogeneic Hematopoietic Stem Cell Transplantation and a Review of the Published Literature. 3243 94