Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a means of investigating further the pathogenesis of intestinal immunopathology, we have attempted to produce a destructive enteropathy by inducing an acute graft-versus-host reaction (GVHR) in mature, immunocompetent mice. Adult (C57b1/10 X DBA/2)F1 (BDF1) mice given C57B1/10(B10) spleen cells develop a severe GVHR which is associated with marked weight loss and high mortality. In the intestine an initial phase of enteropathy characterized by intense crypt hyperplasia is replaced by more severe intestinal damage which includes villus atrophy and loss of intra-epithelial lymphocytes. These pathological alterations are paralleled by the generation of anti-host cytotoxic T lymphocytes (CTL), marked immunosuppression and the loss of natural killer (NK) cells. In contrast to these findings, adult BDF1 mice given DBA/2 donor cells do not develop an acute systemic GVHR and have no CTL or intestinal pathology, despite prolonged splenomegaly and enhanced NK cell activity. Thus, destructive enteropathy can be induced during a GVHR in intact hosts and our results confirm that this enteropathy has a biphasic pattern, with villus atrophy representing the progression of initial crypt hyperplasia in severe forms of disease associated with weight loss and specific CTL.
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PMID:Experimental studies of immunologically mediated enteropathy. V. Destructive enteropathy during an acute graft-versus-host reaction in adult BDF1 mice. 213 68

We have attempted to investigate the relative roles of specific cytotoxic T lymphocytes (CTL) and allospecific suppressor T cells (Ts) in the systemic and intestinal manifestations of acute graft-versus-host reaction (GvHR) in mice. Treatment of adult (C57B1/10 x DBA/2)F1 (BDF1) mice with the suppressor cell-specific toxin 2'-deoxyguanosine (dGuo) inhibited the weight loss and mortality which normally occur after induction of GvHR and C57Bl donor cells. dGuo also delayed the development of a destructive enteropathy as typified by jejunal villus atrophy. Paradoxically, dGuo completely prevented villus atrophy during an acute GvHR in neonatal (CBA x BALB/c)F1 hosts, despite having only a slight ability to inhibit the systemic disease. In both models, dGuo had no effect on the generation of splenomegaly or anti-host CTL, and dGuo-treated mice with GvHR actually had increased proliferative alterations in the intestine, as assessed by crypt hyperplasia. In parallel, dGuo prevented the loss of NK cells which normally occurs in acute GvHR. Thus dGuo inhibits many of the destructive features of systemic and intestinal GvHR without affecting the development of CTL. We conclude that a dGuo-sensitive mechanism causes the transition from a proliferative to a destructive GvHR.
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PMID:Experimental studies of immunologically mediated enteropathy. VI. Inhibition of acute intestinal graft-versus-host reaction in mice by 2'-deoxyguanosine. 214 36

We have tested the hypothesis that interferon-gamma (IFN-gamma) plays a role in the enteropathy of graft-versus-host reaction (GVHR) by treating host mice with a monoclonal antibody directed at this mediator. Two models of GVHR were examined. In the mild proliferative GVHR, which occurs in adult unirradiated (CBA x BALB/c)F1 mice given parental spleen cells, anti-IFN-gamma slightly inhibited the development of splenomegaly and the activation of natural killer (NK) cells in GVHR. Anti-IFN-gamma had no effect on splenomegaly or generation of anti-host cytotoxic T lymphocytes (CTL) during the more severe GVHR in adult BDF hosts, but inhibited the weight loss and mortality normally found in this GVHR. Despite these variable effects on systemic GVHR, anti-IFN-gamma treatment abolished the crypt hyperplasia and increased counts of intraepithelial lymphocytes (IEL) normally found in the jejunum of (CBA X BALB/c)F1 mice with GVHR. In parallel, anti-IFN-gamma-treated BDF1 mice with GVHR did not develop the villus atrophy and intense crypt hyperplasia found in untreated GVHR hosts. These results support the view that IFN-gamma is essential for the development of enteropathy in GVHR and we propose that this mediator may also be involved in the pathogenesis of clinical enteropathies in man.
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PMID:Antibodies to IFN-gamma prevent immunologically mediated intestinal damage in murine graft-versus-host reaction. 250 25

We have used the intestinal phase of the graft-versus-host-reaction (GvHR) in unirradiated F1 mice as a model for enteropathy due to cell-mediated immunity (CMI). Injection of neonatal (CBA x BALB/c)F1 mice less than 48 h old with CBA spleen cells produced an acute GvHR, which was associated with runting and severe intestinal damage, characterized by villus atrophy. These animals developed specific cytotoxic T lymphocyte (CTL) activity and invariably died. In contrast, 7-day-old F1 mice with GvHR developed a proliferative GvHR, characterized by intense splenomegaly, NK cell activation and intestinal crypt hyperplasia. These mice did not lose weight, had no villus atrophy or CTL activity and all recovered. A similar proliferative phase was also found to precede the established GvHR in 1-2-day-old hosts. Induction of a GvHR in 5-day-old hosts produced a disease with some characteristics of both proliferative and destructive GvHR, with some mice developing weight loss and villus atrophy, while others showed only crypt hyperplasia and NK cell activation. However, there was very little specific CTL activity in any of these animals. These results indicate that markedly different forms of GvHR can be induced in mice during the first week of life and that these are associated with different pathological effects. Although the immunological mechanisms which are activated may also differ between the types of GvHR, our findings support the hypothesis that intestinal damage which includes villus atrophy is merely a progressive form of the delayed type hypersensitivity responsible for a proliferative enteropathy.
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PMID:Experimental studies of immunologically mediated enteropathy: IV. Correlation between immune effector mechanisms and type of enteropathy during a GvHR in neonatal mice of different ages. 339 13

We reported that T cell receptor (TcR) gamma delta intestinal intraepithelial lymphocytes (i-IEL) of host origin increased transiently, then decreased drastically at the early stage of non-irradiated acute graft-versus-host disease (GVHD) in mice. We investigated the role of the TcR gamma delta i-IEL of host origin in the pathogenesis of the intestinal lesions that occur during acute GVHD. The acute GVHD was induced in mice which had been depleted of TcR gamma delta by in vivo administration of hamster monoclonal antibody (mAb) against TcR gamma delta. Although the degree of splenomegaly after the induction of acute GVHD in mice treated with anti-TcR gamma delta mAb was similar to that in control mice treated with hamster anti-2,4,6-trinitrophenyl mAb, infiltration of donor-derived T cells into the epithelium, and mitosis and apoptosis of crypt cells in the intestinal mucosa were dramatically suppressed in these mice. This suggest that host TcR gamma delta T cells in i-IEL contribute to the development of enteropathy in acute GVHD in mice.
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PMID:Host intestinal intraepithelial gamma delta T lymphocytes present during acute graft-versus-host disease in mice may contribute to the development of enteropathy. 784 57

Interleukin-1 (IL-1) is an important mediator of inflammation and has been implicated in several forms of immunopathology. Here we have investigated whether IL-1 plays a role in the enteropathy which occurs during a graft-versus-host reaction (GVHR) in mice. Non-irradiated (CBA x BALB/c) F1 mice with GVHR had increased production of IL-1 and treatment with rabbit anti-IL-1 alpha antibodies abolished the crypt hyperplasia and significantly reduced the parallel increase in crypt length which occurs in the jejunum. Antibody treatment had no effect on the accompanying increase in intraepithelial lymphocyte (IEL) counts or on the splenomegaly. Recombinant IL-1 itself produced villus atrophy, crypt hyperplasia and increased IEL counts in normal mice and stimulated the proliferation of an intestinal epithelial cell line in vitro. We propose that IL-1 plays an effector role in immunologically mediated enteropathy, either via direct effects on epithelial cells or secondary to an action on other, stromal cells in the mucosa.
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PMID:A role for interleukin-1 alpha in immunologically mediated intestinal pathology. 824 50

We have previously reported that a nonapeptide thymic hormone, facteur thymique serique (FTS), is involved in the differentiation and activation of intestinal intraepithelial lymphocytes (i-IEL) in mice. In this study, we examined the effect of FTS treatment on enteropathy in a murine model for acute graft-vs.-host disease (GVHD) induced by injection of parental C57BL/6 splenocytes into unirradiated (C57BL/6 x DBA/2) F1 hybrids. FTS treatment significantly protected mice from developing acute GVHD as assessed by mortality rate, splenomegaly and enteropathy. The infiltration of donor-derived TCR alpha beta i-IEL bearing CD8 alpha beta was significantly inhibited in the small intestine of FTS-treated mice, and the frequencies of apoptosis of crypt cells in the intestinal mucosa were decreased in these mice during acute GVHD. These results suggest that FTS treatment contributes to protection against enteropathy of acute GVHD. Thus, FTS may provide a useful approach to control acute GVHD after blood transfusion or bone marrow transplantation.
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PMID:A thymic hormone protects mice from enteropathy during acute graft-versus-host disease. 944 31

Celiac disease is an enteropathy occurring in genetically predisposed individuals due to a dietary intolerance to gluten. Patients with celiac disease may develop a neurological disorder of unknown cause, although autoimmune mechanisms are suspected. We report on a 56-year-old man with celiac disease, who became refractory to a gluten-free diet and died of a rapidly progressive encephalopathy. Magnetic resonance imaging indicated focal lesions of the cerebellum and brainstem, and electrodiagnostic studies suggested an axonal neuropathy. Autopsy revealed a flattened small-bowel mucosa with intraepithelial lymphocytosis, a spectrum of degenerative changes of the intra-abdominal and mediastinal lymph nodes, including cavitary degeneration, and splenomegaly. Histologically, the lymph nodes showed pseudocyst formation and lymphocytic vasculitis with fibrinoid necrosis, and sections of the brain exhibited fibrinoid degeneration of small blood vessels, sparse perivascular lymphocytic infiltrates, and perivascular ischemic lesions. Identical T-cell clones were identified in the duodenum, stomach, lymph nodes, and spleen. This patient had an unusual neurological disorder related to a vasculopathy, probably mediated by a circulating neoplastic clone of activated T cells.
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PMID:Fatal CNS vasculopathy in a patient with refractory celiac disease and lymph node cavitation. 1617 83

A rare case of enteropathy-type T-cell lymphoma (ETL) developed in a 47-year-old Chinese male 6 years after the diagnosis of diffuse large B-cell lymphoma (DLBCL) in the small intestine. The patient initially presented with vague gastrointestinal complaints. Work-up demonstrated an ulcerated mass in the small intestine. Partial resection and histologic examination of the intestine showed a DLBCL, positive for CD20 and Bcl-2, involving the jejunum transmurally. Further staging work-up demonstrated mesenteric and retroperitoneal lymphadenopathy, splenomegaly, and ascites. The patient was treated aggressively with radiotherapy, chemotherapy, and autologous bone marrow transplant, and complete remission was obtained. Six years later, the patient presented with diarrhea and dehydration. Clinical work-up revealed thickening of the small intestinal wall, and biopsies demonstrated ETL based on morphology, immunohistochemistry, and polymerase chain reaction analysis. Celiac disease was diagnosed concurrently. The patient responded to chemotherapy, received allogeneic peripheral blood stem cell transplantation from an HLA-matched sibling donor, and remains in remission. To our best knowledge, this is the first reported case of metachronous ETL and DLBCL. Possible associations between the 2 types of lymphoma are discussed.
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PMID:Enteropathy-type T-cell lymphoma after intestinal diffuse large B-cell lymphoma. 1732 91

We present the first known case of the monoblastic type of myeloid sarcoma (also known as extramedullary myeloid tumor, chloroma, and granulocytic sarcoma) with diffuse involvement of the gastrointestinal tract. The patient originally presented with diarrhea and crampy abdominal discomfort. Endoscopically, the disease showed a diffuse inflammatory process mimicking a number of benign conditions, such as inflammatory bowel disease and autoimmune enteropathy. Sequential biopsies of the upper and lower gastrointestinal tract showed a diffuse infiltrate of increasingly atypical cells. The disease progressed to systemic involvement, including widespread lymphadenopathy, splenomegaly, and pulmonary deposits; the patient died 13 months after the development of initial symptoms. The immunohistochemical and histologic profiles of this case are diagnostic of the monoblastic type of myeloid sarcoma.
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PMID:Extensive involvement of the gastrointestinal tract by a de novo presentation of the monoblastic type of myeloid sarcoma: a case report of a rare entity that is often misdiagnosed. 2001 Jan 58


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