Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parasitic infections and malnutrition coexist in many tropical and subtropical areas. Studies of Leishmania donovani and of experimentally infected Syrian hamsters have provided important insights into the complex interrelationships between malnutrition and this parasitic disease. Malnutrition, which adversely affects cell-mediated immunity, is associated with the development of visceral leishmaniasis (kala-azar) in children living in endemic areas. In turn, L. donovani can cause wasting as well as hepatosplenomegaly, fever, and anemia. Syrian hamsters infected with L. donovani develop a disease that is comparable to that of humans with kala-azar. Weight loss in infected hamsters is associated with splenic macrophage secretion of potentially catabolic cytokines as measured by the D10.G4.1 assay for interleukin-1 and the L929 cytotoxicity assay for tumor necrosis factor/cachectin. Although decreased food intake contributes to wasting in infected hamsters, studies of skeletal muscle function indicate that it is not the sole factor. Leishmania donovani-infected hamsters have also been used to study drugs with the potential to prevent or reverse cachexia.
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PMID:Visceral leishmaniasis: a model for infection-induced cachexia. 163 76

Familial hemophagocytic lymphohistiocytosis (FHL) is a frequently missed and almost uniformly fatal childhood disorder. It is characterized by fever, hepatosplenomegaly, cytopenia, coagulopathy, and hypertriglyceridemia. The pathogenesis of FHL is not known but the above clinical and laboratory findings are compatible with reported in vitro and in vivo effects of several inflammatory cytokines. We measured circulating interferon-gamma (IFN-gamma), tumor necrosis factor/cachectin (TNF), and interleukin-6 (IL-6) in nine children with FHL. During active disease, elevated IFN-gamma was detected in seven of seven children, TNF in six of six, and IL-6 in two of six children studied. Thus, important inflammatory cytokines are augmented in active FHL and may contribute to the pathogenesis of the disease. Soluble CD8 was also increased in seven of seven children, which suggests a pathophysiologic importance of cytotoxic T lymphocytes. Because FHL appears to be associated with a systemic hypercytokinemia, our results also indicate that studies of FHL may contribute to the understanding of cytokine effects in vivo. Moreover, FHL is a hereditary disorder, suggesting that the hypercytokinemia is caused by a genetic defect in cytokine regulation.
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PMID:Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. 195 80

The temporal susceptibility of tumors to induction of necrosis and regression by endotoxin was investigated further with a focus on the role of the putative mediator, tumor necrosis factor (TNF). Production of this factor was shown earlier to require prior activation of the mononuclear phagocytic system (MPS). Transplants of Meth A sarcoma or MOPC315 plasmacytoma had no consistent effect on parameters of MPS function such as hepatosplenomegaly, carbon clearance and non-specific antibacterial resistance at times that they were sensitive to induction of necrosis. Moreover, TNF, quantified by its necrotizing and regressing activity in vivo, could not be detected in the serum of tumor hosts after a necrotizing dose of endotoxin, while much smaller volumes of serum with TNF (TNS) of appropriately treated donor mice showed activity. As repeated incubation of TNS with Meth A cells at 37 degrees C hardly removed its in vivo activity against Meth A, immediate absorption of produced TNF to the tumor cell mass seems a less likely cause. Cytostatic activity, another property attributed to TNF, was hardly increased in post-endotoxin tumor host serum, while TNS is highly cytostatic. It is concluded that induction of tumor necrosis is not dependent on MPS activation. A role of TNF as mediator of the effects of endotoxin still remains uncertain. Furthermore, the present and other data suggest that TNF, like endotoxin, probably acts by an indirect mechanism against tumors in vivo.
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PMID:Role of mononuclear phagocyte function in endotoxin-induced tumor necrosis. 636 47

The Epstein-Barr virus (EBV) has been shown to infect T lymphocytes and is associated with two recently recognized human T-lymphoproliferative disorders: childhood EBV-associated hemophagocytic syndrome (VAHS) representing a primary or active EBV infection of T cells in young children, and the EBV-containing T cell lymphoma in adults predominantly affecting the nose, skin and gastrointestinal tract. In both diseases, hemophagocytic syndrome (HS) accounts for the major cause of mortality. The patients developing HS share common clinicopathologic features such as fever, skin lesions, lung infiltrates, hepatosplenomegaly with jaundice, cytopenias, and coagulopathy. The liver, spleen, lymph nodes, and bone marrow usually show florid histiocytic proliferation with hemophagocytosis in addition to the proliferation of atypical T lymphocytes or immunoblasts. The HS in T cell lymphoma may develop simultaneously with initial lymphoma presentation, at tumor relapse, or even during remission. The cytokines, in particular tumor necrosis factor-alpha, released from the EBV-infected T lymphocytes are presumed to cause the histiocytic activation and the subsequent hemophagocytic process. Chemotherapy or antiviral agents fail to arrest the hemophagocytic process in both diseases. Immunomodulatory treatment incorporating etoposide and intravenous immunoglobulin, however, has been effective in the control of the progression of the hemophagocytic process in a substantial number of VAHS patients. Preliminary data suggest that bone marrow transplantation may be a promising way for eliminating both the virus and the proliferating T cells. Further investigations are mandatory for combating this aggressive hemophagocytic process in EBV-associated T lymphoproliferative disorders.
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PMID:Hemophagocytic syndrome in Epstein-Barr virus-associated T-lymphoproliferative disorders: disease spectrum, pathogenesis, and management. 859 Aug 39

The familial form of hemophagocytic lymphohistiocytosis (HLH) is an inherited disease with disturbed immunomodulation and characterized by fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, and coagulopathy, i.e., findings which are similar to many of the reported biological effects of the inflammatory cytokines. Due to the previously shown hypercytokinemia in active HLH with elevated levels of interleukin (IL)-6, tumor necrosis factor-alpha, and interferon-gamma, it has been suggested that cytokine dysregulation may be of pathophysiological importance. Here we have assayed the serum levels of the members of the IL-1 ligand family, the two agonists IL-1 alpha and IL-1 beta and the antagonist IL-1 receptor antagonist (IL-1ra), in nine children with HLH and cerebrospinal fluid (CSF) specimens from four children. Serum IL-1ra was elevated in all patients with active disease to a degree which correlated well with disease activity. Furthermore, the levels decreased day by day during treatment of a patient who suffered a relapse. Moreover, high levels of IL-1ra were also detected in CSF during active disease. However, IL-1 beta levels were all within normal limits and circulating IL-1 alpha levels were normal in all but two patients.
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PMID:Elevated circulating levels of interleukin-1 receptor antagonist but not IL-1 agonists in hemophagocytic lymphohistiocytosis. 861 86

Although tumor necrosis factor (TNF) initially came to prominence because of its anti-tumor activity, most attention is now focused on its proinflammatory actions. TNF appears to play a critical role in both early and late events involved in inflammation, from localizing the noxious agent and amplifying the cellular and mediator responses at the local site and systemically, to editing (e.g., apoptosis) injured cells or effete immune cells and repairing inflammatory damage. We have generated mice deficient in TNF (TNF-/- mice) and have begun to examine the multiple functions attributed to TNF. TNF-/- mice develop normally and have no gross structural or morphological abnormalities. As predicted, they are highly susceptible to challenge with an infectious agent (Candida albicans), are resistant to the lethality of minute doses of lipopolysaccharide (LPS) following D-galactosamine treatment, have a deficiency in granuloma development, and do not form germinal centers after immunization. Phagocytic activity of macrophages appears relatively normal, as do T cell functions, as measured by proliferation, cytokine release, and cytotoxicity. B cell response to thymus-independent antigens is normal, but the Ig response to thymus-dependent antigen is reduced. Surprisingly, cytokine production induced by LPS appears essentially intact, with the exception of reduced colony-stimulating factor activity. Other unexpected findings coming from our initial analysis are as follows. (i) TNF has low toxicity in TNF-/- mice. (ii) TNF-/- mice show an anomalous late response to heat-killed Corynebacterium parvum. In contrast to the prompt response (granuloma formation, hepatosplenomegaly) and subsequent resolution phase in C. parvum-injected TNF+/+ mice, similarly treated TNF-/- mice show little or no initial response, but then develop a vigorous, disorganized inflammatory response leading to death. These results suggest that TNF has an essential homeostatic role in limiting the extent and duration of an inflammatory process-i.e., an anti-inflammatory function. (iii) In contrast to the expectation that TNF+/+ mice and TNF+/- mice would have identical phenotypes, TNF+/- mice showed increased susceptibility to high-dose LPS lethality, increased susceptibility to Candida challenge, and delayed resolution of the C. parvum-induced inflammatory process, indicating a strong gene dose requirement for different actions of TNF.
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PMID:Characterization of tumor necrosis factor-deficient mice. 922 20

Gaucher's disease (GD) is characterized by hepatosplenomegaly, bone marrow infiltration, osteonecrosis, which may all be associated with the presence of pathological macrophages that contain undegraded glycosphingolipids. Levels of serum cytokines, which are soluble products of mononuclear phagocytes (MNP), were evaluated in 24 GD patients. Levels of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble interleukin-2 receptor (sIL-2R) in GD patients were significantly higher than in normal controls. We attempted to correlate cytokine levels with disease severity. Type I GD patients with more severe clinical manifestations had significantly higher levels of IL-1beta, IL-1Ra and IL-6, relative to type I patients with milder disease. Three patients homozygous for the 1448C mutation with neuropathic type III disease, had significantly higher levels of sIL-2R than type I patients or controls. We speculate that cytokine over-expression may relate to the pathophysiology of some of the clinical manifestations of GD. Thus, the elevated IL-1beta, TNF-alpha and IL-6 levels may induce the bone manifestations, the neutrophil chemotaxis and the increased incidence of hyper-gammaglobulinemia present in GD patients.
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PMID:Cytokines in Gaucher's disease. 1040 Aug 26

A case of angiotropic B-cell lymphoma associated with hemophagocytic syndrome (HPS) has been reported. In addition to fever, pancytopenia, hepatosplenomegaly, and lack of lymphadenopathy, unique clinical features, such as syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and pulmonary infarction, were manifested. Both soluble interleukin-2 receptor (sIL-2R) and IL-6 were elevated in the patient's sera in addition to an increase of serum lactate dehydrogenase and ferritin. In contrast, tumor necrosis factor-alpha and interferon-gamma were within normal ranges. Serum antibodies against Epstein-Barr virus and cytomegalovirus showed a past infection pattern. An autopsy examination revealed systemic intravascular proliferation of lymphoma cells with a B-cell phenotype, confirming the diagnosis of angiotropic B-cell lymphoma. Moreover, SIADH was suggested to result from the infiltration of tumor cells into the pituitary gland. Triple association of angiotropic B-cell lymphoma, HPS and SIADH is quite rare. Therefore, the present case seems to be helpful for clarifying the mechanism for HPS of non-Hodgkin's lymphoma with B-cell origin.
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PMID:Angiotropic B-cell lymphoma with hemophagocytic syndrome associated with syndrome of inappropriate secretion of antidiuretic hormone. 1110 Jul 51

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology and pathogenesis. AOSD is a rare condition, usually presenting with high fever accompanied by systemic manifestations. The disease is a heterogeneous pathological entity with a range of etiologies, manifestations and prognosis. There is no single diagnostic test for AOSD; rather, the diagnosis is based upon clinical criteria such as arthralgia, fever, skin rash, lymphadenopathy, and hepatosplenomegaly. Determination of the procalcitonin level and the biological response to empirical corticosteroid therapy generally helps the diagnosis, while immune-serology, as a 'screening' test, will not add meaningful information in most cases. Treatment consists of anti-inflammatory medications. Non-steroid anti-inflammatory drugs have limited efficacy, corticosteroid therapy and disease-modifying antirheumatic drugs are usually required. Novel therapeutic approaches, such as anti-tumor necrosis factor blockade and stem cell transplantation, are promising. In this chapter we present clinical and laboratory parameters of 18 patients diagnosed with AOSD at our institution between 1997 and 2003, and review the literature.
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PMID:Adult-onset Still's disease. 1545 25

Adult Still disease is characterized by high fever, arthritis, leukocytosis, hepatosplenomegaly, rash, and lymphadenopathy. It affects primarily young adults and is often disabling or even fatal. Many patients achieve long-term remissions, while others may develop a chronic illness refractory to multiple therapies. Polyarthritis or root joint involvement has been identified as a marker of chronic disease. No controlled studies on second-line agents have been published, but anecdotal studies suggest efficacy of a variety of agents including hydroxychloroquine, sulfasalazine, penicillamine, and methotrexate. Although these therapies have been used, optimal treatment of patients with resistant disease remains problematic. High levels of tumor necrosis factor have been noted, and recent report indicates etanercept may be an effective therapy. We report 2 cases of adult-onset Still disease resistant to NSAIDs, steroids, and methotrexate that have been successfully maintained on 5 mg/kg infliximab for 30 and 29 months, respectively, with improvement of signs and symptoms despite a reduction of steroid dosage. In patients with resistant disease, infliximab may be a safe, effective agent. Its use in this disease merits further study.
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PMID:Treatment of resistant adult still disease with infliximab: a report of 2 cases. 1704 13


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