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)

Autoimmune lymphoproliferative syndrome (ALPS) is marked by massive lymphadenopathy, hepatosplenomegaly, autoimmunity and the presence of increased numbers of circulating and tissue TCR-alpha beta, CD4- CD8- T cells. The underlying defect is that of decreased T cell and B cell apoptosis, due in most, but not all, cases to heterozygous mutations of the Fas gene and corresponding defective Fas signaling function. Here we measure in vivo and in vitro cytokine secretion in ALPS to shed light on the relation of apoptosis defects to the development of autoimmunity. In in vivo studies, ALPS patients manifested greatly increased circulating levels of IL-10 (> 100-fold), compared with both healthy individuals and various disease controls; in contrast, their levels of IL-1 beta, IL-4, and IFN-gamma were normal and their levels of IL-2 and TNF-alpha were marginally increased. In parallel in vitro studies, ALPS patients CD4+ DR+ T cells stimulated either with anti-CD3/CD28 or anti-CD2/CD28 produced increased amounts of IL-4 and IL-5 (10 to 20-fold) and decreased amounts of IFN-gamma (4-fold) as compared with those of control CD4+ DR+ T cells. In contrast, ALPS patients' CD4-/CD8- T cells produced very low amounts of cytokines. Finally, ALPS patients' peripheral monocytes/macrophages produced decreased amounts of IL-12 (30-fold) and increased amounts of IL-10 (5-fold). In conclusion, ALPS is marked by the presence of DR+ T cells that exhibit a skewed Th2 cytokine response upon various forms of stimulation. This cytokine response, in the presence of increased circulating IL-10 levels, is likely to define the cytokine milieu that accounts for the humoral autoimmune features of ALPS and, perhaps, of other humoral autoimmune states.
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PMID:Characteristic T helper 2 T cell cytokine abnormalities in autoimmune lymphoproliferative syndrome, a syndrome marked by defective apoptosis and humoral autoimmunity. 902 33

A unique feature of Mycobacterium tuberculosis is its ability to establish latent infection in the human host, which can reactivate to cause disease years later. In the present study, the mechanisms involved in the control of latent tuberculous infection were examined using two murine experimental tuberculosis models. Analysis of the model involving infection of mice with a relatively low inoculum of the virulent Erdman strain of M. tuberculosis indicated that in vivo inhibition of reactive nitrogen intermediate (RNI) production by the nitric oxide synthase inhibitor aminoguanidine resulted in reactivation. This reactivation was evidenced by hepatosplenomegaly, a robust tissue granulomatous reaction, and increased bacillary load. IFN-gamma, TNF-alpha, and inducible nitric oxide synthase were all expressed throughout the latent phase of infection. Reactivation of latent tuberculous infection by aminoguanidine treatment was confirmed using a second murine tuberculosis model based on treatment with antimycobacterial drugs. Results obtained using this drug-based model also suggested the existence of an RNI-independent antimycobacterial mechanism(s) operative in the latent phase of infection. Together, these data suggest that both RNI-dependent and -independent mechanisms contribute to the prevention of tuberculous reactivation.
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PMID:Effects of aminoguanidine on latent murine tuberculosis. 946 39

A 68-year-old man was admitted to our hospital because of fever, jaundice and hepatosplenomegaly. A diagnosis of diffuse large cell, B-cell type malignant lymphoma, associated with hemophagocytic syndrome (LAHS), was made. CT scan revealed lymphadenopathy in the abdominal cavity and multiple tumors in the spleen. Performance status and hepatic coma grade were 4 and II, respectively. Laboratory findings showed bicytopenia (Hb 9.9 g/dl, platelet 35 x 10(3)/microliter), severe liver dysfunction (ALP 1,115 U/l, gamma-GTP 437 U/l, T.Bil 15.4 mg/dl, D.Bil 12.8 mg/dl) and elevated levels of beta 2 microglobulin (12.9 mg/dl), ferritin (2,300 ng/ml) and sIL-2 receptor (36,900 U/ml). Plasma exchange (PE) and continuous hemodiafiltration (CHDF) enabled the patient to undergo diagnostic procedures, irradiation (total 34 Gy) and chemotherapy. Biopsy specimens revealed infiltration of lymphoma cells into the liver and bone marrow. We measured the blood concentrations of TNF-alpha, IL-6, and IL-8 before and after PE and CHDF by the ELISA method, and found normalization of hypercytokinemia after the procedure. It was suggested that initial treatment with PE and CHDF was effective for control of HPS, enabling us to perform chemotherapy for the lymphoma.
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PMID:[Plasma exchange and continuous hemodiafiltration as an initial treatment for diffuse large B-cell lymphoma-associated hemophagocytic syndrome]. 1186 63

Intracardial inoculation of BALB/c mice with Leishmania donovani amastigotes induced progressive visceral leishmaniasis (VL) with increasing splenic parasite load when followed upto 4-month postinfection period. In contrast, the liver parasite load reached maximum around 2-month postinfection period following which it started declining. The infection pattern differed somewhat from the earlier reports on mouse model of VL induced by intravenous inoculation of parasites with respect to the duration as well as magnitude of parasite burden in the organs (liver and spleen) and associated hepatosplenomegaly. Immunosuppression in mice with progressive VL was manifested in the form of impairment of proliferative response of the splenic mononuclear cells (SPMC) to in vitro stimulation with leishmanial antigen or the mitogen concanavalin A (ConA), although ConA stimulated cells were found to be capable of IL-2 and IFN-gamma synthesis. Differential expression of activating (IL-2, IFN-gamma and TNF-alpha) as well as deactivating (IL-4 and TGF-beta) cytokines was demonstrable in the spleen and liver of animals during the course of infection. Further, the synthesis of inducible nitric oxide synthase (iNOS) enzyme increased considerably in the liver as well as in the spleen of 4-month infected animal with parallel increase in the transcripts of the iNOS activating cytokines IFN-gamma and TNF-alpha. The temporal variation in the organ specific immune response could be related to the differential control of parasite burden in the liver and spleen of the infected host.
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PMID:Infection pattern and immune response in the spleen and liver of BALB/c mice intracardially infected with Leishmania donovani amastigotes. 1264 14

Analysis of T-lymphocytes by flowcytometry, estimation of serum TNFa level by solid phase enzyme amplified sensitivity immunoassay (EASIA) and IHAT were done for chronic schistosomiasis mansoni patients without hepatic fibrosis, with hepatosplenomegaly and 20 healthy controls. The sensitivity and specificity of IHAT in schistosomiasis mansoni were 85% & 90% respectively. Chronic schistosomiasis mansoni patients showed increase in CD8% (27.3 +/- 5.3) and decrease in CD4% (44.2 +/- 4.68). Hepatosplenomegaly cases showed increase in CD4% (46.5 +/- 4.1) & decrease in CD8% (23.2 +/- 2.18). Serum level of TNF-a was significantly higher in cases with hepatosplenomegaly compared to either cases of chronic schistosomiasis mansoni or controls. No significant difference was between chronic schistosomiasis mansoni patients and controls. A correlation between hepatosplenonomegaly and increase of CD4 and/or decrease of CD8 and significant high level of TNF-a indicated TNF-alfa role in granuloma formation.
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PMID:Flowcytometric analysis of T-lymphocytes and serum tumour necrosis factor alpha (TNF-alpha) levels in schistosoma mansoni patients. 1838 6

Human health in the past and presently is influenced by the amounts and proportion of chemical elements to which humans have been exposed. Arsenic, as a therapeutic agent was known to ancient Greeks and Romans. Ehrlick introduced organic arsenicals as anti linetic agents but with advent of penicillin these have nearly become obsolete. Once considered toxic, harmful to humans, arsenic is now considered an essential ultra trace element at least in animals. Now the impact of arsenic on health is more from industrial and environmental than medicinal exposure. This article reviews human exposure to arsenic in non occupational population, mostly through drinking water which is a worldwide problem, more so in south East Asia. Sources of arsenic, normal and abnormal levels in blood and tissues levels, old and new methods of estimation of arsenic, mechanism of action of arsenic in experimental animal is briefly reviewed. Old described clinical manifestation of arsenic in humans is briefly reviewed and newly described clinical manifestations in human with special emphasis on atherosclerosis, liver and diabetes are discussed. Proposed biological mechanisms in experimental animals included up regulation of inflammatory signals like cytokines and TNF-alpha, oxidative stress, hypomethylation, decreased DNA repair and apoptosis, cell proliferation, angiogenesis, activation of several enzymes like methyl transferase which converts inorganic arsenic to MMA and DMA, and GSH in in-vivo and in-vitro in experimental rat liver slices. Experimentally NAC (N-Acetyl Cysteine) treatment attenuates oxidative stress in atherosclerosis apoptosis and liver injury. GSH probably plays an important role in deactivation of the intermediate products of arsenic metabolism and prevents peroxidation of membrane lipids. Chronic human exposure has been linked to several systems in the human body: dermal (exfoliative dermatitis, keratosis, vitiligo, skin cancer), peripheral neuropathy, encephalopathy, bronchitis, pulmonary fibrosis, hepatosplenomegaly resembling NCPF, portal hypertension, peripheral vascular disease and BFD, arteriosclerosis and cancers of lung, urinary bladder, other internal organs and diabetes. Experimental and epidemiological evidence support diabetes effect of high level arsenic exposure. Low and moderate exposure to arsenic in drinking water is widely prevalent and may play a role in diabetes prevalence and needs to be studied further. Role of arsenic in Indian arteriosclerosis, diabetes and liver diseases, (cirrhosis, NCPF), need to be studied further. Study of mechanisms and enzymes mentioned need to be studied in humans exposed to arsenic and other xenobiotics. Measuring arsenic exposure, metabolic and biologic effects by newly described and simpler urine proteomics may accelerate our understanding of arsenic on health consequences.
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PMID:Arsenicosis: review of recent advances. 2175 19