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

A new beta-chain hemoglobin variant, Hb Randwick [beta 15(A12)Trp----Gly] was detected in a 43-year-old female of Northern Italian parentage. During investigation for possible diabetes, mild red cell changes were noted and hemoglobin electrophoresis studies were requested. Independently, her sister's assessment had resulted in similar investigations. The most prominent findings were numerous "Hb H"-like inclusions and a positive isopropanol stability test. The hemoglobin variant separated poorly towards the anode at pH 9.2 and the level was estimated to be between 48-50% of the total hemoglobin. The variant beta-chain was partially purified by column chromatography, and its tryptic peptides fractionated by high performance liquid chromatography. Amino acid analysis and sequence data indicated that the tryptophan at residue 15 (A12) had been substituted by a glycine residue. Further study has indicated that eight other family members are heterozygous for the variant; they are clinically normal with no evidence of splenomegaly or history of jaundice, although four of them showed a mild reticulocytosis.
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PMID:Hemoglobin Randwick or beta 15 (A12)Trp----Gly: a new unstable beta-chain hemoglobin variant. 338 7

Two groups of three German shepherd dogs each were inoculated with Leishmania chagasi or Leishmania donovani amastigotes and the infection was followed for 82 days. The dogs developed a persistent infection, became thin, and developed splenomegaly and lymphadenomegaly by 55 days after inoculation. All dogs developed a normocytic, normochromic anemia of increasing severity. Thrombocytopenia and leukopenia occasionally occurred. Blood tryptophan levels were decreased significantly in infected dogs. Increased total serum protein, with hypergammaglobulinemia and hypoalbuminemia, was present in all dogs to various degrees. There was a marked increase in gamma globulins, with smaller increases in alpha and beta globulins. Many of the clinicopathologic changes observed in these dogs were similar to the disease as it occurs in man. The German shepherd dog may be a useful laboratory model for the study of visceral leishmaniasis.
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PMID:Visceral leishmaniasis in the German shepherd dog. I. Infection, clinical disease, and clinical pathology. 671 Aug 16

Cidofovir has shown antiproliferative effects against human papillomavirus (HPV)-positive cells and successfully suppressed the growth of HPV-positive xenografts in athymic nude mice. The present study evaluated the effect of cidofovir on several disease parameters in this animal model. Intratumoral administration of cidofovir resulted in a beneficial effect on body weight gain, a reduction in splenomegaly, a partial restoration of tryptophan catabolism, and diminished the inflammatory state induced by the xenografts. Administration of cidofovir to tumor-free animals did not have a direct effect on these parameters. Beyond suppressing tumor growth, intratumoral treatment with cidofovir ameliorated the pathology associated with HPV-tumor growth.
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PMID:Cidofovir treatment improves the pathology caused by the growth of human papillomavirus-positive cervical carcinoma xenografts in athymic nude mice. 2314 93

Increased pain sensitivity is a comorbidity associated with many clinical diseases, though the underlying causes are poorly understood. Recently, chronic pain hypersensitivity in rodents treated to induce chronic inflammation in peripheral tissues was linked to enhanced tryptophan catabolism in brain mediated by indoleamine 2,3 dioxygenase (IDO). Here we show that acute influenza A virus (IAV) and chronic murine leukemia retrovirus (MuLV) infections, which stimulate robust IDO expression in lungs and lymphoid tissues, induced acute or chronic pain hypersensitivity, respectively. In contrast, virus-induced pain hypersensitivity did not manifest in mice lacking intact IDO1 genes. Spleen IDO activity increased markedly as MuLV infections progressed, while IDO1 expression was not elevated significantly in brain or spinal cord (CNS) tissues. Moreover, kynurenine (Kyn), a tryptophan catabolite made by cells expressing IDO, incited pain hypersensitivity in uninfected IDO1-deficient mice and Kyn potentiated pain hypersensitivity due to MuLV infection. MuLV infection stimulated selective IDO expression by a discreet population of spleen cells expressing both B cell (CD19) and dendritic cell (CD11c) markers (CD19+ DCs). CD19+ DCs were more susceptible to MuLV infection than B cells or conventional (CD19neg) DCs, proliferated faster than B cells from early stages of MuLV infection and exhibited mature antigen presenting cell (APC) phenotypes, unlike conventional (CD19neg) DCs. Moreover, interactions with CD4 T cells were necessary to sustain functional IDO expression by CD19+ DCs in vitro and in vivo. Splenocytes from MuLV-infected IDO1-sufficient mice induced pain hypersensitivity in uninfected IDO1-deficient recipient mice, while selective in vivo depletion of DCs alleviated pain hypersensitivity in MuLV-infected IDO1-sufficient mice and led to rapid reduction in splenomegaly, a hallmark of MuLV immune pathogenesis. These findings reveal critical roles for CD19+ DCs expressing IDO in host responses to MuLV infection that enhance pain hypersensitivity and cause immune pathology. Collectively, our findings support the hypothesis elevated IDO activity in non-CNS due to virus infections causes pain hypersensitivity mediated by Kyn. Previously unappreciated links between host immune responses to virus infections and pain sensitivity suggest that IDO inhibitors may alleviate heightened pain sensitivity during infections.
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PMID:Virus Infections Incite Pain Hypersensitivity by Inducing Indoleamine 2,3 Dioxygenase. 2716 85