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

Plasma samples from mice bearing the BCL1 leukemia were shown to express elevated levels of neutral proteinase activity when assayed with radioiodinated casein as a substrate. Increased plasma proteinase activity reached levels 3-4-fold higher than controls. The increased levels of activity did not correlate with the degree of hepatosplenomegaly or the number of tumor cells in the blood. The onset of the increase in plasma activity correlated with the onset of the leukemic phase of the disease. These findings with the murine leukemia may be analogous to recent findings of abnormal proteinase activity in plasma from patients with acute leukemia.
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PMID:Increased plasma proteinase activity of mice bearing the BCL1 leukemia. 389 42

Human granzyme H is a neutral serine protease that is expressed predominantly in the lymphokine-activated killer (LAK)/natural killer (NK) compartment of the immune system. The gene that encodes this granzyme is located between the granzyme B and cathepsin G genes on human chromosome 14q11.2. Although the murine orthologue of human granzyme H has not yet been identified, murine granzymes C, D, E, F, and G also lie between the murine granzyme B and cathepsin G genes on murine chromosome 14; murine granzymes C, D, and F are also highly expressed in LAK cells, but minimally in cytotoxic T lymphocytes (CTL). We therefore tested whether the 5' flanking region of human granzyme H contains the cis-acting DNA sequences necessary to target a reporter gene to the LAK/NK compartment of transgenic mice. A 1.2-kb fragment of 5' flanking human granzyme H sequence was linked to an SV40 large T-antigen (TAg) reporter gene and used to create six transgenic founder lines. SV40 TAg was specifically expressed in the LAK cells of these mice, but not in resting T or NK cells, in CTL, or in any other tissues. Most mice eventually developed a fatal illness characterized by massive hepatosplenomegaly and disseminated organ infiltration by large malignant lymphocytes. Cell lines derived from splenic tumors were TAg+ and NK1.1(+) large granular lymphocytes and displayed variable expression of CD3, CD8, and CD16. Although these cell lines contained perforin and expressed granzymes A, B, C, D, and F, they did not exhibit direct cytotoxicity. Collectively, these results suggest that the 5' flanking sequences of the human granzyme H gene target expression to an NK/T progenitor compartment and to activated NK (LAK) cells. Mice and humans may therefore share a regulatory "program" for the transcription of NK/LAK specific granzyme genes.
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PMID:The 5' flanking region of the human granzyme H gene directs expression to T/natural killer cell progenitors and lymphokine-activated killer cells in transgenic mice. 992 Aug 46