Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aggressive systemic mastocytosis (ASM) is a clonal mast cell disease characterized by progressive growth of neoplastic cells in diverse organs leading to organopathy. The organ-systems most frequently affected are the bone marrow, skeletal system, liver, spleen, and the gastrointestinal tract. Respective clinical findings (so called C-Findings) include cytopenias, osteolysis (or osteoporosis) with pathologic fractures, hepatosplenomegaly with impaired liver function and ascites, and malabsorption. During the past decade several treatment strategies for ASM have been proposed. One promising approach may be combination treatment with interferon-alpha (IFN-alpha) and glucocorticoids. This concept has been based on the notion that systemic mastocytosis involves multilineage hematopoietic progenitors indicating a relationship with myeloproliferative disorders. However, relatively little is known about the quality of responses to IFN-alpha in ASM and the actual response rates. This may be due in part to the fact that disease criteria for ASM have only recently been established, and no response criteria are available. In the current article, we propose surrogate markers and treatment response criteria for patients with ASM. In addition, we have applied these criteria retrospectively to ASM patients described in the available literature. In these analyses, the calculated rate of major response (=complete resolution of C-Findings) in patients treated with IFN-alpha (with or without additional glucocorticoids) amounts to approximately 21%. This confirms clinical activity in some patients for this drug-combination, but also points to the need to search for more effective strategies in the treatment of patients with aggressive mast cell disorders.
 ...
PMID:Aggressive systemic mastocytosis and related mast cell disorders: current treatment options and proposed response criteria. 1268 63

Autoimmune diseases are characterised by lymphoproliferation in target tissues with B and T lymphocytes often arranged in pseudofollicles, mimicking the structure of peripheral lymph nodes. Target organ tissue damage produces the clinical phenotype which may be diverse ranging from autoimmune endocrinopathies to malabsorption (coeliac disease) to structural damage within bones and joints (rheumatoid arthritis). Recently, B cell depletion has been shown to be effective in many autoimmune conditions suggesting a common pathological origin for these conditions which might be triggered by an autoimmune B cell that has escaped deletion. We postulate that a mutation in a transcription factor early in B cell development might allow persistence and foster proliferation of a clone of autoimmune B cells, capable of producing autoantibodies. A similar common mutation within the JAK2 tyrosine kinase gene has recently been described associated with the myeloproliferative disorders which are also characterised by diverse clinical disease phenotypes. There is considerable evidence that autoimmune diseases could be indolent lymphoproliferative disorders of B-cell origin, extending the forbidden clone hypothesis first proposed in the 1950s.
 ...
PMID:B cell lymphoproliferation and organ-directed self-recognition to explain autoimmunity: back to the past. 2040 69