Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This investigation utilized immunocytochemical and fluorescent protocols to analyze the roles of cellular proliferation and apoptosis in the regulation of differentiation and senescence of the rat small intestinal mucosa. Specifically, the study localized apoptotic zones of the villus through the use of enzymatic tags; established the transition point between cell growth and differentiation, i.e. the point of no return where crypt cells differentiate into absorptive cells with barrier functions; and the role that plasmalemmal, cytoskeletal, junctional and extracellular matrix (ECM) elements may play in the regulation of differentiation and migration of epithelial cells from crypt to villus. Apoptosis was relegated to the villus tip forming a prominent 'apoptotic cuff' of cells. Close scrutiny of these cuffs reveals the presence of apoptotic cells adjacent to non-apoptotic (healthy) cells. Mid-villus epithelial cells were non-apoptotic and all cells in the crypt-villus unit expressed Bcl-2 activity. Intestinal lactase expression was prominent in post-mitotic cells along the villus, while cells in the crypt and base were negative for lactase activity. In contrast, all the cells of the crypt-villus unit were intensely reactive for F-actin. Close scrutiny of isolated cells and frozen sections indicates specific localization of actin in the microvillus region, apical cytoplasm, basolateral and lateral plasmalemma which was in close proximity to fibronectin in the basement lamina. Occludin positive junctional networks were prominent at villus tips, where senescent and apoptotic cells were also most prominent, suggesting that tight junctional integrity was essential to barrier, digestive and absorptive functions in all regions of the mucosa.
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PMID:Apoptosis and differentiation in the crypt-villus unit of the rat small intestine. 1036 52

Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large-cell lymphoma (DLBCL), we observed higher levels of JAK/STAT pathway-related serum cytokines (ie, IL-6, IL-10, epidermal growth factor, and IL-2) compared with controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event-free survival (EFS) than patients with low levels (P > .01) and high IL-10 was correlated with high lactase dehydrogenase (P = .0085) and higher International Prognostic Index scores (P = .01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL-10 on the JAK2 pathway and found that the IL-10/IL-10 receptor complex up-regulated JAK2 signaling. Neutralizing Ab to IL-10 inhibited constitutive and IL-10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2-positive DLBCL cells; there was a minimal effect on phospho-JAK2-negative cells. Apoptosis induced by JAK2 inhibition was dependent on inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients, and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy.
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PMID:Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation. 2232 54