Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coagulopathy is a life-threatening complication of liver cirrhosis. We describe the effect of molecular adsorbent recirculating system (MARS), a cell-free dialysis technique, on the blood coagulation of cirrhotic patients. From February 2002 to July 2002, nine patients--five males (55.5%) and four females (44.4%), age 47-70 yr (median 56)--underwent 12 courses (4-7 sessions each) of MARS. Patients were treated for the following indications: six (66.6%) acute-on-chronic hepatic failure, three (33.3%) intractable pruritus. Platelet count, prothrombin time (PT), international standardized ratio and thromboelastography were measured before and after each MARS session. Coagulation factors II, V, VII, VIII, IX, X, XI, XII, XIII, von Willebrand, lupus anticoagulant, protein C, protein S, antithrombin III, plasminogen, alpha 2 antiplasmin, D-dimer, fibrin monomers, complement, and C(1) inactivator were measured before and at the end of each MARS treatment. We found a statistically significant difference (p < 0.05) in the platelet count, PT, all the thromboelastograph variables (reaction and constant time, alpha angle, and maximal amplitude), factor VIII, von Willebrand, and D-dimer, when measured before and after MARS. Previous reports have shown amelioration of blood coagulation following MARS treatments. However, we document that MARS induces coagulopathy through a platelet-mediated mechanism, whereby platelet may be mechanically destroyed during the passage of blood through the filters and lines. An alternative postulated mechanism is an immune-mediated platelet disruption - coagulopathy.
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PMID:Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system. 1523 11

p63, a member of the p53 family of transcription factors, plays an important role in epithelial development, regulating both cell cycle and apoptosis. Even though p63 activity is regulated mainly at the posttranslational level, the control of p63 protein stability is far from being fully understood. Here, we show that the Hect (homologous to the E6-associated protein C terminus)-containing Nedd4-like ubiquitin protein ligase Itch binds, ubiquitylates, and promotes the degradation of p63. The physical interaction occurs at the border between the PY and the SAM (sterile alpha motif) domains; a single Y504F mutation significantly affects p63 degradation. Itch and p63 are coexpressed in the epidermis and in primary keratinocytes where Itch controls the p63 protein steady-state level. Accordingly, p63 protein levels are significantly increased in Itch knockout keratinocytes. These data suggest that Itch has a fundamental role in the mechanism that controls endogenous p63 protein levels and therefore contributes to regulation of p63 in physiological conditions.
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PMID:The E3 ubiquitin ligase Itch controls the protein stability of p63. 1690 49

A 50-year-old diabetic female presented with highly pruritic vesicles and excoriated lesions over the anterior aspect of both lower legs. The lesions were recurrent over the last two years. She received a lot of medications with partial response. Hb A1c was 10.8% (normal up to 7%). CBC showed microcytic, hypochromic anemia. Serum zinc, folate, IgE, TSH and T4 were all within normal ranges. Biopsy showed epidermal separation secondary to keratinocyte necrosis and minimal monocytic, perivascular infiltrate. Direct immunofluorescence was negative for intraepidermal and subepidremal deposition of immunoglobulin. The dermis was positive for mucin deposition stainable by both PAS and Alcian blue while it was negative for Congo red and APC immunoperoxidase staining for amyloid material. In conclusion, the case was diagnosed as bullosis diabeticorum by distinctive clinical and pathological features and after exclusion of other possible differentials. Pruritus was partially controlled by topical potent steroid and the case was resolved spontaneously after eight months.
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PMID:Pruritic vesicular eruption on the lower legs in a diabetic female. 2419 86

Itch or itchy E3 ubiquitin ligase was initially discovered by genetic studies on the mouse coat color changes, and its deletion results in an itchy phenotype with constant skin scratching and multi-organ inflammation. It is a member of the homologous to E6-associated protein C-terminus (HECT)-type family of E3 ligases, with the protein-interacting WW-domains for the recruitment of substrate and the HECT domain for the transfer of ubiquitin to the substrate. Since its discovery, numerous studies have demonstrated that Itch is involved in the control of many aspects of immune responses including T-cell activation and tolerance and T-helper cell differentiation. Itch is also implicated in other biological contexts such as tumorigenesis, development, and stress responses. Many signaling pathways are regulated by Itch-promoted ubiquitylation of diverse target proteins. Itch is also involved in human diseases. Here, we discuss the major progress in understanding the biological significance of Itch-promoted protein ubiquitylation in the immune and other systems and in Itch-mediated regulation of signal transduction.
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PMID:The E3 ligase Itch in immune regulation and beyond. 2608 4