Background: Regulatory T-cells (T-reg) play a central role in the immunopathogenesis of psoriasis. T-reg cells are both functionally and numerically impaired in psoriasis and they are up-regulated by drug therapy.
Objective: To analyse the circulating CD4+CD25 bright FOXP3+ subset in 14 patients with vulgaris/arthropathic psoriasis treated with biological drugs and to investigate their relationship with the clinical response.
Purpose: We describe and evaluate a new transperineal laparoscopic approach for male patients, designed to facilitate laparoscopic prostatectomy and cystectomy.
Patients And Methods: We operated on 12 patients. We did three laparoscopic prostatectomies and nine laparoscopic cystectomies.
Tyrosine phosphorylation is a newcomer in the mitochondrial signaling and is currently emerging as an important mechanism for regulating mitochondrial processes. But to what extent? By analyzing an updated draft of the mitochondrial tyrosine phosphoproteome, the following observations can be drawn: more than a hundred mitochondrial proteins undergo tyrosine phosphorylation, phosphotyrosine proteins are distributed in each of the submitochondrial compartments, and mitochondrial tyrosine phosphorylated proteins are involved in a variety of functions as metabolism (electron transport chain, Krebs cycle, fatty acid and amino acid metabolism), solute and protein transport, mitochondrial translation machinery, quality protein assessment, oxidative stress, apoptosis, fission, and other. This large and varied collection suggests that tyrosine phosphorylation could be a widespread mechanism in modulating mitochondrial functions.
View Article and Find Full Text PDFIn an attempt to evaluate the contribution of individual protein kinases to the generation of the human phosphoproteome, we performed a global weblogo analysis exploiting a database of 45641 phosphosites (80% pSer, 11% pTyr, 9% pThr). The outcome of this analysis was then interpreted by comparison with similar logos constructed from bona fide phospoacceptor sites of individual pleiotropic kinases. The main conclusions that were drawn are as follows: (i) the hallmarks surrounding phosphorylated Ser/Thr residues are more pronounced than and sharply different from those found around phosphorylated Tyr, which is consistent with the view that local consensus sequences are particularly important for substrate recognition by Ser/Thr protein kinases.
View Article and Find Full Text PDFIn active Graves' orbitopathy (GO), proinflammatory cytokines predominate. Circulating thyroid stimulating hormone (TSH)-receptor antibodies (TRAb) have been correlated with GO clinical activity and severity. In preliminary studies rituximab (RTX), an anti-CD 20 monoclonal antibody, has induced clinical improvement of active GO without a change in serum anti-thyroid antibodies.
View Article and Find Full Text PDFBy comparing the recurrent features of sequences surrounding 86 Ser/Thr residues phosphorylated in peptides from human plasma collected from literature with those generated from the whole human phosphoproteome, and from repertoires of validated substrates of the acidophilic protein kinases CK2 and Golgi casein kinase (GCK), the following conclusions can be drawn: (i) the contribution of Pro-directed and basophilic kinases to the plasma phosphoproteome is negligible, if any, while the contribution of acidophilic kinases is by far predominant; (ii) the plasma weblogo profile is closely reminiscent of that generated by GCK in its substrates, while it neatly differentiates from that generated by CK2; (iii) 58 plasma phosphosites out of 86 display the canonical consensus for GCK (S/T-x-E/pS), while that for CK2 (S/T-x-x-E/D/pS) is found in 15 peptides, all of which also conform to the GCK signature. These observations, in conjunction with a very similar situation disclosed by analyzing the phosphopeptides of the human cerebrospinal fluid collected from literature, support the view that GCK may play a major role in the phosphorylation of proteins secreted into body fluids.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
September 2010
Purpose: To study the clinical involvement of the ocular surface and the in vivo morphology of corneal cells and nerves, in patients affected by active and inactive Graves' orbitopathy (GO).
Methods: The study included 26 consecutive GO patients and 20 age- and sex-matched healthy control subjects. GO was diagnosed on the basis of the criteria of the European Group on Graves' Orbitopathy, and disease activity was evaluated by the Clinical Activity Score (CAS).
Until now, the following are not known: (1) the mechanisms underlying the induction of chemokine (C-X-C motif) ligand 10 (CXCL10) secretion by cytokines in thyrocytes; (2) if pioglitazone is able, like rosiglitazone, to inhibit the interferon (IFN)-γ-induced chemokine expression in Graves disease (GD) or ophthalmopathy (GO); and (3) the mechanisms underlying the inhibition by thiazolidinediones of the cytokines-induced CXCL10 release in thyrocytes. The aims of this study were (1) to study the mechanisms underlying the induction of CXCL10 secretion by cytokines in GD thyrocytes; (2) to test the effect of pioglitazone on IFNγ-inducible CXCL10 secretion in primary thyrocytes, orbital fibroblasts, and preadipocytes from GD and GO patients; and (3) to evaluate the mechanism of action of thiazolidinediones on nuclear factor (NF)-κB activation. The results of the study (1) demonstrate that IFNγ + TNFα enhanced the DNA binding activity of NF-κB in GD thyrocytes, in association with the release of CXCL10; (2) show that pioglitazone exerts a dose-dependent inhibition on IFNγ + TNFα-induced CXCL10 secretion in thyrocytes, orbital fibroblasts, and preadipocytes, similar to the effect observed with rosiglitazone; and (3) demonstrate that thiazolidinediones (pioglitazone and rosiglitazone) act by reducing the IFNγ + TNFα activation of NF-κB in Graves thyrocytes.
View Article and Find Full Text PDFLately, monoclonal antibodies directed to molecules of the immune system have become available. Rituximab (RTX) is a humanized chimeric anti-CD20 monoclonal antibody which blocks the activation and differentiation of B cells. The rationale for use in Graves' disease (GD) and orbitopathy is the potential effect on B-cell mediated immunity.
View Article and Find Full Text PDFBiochem Biophys Res Commun
September 2009
CK2 is a multifunctional kinase, involved in cell growth, apoptosis, DNA integrity preservation, viral infection, and many other biological processes. Based on an analysis of phosphopeptides database derived from phosphoproteomic studies we previously identified a list of potential new CK2 substrates, including, among others, Programmed Cell Death 5 (PDCD5), a protein involved in cell death and down-regulated in different forms of human tumors. Here we provide experimental evidence that PDCD5 is indeed a bona fide substrate of CK2.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
September 2009
Context: The reactivation of Graves' orbitopathy (GO) after radioiodine (RAI) for Graves' disease (GD) is a known effect, and its clinical relevance is controversial. Prevention of RAI-induced GO activation is possible in at-risk patients with oral glucocorticoids (OGC).
Objectives: The aim of the study was to analyze the effects of RAI on GO with or without prophylactic steroids based on known risk factors and to compare the effectiveness of prophylaxis with iv glucocorticoids (IVGC) and OGC.
Neurochem Res
November 2009
Present study was carried out to understand the possible mechanism of neuroprotective action of the root extract of Withania somnifera Dunal (WS). The study is focused on WS mediated inhibition of nitric oxide production, which is known to mediate neurodegeneration during stress. Adult mice (28 +/- 5 g) were exposed to restraint stress for 30 days.
View Article and Find Full Text PDFMitochondrial protein phosphorylation is emerging as a central event in mitochondrial signaling. In particular, tyrosine phosphorylation is proving to be an unappreciated mechanism involved in regulation of mitochondrial functions. Tyrosine kinases and phosphatases have been identified in mitochondrial compartments and there is a steadily increasing number of new identified tyrosine-phosphorylated proteins implicated in a wide spectrum of mitochondrial functions.
View Article and Find Full Text PDFA weblogo has been generated from the sequences surrounding 433 Ser/Thr protein residues whose phosphorylation by protein kinase CK2 had been previously validated ("bona fide" CK2 phosphosites). This has been compared to the weblogo extracted from 2275 putative CK2 phosphosites displaying the motif pS/pT-x1-x2-D/E/pS (where x1 not=P) present in the human phosphoElm database including 10899 naturally occurring phosphosites. The two weblogos are strikingly similar supporting the notion that indeed the 2275 putative sites (accounting for 20.
View Article and Find Full Text PDFRituximab (RTX) has been shown in previous work to improve thyroid-associated ophthalmopathy (TAO), but very little data is available on the effects of RTX in the target tissues. We studied the effects of RTX on peripheral lymphocytes and on the intra-orbital infiltrates in one patient with severe TAO who was treated with two cycles of therapy. Intra-orbital tissues derived at decompression from 3 patients with moderate-severe and 1 with severe TAO, treated with standard immunosuppression, were studied as controls.
View Article and Find Full Text PDFAim: To compare the outcome of various surgical approaches of orbital decompression in patients with Graves' orbitopathy (GO) receiving surgery for disfiguring proptosis.
Method: Data forms and questionnaires from consecutive, euthyroid patients with inactive GO who had undergone orbital decompression for disfiguring proptosis in 11 European centres were analysed.
Results: Eighteen different (combinations of) approaches were used, the swinging eyelid approach being the most popular followed by the coronal and transconjunctival approaches.
Background: The recommended antibiotic prophylaxis by second-generation cephalosporins reduces the incidence of wound infection and empyema, but its effectiveness on postoperative pneumonias (POPs) after major lung resection lacks demonstration. We investigated risk factors and characteristics of POPs occurring when antibiotic prophylaxis by second-generation cephalosporin or an alternative prophylaxis targeting organisms responsible for bronchial colonization was used.
Methods: An 18-month prospective study on all patients undergoing lung resections for noninfectious disease was performed.
Background: Results of pneumonectomy after chemotherapy are controversial, and the procedure is often considered as potentially dangerous.
Methods: Records of patients who underwent pneumonectomy after chemotherapy for non-small cell lung cancer in a single institution in a 6-year period were reviewed retrospectively.
Results: One hundred eighteen patients had pneumonectomy after chemotherapy.
Steroids have been used in the therapy of the moderate to severe forms of Graves' ophthalmopathy (GO) and other autoimmune diseases as they act only as general immunosuppressants. Previous work has shown that blocking the CD-20 receptor on B lymphocytes has significantly affected the clinical course of GO, by rapidly reducing inflammation and the degree of proptosis. We have studied nine patients with Graves' disease, of whom seven had active GO and two, with newly diagnosed hyperthyroidism, only mild lid signs.
View Article and Find Full Text PDFReversible protein-phosphorylation is emerging as a key player in the regulation of mitochondrial functions. In particular tyrosine phosphorylation represents a promising field to highlight new mechanisms of bioenergetic regulation. Utilizing immunoaffinity enrichment of phosphotyrosine-containing peptides coupled to mass spectrometric analysis we detected new tyrosine phosphorylated proteins in rat brain mitochondria after peroxovanadate treatment.
View Article and Find Full Text PDFHyperthyroid Graves' disease (GD) is a B-cell-mediated disease caused by antibodies stimulating the thyroid stimulating hormone (TSH) receptor (TRAb). A proportion of patients (40-60%) present with an associated ophthalmopathy (TAO), a progressive inflammatory autoimmune disease of the retroorbital tissue. We thought that the anti-CD20 monoclonal antibody rituximab (RTX), by inducing transient B-cell depletion, may potentially modify the active inflammatory phase of TAO.
View Article and Find Full Text PDFBackground: The aim of the study was to compare the change in quality of life over 32 weeks in depressed women assuming antidepressant drug with (experimental group) or without (control group) physical exercise from a study which results on objective dimension of outcome were already published.
Methods: Trial with randomized naturalistic control. Patients selected from the clinical activity registries of a Psychiatric University Unit.
Overlooked until recently, mitochondrial protein phosphorylation is now emerging as a key post-translational mechanism in the regulation of mitochondrial functions. In particular, tyrosine phosphorylation represents a promising field to discover new mechanisms of bioenergetic regulation. Tyrosine kinases belonging to the Src kinase family have been observed in mitochondrial compartments, however their substrates are almost unknown.
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