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61.
Complement receptor 2 (CR2) and its physiological ligand, C3d, known for its molecular adjuvant property on the immune response, exhibit opposite effects with regard to autoimmunity. Although CR2 has been implicated in maintaining self-tolerance, recent studies reported a role for C3d signaling to CR2 in tolerance breakdown to self-antigens and the initiation of inflammatory autoimmune pathologies. In the present study, we have investigated the effect of C3d in a model of tolerogenic DNA vaccination encoding the myelin oligodendrocyte glycoprotein (MOG-DNA) which protected mice from the induction of an experimental autoimmune encephalomyelitis (EAE). We show that fusing two or three copies of C3d to MOG overcomes the protective effect of DNA vaccination. Multimeric C3d was able to revert the unresponsiveness state of specific T cells induced by MOG-DNA, independently of a modification in the Th1/Th2 cytokine pattern. Interestingly, the adjuvant effect of C3d was not sufficient to boost the anti-MOG antibody response after DNA vaccination. These findings suggest that C3d might be involved in self-tolerance breakdown and could contribute to the pathogenesis of central nervous system autoimmune disorders. 相似文献
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Korobelnik Jean-François Daien Vincent Faure Céline Tadayoni Ramin Giocanti-Auregan Audrey Dot Corinne Kodjikian Laurent Massin Pascale 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2020,258(3):521-528
Graefe's Archive for Clinical and Experimental Ophthalmology - To report the effectiveness of intravitreal aflibercept (IVT-AFL) treatment for diabetic macular edema (DME) in French clinical... 相似文献
65.
Pierre Bigot Tarek Fardoun Jean Christophe Bernhard Evanguelos Xylinas Julien Berger Morgan Rouprêt Jean-Baptiste Beauval Samuel Lagabrielle Souhil Lebdai Myriam Ammi Hervé Baumert Bernard Escudier Nicolas Grenier Jean-François Hétet Jean-Alexandre Long Philippe Paparel Nathalie Rioux-Leclercq Michel Soulié Abdel-Rahmène Azzouzi Karim Bensalah Jean-Jacques Patard 《World journal of urology》2014,32(1):109-114
Objective
To assess the effect of neoadjuvant targeted molecular therapies (TMTs) on size and level of inferior vena cava tumor thrombi and to evaluate their impact on surgical management.Methods
We retrospectively analyzed the data of 14 patients treated for a clear cell renal cell carcinoma with inferior vena cava thrombi by neoadjuvant TMT before nephrectomy. Clinical, pathological and perioperative data were gathered retrospectively at each institution. The primitive tumor size and the thrombus size were defined by computed tomography before TMT. The tumor thrombus level was defined according to the Novick’s classification.Results
Before TMT, thrombus level was staged I for 1 (7 %), II for 10 (72 %) and III (21 %) for 3 patients. First-line therapy was sunitinib in 11 cases and sorafenib in 3 cases. Median therapy duration was two cycles (1–5). Three patients experienced major adverse effects (grade III) during TMT. Following TMT, 6 (43 %) patients had a measurable decrease, 6 (43 %) had no change, and 2 (14 %) had an increase in the thrombus. One patient (7 %) had a downstage of thrombus level, 12 (85 %) had stable thrombi, and 1 (7 %) had an upstage. Regarding primary tumor, 7 (50 %), 5 (36 %) and 2 (14 %) patients had a decrease, stabilization and an increase in tumor size, respectively.Conclusion
Neoadjuvant TMT appears to have limited effects on renal tumor thrombi. This retrospective study failed to demonstrate a significant impact of neoadjuvant TMT on surgical management of clear cell renal cell carcinoma with inferior vena cava tumor thrombi. 相似文献66.
Mathilde Horn Stephane Potvin Jean-Fran?ois Allaire Gilles C?té Gabriella Gobbi Karim Benkirane Jeanne Vachon Alexandre Dumais 《Revue canadienne de psychiatrie》2014,59(8):441-449
Objective:
Borderline and antisocial personality disorders (PDs) share common clinical features (impulsivity, aggressiveness, substance use disorders [SUDs], and suicidal behaviours) that are greatly overrepresented in prison populations. These disorders have been associated biologically with testosterone and cortisol levels. However, the associations are ambiguous and the subject of controversy, perhaps because these heterogeneous disorders have been addressed as unitary constructs. A consideration of profiles of people, rather than of exclusive diagnoses, might yield clearer relationships.Methods:
In our study, multiple correspondence analysis and cluster analysis were employed to identify subgroups among 545 newly convicted inmates. The groups were then compared in terms of clinical features and biological markers, including levels of cortisol, testosterone, estradiol, progesterone, and sulfoconjugated dehydroepiandrosterone (DHEA-S).Results:
Four clusters with differing psychiatric, criminal, and biological profiles emerged. Clinically, one group had intermediate scores for each of the tested clinical features. Another group comprised people with little comorbidity. Two others displayed severe impulsivity, PD, and SUD. Biologically, cortisol levels were lowest in the last 2 groups and highest in the group with less comorbidity. In keeping with previous findings reported in the literature, testosterone was higher in a younger population with severe psychiatric symptoms. However, some apparently comparable behavioural outcomes were found to be related to distinct biological profiles. No differences were observed for estradiol, progesterone, or DHEA-S levels.Conclusions:
The results not only confirm the importance of biological markers in the study of personality features but also demonstrate the need to consider the role of comorbidities and steroid coregulation. 相似文献67.
Chet E. Holterman Jean-Fran?ois Thibodeau Chelsea Towaij Alex Gutsol Augusto C. Montezano Robin J. Parks Mark E. Cooper Rhian M. Touyz Christopher R.J. Kennedy 《Journal of the American Society of Nephrology : JASN》2014,25(4):784-797
NADPH oxidase (Nox) enzymes are a significant source of reactive oxygen species, which contribute to glomerular podocyte dysfunction. Although studies have implicated Nox1, -2, and -4 in several glomerulopathies, including diabetic nephropathy, little is known regarding the role of Nox5 in this context. We examined Nox5 expression and regulation in kidney biopsies from diabetic patients, cultured human podocytes, and a novel mouse model. Nox5 expression increased in human diabetic glomeruli compared with nondiabetic glomeruli. Stimulation with angiotensin II upregulated Nox5 expression in human podocyte cultures and increased reactive oxygen species generation. siRNA-mediated Nox5 knockdown inhibited angiotensin II–stimulated production of reactive oxygen species and altered podocyte cytoskeletal dynamics, resulting in an Rac-mediated motile phenotype. Because the Nox5 gene is absent in rodents, we generated transgenic mice expressing human Nox5 in a podocyte-specific manner (Nox5pod+). Nox5pod+ mice exhibited early onset albuminuria, podocyte foot process effacement, and elevated systolic BP. Subjecting Nox5pod+ mice to streptozotocin-induced diabetes further exacerbated these changes. Our data show that renal Nox5 is upregulated in human diabetic nephropathy and may alter filtration barrier function and systolic BP through the production of reactive oxygen species. These findings provide the first evidence that podocyte Nox5 has an important role in impaired renal function and hypertension.Albuminuria is a clinical marker of kidney dysfunction that arises in most glomerulopathies and is associated with poor prognoses for ESRD, hypertension, and cardiovascular mortality. Changes to the podocyte (e.g., foot process effacement, hypertrophy, detachment, and loss) underlie the development and progression of albuminuria and thereby highlight the critical role for these cells in upholding the glomerular filtration barrier.1,2 Therefore, identifying factors that induce podocyte injury and loss is essential to understanding the mechanisms of filtration barrier dysfunction.Of the many factors implicated in podocyte dysfunction, excessive production of reactive oxygen species (ROS; oxidative stress) may be particularly important.3–6 Although sources of ROS are numerous, the NADPH oxidase (Nox) family of enzymes yields significant superoxide production in the kidney.7–10 Nox-induced ROS production has been closely linked to various glomerular pathologies. In animal models of minimal change disease, membranous nephropathy, and FSGS, inhibition of Nox activity is associated with decreased podocyte effacement and amelioration of albuminuria.11–14 In models of diabetic nephropathy, treatment with the Nox inhibitor apocynin, as well the antioxidant vitamin E, reduces oxidative stress, podocyte effacement and loss, and albuminuria.6,15,16 Noxs are regulated by many factors, including the renin angiotensin aldosterone system.5,9 Several studies have linked increased renin angiotensin aldosterone system activity to enhanced renal Nox activity and ROS generation.5,17 Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers slow progression of proteinuria in models of diabetes, and these effects may be, in part, independent of their effects on systemic BP,17–20 because direct activation of Nox enzymes through the angiotensin II (AngII)/AT1 receptor (AT1R) pathway leads to oxidative stress. In vitro studies in both human and rodent cell lines have also shown that Nox family member expression and activity are regulated by disease-associated factors, including AngII, ET-1, TGF-β, high glucose, mechanical stretch, and PDGF (factors that are upregulated in the diabetic milieu).3,21–23The roles of Nox4, and to a lesser extent, Nox1 and -2, in the kidney have been examined, but nothing is known regarding the role of the most recently identified member of the Nox family, Nox5. The Nox5 gene is absent from the mouse and rat genomes, making the use of conventional animal models unfeasible. Unlike other Nox family members, Nox5 does not require membrane-bound or cytosolic components, such as p22phox or p47phox, for its activity, but is tightly regulated by changes in intracellular calcium levels.24,25 Nox5 has a large amino terminal EF hand-containing domain that plays a critical role in its calcium-dependent activation along with several phosphorylation sites that alter the sensitivity of Nox5 to intracellular calcium.26–29 Because AngII increases intracellular calcium concentrations, it seems to induce renal Nox5-dependent ROS generation, which was shown in human endothelial cells.23 Here, we show that (1) Nox5 is upregulated in human diabetic glomeruli; (2) AngII stimulates ROS generation in human podocytes in a Nox5-dependent manner, a process associated with actin cytoskeletal reorganization and activation of Rac GTPase, which promotes podocyte motility in vitro; (3) mice that express human Nox5 in a podocyte-specific manner (Nox5βpod+ mice) exhibit renal dysfunction, including albuminuria, podocyte effacement, glomerular basement membrane (GBM) thickening, interstitial fibrosis, and hypertension; and (4) Nox5pod+ mice subjected to streptozotocin (STZ)-induced diabetes develop a more severe kidney phenotype than nontransgenic littermates. These novel data indicate the potential importance of podocyte Nox5 in human renal pathologies, such as diabetic nephropathy. 相似文献
68.
Jean-François Le Brun MD Loic Campion MD Dominique Berton-Rigaud MD Gérard Lorimier MD Frédéric Marchal MD PhD Gwenael Ferron MD Anne Sophie Oger MD François Dravet MD Isabelle Jaffre MD Jean-Marc Classe MD PhD 《Annals of surgical oncology》2014,21(11):3621-3627
Background
Hyperthermic intraperitoneal chemotherapy (HIPEC) and complete surgical removal of the tumor, in relapsing patients may provide a clinical benefit. There is no consensus considering the place of HIPEC for patients who had first ovarian cancer relapse. To assess for possible efficacy of HIPEC on overall survival (OS) rates in this situation, we performed a multi-institutional study.Methods
The current study was a retrospective case control multi-institutional study comparing a group of patients treated with HIPEC to a group of patients treated without HIPEC. Inclusion criteria were first relapse of a serous ovarian carcinoma and >6 months after the end of initial treatment. Exclusion criteria were another pathological subtype of ovarian cancer, a relapse at <6 months after initial treatment, and a second relapse or more. We aimed to assess OS, morbidity, and mortality rates and prognostic factors.Results
From June 1997–July 2011, 42 patients were included, 23 in the HIPEC group and 19 in the control group. Each patient from the two groups had a complete secondary surgery at the time of the first relapse. At 4 years OS was 75.6 % in the HIPEC group and 19.4 % in the control group (p = 0.013). In a multivariate analysis, HIPEC and interval-free before the end of initial treatment were both independent prognostic factors.Conclusion
When compared to the control group, complete secondary surgery and HIPEC appear to afford a better OS rate than complete secondary surgery alone, in case of first ovarian cancer relapse. Further randomized trials are warranted to confirm these results. 相似文献69.
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