323 research outputs found
Laminin-6 and Laminin-5 Are Recognized by Autoantibodies in a Subset of Cicatricial Pemphigoid
We characterized basement membrane zone (BMZ) autoantigens targeted by autoantibodies (AAb) from patients with cicatricial pemphigoid. Serum from a patient with severe oral cicatricial pemphigoid contained IgG anti-BMZ AAb. The AAb labeled a lower BMZ component on salt-split skin and localized to the lower lamina lucida/lamina densa by direct and indirect immunoelectron microscopy (HEM) but did not label blood vessels. The AAb did not react with EHS laminin-1 and type IV collagen, pepsinized human type IV collagen, recombinant entactin, or NC1 domain of type VII collagen by dot blotting and western blotting. We focused our studies on the laminin family, as laminin-5 was identified as an autoantigen in cicatricial pemphigoid. Culture-conditioned media from normal keratinocytes (containing laminin-6 and laminin-5) and JEB keratinocytes (containing laminin-6 but not laminin-5) were studied by western blotting. Under nonreducing conditions, the patient's AAb recognized a 600-kDa protein (laminin-6) intensely and a 400-kDa protein (laminin-5) weakly in normal keratinocyte medium even though abundant laminin-5 was present. In JEB keratinocyte medium, however, the 600-kDa protein (laminin-6) alone was recognized by the patient's AAb. The AAb also immunolabeled BMZ of JEB skin that lacked laminin-5. The AAb from this patient and two other patients with anti-laminin-5 cicatricial pemphigoid immunoprecipitated both laminin-6 an4 laminin-5. Taken together, the results of IEM, non-reducing western blotting, immunoprecipitation, and JEB skin BMZ immunolabeling indicate that laminin-6, as well as laminin-5, is identified by the AAb from a subset of cicatricial pemphigoid patients. We propose the name âanti-laminin cicatricial pemphigoidâ for this subset
Produção de biodiesel e geração de energia elétrica a partir de óleo de mamona em Quixeramobim, CE.
Introdução; Fase agrĂcola - produção de mamona; Fase industria l- extração de Ăłleo e transesterificação; Fase final - geração de energia elĂ©trica; ConsideraçÔes finais.bitstream/CNPA/17471/1/DOC136.pd
Continuous Subcutaneous Insulin Infusion in Patients With Type 2 Diabetes A Cohort Study to Establish the Relationship Between Glucose Control and Plasma Oxidized Low Density Lipoprotein
Background: Oxidative stress is a detrimental feature of diabetes implicated in the progression of the disease and its complications. The relationship between insulin therapy and oxidative stress is complex. This study tested the hypothesis that improved glucose control, rather than insulin dose, is central to reduced oxidative stress in patients with type 2 diabetes following continuous subcutaneous insulin infusion (CSII). Methods: In this 16-week, multicenter study, 54 CSII-naĂŻve patients with type 2 diabetes (age 57 ± 10 years, HbA1c 69 ± 15 mmol/mol [8.5 ± 1.4%], diabetes duration 13 ± 6 years) treated with either oral antidiabetic agents (OAD) alone (n = 17), basal insulin ± OAD (n = 17), or multiple daily injections (MDI) ± OAD (n = 20) were the evaluable group. Diabetes medications except metformin were discontinued, and 16 weeks of CSII was initiated. Insulin dose was titrated to achieve optimal glycemic control. A plasma marker of oxidative stress relevant to cardiovascular disease (oxidized low density lipoprotein [ox-LDL]) was assessed at baseline and week 16. Results: CSII improved glycemic control (HbA1c â13 ± 2 mmol/mol [â1.2 ± 0.2%]; fasting glucose â36.6 ± 8.4 mg/dL; mean glucose excursion â23.2 ± 6.5 mg/dL, mean ± SE; all P .05), but was significantly more pronounced in patients on statins (P = .019). The effect of CSII was more closely correlated to improvements in glucose excursion (P = .013) than to insulin dose (P > .05) or reduction in HbA1c (P > .05). Conclusions: CSII induces depression of plasma ox-LDL associated with change in glucose control, rather than with change in insulin dose. The effect is augmented in patients receiving statins
Retroperitoneal Castleman's tumor and paraneoplastic pemphigus: report of a case and review of the literature
BACKGROUND: Castleman's disease is a rare lymphoproliferative syndrome. Its etiology and pathogenesis are unclear. The disease can be occasionally associated with a paraneoplastic pemphigus (PNP), an autoimmune mucocutaneous disorder commonly seen in neoplasms of lymphocytic origin. CASE PRESENTATION: We present a case of a 63-year old male patient who was referred for surgical treatment of a lately diagnosed retroperitoneal pelvic mass. The patient had been already treated for two years due to progressive diffuse cutaneous lesions histologically consistent with lichen ruber verucosus and pemphigus vulgaris. Intraoperatively a highly vascularized solid mass occupying the small pelvis was resected after meticulous vascular ligation and hemostasis. After surgery and following immunosuppressive treatment a clear remission of the skin lesions was observed. CONCLUSION: Castleman's tumor should be always suspected when a retroperitoneal mass is combined with PNP. In a review of the literature we found 37 additional cases. Complete surgical resection of the tumor can be curative in most of the cases
The Protease Inhibitor Alpha-2-Macroglobuline-Like-1 Is the p170 Antigen Recognized by Paraneoplastic Pemphigus Autoantibodies in Human
Paraneoplastic pemphigus (PNP) is a devastating autoimmune blistering disease, involving mucocutaneous and internal organs, and associated with underlying neoplasms. PNP is characterized by the production of autoantibodies targeting proteins of the plakin and cadherin families involved in maintenance of cell architecture and tissue cohesion. Nevertheless, the identity of an antigen of Mr 170,000 (p170), thought to be critical in PNP pathogenesis, has remained unknown
KlimafolgenabschĂ€tzungen in der Wasserwirtschaft und deren Nutzen fĂŒr die Praxis
KlimafolgenClimate ImpactsDer globale Klimawandel kann regional unterschiedliche Auswirkungen haben. WĂ€hrend sich die wissenschaftliche Forschung vor allem mit der Analyse der Daten beschĂ€ftigt, ist die fachliche Praxis darum bemĂŒht, die Ergebnisse zu interpretieren und Handlungsempfehlungen daraus abzuleiten. Im Zuge des Projektes KliBiW (Globaler Klimawandel â Wasserwirtschaftliche FolgenabschĂ€tzung fĂŒr das Binnenland) wurden die Auswirkungen des Klimawandels auf die Hochwasser- und NiedrigwasserverhĂ€ltnisse in Niedersachsen untersucht. Hierzu wurden die Daten von zwei regionalen Klimamodellen (WETTREG2006 und REMO), beide angetrieben durch das Globalmodell ECHAM5/MPI-OM, rĂ€umlich interpoliert und die NiederschlĂ€ge zum Teil zeitlich disaggregiert, um hoch aufgelöste Klimainformationen bereitzuhalten. AnschlieĂend erfolgte die Kopplung mit einem hydrologischen Modellsystem (PANTA RHEI), das bereits in der Hochwasservorhersagezentrale des NLWKN im Einsatz ist. Ăber Langzeitsimulationen wurden zukĂŒnftige VerĂ€nderungen in den AbflussverhĂ€ltnissen rĂ€umlich und zeitlich differenziert fĂŒr das Aller-Leine Gebiet identifiziert. Als BetrachtungszeitrĂ€ume dienten eine nahe Zukunftsphase (2021 â 2050) und eine ferne Zukunftsphase (2071 â 2100). Die VerĂ€nderungen verschiedener hydrologischer Hoch- und Niedrigwasser-KenngröĂen wurden gegenĂŒber einem Kontrollzeitraum (1971 â 2000) aufgezeigt. Die Auswertungen an 8 Pegeln in Einzugsgebieten >1.000 kmÂČ auf Tageswertbasis und an 6 Pegeln in Einzugsgebieten <1.000 kmÂČ auf Stundenwertbasis zeigten, dass sich die Hochwassersituation zukĂŒnftig verschĂ€rfen kann. WĂ€hrend kleinere HochwĂ€sser hĂ€ufiger auftreten können, nehmen die ScheitelabflĂŒsse insbesondere in der fernen Zukunft zu. Aussagen zu gröĂeren Ereignissen sind aufgrund der groĂen Bandbreite der Ergebnisse jedoch mit erheblichen Unsicherheiten behaftet. Die NiedrigwasserverhĂ€ltnisse zeigten eine Abnahme der AbflĂŒsse, speziell im Sommer, sowie eine Zunahme der Dauer undnder Volumendefizite bei Trockenperioden. Hierbei erschien die VariabilitĂ€t und AusprĂ€gung der Trockenheit in kleineren Einzugsgebieten etwas gröĂer. Die Nutzung dieser Erkenntnisse stellt die fachliche Praxis vor die Herausforderung, die Ergebnisse zu interpretieren und zu kommunizieren. Unsicherheiten in den Modellketten mĂŒssen berĂŒcksichtigt und, wenn möglich, quantifiziert werden. Die abgeleiteten hydrologischen Konsequenzen des Klimawandels können z.B. Anwendung finden in der gesetzlich geforderten BerĂŒcksichtigung der Auswirkungen des Klimawandels auf die Risikogebiete entsprechend der Hochwasserrisikomanagement-Richtlinie (2007/60/EG). Dieser Beitrag gibt einen Ăberblick ĂŒber wasserwirtschaftlich relevante Auswertungen von Klimamodelldaten auf unterschiedlichen rĂ€umlichen Skalen und zeigt anhand ausgewĂ€hlter Beispiele auf, wie primĂ€r im wissenschaftlichen Kontext erhobene Ergebnisse effektiv fĂŒr praxisrelevante Fragestellungen genutzt werden können
BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease.
Interstitial lung disease (ILD) is a complex and heterogeneous disorder that is often associated with autoimmune syndromes. Despite the connection between ILD and autoimmunity, it remains unclear whether ILD can develop from an autoimmune response that specifically targets the lung parenchyma. We examined a severe form of autoimmune disease, autoimmune polyglandular syndrome type 1 (APS1), and established a strong link between an autoimmune response to the lung-specific protein BPIFB1 (bactericidal/permeability-increasing fold-containing B1) and clinical ILD. Screening of a large cohort of APS1 patients revealed autoantibodies to BPIFB1 in 9.6% of APS1 subjects overall and in 100% of APS1 subjects with ILD. Further investigation of ILD outside the APS1 disorder revealed BPIFB1 autoantibodies present in 14.6% of patients with connective tissue disease-associated ILD and in 12.0% of patients with idiopathic ILD. The animal model for APS1, Aireâ»/â» mice, harbors autoantibodies to a similar lung antigen (BPIFB9); these autoantibodies are a marker for ILD. We found that a defect in thymic tolerance was responsible for the production of BPIFB9 autoantibodies and the development of ILD. We also found that immunoreactivity targeting BPIFB1 independent of a defect in Aire also led to ILD, consistent with our discovery of BPIFB1 autoantibodies in non-APS1 patients. Overall, our results demonstrate that autoimmunity targeting the lung-specific antigen BPIFB1 may contribute to the pathogenesis of ILD in patients with APS1 and in subsets of patients with non-APS1 ILD, demonstrating the role of lung-specific autoimmunity in the genesis of ILD
Rebranding asymptomatic type 1 diabetes: the case for autoimmune beta cell disorder as a pathological and diagnostic entity
Injectable gellan gum-based nanoparticles-loaded system for the local delivery of vancomycin in osteomyelitis treatment
Infection spreading in the skeletal system
leading to osteomyelitis can be prevented by the prolonged
administration of antibiotics in high doses. However systemic
antibiotherapy, besides its inconvenience and often
low efficacy, provokes numerous side effects. Thus, we
formulated a new injectable nanoparticle-loaded system for
the local delivery of vancomycin (Vanc) applied in a
minimally-invasive way. Vanc was encapsulated in poly(Llactide-
co-glycolide) nanoparticles (NPs) by double-emulsification.
The size (258 ± 11 nm), polydispersity index
(0.240 ± 0.003) and surface potential (-25.9 ± 0.2 mV)
of NPs were determined by dynamic light scattering and
capillary electrophoresis measurements. They have a
spherical morphology and a smooth topography as
observed using atomic force microscopy. Vanc loading and
encapsulation efficiencies were 8.8 ± 0.1 and
55.2 ± 0.5 %, respectively, based on fluorescence spectroscopy
assays. In order to ensure injectability, NPs were
suspended in gellan gum and cross-linked with ; also a
portion of dissolved antibiotic was added to the system.
The resulting system was found to be injectable (extrusion
force 11.3 ± 1.1 N), reassembled its structure after
breaking as shown by rheology tests and ensured required
burst release followed by sustained Vanc delivery. The
system was cytocompatible with osteoblast-like MG-63
cells (no significant impact on cellsâ viability was detected). Growth of Staphylococcus spp. reference strains
and also those isolated from osteomyelitic joints was
inhibited in contact with the injectable system. As a result
we obtained a biocompatible system displaying ease of
application (low extrusion force), self-healing ability after
disruption, adjustable drug release and antimicrobial
properties
- âŠ