BackgroundAutoimmune retinal degeneration may occur in patients who present with sudden or, less commonly, subacute loss of vision of retinal origin, associated with an abnormal ERG, through the action of autoantibodies against retinal proteins. Often the patients are initially diagnosed with or suspected of having a paraneoplastic retinopathy (PR), such as cancer-associated retinopathy (CAR). However, there is limited information on the occurrence, the specificity of autoantibodies in these patients, and their association with clinical symptoms.MethodsSera were obtained from 193 retinopathy patients who presented with clinical symptoms resembling PR or autoimmune retinopathy (AR), including sudden painless loss of vision, typically associated with visual field defects and photopsias, and abnormal rod and/or cone responses on the electroretinogram (ERG). Sera were tested for the presence of anti-retinal autoantibodies by Western blot analysis using proteins extracted from human retina and by immunohistochemistry. Autoantibody titers against recoverin and enolase were measured by ELISA.ResultsWe identified a higher prevalence of anti-retinal autoantibodies in retinopathy patients. Ninety-one patients' sera (47.1%) showed autoantibodies of various specificities with a higher incidence of antibodies present in retinopathy patients diagnosed with cancer (33/52; 63.5%; p = 0.009) than in retinopathy patients without cancer (58/141; 41.1%). The average age of PR patients was 62.0 years, and that of AR patients was 55.9 years. Autoantibodies against recoverin (p23) were only present in the sera of PR patients, autoantibodies against unknown p35 were more common in patients with AR, while anti-enolase (anti-p46) autoantibodies were nearly equally distributed in the sera of patients with PR and those with AR. In the seropositive patients, the autoantibodies persisted over a long period of time – from months to years. A rebound in anti-recoverin autoantibody titer was found to be associated with exacerbations in visual symptoms but not in the recurrence of cancer. When compared to sera from healthy subjects, autoantibodies against retinal proteins from both groups of patients were cytotoxic to retinal cells, indicating their pathogenic potential.ConclusionsThese studies showed that patients with sudden or subacute, unexplained loss of vision of retinal origin have anti-retinal antibodies in a broad range of specificity and indicate the need for autoantibody screening. Follow-up tests of antibody levels may be useful as a biomarker of disease activity associated with worsening of vision. Moreover, the heterogeneity in autoantibody specificity may explain the variation and complexity of clinical symptoms in retinopathy patients.
Paraneoplastic retinopathies (PR), including cancer-associated retinopathy (CAR) or the closely related melanoma-associated retinopathy (MAR) occur in a small subset of patients with retinal degeneration and systemic cancer. This autoimmune syndrome is characterized by sudden, progressive loss of vision in association with circulating anti-retinal autoantibodies. The PR syndromes are heterogeneous, may produce a number of ocular symptoms, and may be associated with several different neoplasms, including lung, breast, prostate, gynecological, and colon cancer, melanoma, and hematologic malignancies. We examined the onset of retinopathy in correlation to the diagnosis of cancer and the presence of specific anti-retinal autoantibodies in PR patients. In some patients without diagnosed malignant tumors, the onset of ocular symptoms and the presence of autoantibodies preceded the diagnosis of cancer by months to years, including anti-recoverin, antitransducin-α, and anti-carbonic anhydrase II antibodies. Although anti-retinal autoantibodies may not be a good predictor of a specific neoplasm, they can be used as biomarkers for different subtypes of retinopathy. Identification of autoantibodies involved in autoimmune-mediated PR will help elucidate the mechanisms underlying the PR syndromes and develop targeted therapies for these sight-threatening disorders. KeywordsCancer-associated retinopathy; anti-retinal autoantibodies; recoverin; enolase; autoimmune retinopathy Take home message• Retinal autoantigens can be used as biomarkers for different subtypes of CAR.• Autoantibodies to retinal antigens that also recognize tumor autoantigens may be useful biomarkers for the cause and origin of paraneoplastic disease.• In some patients, the onset of ocular symptoms and the detection of anti-retinal autoantibodies may precede the diagnosis of systemic cancer.• The recognition of retinopathy as part of a paraneoplastic syndrome should prompt an immediate search for an occult neoplasm.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. • Early detection of anti-retinal autoantibodies may serve to identify those who are at risk of retinal deterioration and blindness. NIH Public Access
A novel type of hydrolase was purified from culture fluid of Paucimonas (formerly Pseudomonas) lemoignei. Biochemical characterization revealed an unusual substrate specificity of the purified enzyme for amorphous poly((R)-3-hydroxyalkanoates) (PHA) such as native granules of natural poly((R)-3-hydroxybutyrate) (PHB) or poly((R)-3-hydroxyvalerate) (PHV), artificial cholatecoated granules of natural PHB or PHV, atactic poly((R,S)-3-hydroxybutyrate), and oligomers of (R)-3-hydroxybutyrate (3HB) with six or more 3HB units. The enzyme has the unique property to recognize the physical state of the polymeric substrate by discrimination between amorphous PHA (good substrate) and denatured, partially crystalline PHA (no substrate). The pentamers of 3HB or 3HV were identified as the main products of enzymatic hydrolysis of native PHB or PHV, respectively. No activity was found with any denatured PHA, oligomers of (R)-3HB with five or less 3HB units, poly(6-hydroxyhexanoate), substrates of lipases such as tributyrin or triolein, substrates for amidases/nitrilases, DNA, RNA, casein, N-␣-benzoyl-L-arginine-4-nitranilide, or starch. The purified enzyme (M r 36,209) was remarkably stable and active at high temperature (60°C), high pH (up to 12.0), low ionic strength (distilled water), and in solvents (e.g. n-propyl alcohol). The depolymerase contained no essential SH groups or essential disulfide bridges and was insensitive to high concentrations of ionic (SDS) and nonionic (Triton and Tween) detergents. Characterization of the cloned structural gene (phaZ7) and the DNA-deduced amino acid sequence revealed no homologies to any PHB depolymerase or any other sequence of data banks except for a short sequence related to the active site serine of serine hydrolases. A classification of the enzyme into a new family (family 9) of carboxyesterases (Arpigny, J. L., and Jaeger, K.-E. (1999) Biochem. J. 343, 177-183) is suggested.Poly((R)-3-hydroxyalkanoic acids) (PHAs) 1 are a class of storage compounds that are synthesized during unbalanced growth by many bacteria. PHAs are deposited intracellularly in the form of inclusion bodies ("granules") to levels up to 90% of the cellular dry weight. The subject was reviewed recently (1). Poly((R)-3-hydroxybutyric acid) (PHB) is the most abundant polyester in bacteria. Bacterial copolymers containing randomly distributed (R)-3-hydroxybutyric and (R)-3-hydroxyvaleric units (poly(3HB-co-3HV)) have been commercialized for over a decade under the trade name Biopol ® . Any research on the biodegradation of PHA should clearly distinguish between (i) extracellular PHA degradation and (ii) intracellular PHA degradation. (i) Extracellular degradation is the utilization of an exogenous carbon/energy source by a notnecessarily-accumulating microorganism. The source of this extracellular polymer is PHA-released by accumulating cells after death. The ability to degrade PHA is widely distributed among bacteria and depends on the secretion of specific PHA depolymerases that are carboxyesterases (EC 3.1.1) a...
Blends of synthetic atactic poly(3-hydroxybutyrate) (a-PHB) with a natural bacterial isotactic copolymer of 3-hydroxybutyrate with 3-hydroxyvalerate (PHBV) containing 10 mol % of 3HV units were prepared using a simple casting procedure. In the range of compositions explored (10−50% a-PHB), blends of bacterial PHBV and synthetic atactic a-PHB were miscible in the melt and solidified with spherulitic morphology. The influence of a-PHB content on the thermal and mechanical properties of the blends was evaluated. The degree of crystallinity decreased with increasing content of a-PHB in the film samples, and the elongation at break for a sample containing 50% of a-PHB was 30-fold that of pure PHBV. Degradation experiments, both hydrolytic (pH = 7.4, T = 70 °C) and enzymatic (PHB-depolymerase A from Pseudomonas lemoignei, Tris-HCl buffer (pH = 8), T = 37 °C), were performed for both polymers and polymer blends. The rate of enzymatic degradation of the blends was higher than that of PHBV and increased with a-PHB content in the blends studied, whereas pure a-PHB did not biodegrade under these conditions. 3-Hydroxybutyric acid and its dimer were identified by HPLC as biodegradation products of both pure PHBV and its blends with a-PHB. Higher oligomers up to heptamer were detected as degradation products of the blends by APCI-MS and ESI-MS.
Chronic wounds are often recalcitrant to treatment because of high microbial bioburden and the problem of microbial resistance. Silver is a broad-spectrum natural antimicrobial agent with wide applications extending to proprietary wound dressings. Recently, silver nanoparticles have attracted attention in wound management. In the current study, the green synthesis of nanoparticles was accomplished using a natural reducing agent, curcumin, which is a natural polyphenolic compound that is well-known as a wound-healing agent. The hydrophobicity of curcumin was overcome by its microencapsulation in cyclodextrins. This study demonstrates the production, characterization of silver nanoparticles using aqueous curcumin:hydroxypropyl-β-cyclodextrin complex and loading them into bacterial cellulose hydrogel with moist wound-healing properties. These silver nanoparticle-loaded bacterial cellulose hydrogels were characterized for wound-management applications. In addition to high cytocompatibility, these novel dressings exhibited antimicrobial activity against three common wound-infecting pathogenic microbes Staphylococcus aureus , Pseudomonas aeruginosa , and Candida auris .
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.