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1.
Antonie Van Leeuwenhoek ; 110(11): 1435-1443, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28889208

ABSTRACT

Bacteria of the genus Proteus of the family Enterobacteriaceae are facultative human pathogens responsible mainly for urinary tract and wound infections, bacteremia and the development of rheumatoid arthritis (RA). We have analyzed and compared by ELISA the titer of antibodies in plasmas of healthy individuals and in sera of rheumatoid arthritis patients recognizing a potential host cross-reactive epitope (lysine-galacturonic acid epitopes) present in Proteus lipopolysaccharide (LPS). In our experiments LPSs isolated from two mutants of smooth Proteus mirabilis 1959 (O3), i.e. strains R110 and R45, were used. R110 (Ra type mutant) is lacking the O-specific polysaccharide, but possesses a complete core oligosaccharide, while R45 (Re type) has a reduced core oligosaccharide and contains two 3-deoxy-D-manno-oct-2-ulosonic acid residues and one of 4-amino-4-deoxy-L-arabinopyranose residues. Titer of P. mirabilis S1959 LPS-specific-antibodies increased with the age of blood donors. RA and blood donors' sera contained antibodies against S and Ra and Re type of P. mirabilis O3 LPSs. Antibodies recognizing lysine-galacturonic acid epitopes of O3 LPS were detected by ELISA in some plasmas of healthy individuals and sera of rheumatoid arthritis patients. RA patients antibodies reacting with P. mirabilis S1959 S and R LPSs may indicate a potential role of anti-LPS antibodies in molecular mimicry in RA diseases.


Subject(s)
Antibodies, Bacterial/immunology , Arthritis, Rheumatoid/immunology , Lipopolysaccharides/immunology , O Antigens/immunology , Proteus mirabilis/immunology , Adult , Age Factors , Aged , Antibodies, Bacterial/blood , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/microbiology , Enzyme-Linked Immunosorbent Assay , Epitopes/immunology , Female , Humans , Lipopolysaccharides/isolation & purification , Male , Middle Aged , Mutation/immunology , O Antigens/chemistry , Protein Binding/immunology , Proteus mirabilis/chemistry , Proteus mirabilis/genetics , Vaccines, Synthetic/immunology , Young Adult
2.
PLoS One ; 11(9): e0162495, 2016.
Article in English | MEDLINE | ID: mdl-27606812

ABSTRACT

BACKGROUND: Solitary pink lesions in differential diagnosis with hypopigmented/amelanotic melanoma present a diagnostic challenge in daily practice and are regularly referred for second expert opinion. Reflectance confocal microscopy (RCM) has been shown to improve diagnostic accuracy of dermoscopically equivocal pink lesions. No studies have been performed to evaluate the effect of adding a second expert reader and automatic removal of lesions with discordant management recommendations and its potential effect on diagnostic sensitivity and final management of these lesions in retrospective or telemedicine settings. OBJECTIVE: To improve diagnostic accuracy and reduce potential mismanagement of dermoscopically equivocal pink cutaneous lesions by implementing double reader concordance evaluation of RCM images. METHODS: 316 dermoscopically equivocal pink lesions with dermoscopy-RCM image sets were evaluated retrospectively. Accuracy of three readers was evaluated by single reader evaluation of dermoscopy only and dermoscopy-RCM image sets and finally by double reader evaluation of dermoscopy-RCM image sets. Lesions with discordant diagnosis between two readers were automatically recommended for excision. RESULTS: Dermoscopy only evaluation resulted in an overall sensitivity of 95.9% and specificity of 33.6%, with 1 of 12 amelanotic melanomas mismanaged. Dermoscopy-RCM image set single reader evaluation resulted in an overall sensitivity of 93.9% and overall specificity of 54.2%, with 1 of 12 melanomas mismanaged. Dermoscopy-RCM image set double reader concordance evaluation resulted in an overall sensitivity of 98.3% and specificity of 42.7%, with no amelanotic melanoma mismanagement. CONCLUSION: Evaluation of dermoscopy-RCM image sets of equivocal pink lesions by a single reader in telemedicine settings is limited by the potential for misdiagnosis of dangerous malignant lesions. Double reader concordance evaluation with automatic referral of lesions for removal in the case of discordant diagnosis improves the diagnostic sensitivity in this subset of lesions and reduce potential misdiagnosis in settings where a second expert opinion may be employed.


Subject(s)
Dermoscopy/methods , Melanoma/diagnosis , Microscopy, Confocal/methods , Skin Neoplasms/diagnosis , Telemedicine/methods , Confidence Intervals , Humans , ROC Curve , Melanoma, Cutaneous Malignant
3.
Am J Transplant ; 16(1): 221-34, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26227106

ABSTRACT

We previously described early results of a nonchimeric operational tolerance protocol in human leukocyte antigen (HLA)-identical living donor renal transplants and now update these results. Recipients given alemtuzumab, tacrolimus/MPA with early sirolimus conversion were multiply infused with donor hematopoietic CD34(+) stem cells. Immunosuppression was withdrawn by 24 months. Twelve months later, operational tolerance was confirmed by rejection-free transplant biopsies. Five of the first eight enrollees were initially tolerant 1 year off immunosuppression. Biopsies of three others after total withdrawal showed Banff 1A acute cellular rejection without renal dysfunction. With longer follow-up including 5-year posttransplant biopsies, four of the five tolerant recipients remain without rejection while one developed Banff 1A without renal dysfunction. We now add seven new subjects (two operationally tolerant), and demonstrate time-dependent increases of circulating CD4(+) CD25(+++) CD127(-) FOXP3(+) Tregs versus losses of Tregs in nontolerant subjects (p < 0.001). Gene expression signatures, developed using global RNA expression profiling of sequential whole blood and protocol biopsy samples, were highly associative with operational tolerance as early as 1 year posttransplant. The blood signature was validated by an external Immune Tolerance Network data set. Our approach to nonchimeric operational HLA-identical tolerance reveals association with Treg immunophenotypes and serial gene expression profiles.


Subject(s)
Biomarkers/analysis , HLA Antigens/genetics , HLA Antigens/immunology , Kidney Failure, Chronic/immunology , Kidney Transplantation , Transplantation Chimera/immunology , Transplantation Tolerance/immunology , Adult , Aged , Female , Follow-Up Studies , Gene Expression Profiling , Genomics/methods , Glomerular Filtration Rate , Graft Survival , Histocompatibility , Humans , Immunophenotyping , Kidney Failure, Chronic/genetics , Kidney Failure, Chronic/surgery , Kidney Function Tests , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Transplantation Chimera/genetics
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