Pathological features and outcomes of incidental renal cell carcinoma in candidate solid organ donors

( Francesca Ambrosi ),( Costantino Ricci ),( Deborah Malvi ),( Carlo De Cillia ),( Matteo Ravaioli ),( Michelangelo Fiorentino ),( Massimo Cardillo ),( Francesco Vasuri ),( Antonia D’errico ) 대한신장학회 2020 Kidney Research and Clinical Practice Vol.39 No.4

Background: We report the findings of a single Italian center in the evaluation of renal lesions in deceased donors from 2001 to 2017. In risk evaluation, we applied the current Italian guidelines, which include donors with small (< 4 cm, stage pT1a) renal carcinomas in the category of non-standard donors with a negligible risk of cancer transmission. Methods: From the revision of our registries, 2,406 donors were considered in the Emilia Romagna region of Italy; organs were accepted from 1,321 individuals for a total of 3,406 organs. Results: The evaluation of donor safety required frozen section analysis for 51 donors, in which a renal suspicious lesion was detected by ultrasound. Thirty-two primary renal tumors were finally diagnosed: 26 identified by frozen sections and 6 in discarded kidneys. The 32 tumors included 13 clear cell renal cell carcinomas (RCCs), 6 papillary RCCs, 6 angiomyolipomas, 5 oncocytomas, 1 chromophobe RCC, and 1 papillary adenoma. No cases of tumor transmission were recorded in follow-up of the recipients. Conclusion: Donors with small RCCs can be accepted to increase the donor pool. Collaboration in a multidisciplinary setting is fundamental to accurately evaluate donor candidate risk assessment and to improve standardized protocols for surgeons and pathologists.

Major Histocompatibility Class Ⅱ HLA-DRα Gene Expression in Thyrocytes : Counter Regulation by the Class Ⅱ Transactivator and the Thyroid Y Box Protein

MONTANI, VALERIA,TANIGUCHI, SHIN-ICHI,SHONG, MINHO,SUZUKI, KOICHI,OHMORI, MASAYUKI,GIULIANI, CESIDIO,NAPOLITANO, GIORGIO,SAJI, MOTOYASU,FIORENTINO, BRUNO,REIMOLD, ANDREAS M.,TING, JENNY P.-Y,KOHN, LEO 충남대학교 생물공학연구소 1999 생물공학연구지 Vol.7 No.-

Aberrant expression of major histocompatibility complex(MHC) classⅡ proteins on thyrocytes, which is associated with autoimmune thyroid disease, is mimicked by γ-interferon (γ-IFN). To define elements and factors that regulate classⅡ gene expression in thyrocytes and that might be involved in aberrant expression, we have studied γ-IFN-induced HLA-DRα gene expression in rat FRTL-5 thyroid cells. The present report shows that classⅡ expression in FRTL-5 thyrocytes is positively regulated by the classⅡ transactivator (CIITA), and that CIITA mimics the action of γ-IFN. Thus as is the case for γ-IFN, several distinct and highly conserved elements on the 5'-flanking region of the HLA-DRα gene, the S, X_1, X_2, and Y boxes between -137 to -65 bp, are required for classⅡ gene expression induced by pCIITA transfection in FRTL-5 thyroid cells. CIITA and γ-IFN do not cause additive increases in HLA-DRα gene expression in FRTL-5 cells, consistent with the possibility that CIITA is an intermediate factor in the γ-IFN pathway to increased classⅡ gene expression. Additionally, γ-IFN treatment of FRTL-5 cells induces an endogenous CIITA transcript; pCIITA transfection mimics the ability of γ-IFN treatment of FRTL-5 thyroid cells to increase the formation of a specific and novel protein/DNA complex containing CBP, a coactivator of CRE binding proteins important for cAMP-induced gene expression; and the action of both γ-IFN and CIITA to increase classⅡ gene expression and increase complex formation is reduced by cotransfection of a thyroid Y box protein, which suppresses MHC classⅠ gene expression in FRTL-5 thyroid cells and is a homolog of human YB-1, which suppresses MHC classⅡ expression in human glioma cells. we conclude that CIITA and TSH receptor suppressor element binding protein-1 are components of the γ-IFN-regulated transduction system which, respectively, increase or decrease classⅡ gene expression in thyrocytes and may, therefore, be involved in aberrant classⅡ expression associated with autoimmune thyroid disease. (Endocrinology 139: 280-289, 1998)

Regulation of Major Histocompatibility Class Ⅱ Gene Expressino in FRTL-5 Thyrocytes : Opposite Effects of Interferon and Methimazole

MONTANI, VALERIA,SHONG, MINHO,TANIGUCHI, SHIN-ICHI,SUZUKI, KOICHI,GIULIANI, CESIDIO,NAPOLITANO, GIORGIO,SAITO, JUN,SAJI, MOTOYASU,FIORENTINO, BRUNO,REIMOLD, ANDREAS M.,SINGER, DINAH S.,KOHN, LEONARD D 충남대학교 생물공학연구소 1999 생물공학연구지 Vol.7 No.-

Aberrant expression of major histocompatibility complex (MHC) classⅡ antigens is associated with autoimmune thyroid disease; aberrant expression duplicating the autoimmune state can be induced by interferon-γ (IFNγ). We have studied IFNγ-induced human leukocyte antigen (HLA)-DRα gene expression in rat FRTL-5 thyroid cells to identify the elements and factors important for aberrant expression. Using an HLA-DRα 5'-flanking region construct from-176 to +45 bp coupled to the chloramphenicol acetyltransferase reporter gene, we show that there is no basal classⅡ gene expression in FRTL-5 thyroid cells, that IFNγ can induce expression, and, as is the case for antigen-presenting cells from the immune system, that IFNγ-induced expression requires several highly conserved elements on the 5'-flanking region, which, from 5' to 3', are the S, X_1, X_2, and Y boxes. Methimazole (MMI), a drug used to treat patients with Graves' disease and experimental thyroiditis in rats or mice, can suppress the IFNγ-induced increase in HLA-DRα gene expression as a function of time and concentration; MMI simultaneously decreases IFNγ-induced endogenous antigen presentation by the cell. Using gel shift assays and the HLA-DRα 5'-flanking region from -176 or -137 to +45 bp as radiolabeled probes, we observed the formation of a major protein-DNA complex with extracts from FRTL-5 cells untreated with IFNγ, termed the basal or constitutive complex, and formation of an additional complex with a slightly faster mobility in extracts from cells treated with IFNγ. MMI treatment of cells prevents IFNγ from increasing the formation of this faster migrating complex. Formation of both complexes is specific, as evidenced in competition studies with unlabeled fragments between -137 and -38 bp from the start of transcription; nevertheless, they can be distinguished in such studies. Thus, high concentrations of double stranded oligonucleotides containing the sequence of the Y box, but not S, X_1, or X_2 box sequences, can prevent formation of the IFNγ-increased faster migrating complex, but not the basal complex. Both complexes involve multiple proteins and can be distinguished by differences in their protein composition. Thus, using specific antisera, we show that two cAMP response element-binding proteins, activating transcription factor-1 and/or -2, are dominant proteins in the upper or basal complex. The upper or basal complex also includes c-Fos, Fra-2, Ets-2, and Oct-1. A dominant protein that distinguishes the IFNγ-increased lower complex is CREB-binding protein (CBP), a coactivator of cAMP response element-binding proteins. We, therefore, show that aberrant expression of MHC classⅡ in thyrocytes, induced by IFNγ, is associated with the induction or increased formation of a novel portein-DNA complex and that its formation as well as aberrant classⅡ expression are suppressed by MMI, a drug used to treat human and experimental autoimmune thyroid disease. Its component proteins differ from those in a major, basal, or constitutive protein-DNA complex formed with the classⅡ 5'-flanking region in cells that are not treated with IFNγ and that do not express the classⅡ gene. (Endocrinology 139: 290-302, 1998)

2016 American College of Rheumatology/European League Against Rheumatism criteria for minimal, moderate, and major clinical response in adult dermatomyositis and polymyositis : An International Myositis Assessment and Clinical Studies Group/Paediatric Rh

Aggarwal, Rohit,Rider, Lisa G,Ruperto, Nicolino,Bayat, Nastaran,Erman, Brian,Feldman, Brian M,Oddis, Chester V,Amato, Anthony A,Chinoy, Hector,Cooper, Robert G,Dastmalchi, Maryam,Fiorentino, David,Ise H. K. Lewis 2017 Annals of the rheumatic diseases Vol.76 No.5

<P>To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. Consensus was reached for a conjoint analysis-based continuous model using absolute per cent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were >= 20, >= 40, and >= 60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/ PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (p< 0.001). The response criteria for adult DM/ PM consisted of the conjoint analysis model based on absolute per cent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.</P>

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Adult Dermatomyositis and Polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rhe

Aggarwal, Rohit,Rider, Lisa G.,Ruperto, Nicolino,Bayat, Nastaran,Erman, Brian,Feldman, Brian M.,Oddis, Chester V.,Amato, Anthony A.,Chinoy, Hector,Cooper, Robert G.,Dastmalchi, Maryam,Fiorentino, Davi John Wiley & Sons, Inc. 2017 Arthritis & Rheumatology Vol.69 No.5

<P>Conclusion. The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute percent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.</P>