Comprehensive clinical, histopathologic, and immunohistochemical criteria for the classification of tumid LE are proposed that differentiate tumid LE from other cutaneous disorders that may be clinically and histologically indistinguishable. The chronic, benign course indicates that tumid LE be classified as a form of chronic cutaneous LE, although it may be a cutaneous feature of systemic LE.
With the aim of incorporating a recognition element that acts as a fluorescent probe upon binding to DNA, three novel pyrrole (P) and imidazole (I)-containing polyamides were synthesized. The compounds contain a p-anisylbenzimidazolecarboxamido (Hx) moiety attached to a PP, IP, or PI unit, giving compounds HxPP (2), HxIP (3), and HxPI (4), respectively. These fluorescent hybrids were tested against their complementary nonfluorescent, non-formamido tetraamide counterparts, namely, PPPP (5), PPIP (6), and PPPI (7) (cognate sequences 5'-AAATTT-3', 5'-ATCGAT-3', and 5'-ACATGT-3', respectively). The binding affinities for both series of polyamides for their cognate and noncognate sequences were ascertained by surface plasmon resonance (SPR) studies, which revealed that the Hx-containing polyamides gave binding constants in the 10(6) M(-1) range while little binding was observed for the noncognates. The binding data were further compared to the corresponding and previously reported formamido-triamides f-PPP (8), f-PIP (9), and f-PPI (10). DNase I footprinting studies provided additional evidence that the Hx moiety behaved similarly to two consecutive pyrroles (PP found in 5-7), which also behaved like a formamido-pyrrole (f-P) unit found in distamycin and many formamido-triamides, including 8-10. The biophysical characterization of polyamides 2-7 on their binding to the abovementioned DNA sequences was determined using thermal melts (ΔT(M)), circular dichroism (CD), and isothermal titration calorimetry (ITC) studies. Density functional calculations (B3LYP) provided a theoretical framework that explains the similarity between PP and Hx on the basis of molecular electrostatic surfaces and dipole moments. Furthermore, emission studies on polyamides 2 and 3 showed that upon excitation at 322 nm binding to their respective cognate sequences resulted in an increase in fluorescence at 370 nm. These low molecular weight polyamides show promise for use as probes for monitoring DNA recognition processes in cells.
Summary
Background
The European League Against Rheumatism/American College of Rheumatology classification criteria for inflammatory myopathies are able to classify patients with skin‐predominant dermatomyositis (DM). However, approximately 25% of patients with skin‐predominant DM do not meet two of the three hallmark skin signs and fail to meet the criteria.
Objectives
To develop a set of skin‐focused classification criteria that will distinguish cutaneous DM from mimickers and allow a more inclusive definition of skin‐predominant disease.
Methods
An extensive literature review was done to generate items for the Delphi process. Items were grouped into categories of distribution, morphology, symptoms, antibodies, histology and contextual factors. Using REDCap™, participants rated these items in terms of appropriateness and distinguishing ability from mimickers. The relevance score ranged from 1 to 100, and the median score determined a rank‐ordered list. A prespecified median score cut‐off was decided by the steering committee and the participants. There was a pre‐Delphi and two rounds of actual Delphi.
Results
There were 50 participating dermatologists and rheumatologists from North America, South America, Europe and Asia. After a cut‐off score of 70 during the first round, 37 of the initial 54 items were retained and carried over to the next round. The cut‐off was raised to 80 during round two and a list of 25 items was generated.
Conclusions
This project is a key step in the development of prospectively validated classification criteria that will create a more inclusive population of patients with DM for clinical research.
What's already known about this topic?
Proper classification of patients with skin‐predominant dermatomyositis (DM) is indispensable in the appropriate conduct of clinical/translational research in the field.
The only validated European League Against Rheumatism/American College of Rheumatology criteria for idiopathic inflammatory myopathies are able to classify skin‐predominant DM. However, a quarter of amyopathic patients still fail the criteria and does not meet the disease classification.
What does this study add?
A list of 25 potential criteria divided into categories of distribution, morphology, symptomatology, pathology and contextual factors has been generated after several rounds of consensus exercise among experts in the field of DM.
This Delphi project is a prerequisite to the development of a validated classification criteria set for skin‐predominant DM.
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