ABSTRACT
Tumor necrosis factor-? (TNF-?) inhibitors are biologic agents that are currently in wide use for the treatment of psoriasis as well as other inflammatory diseases. Following reports of thrombocytopenia as a potential adverse effect of anti-TNF-? therapy, we performed a retrospective study to determine the frequency of thrombocytopenia, defined as a platelet count <50x109 cells/L, in a cohort of 187 psoriatic patients treated with anti-TNF-? agents over a nine-year period. Although none of our patients met serologic criteria for thrombocytopenia or displayed clinical manifestations of thrombocytopenia, two patients developed platelet counts below 100×109 cells/L. Thrombocytopenia induced by anti-TNF-? agents is a potential adverse effect, it is a rare occurrence that will require further investigation in large, placebo-controlled, double-blind, prospective studies.
Subject(s)
Anti-Inflammatory Agents/adverse effects , Antibodies, Monoclonal/adverse effects , Immunoglobulin G/adverse effects , Psoriasis/drug therapy , Thrombocytopenia/chemically induced , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Blood Cell Count , Etanercept , Female , Humans , Immunoglobulin G/therapeutic use , Infliximab , Male , Middle Aged , Platelet Count , Psoriasis/immunology , Psoriasis/pathology , Receptors, Tumor Necrosis Factor/therapeutic use , Retrospective Studies , Thrombocytopenia/epidemiology , Tumor Necrosis Factor-alpha/metabolism , Young AdultABSTRACT
The distal arm of the fourth ("dot") chromosome of Drosophila melanogaster is unusual in that it exhibits an amalgamation of heterochromatic properties (e.g., dense packaging, late replication) and euchromatic properties (e.g., gene density similar to euchromatic domains, replication during polytenization). To examine the evolution of this unusual domain, we undertook a comparative study by generating high-quality sequence data and manually curating gene models for the dot chromosome of D. virilis (Tucson strain 15010-1051.88). Our analysis shows that the dot chromosomes of D. melanogaster and D. virilis have higher repeat density, larger gene size, lower codon bias, and a higher rate of gene rearrangement compared to a reference euchromatic domain. Analysis of eight "wanderer" genes (present in a euchromatic chromosome arm in one species and on the dot chromosome in the other) shows that their characteristics are similar to other genes in the same domain, which suggests that these characteristics are features of the domain and are not required for these genes to function. Comparison of this strain of D. virilis with the strain sequenced by the Drosophila 12 Genomes Consortium (Tucson strain 15010-1051.87) indicates that most genes on the dot are under weak purifying selection. Collectively, despite the heterochromatin-like properties of this domain, genes on the dot evolve to maintain function while being responsive to changes in their local environment.
Subject(s)
Chromosomes, Insect/genetics , Drosophila/genetics , Evolution, Molecular , Genome, Insect/genetics , Animals , Chromosome Mapping , Drosophila/classification , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Euchromatin/genetics , Genes, Insect/genetics , Heterochromatin/genetics , INDEL Mutation/genetics , Open Reading Frames/genetics , Species Specificity , Synteny , Tandem Repeat Sequences/geneticsABSTRACT
Becker melanosis, also known as Becker nevus, is a relatively common cutaneous hamartoma. The condition is classically characterized by a unilateral, hyperpigmented patch with varying degrees of hypertrichosis on a peripubertal individual. As Becker nevi are generally singular in a given individual, there are very few reported cases of multiple or bilateral lesions. We herein report a rare case of bilateral, symmetrical, non-syndromic Becker melanosis and we discuss possible pathogenesis and current treatment options.
