Eosinophilic fasciitis in a young male auto mechanic exposed to organic solvents.

We report a case of eosinophilic fasciitis in a teenage auto mechanic who was most likely affected by occupational exposure to organic solvents, including the aromatic hydrocarbons benzene, trimethylbenzene, naphthalene, toluene, and xylene. The patient presented with an 8-month history of painful induration of his extremities and an abnormal gait. A deep excisional biopsy of the fascia was obtained, demonstrating subcutaneous fibrosis with perivascular and interstitial inflammation, with lymphocytes and plasma cells spilling into the sclerosed fascia, and focal fibrinoid necrosis. Treatment was begun with intravenous pulse doses of methylprednisolone, prednisone (20 mg daily), and subcutaneous methotrexate (25 mg weekly), and the patient's painful induration had resolved and gait had normalized at the 6-month follow-up. Our case suggests that exposure to organic solvents could be implicated in the pathogenesis of eosinophilic fasciitis and highlights the importance of a thorough occupational history to prevent repeat exposures to potentially causative agents.

Fever and rash in children: important diagnostic considerations.

The association of fever with illness has been known for years. A febrile child may have rash, and physicians need to know when this symptom combination is a benign versus a pathologic clinical presentation. In other terms, potential etiologies are either infectious or non-infectious. With scrupulous, methodical history taking and careful, serial physical examination, the treating physician will find hints to assess and solidify an appropriate diagnosis, and chose an appropriate treatment.

Juvenile idiopathic arthritis and exposure to fine particulate air pollution.

OBJECTIVES: Inhalation of fine particulate matter, including particles with an aerodynamic diameter less than or equal to a 2.5-microm cut point (PM2.5), has been associated with systemic inflammation and the clinical presentation of various cardiopulmonary heath events. The urban area along Utah's Wasatch Mountains has high PM2.5 concentrations during periods of stagnant air conditions. Short-term inhalation exposures may trigger inflammatory events presenting as symptom onset in new patients with juvenile idiopathic arthritis (JIA). This study evaluated potential associations between JIA symptom onset and temporal changes in regional air pollution measured by stagnant air conditions and PM2.5 concentrations. METHODS: A case-crossover design was used to analyze associations of regional ambient PM2.5 concentrations with onset date of 338 JIA cases living on Utah's Wasatch Front. Patients were drawn from the Intermountain States Database of Childhood Rheumatic Diseases (1993-2006). Time trends, seasonality, month, and weekday were controlled for by matching. Selected exposure windows of PM2.5 and stagnant air days were used in the model to determine the effect of short term cumulative exposure on JIA symptom onset. RESULTS: Increased concentrations of PM2.5 and stagnant air conditions in the preceding 14 days were associated with significantly elevated risk of JIA onset in preschool aged children (RR=1.60, 95% CI 1.00-2.54) but not older children. Elevated risk was larger in males and in systemic onset JIA. CONCLUSION: Exposure to stagnant polluted air may be an environmental risk factor for JIA in young children, potentially triggered by pollution-induced pulmonary mediated inflammation.

DNA binding of the transcription factor PO-B is regulated during differentiation of HL-60 cells.

We have previously purified a transcription factor, PO-B, whose DNA binding capacity is increased by dephosphorylation and which contributes significantly to the basal transcription of genes such as pro-opiomelanocortin (Wellstein A., et al., J. Biol. Chem., 266: 12234-12241, 1991). In the present study, we describe several new properties of PO-B which suggest that the function of this transcription factor is not confined to regulation of gene expression in the pituitary. Furthermore, we present the first evidence for a signal transduction pathway that modulates the interactions of PO-B with DNA. We detected PO-B DNA binding activity in a number of mammalian cell lines (HeLa, C127, and AtT-20). However, PO-B was undetectable in extracts from undifferentiated HL-60 (U-HL-60) and CV-1 cells. Further characterization of these PO-B-negative extracts, by mixing experiments with PO-B-positive extracts, revealed that the U-HL-60 extracts, but not CV-1, contained enzymatic activity capable of increasing the mobility of the PO-B-DNA complex on nondenaturing gels. Concomitantly, there was also a reduction in the overall amount of PO-B bound to its cognate element. Immunoprecipitation with an antiserum to the protein kinase ERK 1 removed the modulatory activity from the U-HL-60 extracts, as did incubation with an ERK substrate peptide. Whole cell extracts from HL-60 cells which had been treated for 96 h with the macrophage-differentiating phorbol ester 12-O-tetradecanoylphorbol-13-acetate contained no modulatory activity. Furthermore, PO-B could be detected in these extracts. We conclude that an ERK or ERK-regulated protein in U-HL-60 cellular extracts regulates PO-B DNA binding and that some portion of the increase in PO-B DNA binding during HL-60 differentiation may arise from alterations in this regulatory activity.

Cloning and expression of a novel human DNA binding protein, PO-GA.

We have cloned a novel human DNA-binding protein from a HeLa cDNA expression library using the cognate DNA binding site of a transcription factor, PO-B. Further hybridization screening with the initial clone produced contiguous cDNA sequence of 4508 bp and a complete open reading frame encoding a 128 kDa protein, PO-GA. Northern analysis revealed a wide distribution of PO-GA mRNA in most human tissue. However, PO-GA mRNA levels were lower in lung and kidney and undetectable in placental tissue. A DNA-binding fragment of PO-GA expressed in E. Coli bound selectively to the PO-B element and other GA-rich double-stranded DNA sequences and to certain single-stranded DNA sequences. PO-GA has regions of homology to E. coli and yeast DNA ligases, and to proteins involved in DNA repair. Thus, in addition to a potential role in transcription, PO-GA may also be involved in DNA repair or replication.

Structural implications of spectroscopic characterization of a putative zinc finger peptide from HIV-1 integrase.

The N-terminal domain of human immunodeficiency virus (HIV-1) integrase (IN) contains the sequence motif His-Xaa3-His-Xaa23-Cys-Xaa2-Cys, which is strongly conserved in all retroviral and retrotransposon IN proteins. This structural motif constitutes a putative zinc finger in which a metal ion may be coordinately bound by the His and Cys residues. A recombinant peptide, IN(1-55), composed of the N-terminal 55 amino acids of HIV-1 IN was expressed in Escherichia coli and purified. Utilizing a combination of techniques including UV-visible absorption, circular dichroism, Fourier transform infrared, and fluorescence spectroscopies, we have demonstrated that metal ions (Zn2+, Co2+, and Cd2+) are bound with equimolar stoichiometry by IN(1-55). The liganded peptide assumes a highly ordered structure with increased alpha-helical content and exhibits remarkable thermal stability. UV-visible difference spectra of the peptide-Co2+ complexes directly implicate thiols in metal coordination, and Co2+ d-d transitions in the visible range indicate that Co2+ is tetrahedrally coordinated. Mutant peptides containing conservative substitutions of one of the conserved His or either of the Cys residues displayed no significant Zn(2+)-induced conformational changes as monitored by CD and fluorescence spectra. We conclude that the N terminus of HIV-1 IN contains a metal-binding domain whose structure is stabilized by tetrahedral coordination of metal by histidines 12 and 16 and cysteines 40 and 43. A preliminary structural model for this zinc finger is presented.