ABSTRACT
Dyskeratosis congenita (DC) is a disorder of poor telomere maintenance and is related to 1 or more mutations that involve the vertebrate telomerase RNA component. Most affected patients develop mucocutaneous manifestations and cytopenias in the peripheral blood between 5 and 15 years of age. DC patients may also develop pulmonary complications including fibrotic interstitial lung disease and pulmonary vascular abnormalities. The radiologic and pathologic features of pulmonary fibrosis associated with DC are poorly defined. Herein, we report 2 new DC cases and suggest that the radiologic and histopathologic findings may resemble usual interstitial pneumonia but may not neatly fit into the current classification of interstitial lung disease.
Subject(s)
Dyskeratosis Congenita/complications , Lung Diseases, Interstitial/etiology , Pulmonary Fibrosis/etiology , Biopsy , Cell Cycle Proteins/genetics , Chronic Disease , DNA Mutational Analysis , Dyskeratosis Congenita/diagnosis , Dyskeratosis Congenita/genetics , Female , Genetic Predisposition to Disease , Humans , Lung Diseases, Interstitial/classification , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/genetics , Male , Middle Aged , Mutation , Nuclear Proteins/genetics , Pedigree , Phenotype , Predictive Value of Tests , Pulmonary Fibrosis/classification , Pulmonary Fibrosis/diagnosis , Pulmonary Fibrosis/genetics , RNA/genetics , Telomerase/genetics , Tomography, X-Ray Computed , Young AdultSubject(s)
Histiocytic Sarcoma/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Neoplasm Recurrence, Local/diagnostic imaging , Adult , Bronchoalveolar Lavage Fluid , Fluorodeoxyglucose F18 , Histiocytic Sarcoma/pathology , Humans , Image-Guided Biopsy , Lung/pathology , Lung Neoplasms/pathology , Male , Neoplasm Recurrence, Local/pathology , Radionuclide Imaging , RadiopharmaceuticalsABSTRACT
BACKGROUND & AIMS: Muc3 intestinal mucin contains an extracellular cysteine-rich domain with 2 epidermal growth factor (EGF)-like motifs. The aim of this study was to determine the functional properties of Muc3 proteins. METHODS: Glutathione S-transferase-fusion proteins containing both Muc3 EGF-like domains (m3EGF1,2) or truncated versions (m3EGF1 and m3EGF2) were purified from Escherichia coli. Mouse colon (young adult mouse colon) and human A431 and LoVo cells were examined for migration and tyrosine phosphorylation in response to recombinant proteins. LoVo cells were transfected with a human MUC3A transmembrane-EGF1,2 construct and a stable clone was isolated (LhM3c14). Endogenous MUC3A in LoVo was inhibited by specific small interfering RNA transfection. Apoptosis was quantitated by nuclear morphology or terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling assay. Colitis was induced in mice by oral 5% dextran sodium sulfate or rectal 5% acetic acid, followed by enema treatments. RESULTS: m3EGF1,2 stimulated cell migration in all cell lines, but did not induce proliferation. Migration was inhibited by a tyrosine phosphorylation inhibitor, genistein, but not by the EGF receptor inhibitor, tyrphostin (AG1478). Inhibition of endogenous MUC3A in LoVo reduced baseline migration. Tyrosine phosphorylation of ErbB receptors was not observed after treatment of cells with m3EGF1,2. LoVo cells pretreated with m3EGF1,2 and transfected LhM3c14 cells showed reduced apoptosis in response to tumor necrosis factor alpha or Fas-receptor stimulation. Administration of m3EGF1,2 per rectum significantly reduced mucosal ulceration and apoptosis in experimental acute colitis. Truncated proteins m3EGF1 and m3EGF2 had no effect. CONCLUSIONS: The Muc3 mucin cysteine-rich domain plays an active role in epithelial restitution, and represents a potential novel therapeutic agent for intestinal wound healing.
Subject(s)
Apoptosis/drug effects , Cell Movement/drug effects , Epidermal Growth Factor/pharmacology , Mucins/pharmacology , Wound Healing/drug effects , Amino Acid Sequence , Animals , Cell Proliferation/drug effects , Cells, Cultured , Cysteine , ErbB Receptors/drug effects , Humans , Mice , Molecular Sequence Data , Mucin-3 , Mucins/chemistry , Protein Structure, Tertiary , Recombinant Proteins/pharmacologyABSTRACT
BACKGROUND: Construction and farming are characterized by small independently operated enterprises; few are included in hearing loss prevention programs. This study describes perceived and measured hearing ability among construction laborers and farmers in order to further the Healthy People 2010 goal to reduce noise-induced hearing loss (NIHL). METHODS: Construction laborers (n = 147) and farmers (n = 150) had screening audiograms at their workplace and a farm show, respectively. The relationship of the audiograms with a one-item measure of perceived hearing ability was explored using non-parametric statistics. RESULTS: At the 4,000 Hz frequency, indicative of NIHL, a high percentage of both groups exhibited hearing loss greater than 25 dB: laborers 53%, farmers 67%. Perceived hearing ability was significantly worse (P < 0.05) for workers with a measured hearing loss. The sensitivities of perceived hearing loss compared to audiometry ranged from 0.30 to 0.72 suggesting that perceived hearing loss was not a good indicator of actual hearing loss in this sample. CONCLUSIONS: The poor relationship between perceived and actual hearing loss in this study suggests that best practice requires inclusion of audiometric screening as part of a complete hearing loss prevention program. Future development of an improved instrument to measure perceived hearing ability may be useful in assessing this dimension of hearing.
