A5061333968- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Genomics and Rare Diseases
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Pleural and Pulmonary Diseases
- Genetic factors in colorectal cancer
- Helicobacter pylori-related gastroenterology studies
- Lipoproteins and Cardiovascular Health
- Medical Imaging and Pathology Studies
- Fungal Infections and Studies
- Diagnosis and treatment of tuberculosis
- Genomic variations and chromosomal abnormalities
- Occupational and environmental lung diseases
- Nonmelanoma Skin Cancer Studies
- Endometrial and Cervical Cancer Treatments
- Protease and Inhibitor Mechanisms
- Occupational exposure and asthma
- Angiogenesis and VEGF in Cancer
- Bone and Joint Diseases
- Infectious Diseases and Tuberculosis
- Drug-Induced Adverse Reactions
- Genetic Associations and Epidemiology
- Pneumocystis jirovecii pneumonia detection and treatment
- RNA Research and Splicing
Color (United States)
2018-2020
University of British Columbia
2007-2020
Vancouver General Hospital
2007-2008
BC Cancer Agency
2000-2007
University of Manitoba
1989-2000
University of Alabama at Birmingham
2000
Cornell University
2000
National Cancer Institute
1991
National Institutes of Health
1991
Health Sciences Centre
1988-1989
Transforming growth factor-α (TGF-α) can regulate cell and differentiation as well production of extracellular matrix proteins. Elevated TGF-α has been associated with human rodent chronic inflammatory fibrotic diseases. Using immunohistochemical staining, we have examined lung sections patients advanced idiopathic pulmonary fibrosis (IPF), a disease characterized by inflammation demonstrated marked consistent increase in TGF-β epithelial cells macrophages when compared to nonspecific those...
Although it is recognized that three isoforms of transforming growth factor-beta (TGF-beta) exist in mammals, their expression, distribution, and function injury repair are not well characterized. Using immunohistochemistry antibodies to synthetic peptides TGF-beta 1, 2, 3, we determined the distribution lung sections with acute chronic lesions idiopathic pulmonary fibrosis (IPF), asbestosis hypersensitivity pneumonitis, as non-specific pneumonitis. In advanced honeycombing, irrespective...
Idiopathic pulmonary fibrosis (IPF; a progressive lung disease) is characterized by parenchymal remodeling with enlarged air spaces called honeycomb cysts and palisades of fibroblasts fibroblast foci. In IPF, epithelial cells covering foci aberrantly express the active conformation potent fibrogenic cytokine transforming growth factor-β1 (TGF-β1). Using explanted rat slices, we transfected alveolar retrovirus pMX containing site-directed mutation in which Cys223 Cys225 were substituted...
Accurate and consistent variant classification is imperative for incorporation of rapidly developing sequencing technologies into genomic medicine improved patient care. An essential requirement achieving standardized reliable interpretation data sharing, facilitated by a centralized open-source database. Familial hypercholesterolemia (FH) an exemplar the utility such resource: it has high incidence, favorable prognosis with early intervention treatment, cascade screening can be offered to...
Recent advancements in next-generation sequencing have greatly expanded the use of multi-gene panel testing for hereditary cancer risk. Although genetic helps guide clinical diagnosis and management, recommendations are based on personal family history ethnicity, many carriers being missed. Herein, we report results from 23,179 individuals who were referred 30-gene risk, independent current guidelines-38.7% would not met National Comprehensive Cancer Network criteria testing. We identified a...
Idiopathic pulmonary fibrosis (IPF) is a progressive fatal fibrotic lung disease. Transforming growth factor (TGF)-β1 present in biologically active conformation the epithelial cells lining lesions with advanced IPF. To determine role of aberrant expression TGF-β1 by alveolar (AECs), AECs explanted normal rat lungs were transfected gene using retrovirus pMX-L-s223,225-TGF-β1. In situ hybridization digoxigenin-labeled cDNA puromycin resistance contained pMX demonstrated that...
To determine if there is a statistically significant difference in the computed tomography (CT)-guided trans-thoracic needle biopsy diagnostic rate, complication and degree of pathologist confidence diagnosis between core (CNB) fine aspiration (FNAB).A retrospective cohort design was used to compare confidence, biopsy-related complications pneumothorax, chest tube placement, pulmonary hemorrhage, hemoptysis, admission hospital, length stay 251 transthoracic biopsies obtained via CNB (126) or...
Mutations responsible for inherited disease may act by disrupting normal transcriptional splicing. Such mutations can be difficult to detect, and their effects characterize, because many lie deep within exons or introns where they alter splice enhancers silencers introduce new acceptors donors. Multiple mutation-specific genome-wide approaches have been developed evaluate these classes of mutations. We a complementary experimental approach, cBROCA, which yields qualitative quantitative...
Transforming growth factor (TGF)-beta1 is an important regulator of inflammation and fibrosis. TGF-beta1 usually secreted as a biologically latent protein called (L-TGF-beta1). L-TGF-beta1 has no biologic effect unless converted to its active form. Using well-recognized model lung injury induced by the antineoplastic antibiotic bleomycin (Blm), we demonstrated that 7 d after intratracheal Blm administration, total TGF-beta was maximally increased. This induction due production alveolar...
Three isoforms of transforming growth factor-beta (TGF-beta) are found in mammalian cells and potent regulators inflammation, connective tissue synthesis, cellular proliferation, differentiation. To determine the distribution regulation TGF-beta during pulmonary injury, a rat model bleomycin-induced lung inflammation repair was used. Using immunohistochemistry, we demonstrate that 2 3 were localized to alveolar macrophages as well epithelial smooth muscle both normal lungs obtained at all...
Advances in genome sequencing have led to a tremendous increase the discovery of novel missense variants, but evidence for determining clinical significance can be limited or conflicting. Here, we present Learning from Evidence Assess Pathogenicity (LEAP), machine learning model that utilizes variety feature categories classify and achieves high performance multiple genes different health conditions. Feature include functional predictions, splice population frequencies, conservation scores,...
Abstract Background Gefitinib, a small molecule tyrosine kinase inhibitor of the Epidermal Growth Factor Receptor ( EGFR ), has shown limited efficacy in treatment lung cancer. Recognized clinical predictors response to this drug, specifically female, non-smoker, Asian descent, and adenocarcinoma, together suggest genetic basis for drug response. Recent studies have addressed relationship between either sequence mutations or increased copy number specific receptor kinases. We set out examine...
In a rat model of lung injury induced bythe antineoplastic antibiotic, bleomycin, there is loss type I alveolar epithelial cells (AECs) followed by infiltration activated inflammatory cells, II AEC proliferation, and fibrosis. At 4 7 days after bleomycin administration macrophages have increased production release active transforming growth factor (TGF)- β 1, an inhibitor cell proliferation. Paradoxically at these same time intervals concomitant induction For TGF- -mediated signal...
A case of extra‐mammary Paget's disease with a mucin‐negative small biopsy is reported. Study series vulvar demonstrated that areas devoid much in the mm range are frequently found, creating conditions for diagnostic problems biopsies. In this situation, positive immunoreactions carcinoembryonic antigen and low molecular weight cytokeratins negative reaction S‐100 protein serves to differentiate from other pagetoid lesions.
The clinical diagnosis or sapheno-femoral incompetence is frequently inaccurate. Using a simple Doppler technique described below 94% of 155 limbs in 107 patients were correctly diagnosed. In the same group cough impulse test gave an accurate positive result only 79%, while first 100 series tourniquet and tap tests even less reliable. Since readily applicable to large numbers it concluded that will be use distinguishing those whom surgery required from others compression sclerotherapy effective.
The relevance of large copy number variants (CNVs) to hereditary disorders has been long recognized, and population sequencing efforts have chronicled many common structural (SVs). However, limited data are available on the clinical contribution rare germline SVs. Here, a detailed characterization SVs identified using targeted next-generation was performed. Across 50 genes associated with cancer cardiovascular disorders, minimum 828 unique were reported, including 584 fully characterized...