Biomedical subjects

Jill Ohar

Publications and source records attributed to Jill Ohar.

5 recordsLinked to original sources

PubMed2024

Design of the SPIROMICS Study of Early COPD Progression: SOURCE Study.

BACKGROUND: The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition. OBJECTIVES: Accordingly, with National Heart, Lung and Blood Institute support, we initiated the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression. METHODS/DISCUSSION: SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global initiative for chronic Obstructive Lung Disease (GOLD) groups 0-2 or with preserved ratio-impaired spirometry; and an additional n=40 never-smoker controls. Participants undergo baseline and 3-year follow-up visits, each including high-resolution computed tomography, respiratory oscillometry and spirometry (pre- and postbronchodilator administration), exhaled breath condensate (baseline only), and extensive biospecimen collection, including sputum induction. Symptoms, interim health care utilization, and exacerbations are captured every 6 months via follow-up phone calls. An embedded bronchoscopy substudy involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture. CONCLUSION: SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.

SPIROMICS↗

PubMed2004

Changing patterns in asbestos-induced lung disease.

STUDY OBJECTIVES: To determine patterns in asbestos-induced lung diseases found in older, less exposed workers. DESIGN: Review of a database evaluating lung function, smoking status, form of asbestos-induced lung disease, and radiograph abnormalities. SETTING: Outpatient clinic. PARTICIPANTS: A total of 3383 asbestos-exposed workers referred for independent medical evaluation, including control subjects who lacked asbestos-specific radiograph abnormalities (n = 243), subjects with low International Labor Organization (ILO) scores (n = 2,685), high ILO scores (n = 312), bronchogenic cancer (n = 63), and mesothelioma (n = 80). Of these, 3,327 workers have specific smoking status information and 3,312 workers have lung volume measures. INTERVENTIONS: Chest radiographs were interpreted by a certified B-reader, and abnormalities were quantified according to the ILO scoring system. Spirometry and lung volume measurement were performed. Subjects completed a self-administered questionnaire that was reviewed at the time of examination. Control subjects were screened on two separate occasions at least 10 years apart to exclude subclinical or slowly progressive asbestos-induced lung disease. MEASUREMENTS AND RESULTS: The mean age of the population was 65.1 +/- 9.9 years, and the latency was 41.4 +/- 10.1 years (+/- SD). Most subjects (41.8%) had normal pulmonary function. Obstruction was the most common pulmonary function abnormality (25.4%), followed by restriction (19.3%) and a mixed pattern (6.0%). Most subjects (79.4%) had low ILO scores. Benign pleural abnormalities were the only findings in 54% of subjects with low ILO score. Subjects with high ILO scores were older, smoked more, and had a longer latency than subjects with low ILO scores and control subjects. Smokers were younger, had a shorter latency, and had paradoxically greater ILO scores than nonsmokers. Subjects with bronchogenic cancer and mesothelioma had longer latencies than control subjects and subjects with benign asbestos-induced lung disease. CONCLUSIONS: Asbestos-induced lung disease today is characterized by low ILO scores, long latencies, greater disease magnitude in smokers, and a normal or obstructive pattern of pulmonary function abnormality. Spirometric evaluation in the absence of lung volume measurements caused misclassification that resulted in overestimation of the presence of a restrictive pattern of pulmonary function.

Adult↗

PubMed2003

Association between genetic polymorphisms in the prostate-specific antigen gene promoter and serum prostate-specific antigen levels.

BACKGROUND: Recent evidence suggests that genetic variation in the promoter of the prostate-specific antigen (PSA) gene may contribute to individual variation in serum PSA levels. However, polymorphisms associated with variations in PSA levels have not been identified. METHODS: We used the polymerase chain reaction to amplify the promoter region of the PSA genes (nucleotide positions -3873 to -5749 with respect to the start of transcription) of 409 healthy white men at risk for lung disease. Polymerase chain reaction products were sequenced to identify polymorphisms in the PSA gene promoter and to genotype the men for common single nucleotide polymorphisms (SNPs) and were cloned into luciferase reporter constructs to assay PSA promoter activity in human LNCaP prostate cancer cells. Analysis of variance was used to test the association of polymorphism frequencies with mean serum PSA levels. All statistical tests were two-sided. RESULTS: The -4643G/A SNP (G allele) had a 21.2% prevalence and was associated with increases in serum PSA levels (P =.017) and PSA promoter activity (P<.001). The -5412C/T SNP (C allele) had a 22.0% prevalence and was associated with an increase in serum PSA levels (P =.0015). The -5429T/G SNP (G allele) had a 23.0% prevalence, was associated with an increase in serum PSA levels (P =.021), and was in linkage disequilibrium with the -5412C/T SNP. The promoter activity of the -5412 C/-5429 G haplotype was higher than that of the -5412 T/-5429 T haplotype (P<.001). CONCLUSIONS: Genetic variations in the PSA promoter are associated with serum PSA levels in men without prostatic disease. PSA promoter genotype information may help to refine models of PSA cutoff values.

Aged↗

PubMed2002

Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk.

Deletions on human chromosome 8p22-23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC) have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in several processes proposed to be relevant to prostate carcinogenesis. Here we report the results of genetic analyses that indicate that mutations in MSR1 may be associated with risk of prostate cancer. Among families affected with HPC, we identified six rare missense mutations and one nonsense mutation in MSR1. A family-based linkage and association test indicated that these mutations co-segregate with prostate cancer (P = 0.0007). In addition, among men of European descent, MSR1 mutations were detected in 4.4% of individuals affected with non-HPC as compared with 0.8% of unaffected men (P = 0.009). Among African American men, these values were 12.5% and 1.8%, respectively (P = 0.01). These results show that MSR1 may be important in susceptibility to prostate cancer in men of both African American and European descent.

Aged↗

PubMed2002

Association studies of serum prostate-specific antigen levels and the genetic polymorphisms at the androgen receptor and prostate-specific antigen genes.

Testing for serum prostate-specific antigen (PSA) levels has been widely used to screen for prostate cancer. However, PSA testing has low specificity and sensitivity because PSA is not prostate cancer-specific. PSA is encoded by the APS gene, and the expression of this gene is regulated by androgens. W. Xue et al. Cancer Res., 60: 839-841, 2000 reported recently that serum PSA levels are associated with a G/A polymorphism at androgen responsive element 1 (ARE1) of APS and/or the CAG repeats in exon 1 of the androgen receptor (AR) gene. This result, if confirmed, may significantly increase the specificity and sensitivity of PSA testing by incorporating genotype-specific thresholds. In this study, we tested for the association between serum PSA levels and these single nucleotide polymorphisms (SNPs) in a large sample of 518 men. For the AR gene, we observed slightly (but not statistically significant) higher mean serum PSA levels in men with shorter CAG repeats (<or=21) or shorter GGC repeats (<or=16). For the ARE1 of the APS, we found slightly (but not statistically significant) lower PSA levels in men with the AA genotype. It is worth noting that this observation is opposite to the findings of W. Xue et al. Cancer Res., 60: 839-841, 2000. We hypothesize that the effects of ARE1 and AR genotypes on mean PSA levels may reflect the effect of other causal polymorphisms in these genes, which are in linkage disequilibrium with these polymorphisms. A systematic approach is required to identify sequence variants in these genes and other related genes, and to test for an association between these variants and PSA levels in large samples.

Adult↗