44 research outputs found

    Deletion Mutations in an Australian Series of HNPCC Patients

    Get PDF
    Hereditary non polyposis colorectal cancer (HNPCC) is characterized by the presence of early onset colorectal cancer and other epithelial malignancies. The genetic basis of HNPCC is a deficiency in DNA mismatch repair, which manifests itself as DNA microsatellite instability in tumours. There are four genes involved in DNA mismatch repair that have been linked to HNPCC; these include hMSH2, hMLH1, hMSH6 and hPMS2. Of these four genes hMLH1 and hMSH2 account for the majority of families diagnosed with the disease. Notwithstanding, up to 40 percent of families do not appear to harbour a change in either hMSH2 or hMLH1 that can be detected using standard screening procedures such as direct DNA sequencing or a variety of methods all based on a heteroduplex analysis

    Production cow-calf responses from perennial forage-based and integrated beef-cropping systems

    Get PDF
    An experiment was conducted to measure production responses of an alternative cow-calf production system integrated into a cropping system without access to perennial forage compared to a traditional cow-calf system utilizing perennial forage. Multiparous, cross-bred beef cows (n = 160; average age = 6.2 ± 2.8 yr) were utilized in a randomized complete block experimental design and unstructured treatment design. Upon initiation, cows were blocked by age and stratified by source, assigned randomly to one of two production systems, each with four replicates (n = 20 cows/replicate). Once allotted to their treatment groups, cows remained in their experimental units for the duration of the experiment. Treatments were: 1) a traditional system consisting of April to May calving with smooth bromegrass pasture and grazed corn residue as forage resources (TRAD); 2) an alternative system consisting of July to August calving utilizing partial-drylot feeding, summer-planted oats, and corn residue grazing (ALT). There were no differences (P ≥ 0.27) in calving rates (91.8 vs. 86.7 ± 2.92%), pregnancy rates (89.3 vs. 89.9 ± 2.66%), and weaning rates (87.2 vs. 82.3 ± 3.29%) for TRAD vs. ALT, respectively. However, there was an increase (P = 0.04) in the rate of twin offspring in ALT (2.9 vs. 9.4 ± 2.36% for TRAD vs. ALT, respectively). One calf from the set of twins was selected randomly at birth to be removed from the experiment, so the production data are only from single calves. There was no difference (P = 0.47) in calf body weight at birth (40 vs. 39 ± 0.7 kg for TRAD vs. ALT, respectively). At weaning, calves in the ALT system were lighter (P \u3c 0.01) at the same day of age (184 vs. 229 ± 5.5 kg) compared to TRAD calves. Cows from the ALT system had fewer (P \u3c 0.01) kg weaned per cow exposed to bull (150 vs. 199 ± 7.2 kg) compared to TRAD cows. Apart from the twinning rate, no differences in reproductive performance were observed among systems. However, reduced weaning weights and kilogram of weaned calf per cow exposed may negatively impact revenue to the cow-calf enterprise of the ALT system

    Frequency of the Common MYH Mutations (G382D and Y165C) in MMR Mutation Positive and Negative HNPCC Patients

    Get PDF
    Recently mutations in the MYH gene have been associated with a milder form of adenomatous polyposis which is characterized by a variable level of colonic polyps ranging from a few to several hundred. In the context of HNPCC it is not unusual to identify patients with a smattering of polyps. The MYH gene product is involved in DNA repair and indeed the hMSH2/hMSH6 complex (both genes being essential elements of the DNA mismatch repair pathway) is required to stimulate MYH activity. We reasoned that because of the clinical similarity of a subset of HNPCC patients to those described with MYH mutations and the role of the hMSH2/hMSH6 complex in the activation of MYH protein that MYH mutations may account for a small proportion of HNPCC patients. In a study of 442 HNPCC patients we identified MYH mutations at the same frequency as that expected in the general population. Nevertheless, two HNPCC families were identified harbouring biallelic changes in MYH

    The Association of the COMT V158M Polymorphism with Endometrial/Ovarian Cancer in HNPCC Families Adhering to the Amsterdam Criteria

    Get PDF
    Catechol-O-methyltransferase (COMT) is vital for the conjugation of catechol estrogens that are produced during oestrogen metabolism. The efficiency of this process varies due to a polymorphism in COMT, which changes valine to methionine (V158M). The Met genotypes slow the metabolism of catechol oestrogens, which are agents that are capable of causing DNA damage through the formation of DNA adducts and reactive oxygen species (ROS) production. The slower metabolism of catechol oestrogens results in there being a higher circulating concentration of these oeastrogens and consequently greater probability of DNA damage. To determine whether metabolic inefficiencies of oeastrogen metabolism are associated with the development of malignancy in hereditary non-polyposis colorectal cancer (HNPCC), we studied the V158M polymorphism in COMT in a large cohort of 498 HNPCC patients from Australia and Poland that were either mutation positive (n = 331) or negative (n = 167) for mismatch repair (MMR) gene mutations (hMLH1 or hMSH2). HNPCC is a familial predisposition to colorectal cancer (CRC) and extracolonic cancers that include endometrial cancer

    Evaluation of growth performance, carcass characteristics, and methane and CO\u3csub\u3e2\u3c/sub\u3e emissions of growing and finishing cattle raised in extensive or partial-intensive cow-calf production systems

    Get PDF
    An experiment was conducted over 2 yr to measure performance and greenhouse gas (GHG) emissions of weaned calves from two cow-calf production systems. Crossbred steers and heifers (n = 270, initial body weight (BW) = 207 kg, SD = 35) were used in a randomized complete block design, with treatments applied to the cow-calf system. Treatments were: 1) a traditional system consisting of April to June calving with smooth bromegrass pasture and grazed corn residue as forage resources (TRAD); 2) an alternative system consisting of July to September calving utilizing partial-drylot feeding, summer-planted oats, and corn residue grazing (ALT). Calves from both production systems were weaned at the same age and grown (diet NEg = 1.05 Mcal kg–1) for approximately 117 d. The calves then transitioned to a high-grain finishing diet (year 1: NEg = 1.32 Mcal kg–1; year 2: NEg = 1.39 Mcal kg–1) and fed to a targeted 1.52 cm backfat. Growth performance in the grower phase resulted in greater (P \u3c 0.01) average daily gain (1.39 vs. 1.22 ± 0.02 kg), greater gain:feed (P \u3c 0.01; 0.157 vs. 0.137 ± 0.003) for ALT calves compared to TRAD calves, However, a lower initial BW (P \u3c 0.01; 185 vs. 229 ± 4.9 kg) resulted in a lower ending BW (P \u3c 0.01; 347 vs. 371 ± 2.9 kg) for ALT calves compared to TRAD calves in spite of improved growth performance. In the finisher phase, ALT calves gained less (1.52 vs. 1.81 ± 0.218 kg; P = 0.02), were less efficient (0.139 vs. 173 ± 0.0151; P = 0.01) but exhibited similar hot carcass weights (HCW) (388 vs. 381 ± 3.8 kg; P = 0.14) compared to TRAD calves. Each pen of calves was put into a large pen-scale chamber that continuously measured carbon dioxide (CO2 ) and methane (CH4 ) for 5 d during the grower and finisher phases. The average CH4 and CO2 production per unit of feed intake was used to calculate total GHG emissions over the entire grower and finisher phase. Overall, there were no differences (P ≥ 0.17) between treatments for CH4 per day and per kilogram dry matter intake (DMI). However, ALT calves tended to produce less (P ≤ 0.10) CO2 per day and per kilogram DMI than TRAD calves. Overall, methane emissions were greater in ALT calves (110.7 vs. 92.2 ± 8.3 g CH4 kg–1 HCW; P = 0.04) than TRAD calves. The ALT calves required 27 additional days on feed to market, which resulted in more total CH4 per animal across the entire feeding period (P = 0.02) than TRAD calves. Production systems that reduce days to market to achieve similar HCW may reduce GHG emissions

    A Comparison Between Denaturing Gradient Gel Electrophoresis and Denaturing High Performance Liquid Chromatography in Detecting Mutations in Genes Associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the Identification of 9 New Mutations Previously Unidentified by DGGE

    Get PDF
    Denaturing high performance liquid chromatography is a relatively new method by which heteroduplex structures formed during the PCR amplification of heterozygote samples can be rapidly identified. The use of this technology for mutation detection in hereditary non-polyposis colorectal cancer (HNPCC) has the potential to appreciably shorten the time it takes to analyze genes associated with this disorder. Prior to acceptance of this method for screening genes associated with HNPCC, assessment of the reliability of this method should be performed. In this report we have compared mutation and polymorphism detection by denaturing gradient gel electrophoresis (DGGE) with denaturing high performance liquid chromatography (DHPLC) in a set of 130 families. All mutations/polymorphisms representing base substitutions, deletions, insertions and a 23 base pair inversion were detected by DHPLC whereas DGGE failed to identify four single base substitutions and a single base pair deletion. In addition, we show that DHPLC has been used for the identification of 5 different mutations in exon 7 of hMSH2 that could not be detected by DGGE

    Awareness and implementation of tobacco dependence treatment guidelines in Arizona: Healthcare Systems Survey 2000

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>This paper presents findings from the Tobacco Control in Arizona Healthcare Systems Survey, conducted in 2000. The purpose of the survey was to assess the status of Arizona healthcare systems' awareness and implementation of tobacco cessation and prevention measures.</p> <p>Methods</p> <p>The 20-item survey was developed by The University of Arizona HealthCare Partnership in collaboration with the Arizona Department of Health Services Bureau of Tobacco Education and Prevention. It was mailed to representatives of Arizona's 40 healthcare systems, including commercial and Medicare managed care organizations, "managed Medicaid" organizations, Veterans Affairs Health Care Systems, and Indian Health Service Medical Centers. Thirty-three healthcare systems (83%) completed the survey.</p> <p>Results</p> <p>The majority of healthcare systems reported awareness of at least one tobacco cessation and prevention clinical practice guideline, but only one third reported full guideline implementation. While a majority covered some form of behavioral therapy, less than half reported covering tobacco treatment medications. "Managed Medicaid" organizations administered through the Arizona Health Care Cost Containment System were significantly less likely to offer coverage for behavioral therapy and less likely to cover pharmacotherapy than were their non-Medicaid counterparts in managed care, Veterans Affairs Health Care Systems and Indian Health Service Medical Centers.</p> <p>Conclusion</p> <p>Arizona healthcare system coverage for tobacco cessation in the year 2000 was comparable to national survey findings of the same year. The findings that only 10% of "Managed Medicaid" organizations covered tobacco treatment medication and were significantly less likely to cover behavioral therapy were important given the nearly double smoking prevalence among Medicaid patients. Throughout the years of the program, the strategic plan of the Arizona Department of Health Services Bureau of Tobacco Education and Prevention has included the goal of identifying and eliminating tobacco related disparities for special populations, including low-income groups. Of importance, in 2008 the Arizona Health Care Cost Containment System was authorized to provide tobacco cessation pharmacotherapy as a covered benefit for its members.</p

    Impaired phagocytosis of apoptotic cells by macrophages in chronic granulomatous disease is reversed by IFN-γ in a nitric oxide-dependent manner

    Get PDF
    Immunodeficiency in chronic granulomatous disease (CGD) is well characterized. Less understood are exaggerated sterile inflammation and autoimmunity associated with CGD. Impaired recognition and clearance of apoptotic cells resulting in their disintegration may contribute to CGD inflammation. We hypothesized that priming of macrophages (Ms) with IFN-γ would enhance impaired engulfment of apoptotic cells in CGD. Diverse M populations from CGD (gp91(phox)(-/-)) and wild-type mice, as well as human Ms differentiated from monocytes and promyelocytic leukemia PLB-985 cells (with and without mutation of the gp91(phox)), demonstrated enhanced engulfment of apoptotic cells in response to IFN-γ priming. Priming with IFN-γ was also associated with increased uptake of Ig-opsonized targets, latex beads, and fluid phase markers, and it was accompanied by activation of the Rho GTPase Rac. Enhanced Rac activation and phagocytosis following IFN-γ priming were dependent on NO production via inducible NO synthase and activation of protein kinase G. Notably, endogenous production of TNF-α in response to IFN-γ priming was critically required for inducible NO synthase upregulation, NO production, Rac activation, and enhanced phagocytosis. Treatment of CGD mice with IFN-γ also enhanced uptake of apoptotic cells by M in vivo via the signaling pathway. Importantly, during acute sterile peritonitis, IFN-γ treatment reduced excess accumulation of apoptotic neutrophils and enhanced phagocytosis by CGD Ms. These data support the hypothesis that in addition to correcting immunodeficiency in CGD, IFN-γ priming of Ms restores clearance of apoptotic cells and may thereby contribute to resolution of exaggerated CGD inflammation
    corecore