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Biomedical subjects

C Morrison

Publications and source records attributed to C Morrison.

At least 37 records · Page 2Linked to original sources

Homologous DNA recombination in vertebrate cells.

The RAD52 epistasis group genes are involved in homologous DNA recombination, and their primary structures are conserved from yeast to humans. Although biochemical studies have suggested that the fundamental mechanism of homologous DNA recombination is conserved from yeast to mammals, recent studies of vertebrate cells deficient in genes of the RAD52 epistasis group reveal that the role of each protein is not necessarily the same as that of the corresponding yeast gene product. This review addresses the roles and mechanisms of homologous recombination-mediated repair with a special emphasis on differences between yeast and vertebrate cells.

Alleles↗

Reverse genetic studies of homologous DNA recombination using the chicken B-lymphocyte line, DT40.

DT40 is an avian leucosis virus-transformed chicken B-lymphocyte line which exhibits high ratios of targeted to random integration of transfected DNA constructs. This efficient targeted integration may be related to the ongoing diversification of the variable segment of the immunoglobulin gene through homologous DNA recombination-controlled gene conversion. DT40s are a convenient model system for making gene-targeted mutants. Another advantage is the relative tractability of these cells, which makes it possible to disrupt multiple genes in a single cell and to generate conditionally gene-targeted mutants including temperature-sensitive mutants. There are strong phenotypic similarities between murine and DT40 mutants of various genes involved in DNA recombination. These similarities confirm that the DT40 cell line is a reasonable model for the analysis of vertebrate DNA recombination, despite obvious concerns associated with the use of a transformed cell line, which may have certain cell-line-specific characteristics. Here we describe our studies of homologous DNA recombination in vertebrate somatic cells using reverse genetics in DT40 cells.

Animals↗

Association of dietary antioxidants and waist circumference with pulmonary function and airway obstruction.

Dietary antioxidants, waist circumference, and pulmonary function were measured in the Fourth Scottish MONICA cross-sectional survey of 865 men and 971 women aged 25-64 years. Waist circumference was inversely related to forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), even after adjustment for age, height, weight, working status, energy intake, and smoking variables in a multiple linear regression model (men: beta = -0.017 for FEV1 l/cm, p < 0.01 and beta = -0.008 for FVC, p = 0.04; women: beta = -0.009 for FEV1, p < 0.01 and beta = -0.007 for FVC, p = 0.01). After additional adjustment for waist circumference, estimated vitamin C and beta-carotene intakes were positively associated with lung function in men (vitamin C: beta = 0.102 for FEV1 l/mg/day, p = 0.03; beta-carotene: beta = 0.073 for FVC l/g/day, p = 0.02). Retinol and vitamin E were not significantly related to lung function for either sex. A case-control study of airway obstruction showed that waist circumference was significantly associated, while vitamin C could be protective. The study suggests that adequate intake of antioxidants and avoidance of increasing girth could help to preserve lung function.

Adult↗

Scc1/Rad21/Mcd1 is required for sister chromatid cohesion and kinetochore function in vertebrate cells.

Proteolytic cleavage of the cohesin subunit Scc1 is a consistent feature of anaphase onset, although temporal differences exist between eukaryotes in cohesin loss from chromosome arms, as distinct from centromeres. We describe the effects of genetic deletion of Scc1 in chicken DT40 cells. Scc1 loss caused premature sister chromatid separation but did not disrupt chromosome condensation. Scc1 mutants showed defective repair of spontaneous and induced DNA damage. Scc1-deficient cells frequently failed to complete metaphase chromosome alignment and showed chromosome segregation defects, suggesting aberrant kinetochore function. Notably, the chromosome passenger INCENP did not localize normally to centromeres, while the constitutive kinetochore proteins CENP-C and CENP-H behaved normally. These results suggest a role for Scc1 in mitotic regulation, along with cohesion.

Animals↗

Celera buys Axys.

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Biotechnology↗

Aspiration cytopathology of metastatic mucinous papillary thyroid carcinoma.

The light microscopic histopathology and cytopathology of papillary thyroid carcinoma (PTC) and its variants is amply depicted in reviews, books, and book chapters. One of the changes in PTC, however, that is infrequently discussed or illustrated in the literature is that of mucinous metaplasia. In the aspiration cytopathology literature, we are aware of only a rare report of PTC exhibiting extensive mucinous metaplasia. We present an example correlating the histopathology and fine needle aspiration cytopathology of a PTC that had metastasized on several separate occasions to cervical lymph nodes, and in the process demonstrated mucinous transformation. Without a prior history of PTC, the aspirate smears and tissue sections could have been mistaken easily for metastatic clear cell carcinoma of non-thyroidal origin. Mucinous metaplasia represents an extremely uncommon, but nonetheless potential, pitfall in the aspiration cytopathology and histopathology of metastatic PTC.

Adenocarcinoma, Mucinous↗

New polymorphisms in the interleukin-10 gene--relationships to myocardial infarction.

BACKGROUND: Interleukin-10 (IL-10) is a cytokine with anti-inflammatory and B-cell-stimulating activity. IL-10 is expressed in human atherosclerotic plaques and recent studies have shown the involvement of IL-10 in the atherosclerotic process. Therefore, we hypothesized that polymorphisms in the IL-10 gene might be associated with a predisposition to coronary heart disease. MATERIALS AND METHODS: To identify new polymorphisms in the human IL-10 gene, the entire coding sequence and the 3' flanking sequence of the gene were screened by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCR) followed by sequencing. The polymorphisms identified, and three others which have been previously described in the promoter region of the IL-10 gene (G-1082A, C-819T, C-592A), were then investigated in the ECTIM Study, a large population-based case-control study of myocardial infarction. RESULTS: Four new polymorphisms were identified: one in exon 1 (G+78/ex1A), which predicts a Glycine to Arginine change at position 15 in the putative signal peptide of the protein, two in the intron 3 (C+19/in3T, T+953/in3C) and one in the 3' flanking region (C+117T). All the IL-10 polymorphisms were in complete or nearly complete pairwise linkage disequilibrium. No case-control difference was found in genotype or allele frequencies for any of the polymorphisms. CONCLUSIONS: Our results suggest that IL-10 polymorphisms are not associated with an increased risk of myocardial infarction.

Adult↗

Association studies between haemochromatosis gene mutations and the risk of cardiovascular diseases.

BACKGROUND: Haemochromatosis is a common genetic disorder, inherited as an autosomal recessive trait that results in a progressive accumulation of iron in most tissues of the body. Positive association studies have been recently published between cardiovascular diseases and heterozygosity for the major mutation C282Y in the haemochromatosis gene HFE. METHODS: In the present work, we have determined the HFE genotypes for C282Y and H63D in subjects from two case-control studies: the ECTIM and GENIC studies, designed to identify genetic variants associated with myocardial and brain infarction, respectively. In addition, we tested whether HFE mutations were associated with the degree of arteriosclerosis assessed non-invasively by Doppler ultrasonography on the carotid and femoral arteries, in a group of apparently healthy individuals (the AXA Study). RESULTS: The prevalence of 282Y, and 63D allele carriers, did not differ between cases and controls in the ECTIM and in the GENIC studies, while 63D but not 282Y carriers were more numerous among subjects with atherosclerotic plaques in the AXA Study. CONCLUSIONS: These three studies do not provide consistent evidence supporting the hypothesis that HFE mutations are associated with an increased risk of cardiovascular disease and with the development of arteriosclerosis.

Adolescent↗

Cystic synovial sarcoma.

A case of synovial sarcoma of the paraspinal region showing massive cystic changes is described. The tumor presented in a 53-year-old white woman who noticed a lump on the upper aspect of her back. Magnetic resonance imaging of the cervical spine showed a heterogeneous paraspinal mass with well-defined margins and a multilocular quality with foci of hemorrhage. Fine needle aspiration of the mass showed clusters of polygonal cells admixed with a scattered spindle cell component. Surgical excision of the mass showed a well-circumscribed but nonencapsulated tumor that showed multiple small cystic structures on cross-section. Histologic examination showed a biphasic neoplasm characterized by bland-appearing glandular elements embedded in a moderately cellular spindle cell stroma. The tumor contained multiple cysts of varying size. Immunohistochemical studies showed the glandular component to be positive for cytokeratin and epithelial membrane antigen. The spindle cell component was immunoreactive for cytokeratin, vimentin, bcl-2, and CD99. Stains for muscle-specific actin, smooth muscle actin, S-100 protein, and CD34 were negative. Cytogenetic analysis showed a balanced reciprocal translocation involving chromosomes X and 18, in addition to other clonal abnormalities. Synovial sarcoma should be considered in the differential diagnosis of cystic lesions involving the soft tissues. Magnetic resonance imaging is considered the procedure of choice for the evaluation of soft tissue tumors because of its superior soft tissue contrast and multiplanar imaging capability. While the imaging features of soft tissue tumors are often nonspecific, magnetic resonance imaging may provide helpful clues, thus narrowing the differential diagnosis. Immunohistochemical studies and cytogenetic analysis may be very helpful for establishing the correct diagnosis in cases with this unusual presentation. Ann Diagn Pathol 5:48-56, 2001.

Biomarkers, Tumor↗

Histologic distribution of fatal rotaviral infection: an immunohistochemical and reverse transcriptase in situ polymerase chain reaction analysis.

Rotaviral infection is the most common cause of gastroenteritis in young children. Although rotavirus infection has a high morbidity and mortality rate in animals, in most cases in the United States the disease appears to be self-limited in humans. We report on 2 cases of fatal rotaviral infection in a 1 year old and a 4 year old. In each case, the illness showed a rapid systemic course dominated by cardiac and central nervous system involvement; in one case, rotaviral infection was documented by stool culture. Viral RNA was localized by reverse transcriptase in situ polymerase chain reaction to the mucosal cells of the small and large intestine and to many other tissues, including the heart and central nervous system, where it was noted in the endothelial cells of the microvasculature. Immunohistochemical analysis for the virus showed an identical histologic distribution in the intestinal epithelial cells and the systemic microvasculature. It is concluded that rotaviral infection can lead to a fatal disseminated infection in humans and the mechanism of this complication is based on a diffuse endothelialitis and concomitant tissue damage.

Child, Preschool↗

Proposed preliminary core set measures for disease outcome assessment in adult and juvenile idiopathic inflammatory myopathies.

In order to develop a preliminary core set of disease outcome measures for use in clinical trials of idiopathic inflammatory myopathies (IIM), we evaluated those measures used in previous trials, assessed the validation of published instruments and discussed these at an international consensus conference. The initial proposals were further refined by a multidisciplinary group of adult and paediatric specialists experienced in IIM using the Delphi method. The proposed preliminary core set of disease activity measures consists of five domains: physician and patient/parent global assessments of disease activity; muscle strength; physical function; serum activity of muscle enzymes; and an assessment tool to capture extra-skeletal muscle disease activity. The group recommended further development of a core set of disease damage measures for assessment of persistent changes in anatomy, pathology and function of at least 6 months' duration. The group recommended that patient-reported outcomes should include generic health-related quality of life assessments using the Medical Outcomes Study 36-item Short Form (SF-36) health survey in adult IIM patients and a validated quality of life instrument for paediatric patients. We propose the core set of outcome measures as a minimum group of assessments to include in all IIM therapeutic studies. The use of this core set should assist in standardizing outcome measurement and in optimizing therapeutic trials in myositis.

Adult↗