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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
PubMed1998

Should we screen for asymptomatic left ventricular dysfunction to prevent heart failure?

A programme to detect and treat asymptomatic left ventricular dysfunction would seem to fulfil all five principles of screening. Indeed, such a programme would appear to be at least as firmly based as those already in existence for, for example, cervical and breast cancer. Further evaluation of the screening of high risk groups to detect asymptomatic left ventricular systolic dysfunction with the aim of giving treatment to prevent the development of heart failure is merited.

Clinical Trials as Topic↗
PubMed1998

Homologous recombination, but not DNA repair, is reduced in vertebrate cells deficient in RAD52.

Rad52 plays a pivotal role in double-strand break (DSB) repair and genetic recombination in Saccharomyces cerevisiae, where mutation of this gene leads to extreme X-ray sensitivity and defective recombination. Yeast Rad51 and Rad52 interact, as do their human homologues, which stimulates Rad51-mediated DNA strand exchange in vitro, suggesting that Rad51 and Rad52 act cooperatively. To define the role of Rad52 in vertebrates, we generated RAD52(-/-) mutants of the chicken B-cell line DT40. Surprisingly, RAD52(-/-) cells were not hypersensitive to DNA damages induced by gamma-irradiation, methyl methanesulfonate, or cis-platinum(II)diammine dichloride (cisplatin). Intrachromosomal recombination, measured by immunoglobulin gene conversion, and radiation-induced Rad51 nuclear focus formation, which is a putative intermediate step during recombinational repair, occurred as frequently in RAD52(-/-) cells as in wild-type cells. Targeted integration frequencies, however, were consistently reduced in RAD52(-/-) cells, showing a clear role for Rad52 in genetic recombination. These findings reveal striking differences between S. cerevisiae and vertebrates in the functions of RAD51 and RAD52.

Animals↗
PubMed1998

The obesity gene in swine: sequence and expression of porcine leptin.

Leptin is a 16-kDa protein secreted by adipocytes that has been proposed to regulate feed intake in mice, rats, and humans. The present study was designed to characterize porcine leptin structure and expression. Successful RT-PCR resulted in development of a cDNA clone to the full length coding region of porcine leptin. Sequence data demonstrate 85% base homology to rodent, 88% to human, and a 92% homology to the bovine sequence. For assessment of porcine leptin gene expression, total RNA was extracted from the subcutaneous adipose tissue of genetically selected high backfat pigs and from contemporary crossbred swine. Total RNA derived from genetically selected high fat pigs contained 113% higher (P < .05) concentrations of porcine leptin mRNA than total RNA derived from contemporary crossbred pigs. Western blotting was used to evaluate serum levels of porcine leptin in genetically selected high backfat and contemporary, crossbred pigs. Relative levels of porcine leptin in sera from obese swine were approximately 306% higher (P < .05) than levels present in sera from contemporary, crossbred swine. These data indicate that leptin is expressed in pigs, the expressed protein is secreted into the bloodstream, and obese swine express higher levels of leptin mRNA and protein than nonobese swine at similar body weight.

Adipose Tissue↗
PubMed1998

Fibromyalgia and its primary care implications.

Fibromyalgia is a complex condition affecting up to six million patients. In this literature review, the prevalence, proposed etiology, differential diagnosis, and signs and symptoms of the disorder are presented. Diagnostic criteria, treatment options, and the importance of patient education are explored.

Diagnosis, Differential↗
PubMed1997

PARP is important for genomic stability but dispensable in apoptosis.

Mice lacking the gene encoding poly(ADP-ribosyl) transferase (PARP or ADPRT) display no phenotypic abnormalities, although aged mice are susceptible to epidermal hyperplasia and obesity in a mixed genetic background. Whereas embryonic fibroblasts lacking PARP exhibit normal DNA excision repair, they grow more slowly in vitro. Here we investigated the putative roles of PARP in cell proliferation, cell death, radiosensitivity, and DNA recombination, as well as chromosomal stability. We show that the proliferation deficiency in vitro and in vivo is most likely caused by a hypersensitive response to environmental stress. Although PARP is specifically cleaved during apoptosis, cells lacking this molecule apoptosed normally in response to treatment with anti-Fas, tumor neurosis factor alpha, gamma-irradiation, and dexamethasone, indicating that PARP is dispensable in apoptosis and that PARP-/- thymocytes are not hypersensitive to ionizing radiation. Furthermore, the capacity of mutant cells to carry out immunoglobulin class switching and V(D)J recombination is normal. Finally, primary PARP mutant fibroblasts and splenocytes exhibited an elevated frequency of spontaneous sister chromatid exchanges and elevated micronuclei formation after treatment with genotoxic agents, establishing an important role for PARP in the maintenance of genomic integrity.

Animals↗
PubMed1997

Effect of socioeconomic group on incidence of, management of, and survival after myocardial infarction and coronary death: analysis of community coronary event register.

OBJECTIVE: To investigate the effect of socioeconomic group (with reference to age and sex) on the rate of, course of, and survival after coronary events. DESIGN: Community coronary event register from 1985 to 1991. SETTING: City of Glasgow north of the River Clyde, population 196,000. SUBJECTS: 3991 men and 1551 women aged 25-64 years on the Glasgow MONICA coronary event register with definite or fatal possible or unclassifiable events according to the criteria of the World Health Organisation's MONICA project (monitoring trends and determinants in cardiovascular disease). MAIN OUTCOME MEASURES: Rate of coronary events; proportion of subjects reaching hospital alive; case fatality in admitted patients and in community overall. RESULTS: Event rates increased with age for both sexes and were greater in men than women at all ages. The rate increased 1.7-fold in men and 2.4-fold in women from the least (Q1) to the most (Q4) deprived socioeconomic quarter. The socioeconomic gradient decreased with age and was steeper for women than men. The proportion treated in hospital (66%) decreased with age, was greater in women than men, and decreased in both sexes with increasing deprivation (age standardised odds ratio 0.82 for Q4 v Q1) Case fatality in hospital (20%) increased with age, was greater for women than men when age was standardised, and showed no strong socioeconomic pattern. Overall case fatality in the community (50%) increased with age, was similar between the sexes, and increased from Q1 to Q4 (age standardised odds ratio 1.12 in men, 1.18 in women). CONCLUSIONS: Socioeconomic group affects not only death rates from myocardial infarction but also event rates and chance of admission. This should be taken into account when different groups of patients are compared. Because social deprivation is associated with so many more deaths outside hospital, primary and secondary prevention are more likely than acute hospital care to reduce the socioeconomic variation in mortality.

Adult↗
PubMed1997

Genetic interaction between PARP and DNA-PK in V(D)J recombination and tumorigenesis.

Poly(ADP-ribose) polymerase (PARP) and DNA-dependent protein kinase (DNA-PK) are DNA break-activated molecules, Although mice that lack PARP display no gross phenotype and normal DNA excision repair, they exhibit high levels of sister chromatid exchange, indicative of elevated recombination rates. Mutation of the gene for DNA-PK catalytic subunit (Prkdc) cases defective antigen receptor V(D)J recombination and arrests B- and T-lymphocyte development in severe combined immune-deficiency (SCID) mice. SCID V(D)J recombination can be partly rescued in T-lymphocytes by either DNA-damaging agents (gamma-irradiation and bieomycin) or a null mutation of the p53 gene, possibly because of transiently elevated DNA repair activity in response to DNA damage or to delayed apoptosis in the absence of p53. To determine whether the increased chromosomal recombination observed in PARP-deficient cells affects SCID V(D)J recombination, we generated mice lacking both PARP and DNA-PK. Here, we show that thymocytes of SCID mice express both CD4 and CD8 co-receptors, bypassing the SCID block. Double-mutant T-cells in the periphery express TCR beta, which is attributable to productive TCR beta joints. Double-mutant mice develop a high frequency of T-cell lymphoma. These results demonstrate that increased recombination activity after the loss of PARP anti-recombinogenic function can rescue V(D)J recombination in SCID mice and indicate that PARP and DNA-PK cooperate to minimize genomic damage caused by DNA strand breaks.

Animals↗
PubMed1996

Extrachromosomal recombination occurs efficiently in cells defective in various DNA repair systems.

A series of different frameshift mutations of a firefly luciferase reporter plasmid was created so that no activity was obtained when they were transfected into mammalian cells. Co-transfection of these constructs with short fragments of the original sequence resulted in luciferase activity in different cell lines (A-549, NIH 3T3 and Jurkat). The level of this activity was dependent on the length of the fragment, regardless of cell line examined. Two different transfection techniques (lipofection and adenovirus-enhanced gene transfer) gave similar results. It was shown by polymerase chain reaction that expression of detectable luciferase required recombination of the transfected molecules. Cells with defined defects in DNA repair pathways were examined for their ability to perform this extrachromosomal recombination. Cells lacking normal Ku p80, (ADP-ribosyl)transferase, MLH1 or XP-C were all capable of restoring expression to the frameshifted constructs. Given the pivotal roles of the above molecules in the pathways of DNA repair, it seems that this recombination derives from a different activity.

3T3 Cells↗
PubMed1996

Sex differences in myocardial infarction and coronary deaths in the Scottish MONICA population of Glasgow 1985 to 1991. Presentation, diagnosis, treatment, and 28-day case fatality of 3991 events in men and 1551 events in women.

BACKGROUND: Scottish MONICA used medical and medico-legal records and World Health Organization MONICA Project criteria to register coronary events in 25- to 64-year-old residents of the high-incidence area of north Glasgow from 1985 to 1991. METHODS AND RESULTS: Age-standardized data from 3991 episodes of nonfatal definite myocardial infarction and coronary deaths in men (mean age, 55.5 years) were compared with 1551 in women (57.0 years). Many results, such as the overall 28-day fatality rates of 49.8% in men and 48.5% in women, showed insignificant differences. However, 74.3% of deaths in men occurred out of hospital versus 67.8% in women (P = .0004). After admission to hospital, fatality rates in women were 14% higher (P = .07) and after admission to coronary care, 22% higher (P = .04). Women were more often widowed. Fewer had a history of previous myocardial infarction, but the prevalence of angina pectoris, of smoking, and of chest pain in the attack was the same as in men; more had shock, syncope, and breathlessness. More consulted a doctor before admission to hospital, which delayed their coming under care. More men had ECG Q-wave progression, and more women had smaller ECG changes. This, and marginally reduced chances of direct admission to coronary care, of thrombolysis, of aspirin, and of beta-blockers, did not explain women's excess hospital fatality. CONCLUSIONS: Acute coronary events appear to be recognized and treated fairly equally in men and women 25 to 64 years old in Glasgow, so differences are small but subtle. More men die suddenly out of hospital; the reason why more women die after arrival may be because the equivalent number of men have already died outside.

Acute Disease↗
PubMed1996

Clinical outcomes of two early postpartum IUD insertion programs in Africa.

Postpartum IUD insertion programs are new to Africa and few have been carefully evaluated. Also, data on the clinical outcomes of postpartum IUD insertions using the Copper T 380A IUD are sparse. Therefore, we conducted a study to evaluate introductory postpartum IUD programs using the Copper T 380A IUD in Kenya and Mali. Postpartum IUD acceptors in Kenya (n = 224) and Mali (n = 110) were interviewed at baseline and at 1, 3, amd 6 months after delivery. We compared expulsion, medical removal, and discontinuation rates by insertion characteristics in each country. Six-month cumulative expulsion rates were lower for immediate insertions (those within 10 minutes of placental delivery) than for late insertions (generally between 10 minutes and 72 hours after placental delivery) in both Kenya (0.01 vs 0.05) and Mali (0.15 vs 0.27). Medical removals occurred in 1% and 7% of Kenyan and Malian acceptors, respectively, while pelvic infections were rare in both countries (< or = 2%). Differences in 6-month cumulative discontinuation rates between immediate and late insertions were not significant in either Kenya (0.05 vs 0.07) or in Mali (0.24 vs 0.32). This study suggests that postpartum IUD insertions can be performed safely with acceptable expulsion rates in African settings. Previous studies of other IUDs showed that expulsion rates are lower for immediate insertions compared with late postpartum insertions. This study suggests that these findings can be extended to the Copper T 380A IUD.

Adult↗
PubMed1996

Motivation to participate, exercise affect, and outcome behaviors toward physical activity.

Recently researchers have focused attention on understanding the relationship between motivation to participate and affective states associated with adherence to exercise and psychological outcomes of participation. It was hypothesized that intrinsic motivation toward an activity will heighten the associated positive affect, thereby leading to increased participation and higher perceived competence and satisfaction. The presently devised models tested the above hypothesis with 130 college students enrolled in psychology classes. They were asked to complete the Motivation for Physical Activity Measure, the Sport Enjoyment Questionnaire, and general demographic questions assessing adherence to exercise and perceived competence and satisfaction. Partial support for these path models was shown as intrinsic motivation was a predictor of affect and perceived competence and satisfaction, while extrinsic motivation predicted adherence for men only. These results provide a model to enhance the understanding of exercise-related behavior in the general population and the study of the relationship of motivation with affect toward exercise.

Adolescent↗
PubMed1995

A model for magnetization transfer in tissues.

Magnetization transfer in several tissues is measured and successfully modeled using a two-pool model of exchange. The line shape for the semi-solid pool is characterized by a superLorentzian and the liquid pool by a Lorentzian. The tissues investigated were white and gray matter, optic nerve, muscle, and liver. All tissues the authors studied are characterized by the same model but differ in the parameter values of the model. Blood and cerebral spinal fluid (CSF) were also investigated. The two-pool model with a Lorentzian line shape for both the semi-solid and liquid pools modeled the magnetization transfer in blood. In CSF, as expected, there is no measurable exchange of magnetization. The T2B associated with the semi-solid pool was short (approximately 10 microseconds) for all tissues indicating a fairly rigid semi-solid pool. In addition characterization of the line shape as superLorentzian indicates molecules such as integral membrane proteins or lipids in membranes are likely molecules participating in the exchange. Conversely, in blood large globular proteins are indicated due to the Lorentzian nature of the semi-solid pool and a T2B approximately 300 microseconds.

Animals↗
PubMed1995

Modeling magnetization transfer for biological-like systems using a semi-solid pool with a super-Lorentzian lineshape and dipolar reservoir.

Magnetization transfer is modeled as an exchange between a liquid pool and a semi-solid pool where the semi-solid pool has, in addition to the Zeeman reservoir, a dipolar reservoir. The lineshape for the liquid pool is characterized by the usual Lorentzian, whereas the semi-solid pool is characterized as a super-Lorentzian. Three systems were investigated: (1) a membrane mixture of a phosphatidylcholine lipid (POPC) and cholesterol; (2) lyophilized white matter at eight solid concentrations ranging from 1 to 24%; and (3) fresh white matter. In all systems, this model fitted the experimental data well with the effect of the dipolar reservoir being most important for the membrane mixture. For the tissue, the dipolar reservoir is not required and the two-pool model with a single Zeeman reservoir for the semi-solid spins characterizes the experimental data equally well.

Animals↗