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Biomedical subjects

C Morrison

Publications and source records attributed to C Morrison.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1995

In vitro biocompatibility testing of polymers for orthopaedic implants using cultured fibroblasts and osteoblasts.

The biocompatibility of two polymers for potential use as orthopaedic implant materials in an isoelastic hip prosthesis was investigated. The interactions of polyetheretherketone (PEEK) and epoxy resin polymers (with and without carbon fibre reinforcement) with both fibroblasts and osteoblasts were tested using cell protein, intracellular reduced glutathione (GSH), leakage of lactate dehydrogenase and the MTT assay as indices of cellular cytotoxicity. The epoxy resin polymer was slightly cytotoxic to and inhibited the growth rate of fibroblasts (as assessed by total cell protein), and depleted GSH in both cell types. In contrast, the PEEK material did not display overt signs of cytotoxicity and, in fact, increased osteoblast cell protein content. This suggests that, of these two materials, PEEK would be the one of choice for development of an isoelastic implant and, in view of its stimulatory effect on osteoblast protein content, it may encourage ingrowth of bone around the prosthesis and thus minimize joint loosening.

3T3 Cells↗
PubMed1995

Divalproex sodium and other medications for headache following craniotomy for acoustic neuroma.

Multiple pharmacologic agents were used in attempt to relieve a constant and severe headache in a 47-year-old patient following craniotomy for removal of an acoustic neuroma. Possible etiologies for the unremitting headache are presented. Response to various pharmacologic agents are listed and discussed. During the postoperative course of two surgeries on this patient, it was possible to propose an etiology for the headache by analyzing the mechanisms of each therapeutic agent, along with the patient's response. Divalproex sodium provided complete relief, suggesting the headache is attributable to cell membrane instability.

Anticonvulsants↗
PubMed1995

Maternity services for drug misusers in England and Wales: a national survey.

A postal questionnaire was sent to the 213 National Health Service maternity units in England and Wales to identify their current involvement with drug misusers. The response rate was 89.5%. Data indicated that only 29% had formal links with their local drug agency. Child protection case conferences were automatically convened in 52%, and 57% routinely admitted babies to high dependency areas. Twenty-seven per cent of the units did not offer hepatitis B screening to pregnant women, and 32% did not offer hepatitis B prophylaxis to babies whose mothers were infected. Local Health purchasing authorities should ensure that their providers are offering appropriate services to pregnant drug misusers in order to encourage such women to seek help without fear of discrimination. Liaison between health care agencies should be encouraged and areas with low levels of drug misuse should receive help with formulating policies, and training, from units with more experience.

England↗
PubMed1994

The impact of the PCR plateau phase on quantitative PCR.

The quantitative use of the polymerase chain reaction (PCR) is often compromised by the variability of the amplification. The most useful system for quantitation by PCR involves the use of controls which are almost identical to the target and which can be amplified using the same primers as the sequences of interest. In this paper, we use a model system consisting of differently sized targets amplifiable with varying primers to demonstrate the effects of the plateau phase of PCR on quantitation by PCR. This model confirms two commonly observed results: (i) when varying amounts of a single target are amplified, a constant maximum level of product is obtained and (ii) coamplification of different concentrations of different targets results in retention of the initial proportions. The inherent contradiction in these results is examined by replacement of the key elements of the reaction including enzyme, dNTPs or primers, none of which have an effect on the plateau. Pyrophosphate is found to exert no inhibitory effect on the reaction, nor does the exonuclease action of the enzyme cause the plateau. Levels of amplification attained during amplification are both theoretically and empirically defined as being insufficient to lead to the plateau due to competition between self-annealing of product DNAs and primer binding. We conclude that, pending further biochemical enquiry into the enzyme(s) used in the PCR, none of reasons conventionally proposed for the plateau phase of the PCR are sufficient to explain the phenomenon. This being so, we define the plateau as being a feature of the reaction as a whole and, since the onset of this phase is simultaneous for all amplicons, quantitation using the internal control system need not require exponential amplification. This therefore greatly simplifies the quantitative application of PCR.

Animals↗