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Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 91 records · Page 5Linked to original sources

Mental health professionals' attire.

OBJECTIVE: Our aim was to obtain mental health patients' views on psychiatrists' and case managers' attire. METHODS: Eighty-six patients treated at a community mental health service were surveyed. Various types of commonly worn attire were listed. Respondents were asked to choose what they thought was most appropriate for their psychiatrist and case manager to wear. RESULTS: Over 50% of respondents felt that psychiatrist or case manager dress was not an important issue. However, those who felt that it was preferred less formal attire. CONCLUSIONS: Psychiatrists and case managers in a community mental health team could consider adopting less formal attire. This conclusion is limited by the small sample and may be relevant to rural areas only. Further research is needed in urban centres. Implications of these findings are discussed.

Adult

Low p27 expression predicts poor disease-free survival in patients with prostate cancer.

PURPOSE: p27 is an inhibitor of the cell cycle with potential tumor suppressor function. Decreased levels of p27 protein expression have been correlated with poor prognosis in patients with breast and colorectal carcinomas. Although as many as a third of patients with clinically localized prostate cancer will have relapse after radical prostatectomy, predicting who will have recurrence remains enigmatic. We examined the ability of p27 protein levels to predict outcome in patients with clinically localized disease who underwent radical prostatectomy. MATERIALS AND METHODS: p27 protein expression was evaluated in 86 patients with clinical stage T1-2 prostate cancer who were treated with radical prostatectomy. Archived paraffin embedded specimens were sectioned and immunostained with p27 antibody, and scored by 2 independent observers in a blinded fashion. The absence or presence of p27 protein was then correlated with biochemical relapse in univariate and multivariate analyses. RESULTS: In a multivariate analysis that included age, preoperative prostate specific antigen, Gleason score and pathological stage p27 was a strong independent predictor of disease-free survival (p = 0.0184, risk ratio 3.04), second only to pathological stage (p = 0.0001, risk ratio 6.73). Even more strikingly, multivariate analysis demonstrated that p27 was the strongest predictor of biochemical recurrence (p = 0.0081, risk ratio 4.99) among factors studied in patients with pathological T2a-T3b disease. CONCLUSIONS: Absent or low levels of p27 protein expression appear to be an adverse prognostic factor in patients with clinically organ confined disease treated by radical prostatectomy. This marker appears to be especially useful in those patients in whom surgery is believed to be potentially curative, that is patients with pathological T2-T3b disease. Patients with low or absent p27 protein expression may be candidates for novel adjuvant therapies.

Aged

The effects of New York state's ban on multiple listing for cadaveric kidney transplantation.

OBJECTIVE: To study the effectiveness of a 1990 ban by New York state on entry to more than one waiting list for a cadaver kidney transplant, and the impact of the ban on equity in access to transplantation. DATA SOURCES: (1) Waiting list files from the Organ Procurement and Transplantation Network, (2) the Health Care Financing Administration's Medicare Program Management and Medical Information System, and (3) U.S. Census Public Use Files. STUDY DESIGN: Multivariate hazard models were used to estimate the impact of the ban of the overall odds of multiple listing and on the odds of multiple listing at in-state and out-of-state transplant centers. After estimating the relationship between multiple listing and subsequent transplantation, we used simulation techniques to estimate the effects of a complete multiple listing ban on group waiting time differentials. Independent variables included demographic/socioeconomic characteristics, measures of ESRD severity, general transplantation suitability, measures that affect the likelihood of finding a good donor organ, and measures of the productivity of the transplant/dialysis center. PRINCIPAL FINDINGS: The ban was associated with a 66 percent reduction in the rate of multiple listing for New York patients, and multiple listing at in-state transplant centers declined by 87 percent. Simulation results suggested that even a completely effective ban would produce only small, mixed equity effects. CONCLUSIONS: While the ban was effective in reducing the proportion of patients who registered at multiple transplant centers, taken together the results suggest that banning multiple listing is not likely to result in large improvements in equity in access to transplantation.

Adolescent

An in vitro bovine pericardial hemocompatibility testing system.

BACKGROUND AND AIMS OF THE STUDY: Bovine pericardium has been used as a biomaterial for heart valves since the late 1960s. Cross-linking agents have been applied routinely to reduce host-tissue response, including antigenicity, and to improve tissue leaflet durability. Evaluation of improvements in bovine pericardial valve leaflet calcification and flexibility require that in vitro systems be developed to correlate data with results from in vivo studies. This study describes an in vitro test system used to evaluate the effects of two surface-modifying treatments on pericardial tissue hemocompatibility. METHODS: Non-fixed and glutaraldehyde fixation-processed (GA) bovine pericardial tissues were exposed to anticoagulated whole blood for 60 min. Blood was then removed, and platelet-poor plasma prepared and frozen at -70 degrees C until analyzed for kallikrein activation and release of platelet factor 4 (PF4). Blood-exposed tissue samples were analyzed for fibrin (ogen) binding with an anti-fibrinogen antibody and for tissue cellular responsiveness (blood cell adherence and aggregation) by scanning electron microscopy. RESULTS: Conditions were determined for minimum extent of pumping action by the minicam system required to allow for solution movement while not tearing or wearing the tissue. A blood-tissue exposure time of 60 min provided sufficient first-pass exposure to evaluate the acute blood-tissue response. The relative degree of both kallikrein activation and PF4 release was greater in the non-fixed tissue but a greater number of fibrin(ogen) molecules per cm2 was found on GA-treated tissue. Scanning electron microscopy showed a differential cell response of non-fixed tissue compared with GA-treated tissue. CONCLUSION: This non-static test system demonstrated great promise for use in routine in vitro hemocompatibility testing of blood-contacting biological biomaterials.

Animals

Family and sociodemographic influences on patterns of leaving home in postwar Britain.

We identify child-level and parent-level characteristics associated with children's patterns of leaving home. We use a multilevel discrete-time hazards model to examine the impact of family and demographic factors at both levels, and utilize the Alternating Conditional Expectation algorithm optimally to transform the dependent and independent variables. We find that measured variables at both the child and the parent level have important influences, as do period and cohort factors. However, unmeasured parent-level factors have an influence on the departure of children that is broadly similar in magnitude to measured factors.

Adolescent

Propylene glycol toxicosis in a mare.

Propylene glycol and mineral oil are commonly used in the veterinary profession for treatment of bovine ketosis and equine impactions, respectively. Accidental administration of 6.0 ml propylene glycol/kg of body weight in horses causes severe depression, ataxia and malodorous breath and feces. However, appropriate medical therapy can result in successful treatment of this toxicosis.

Animals

Proliferation, apoptosis and cell cycle regulation in prostatic carcinogenesis.

Cancer progression occurs because of imbalance in the processes of proliferation, differentiation and programmed cell death. In prostate cells, these processes are regulated at least in part by androgens. Structural alterations occur in a variety of genes regulating such processes. In order to obtain meaningful information on the biologic behavior of prostate cancers, it is important to assess androgen dependence and alterations in key genes regulating cell cycle kinetics as well as the aberrant response in cellular proliferation and death that such genetic events bring about. Most genetic alterations resulting in cancer progression alter normal cell cycle progression. Assessment of cell division cycle alterations by means of quantitative methods may have prognostic value, while interference with cell cycle regulatory proteins may result in powerful therapeutic tools. Here we review the methodologies utilized in the assessment of cell cycle kinetics and the abnormalities in proliferation and apoptosis encountered in prostate cancer. In addition, alterations in novel, important genes likely to have an impact on the behavior of prostate cancer and its precursor lesions are discussed. Molecular assessment of genetic alterations in genes that play a pivotal role in prostate cancer coupled with quantitative cytometry of cell kinetics may be utilized for a more precise evaluation of biologic behavior of prostate neoplasms.

Animals

Smoking cessation interventions for dental patients--attitudes and reported practices of dentists in the Oxford region.

OBJECTIVE: To investigate various aspects of dentists' beliefs and practices with respect to helping their patients stop smoking. DESIGN: Postal questionnaire survey conducted in 1996. SETTING: The general dental practitioners on the health authority lists of Berkshire, Buckinghamshire, Northamptonshire and Oxfordshire. SUBJECTS: The 869 dentists registered on 1 April 1996. RESULTS: A high response rate (78%; 674/869) was obtained. The majority of respondents (82%; 95% CI: 79, 85) thought dentists should encourage their patients to stop smoking although only 37% (95% CI: 34, 41) believed dentists to be effective in smoking cessation and even fewer (18%; 95% CI: 15, 21) routinely recorded their patients' smoking status. Of respondents, 51% (95% CI: 46, 55) said they always discussed smoking with patients who had periodontal problems but only 9% (95% CI: 7, 12) always did so with patients who had no major oral health problem. Newer graduates were more likely to routinely record their patients' smoking status (P = 0.02), and to think that doctors' advice (P = 0.001) and nicotine replacement therapy (P < 0.001) were effective in promoting smoking cessation. Dentists in mainly private practices were more active than those in NHS or mixed practices in recording patients' smoking status (P < 0.001) and in discussing smoking (P = 0.002). CONCLUSIONS: Most respondents thought that dentists should encourage their patients to stop smoking but few are active in this area.

Attitude of Health Personnel

Twinning rates.

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Birth Rate

Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast.

We demonstrate that in Saccharomyces cerevisiae, the tandem array of ribosomal RNA genes (RDN1) is a target for integration of the Ty1 retrotransposon that results in silencing of Ty1 transcription and transposition. Ty1 elements transpose into random rDNA repeat units and are mitotically stable. In addition, we have found that mutation of several putative modifiers of RDN1 chromatin structure abolishes silencing of Ty1 elements in the rDNA array. Disruption of SIR2, which elevates recombination in RDN1, or TOP1, which increases psoralen accessibility in rDNA, or HTA1-HTB1, which reduces histone H2A-H2B levels and causes localized chromatin perturbations, abolishes transcriptional silencing of Ty1 elements in RDN1. Furthermore, deletion of the gene for the ubiquitin conjugating enzyme Ubc2p, which ubiquitinates histones in vitro, derepresses not only Ty1 transcription but also mitotic recombination in RDN1. On the basis of these results, we propose that a specialized chromatin structure exists in RDN1 that silences transcription of the Ty1 retrotransposon.

Base Sequence

The role of leukemia inhibitory factor in skeletal muscle regeneration.

Although a number of cytokines have been implicated in tissue regeneration, it is unknown which ones actually function in vivo. Here, we use mice with a targeted mutation in the leukemia inhibitory factor (LIF) gene to examine the role of LIF in muscle regeneration. Using a muscle crush model, we show that muscle regeneration in LIF knockout mice is significantly, reduced compared to control littermates. Further, targeted infusion of LIF in both normal and LIF knockout animals stimulated muscle regeneration, but the stimulation observed was much greater in the mutant animals than in controls. In contrast, interleukin-6 and transforming growth factor-alpha, which also stimulate myoblast proliferation in vitro, had no effect on regeneration. These findings demonstrate directly that LIF is involved in regeneration of injured muscle and points to the use of LIF as a therapeutic agent in the treatment of neuromuscular disease.

Animals

Minimizing racial disparity regarding receipt of a cadaver kidney transplant.

This report describes the impact of race on waiting list entry and receipt of a cadaver kidney transplant, after accounting for self-reported income, health and functional status, and patients' attitudes about dialysis and transplantation as treatment alternatives. Previous studies did not account for these race-related factors and therefore produced biased estimates of the impact of race on waiting list entry and receipt of a transplant. Data for this investigation came from a telephone survey of a national sample of 456 end-stage renal disease patients and from files maintained by the United Network for Organ Sharing and the Health Care Financing Administration. Proportional hazard models were estimated with these data. The results indicated that approximately 60% of the differences between black and white waiting list entry rates and 52% of the black-white differences in transplantation rates were due to race-related differences in socioeconomic status, health and functional status, severity of illness, biological factors, the existence of contraindications to transplantation, transplant center characteristics, and patients' attitudes about dialysis and transplantation. Potential ways to narrow racial differences further include better education about treatment alternatives for black patients, more vigorous efforts to obtain donor organs from minorities, continued research and thoughtful policy on the access-related impacts of United Network for Organ Sharing point system variances, and consolidation of some smaller waiting lists into larger regional lists.

Adolescent

Cytokines which signal through the LIF receptor and their actions in the nervous system.

A number of different cytokines, each initially characterized on the basis of very different biological activities, all have very similar signalling pathways and share a similar tertiary structure. These cytokines include leukaemia inhibitory factor, ciliary neuronotrophic factor, oncostatin M, growth-promoting activity and cardiotrophin 1. They all have been found to regulate a number of properties of cells of the developing and mature nervous system in vitro and thus are neuroregulatory cytokines. The actions of these cytokines include regulation of neurotransmitter phenotype, differentiation of neuronal precursor cells both in the peripheral nervous system and in the spinal cord, survival of differentiated neurons, and regulation of development of both astrocytes and oligodendrocytes. In addition, studies in animal models show that these factors can rescue sensory and motor neurons from axotomy-induced cell death, which suggests that they can act as trauma factors for injured neurons. Analysis of the expression patterns of the different neuroregulatory cytokines and their receptors reveals that the receptors are expressed throughout nervous system development and following trauma, whereas the cytokines show temporal and spatial specific expression patterns. This is consistent with the idea that specific cytokines have specific roles in neural development and repair, but that their signalling pathways are shared. The phenotypes of the receptor knockouts show clear deficits in nervous system development, indicating a crucial role for LIF receptor signalling. Knockouts of individual cytokines are less dramatic, but LIF and CNTF knockouts do reveal deficits in maintenance of motor neurons or following trauma. Thus, whereas LIF and CNTF have clear roles in maintenance and following trauma, it is unclear which of the cytokines is involved in nervous system development. In clinical terms, these findings add further support to the use of these cytokines in nervous system trauma and disease.

Animals

TP53 mutation in ovarian carcinoma.

This short report describes the detection of mutations of the TP53 tumour suppressor gene in sporadic ovarian carcinomas using archival paraffin-embedded tissues and automated fluorescent DNA sequencing. TP53 mutations were detected in eight tumours. Missense mutations predominated and all were transitions. Mutations were commonest in late-stage serous tumours. In three cases, where tissue was available, the mutations were homogeneous throughout several sections of the bilateral ovarian tumours and in omental metastases. These data confirm the findings of previous investigations describing TP53 mutation in ovarian carcinoma and demonstrate that archival paraffin-embedded tissues can be used for such analyses.

DNA Mutational Analysis

Infertility treatment and multiple birth rates in Britain, 1938-94.

Trends in multiple birth rates are thought to have been substantially affected by subfertility treatments in the last 25 years, but there are few quantitative assessments of this. This paper examines trends in twin and higher multiple birth rates separately in Scotland, England and Wales and compares their course with corresponding multiple birth rates in the Oxford Record Linkage Study area, where the proportions following subfertility treatment are documented. National data on prescriptions for subfertility treatments reinforce the view that they have had a major effect on the trends, and currently perhaps 60% of triplet and higher order births and 15% of twins follow their use in Britain.

Birth Rate

Neural stem cells.

This article is concerned with the idea that neural precursor cells in vertebrates can self-renew and give rise to all cell types within the nervous system. Supportive evidence for this notion of neural stem cells comes from clonal analyses undertaken both in vivo and in vitro. Neural stem cells also give rise to other cells in the body, including skin melanocytes and a range of mesenchymal cells in the head and neck. What determines the fate of these stem cells is their initial location within the developing neural tube and their final location post migration from the proliferative zone of the neural tube. A population of cells in the adult brain also have the characteristics of classical stem cells, a finding that opens the way for potential replacement therapy in nervous system-degenerative diseases. Much of the work in our laboratory has been concerned with the regulation of expansion and differentiation of these cells into their myriad progeny and the role of a series of various growth factors in this process. Different factors, such as members of the fibroblast growth factor family, act at different times to regulate stem cell proliferation and differentiation. Some factors, including members of the TGF beta superfamily, appear to be directly involved in the specification of cell fate. Finally, we are beginning to be able to determine the steps in the development of some lineages from multipotential stem cell to fully functional differentiated cell.

Animals

Delayed early embryonic lethality following disruption of the murine cyclin A2 gene.

In higher eukaryotes, cell cycle progression is controlled by cyclin dependent kinases (Cdks) complexed with cyclins. A-type cyclins are involved at both G1/S and G2/M transitions of the cell cycle. Cyclin A2 activates cdc2 (Cdk1) on passage into mitosis and Cdk2 at the G1/S transition. Antisense constructs, or antibodies directed against cyclin A2 block cultured mammalian cells at both of these transitions. In contrast, overexpression of cyclin A2 appears to advance S phase entry and confer anchorage-independent growth, and can lead to apoptosis. A second A-type cyclin, cyclin A1 has been described recently which, in the mouse, is expressed in germ cells but not somatic tissues. To address the possible redundancy between different cyclins in vivo and also the control of early embryonic cell cycles, we undertook the targeted deletion of the murine cyclin A2 gene. The homozygous null mutant is embryonically lethal, demonstrating that the cyclin A2 gene is essential. Surprisingly, homozygous null mutant embryos develop normally until post-implantation, around day 5.5 p.c. This observation may be explained by the persistence of a maternal pool of cyclin A2 protein until at least the blastocyst stage, or an unexpected role for cyclin A1 during early embryo development.

Animals