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Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1997

Managing an increasingly complex system.

A study of more than 170,000 health care workers (including 47,692 registered nurses [RNs]) in 138 acute care health care organizations revealed that the role of the RN is characterized by excessive numbers of activities, a loss of focus on the professional components of nursing and significant activity overlap with other job classes. Additionally, the study found that these characteristics were related to reduced morale, decreased patient and physician satisfaction with care and increased health care costs. The results of this study suggest a need for nursing leaders to develop new methods for controlling the complexity of health care systems, particularly the complexity of the RN role. Controlling complexity requires better tools for identifying system inefficiencies, more advanced skills in cross-functional work process diagnostics and more effective strategies for reducing complexity across health care systems.

Delivery of Health Care↗
PubMed1996

Wild-type p53 negatively regulates the expression of a microtubule-associated protein.

The product of the p53 tumor suppressor gene has a well-documented activity as a transcriptional activator, and several studies indicate that this function is at least in part essential for the ability of p53 to suppress cellular proliferation. However, there is growing evidence that some activities of wild-type p53 may be independent of its trans-activation function; in fact, recent investigations have indicated that the transcriptional repression function of p53, rather than its trans-activation function, may be influential in p53-mediated apoptosis. The focus of this study has been on the identification of genes that exhibit decreased expression during p53-dependent apoptosis, and therefore represent potential p53-repressed genes influential in programmed cell death. This report identifies the gene encoding the microtubule-associated protein MAP4 as one whose mRNA and protein expression decrease in cells following induction of wild-type p53. Importantly, decreased MAP4 expression following p53 induction can be inhibited by molecules that prevent p53-mediated transcriptional repression and apoptosis, such as the adenovirus E1B-19K protein and the Wilms tumor gene product WT1. Additionally, overexpression of MAP4 in cells induced to undergo p53-dependent apoptosis significantly delays this process, indicating that the negative regulation of this gene by p53 may be influential in the rapid progression of apoptosis.

Adenovirus E1B Proteins↗
PubMed1996

Glial cell line-derived neurotrophic factor promotes the development of adrenergic neurons in mouse neural crest cultures.

Growth of mouse neural crest cultures in the presence of glial cell line-derived neurotrophic factor (GDNF) resulted in a dramatic dose-dependent increase in the number of tyrosine hydroxylase (TH)-positive cells that developed when 5% chicken embryo extract was present in the medium. In contrast, growth in the presence of bone morphogenetic protein (BMP)-2, BMP-4, BMP-6, transforming growth factor (TGF) beta 1, TGF-beta 2, and TGF-beta 3 elicited no increase in the number of TH-positive cells. The TH-positive cells that developed in the presence of GDNF had neuronal morphology and contained the middle and low molecular weight neurofilament proteins. Numerous TH-negative cells with the morphology of neurons also were observed in GDNF-treated cultures. Analysis revealed that the period from 6 to 12 days in vitro was the critical time for exposure to GDNF to generate the increase in TH-positive cell number. The growth factors neurotrophin-3 and fibroblast growth factor-2 elicited increases in the number of TH-positive cells similar to that seen in response to GDNF. In contrast, nerve growth factor was unable to substitute for GDNF. These findings extend the previously reported biological activities of GDNF by showing that it can act on mouse neural crest cultures to promote the development of neurons.

Animals↗
PubMed1996

Cyclin D1 and p21/waf1 are both involved in p53 growth suppression.

Overexpression of the wild type p53 gene in normal and transformed cells induces G1 arrest of cellular proliferation. In cell lines carrying the valine 135 temperature-sensitive p53 mutant gene, restoration of wild type p53 protein conformation at the permissive temperature causes an increase in the levels of cyclin D1, as well as the cyclin/cdk inhibitor p21/waf1. Accumulation of cyclin D1 is the result both of (post)transcriptional and post-translational regulatory mechanisms. Ablation of cyclin D1 induction by antisense cDNA microinjection significantly delays the onset of growth arrest, indicating that increased cyclin D1 levels likely contribute to wild type p53 G1 arrest. Whereas antisense ablation of either cyclin D1 or p21/waf1 can delay the onset of p53-induced growth arrest, ablation of neither is able to overcome a pre-existing p53-induced G1 block. In summary, the accumulated evidence indicate that induction of both cyclin D1 and p21/waf1 are involved in establishing the p53-mediated growth arrest in murine cell lines expressing temperature sensitive p53 protein.

Amino Acid Sequence↗
PubMed1996

p53 mutation, allele loss on chromosome 17p, and DNA content in ovarian carcinoma.

The aim of this investigation was to explore the relationships between p53 mutation, DNA aneuploidy, 17p deletions, and clinical stage in ovarian cancer. Nuclear suspensions were obtained by tissue disaggregation, stained with propidium iodide, and analysed on a Coulter EPICS Elite flow cytometer. DNA cell cycle analysis was performed using Multicycle software (Phoenix Flow Systems). DNA extracted from paraffin-embedded archival carcinomas/non-tumour tissue was used as template for PCR amplification of the microsatellite dinucleotide repeat polymorphism D17S513, a locus telomeric to p53 on 17p13.1. Allele loss at D17S513 was detected in 64.5 per cent of carcinomas (20 of 31 informative cases). DNA aneuploidy was detected in 20 of 54 (37 per cent) carcinomas. Eight of ten cases previously shown to harbour p53 mutations showed aneuploid DNA content. Although ten other DNA aneuploid cases had shown no p53 mutations, the results show a statistically significant association between p53 mutation and DNA aneuploidy (P < 0.01). Furthermore, the mean DNA index of the DNA aneuploid cases was significantly higher in p53 mutant cases compared with those showing no p53 mutation (P = 0.02). There was also a significant association between p53 mutations and stage, between ploidy and stage, and between allelic deletions at D17S513 or p53 and stage, but not between these allelic deletions and ploidy. p53 mutations appear to be associated with DNA aneuploidy in ovarian cancer independently of 17p deletions. p53 mutations, DNA aneuploidy, and 17p deletions are associated with late stage.

Alleles↗
PubMed1996

Leukemia inhibitory factor and interleukin-6 are produced by diseased and regenerating skeletal muscle.

The process of skeletal muscle regeneration following injury or disease involves locally produced growth factors which control cellular proliferation and differentiation. Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) have previously been shown to promote the proliferation of myoblasts in vitro, and thus may be involved in muscle regeneration. In the present investigation, the in vivo expression of these two myogenic growth factors was examined in regenerating muscle after a crush injury of wild type mice, and in diseased skeletal muscle and diaphragm of the mdxmouse. Using Reverse transcription polymerase chain reaction we have demonstrated that while normal muscle rarely expresses mRNA for these two molecules, there is significant up-regulation following injury, coinciding with the active period of muscle regeneration. This suggests these molecules act as locally produced trauma factors. This observation is reinforced in mdxmouse muscle, which is undergoing a cycle of degeneration and regeneration, and expresses both LIF and IL-6. Using in situ hybridization we have localized mRNA for LIF expression in the mdx diaphragm, suggesting that local production of these molecules by regenerating muscle itself, as well as by other cells in muscle, plays an important role in muscle regeneration.

Animals↗
PubMed1996

Peroxynitrite augments fMLP-stimulated chemiluminescence by neutrophils in human whole blood.

The neutrophil respiratory burst was examined by the technique of luminol-dependent chemiluminescence (LDCL) triggered by submaximal concentrations of N-formyl-methionyl-leucyl-phenylalanine (fMLP) in diluted whole blood. We sought to identify the chemical species responsible for LDCL in whole blood, to examine the role of leukotriene B4 (LTB4) and other arachidonic acid metabolites as mediators of the fMLP signaling pathway, and to investigate the effect of peroxynitrite on this response. Both sodium azide and taurine significantly inhibited LDCL (93% inhibition with 100 microM azide, 52% inhibition with 10 mM taurine). More modest inhibition was seen with superoxide dismutase (SOD), catalase, the nitric oxide synthase inhibitor monomethyl-L-arginine (L-NMMA), and with inhibitors of the cyclooxygenase (indomethacin), lipoxygenase (AA-861; no effect), and cytochrome P-450 (SKF 525-A) pathways of arachidonic acid metabolism. The nitric oxide donor SIN-1 (1-100 microM) and peroxynitrite (10-300 microM) also augmented fMLP-induced LDCL. The augmentation seen with peroxynitrite and SIN-1 was attenuated by SOD. Despite the increase in LDCL, peroxynitrite caused a dose-related inhibition of fMLP-stimulated LTB4 release. In summary, our results indicate that (1) LDCL elicited by fMLP in diluted whole blood appears primarily mediated by hypochlorous acid derived from myeloperoxidase; (2) pretreatment with the nitric oxide donor SIN-1 or with peroxynitrite augments LDCL; and (3) LTB4 release does not contribute to fMLP-stimulated LDCL or in the modulation of LDCL by SIN-1 or peroxynitrite.

Antioxidants↗
PubMed1996

Semistructured child sexual abuse interviews: interview and child characteristics related to credibility of disclosure.

This study provided the first empirical description of child and interviewer behaviors occurring within semistructured assessment interviews with children suspected of being victims of sexual abuse. Specifically, relationships between child and interviewer characteristics and interview credibility were examined. Using the Child Abuse Interview Interaction Coding System (CAIICS, Wood, 1990), 55 videotaped interviews of high-risk sex abuse cases seen at a multidisciplinary assessment center were behaviorally coded. Support was found for the interrater reliability and criterion related validity of the CAIICS was found. Results also revealed that children were initially rated as relaxed and displayed few emotional behaviors. Thus, the assumption that a credible disclosure of abuse must necessarily include the display of emotion by the child was not supported. Second, several behavioral differences between preschool and school-aged children were identified: however, no meaningful gender differences were found. Third, supporting evidence was found for both age and gender effects in judgments of interview credibility, with girls and school-aged children judged as more credible. Fourth, while the interviewer did engage in so called leading behaviors, these behaviors were not found to be related to rating of interview credibility. However, interviewer behaviors may have affected interview credibility through an intervening variable. Finally, implications, for further use of the CAIICS for examining interviewer-child interactions, evaluating standards of practice, and assisting with interviewer training are discussed.

Child↗
PubMed1996

Up-regulation of leukaemia inhibitory factor and interleukin-6 in transected sciatic nerve and muscle following denervation.

Leukaemia inhibitory factor (LIF) and Interleukin-6 (IL-6) are multifunctional cytokines that are related on the basis of their predicted structural similarities and shared signal transducing receptor components. Both these factors stimulate myoblast proliferation, and whereas LIF is neurotrophic for sensory neurons, and for the motor neurons which innervate muscle, IL-6 has only been reported to act on a population of septal neurons in the brain. We have looked at the effect of peripheral nerve trauma on the expression of these factors. We show here that whereas LIF and IL-6 mRNAs are expressed in low levels in normal sciatic nerve and skeletal muscle, there is significant up-regulation in the nerve segments after injury, with proximally and distally. There is also an increase in LIF and IL-6 expression in the denervated muscle located largely in the muscle cells. In addition, while there is retrograde axonal transport of LIF by the sciatic nerve, IL-6 is not retrogradely transported, and as a result, IL-6 does not stimulate the survival of sensory neurons in vitro. Both growth factors are produced by Schwann cells. These results show a rapid response in the expression of these genes after injury and suggest that LIF and IL-6 act as trauma factors but with different roles in injured peripheral nerve.

Animals↗
PubMed1996

Fluorescence in situ hybridisation with chromosome-specific centromeric probes: a sensitive method to detect aneuploidy.

Cytochalasin B-blocked binucleate human lymphocytes from female donors have been used to measure micronucleus induction and other aneuploidy events after treatment with colchicine, vinblastine or carbendazim. For the aneuploidy events, centromeric probes for 6 selected chromosomes (1, 8, X, 11, 17, 18) were used to measure chromosome loss, addition and non-disjunction in the interphase nuclei of these binucleate cells. The chromosomes were probed in pairs using Cy-3 (red) and FITC (green) labels for the 2 different centromeric regions. For colchicine, the total non-disjunction frequencies for chromosomes 1 and 8 were similar to the total micronucleus frequencies, but were detected as significant at lower concentrations. For vinblastine (chromosomes 1 and 8) and carbendazim (all 6 chromosomes) the frequencies of non-disjunction far exceeded (7 and > 2-fold, respectively) the peak frequencies of micronucleus induction. Although most chromosomes exhibited similar sensitivity in all the aneuploidy events measured, there was an indication that chromosome X was more than susceptible to non-disjunction than the other chromosomes. We believe that measurement of non-disjunction in binucleate human lymphocytes using chromosome specific centromeric probes offers a sensitive method for detection of aneuploidy and is particularly appropriate for the establishment of thresholds.

Adult↗
PubMed1996

Hemangiopericytoma: a report of two cases arising on the lip.

Hemangiopericytoma is a rare tumour of pericytes; represents 1% of all vasoformative tumours and 15-25% of those which occur in the head and neck. We present two cases of hemangiopericytoma occurring on the lower lip and report the use of cryosurgery to treat the most recent case.

Adolescent↗
PubMed1996

Comparison of anaerobic components of the Wingate and Critical Power tests in males and females.

The purpose of the study was to reexamine the relationship between the Wingate and Critical Power tests of anaerobic capacity (AC) and anaerobic reserve (AR), respectively. A second purpose was to observe gender differences. Both tests were administered to 16 female and 13 male subjects (N = 29) on a Monark cycle ergometer with six subjects repeating AR measurement. The results show that AC (240.2 +/- 30.5 J-kg-1, calculated from total work for 30 s) and AR (184.0 +/- 1.2 J.kg-1) were not well-correlated (r = 0.07, P > 0.72). When expressed as total energy independent of body mass, the relationship was significant but low (r = 0.41, P > 0.02). Since AR was 23% lower than AC, which is believed to underestimate true anaerobic capacity, the data suggest that the Critical Power and Wingate tests do not assess the same anaerobic compartments. AR from the Critical Power test may not include the energy component of anaerobic glycolysis. Therefore, intrinsic methodological and theoretical differences between the tests make the absolute comparison of AC and AR problematic.

Adult↗
PubMed1996

The herpes simplex virus type 1 UL8 protein influences the intracellular localization of the UL52 but not the ICP8 or POL replication proteins in virus-infected cells.

We have developed a panel of 14 monoclonal antibodies (MAbs) to POL, the catalytic subunit of herpes simplex virus type 1 (HSV-1) DNA polymerase encoded by gene UL30, and one MAb to the UL52 protein, another of the seven proteins essential for replication of HSV DNA. The approximate locations of the epitopes of the polymerase-specific MAbs were identified using truncated polymerase molecules, and the antibodies were characterized in a number of immunological assays allowing eight different specificities to be recognized. These MAbs, together with a polyclonal antibody raised in rabbits against a third DNA replication protein, ICP8, were used to localize the respective proteins by immunofluorescence in cells infected with wild-type HSV-1 or the DNA replication-defective mutants ambUL8 or 2-2. In BHK cells infected with ambUL8, a mutant with an amber termination codon within the coding region of gene UL8, the UL52 protein did not enter the nucleus, although ICP8 and POL entered the nucleus in a normal fashion. The failure of the UL52 protein to be correctly transported to the nucleus was also observed in both HFL and Vero cells infected with ambUL8. In contrast, UL52 protein was transported to the nucleus in BHK cells infected with wild-type HSV-1 or with 2-2, a mutant lacking a functional UL9 protein.

Animals↗
PubMed1996

Continuous thoracic epidural analgesia versus combined spinal/thoracic epidural analgesia on pain, pulmonary function and the metabolic response following colonic resection.

BACKGROUND: The neuroendocrine response following major surgery has not been previously influenced by either regional anaesthetic techniques or opioid analgesia probably due to insufficient intraoperative afferent neural blockade. In this study we attempted to determine whether significant inhibition of these pathways could be achieved by combining preoperative high spinal anaesthesia with postoperative thoracic epidural anaesthesia. In theory too, there may be additional benefits over perioperative thoracic epidural anaesthesia on pain and pulmonary dysfunction. METHODS: 20 ASA 1-3 patients undergoing elective colonic surgery were studied. Gp 1 (n = 10) received a high spinal intraoperative block to T4 using 6mls of 0.5% bupivacaine plus continuous epidural 0.125% bupivacaine/0.0025% diamorphine. Gp 2 (n = 10) patients received epidural 0.5% bupivacaine block to T4 plus continuous epidural infusion of 0.125% bupivacaine/0.0025% diamorphine. We measured a) plasma glucose and cortisol at 0, 1, 2, 3, 4, 8 and 24 h; b) forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and peak flow rate (PFR) preoperatively, at 8 and 24 h; c) visual analogue pain scores (VAS 0-10) at rest, cough and mobilisation at 8 and 24 h; d) block height every hour for 12 hours then 3 hourly; e) 24-hour urine volumes for dopamine, adrenaline and noradrenaline f) 24-hour PCA morphine requirements. RESULTS: The two groups did not differ in age, sex, height, weight, duration of surgery, blood loss or serum albumin. Pain relief was excellent and similar in both groups. The average 24 hour morphine consumption was 10 mg in both groups with no differences in the block height. All the patients had a 30-50% reduction in FEV1, FVC and PFR (P > 0.05). Metabolically, there was no statistical difference between the 2 groups except a higher rise in glucose in Gp1 at 2 and 3 h (P = 0.0312 and 0.014). 24-hour catecholamine studies showed no differences for noradrenaline (P = 0.8), adrenaline (P = 0.47) and dopamine (P = 0.36). CONCLUSIONS: Thoracic epidural bupivacaine/diamorphine infusion provided excellent postoperative analgesia following colonic surgery. An intraoperative combined spinal/epidural technique conferred no additional benefit on analgesia, pulmonary function and the neuroendocrine response.

Adult↗
PubMed1996

Leukaemia inhibitory factor or related factors promote the differentiation of neuronal and astrocytic precursors within the developing murine spinal cord.

Previously we have shown that leukaemia inhibitory factor (LIF) potentiates the development of murine spinal cord neurons in vitro, suggesting that it, or related factors, may play an important regulatory role in neuronal development. We have further investigated this role and show here that the generation of neurons in cultures of embryonic day 10 spinal cord cells is inhibited by antibodies to the beta subunit of the LIF receptor. Since there are more undifferentiated precursors in antibody-treated cultures than in control and LIF-treated cultures, it is concluded that the primary action of LIF, or related molecules, is to promote neuronal differentiation, not precursor survival. In addition, the failure of LIF to support neuronal survival in the period immediately following differentiation suggests that the increased numbers of neurons generated with LIF are not attributable to its neurotrophic action. By selecting neuronal precursors on the basis of their inability to express class 1 major histocompatibility complex molecules, it was shown that LIF acted directly upon these cells and not via an intermediary cell. LIF also appears to be involved in regulating the differentiation of astrocytes, since it increases the number of glial fibrillary protein (GFAP)-positive cells present in the cultures and since the spontaneous production of GFAP-positive cells is blocked by antibodies to the LIF beta receptor. These findings suggest that LIF or related factors promote the differentiation of neural precursors in the spinal cord, but that they are not involved in preferentially promoting precursors down a specific differentiation pathway.

Animals↗
PubMed1996

Neural tube defects 1974-94--down but not out.

AIMS: To describe accurately the total prevalence of neural tube defects (NTDs) in England and Wales over time, and to provide a benchmark up to 1994. METHODS: National data about NTDs reported as births or terminations are available from 1974-94, but reporting is incomplete. A local register of NTDs covering Oxfordshire/west Berkshire from 1965-94 was used to validate national data for the locality, using the method of capture and recapture, and hence to estimate incompleteness of reporting nationally. RESULTS: National underreporting is consistent at about two thirds of the true number of cases reaching at least the second trimester. The local register is much more complete, but time trends locally and nationally are similar. In England and Wales total prevalence declined from about 34 per 10000 live and stillbirths in 1974 to a plateau of just under 8 per 10000 in the 1990s. CONCLUSIONS: The decline in NTD prevalence is real and seems to have stopped. How this relates to changes in diet or the practice of vitamin supplementation is unknown, and the implications of the plateau are uncertain. OPCS figures of 500 NTDs annually in England and Wales represent about two thirds of the true number of cases.

England↗
PubMed1996

A distinct cyclin A is expressed in germ cells in the mouse.

In this paper, the existence of two A-type cyclins in the mouse is demonstrated. In the adult mouse, the expression of cyclin A1, which has greatest sequence identity with Xenopus cyclin A1, is restricted to germ cells. In contrast cyclin A2, which has greatest sequence identity with human cyclin A and Xenopus cyclin A2, is expressed in all tissues analysed. In order to explore the function of cyclin A1 in germ cells, its expression during the meiotic cell cycle and its associated kinase subunits have been characterised in the testis. The levels of cyclin A1 mRNA rise dramatically in late pachytene spermatocytes and become undetectable soon after completion of the meiotic divisions; thus its expression is cell cycle regulated. In lysates of germ cells from adult testes, cyclin A1 is present in p13suc1 precipitates, and cyclin A1 immunoprecipitates possess histone H1 kinase activity. Three kinase partners of cyclin A1 were identified: p34cdc2, a polypeptide of 39 x 10(3) M(r) that is related to p33cdk2 and, in lesser quantities, p33cdk2. Cyclin A1 was also detected in oocytes; in metaphase I and metaphase II oocytes, a proportion of the cyclin A1 colocalises with the spindle, possibly suggestive of a functional interaction. These data indicate that mammalian germ cells contain cyclin A1-dependent kinases that either act as a substitute for, or in addition to, the cyclin A2-dependent kinases characterised in somatic tissues.

Amino Acid Sequence↗