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Biomedical subjects

P Morrison

Publications and source records attributed to P Morrison.

At least 55 records · Page 3Linked to original sources

The use of behavioural mapping in a study of seclusion.

As part of a larger study into the use of seclusion we set out to examine some of the antecedents that led to patients being secluded in one locked psychiatric ward. Behavioural mapping was used to chart the location of incidents that resulted in seclusion. Incidents were observed in several ward areas but most of these occurred in the day room and the dining room. This finding enabled us to question the ward policy of confining patients to these areas to facilitate nursing observation and management. The policy may have contributed to the number of disturbances by limiting personal space for patients. Literature on body buffer zones, crowding and territoriality is used to clarify and interpret the findings.

Female↗

Mutation of Di-leucine residues in the juxtamembrane region alters EGF receptor expression.

Di-leucine motifs have been implicated in the internalization or degradation of many membrane proteins. The epidermal growth factor receptor (EGFR) contains two di-leucine residues at 658 (TLRRLLQER) and 679 (NQALLRIL). To determine the role of these di-leucine motifs in regulating EGF receptor expression, activity, or ligand-induced degradation, the di-leucine residues at positions 658 or 679 were mutated to di-alanine residues, and the mutant receptors were stably expressed in CHO cells. The results indicate that mutation of either di-leucine motif generates and promotes cell surface expression of carboxy-truncated EGF receptors (M(r) 120, 140 kDa) that do not undergo EGF-induced autophosphorylation or degradation. In contrast, full-length EGF receptors (170 kDa) containing di-alanine substitutions resemble wild type receptors in that they respond to EGF by autophosphorylation, their tyrosine kinase activity is inhibited by protein kinase C, and they are degraded. The level of autophosphorylation of the 170 kDa mutant receptors and EGF-induced tyrosine phosphorylation of other cellular proteins is lower than that of the wild type receptor, consistent with formation of kinase-inactive heterodimers between the truncated and full-length mutant receptors. These results demonstrate that removal of either of the di-leucines leads to generation of inactivating carboxy-truncated receptors, suggesting that the two di-leucine motifs within the juxtamembrane region of the EGFR are important for ensuring normal receptor expression.

Alanine↗

A previously undescribed mutation within the tetramerisation domain of TP53 in a family with Li-Fraumeni syndrome.

We report details of a family with classic Li-Fraumeni syndrome in which there is a mutation in codon 344 of the tumour suppressor gene TP53. Codon 344 is a key residue within the tetramerisation domain, and the amino acid substitution of a proline for a leucine is predicted to have profound implications for tetramerisation and potentially DNA binding. This is the first report of a mutation at this residue in either sporadic tumours or in the germline and the first report of a germline mutation within the tetramerisation domain. The family does not appear to be remarkable in the spectrum of tumours, and there is loss of the wild-type allele in a leiomyosarcoma from the proband. A cell line has been established from the tumour of the proband and cytogenetic and molecular studies carried out, providing an extensive analysis in this family.

Adult↗

Role of mitogen-activated protein kinase kinase in regulation of the epidermal growth factor receptor by protein kinase C.

The epidermal growth factor receptor (EGFR) is regulated by at least two mechanisms involving protein kinase C (PKC), inhibition of EGF binding and inhibition of EGF-stimulated tyrosine kinase activity. In this study we investigated whether mitogen-activated protein kinase (MAPK) mediates the inhibitory effects of PKC on EGFR binding or kinase activity by pretreating NIH3T3 and Chinese hamster ovary cells expressing the EGFR with PD98059, an inhibitor of MAPK/extracellular signal-regulated kinase kinase (MEK). We also determined whether substitution of cysteine for threonine at residue 669, the site of MAPK phosphorylation of the EGFR, alters the inhibition of kinase activity by PKC. The results indicate that 1) PKC down-regulates EGFR tyrosine kinase activity by an MEK-dependent mechanism presumably involving MAPK; 2) the inhibition by PKC is not a direct result of phosphorylation of the EGFR by PKC or MAPK; 3) activation of MAPK is not sufficient to regulate EGFR kinase activity; and 4) PKC-mediated down-regulation of EGF binding and EGFR kinase activity occur by different mechanisms. These data are consistent with a model for regulation of the EGFR by other receptors whereby their activation of PKC, in conjunction with MAPK, results in the phosphorylation of a protein(s) that modulates EGFR kinase activity.

3T3 Cells↗

A study of the official records of seclusion.

The official records of seclusion on one locked ward in a city hospital were analysed. In the first instance we examined the frequency of seclusion, the sex and type of the patients secluded over a 4-year period. Following the introduction of a new recording system, a more detailed analysis of all the official records of seclusion over a 2-year period was then carried out (n = 225). The findings are presented here as simple frequency counts and provide a detailed picture of the use of seclusion in this particular area. They include details about the way in which seclusion was used on the ward and the reasons staff provided for secluding patients. The use of official records as research data illustrate how important insights into the daily care of psychiatric patients may be explored in a fruitful manner.

Australia↗

Quality in provision of forensic psychiatric services: room for improvement.

Highlights some of the tensions which impede the development of an effective and efficient system of service delivery in forensic psychiatry. Reports on an investigation exploring the quality of care in a relatively small unit providing forensic psychiatric care in a secure setting and the constraints which impede the development of such services. Discusses the findings from the investigation which point to the need for the organizational structure surrounding forensic psychiatric care to be altered so that there are no perverse incentives for purchasers of services and to enable the contracting process, considering both cost and quality issues, to take place on a level playing field.

Australia↗

Somatic mutations in the hMSH2 gene in microsatellite unstable colorectal carcinomas.

Microsatellite instability is frequently seen in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC). Germline mutations in the mismatch repair gene hMSH2 account for approximately 50% of these cases. Tumors from sporadic cases also exhibit this microsatellite instability phenotype, although at a lower frequency, and very few somatically derived mutations have so far been reported in such tumors. In this study DNA from 23 primary colorectal carcinomas (four familial and 19 sporadic cases) exhibiting microsatellite instability were screened for mutations in the hMSH2 gene using constant denaturant gel electrophoresis (CDGE). Among the sporadic cases, five (26%) were found to have somatically derived mutations. One tumor revealed two different mutations, possibly leading to a homozygous inactivation of the gene. One of the four familial cases was classified as having HNPCC, and a germline as well as a somatic mutation were found in this tumor. These results demonstrate that a considerable proportion of sporadic colorectal cancers with microsatellite instability, have somatic mutations in the hMSH2 gene.

Adult↗

Staffing levels and seclusion use.

In this paper the role of staffing levels as a determinant of seclusion use in one psychiatric hospital is examined. A detailed review of the official records of seclusion over a 2-year period was completed (n = 225). The staffing levels on shifts when seclusions were initiated were compared with similar shifts when seclusions were not used on the same ward. Statistical analysis revealed a highly significant difference between the levels of staffing: Wilcoxon matched pairs signed-ranks test, Z = -5.8675, two-tailed, P = 0.001. This finding suggests that staffing levels play a crucial role in the practice of seclusion. However, the overall staffing level must be considered along with other factors in the makeup of the staff group, including the ratio of female to male staff and the experience level of those staff. These findings have important implications for those involved in the management and practice of seclusion as well as the patients who are secluded.

Female↗

Cloning of the cDNA for a hematopoietic cell-specific protein related to CD20 and the beta subunit of the high-affinity IgE receptor: evidence for a family of proteins with four membrane-spanning regions.

We report the cloning of the cDNA for a human gene whose mRNA is expressed specifically in hematopoietic cells. A long open reading frame in the 1.7-kb mRNA encodes a 214-aa protein of 25 kDa with four hydrophobic regions consistent with a protein that traverses the membrane four times. To reflect the structure and expression of this gene in diverse hematopoietic lineages of lymphoid and myeloid origin, we named the gene HTm4. The protein is about 20% homologous to two other "four-transmembrane" proteins; the B-cell-specific antigen CD20 and the beta subunit of the high-affinity receptor for IgE, Fc epsilon RI beta. The highest homologies among the three proteins are found in the transmembrane domains, but conserved residues are also recognized in the inter-transmembrane domains and in the N and C termini. Using fluorescence in situ hybridization, we localized HTm4 to human chromosome 11q12-13.1, where the CD20 and Fc epsilon RI beta genes are also located. Both the murine homologue for CD20, Ly-44, and the murine Fc epsilon RI beta gene map to the same region in murine chromosome 19. We propose that the HTm4, CD20, and Fc epsilon RI beta genes evolved from the same ancestral gene to form a family of four-transmembrane proteins. It is possible that other related members exist. Similar to CD20 and Fc epsilon RI beta, it is likely that HTm4 has a role in signal transduction and, like Fc epsilon RI beta, might be a subunit associated with receptor complexes.

Amino Acid Sequence↗

Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for msh2 mutations.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in genes such as hMSH2 and hMLH1, which encode components of a DNA mismatch repair system. The MSH2 genomic locus has been cloned and shown to cover approximately 73 kb of genomic DNA and to contain 16 exons. The sequence of all the intron-exon junctions has been determined and used to develop methods for analyzing each MSH2 exon for mutations. These methods have been used to analyze two large HNPCC kindreds exhibiting features of the Muir-Torre syndrome and demonstrate that cancer susceptibility is due to the inheritance of a frameshift mutation in the MSH2 gene in one family and a nonsense mutation in the MSH2 gene in the other family.

Amino Acid Sequence↗

Self-disclosure and nursing students: the replication of a Jourard study.

A person's willingness to disclose things about him or herself is an important facet of all social interaction. In professional helping relationships effective management of treatment and therapy may depend ultimately on a person's self-disclosures. Sidney Jourard claimed in 1971 that "disclosure begets disclosure". It is important therefore to explore professional helpers' willingness to disclose things about themselves, as this may influence the dialogue which they have with their clients and patients. In this paper we describe a replication of a small study carried out by Sidney Jourard in 1961. An opportunistic sample of 25 undergraduate nursing students was asked to complete Jourard's self-disclosure questionnaire. Analysis of the findings suggested that, overall, the students in this study were more self-disclosing than was the case in the earlier study. Other findings are noted as are the limitations of this form of exploration of self-disclosure.

Adolescent↗

Role of threonine residues in regulation of the epidermal growth factor receptor by protein kinase C and mitogen-activated protein kinase.

Epidermal growth factor (EGF) receptor tyrosine kinase activity is down-regulated by a number of growth-modulating agents that activate protein kinase C and/or mitogen-activated protein (MAP) kinases. Although the mechanism is unclear, it has been hypothesized that phosphorylation of specific threonine residues leads to inhibition of the EGF receptor tyrosine kinase. Two sites phosphorylated on the EGF receptor in response to phorbol esters are possible mediators of this effect: threonine 654, the target of protein kinase C, and threonine 669, the target of MAP kinase and the major site of phosphorylation on the EGF receptor. In order to investigate the role of these residues in receptor regulation, we substituted glutamic acid to mimic the negative charge introduced by phosphorylation at these sites. The wild-type and mutant receptor cDNAs were then transfected into CHO cells that lack endogenous EGF receptor. The EGF binding properties of the mutant receptors were similar to those of the wild-type EGF receptors. EGF stimulated tyrosine kinase activity and DNA synthesis in cells expressing both mutant receptors, indicating that the mutant EGF receptors are biologically active. Treatment of cells with phorbol esters inhibited the high affinity EGF binding and tyrosine kinase activities of both mutant and wild-type EGF receptors. These results indicate that acidic residues at either the Thr-654 or Thr-669 site modulate but do not block EGF receptor signalling. Furthermore, this data demonstrates that the mutant EGF receptors are still a target for inhibition by phorbol esters. Thus, events other than phosphorylation of Thr-654 or Thr-669 appear to be required for receptor down-regulation by protein kinase C or MAP kinase.

Animals↗