Search PubMed⌕ Search

Biomedical subjects

D Gorman

Publications and source records attributed to D Gorman.

At least 55 records · Page 3Linked to original sources
PubMed1998

Leukocystatin, a new Class II cystatin expressed selectively by hematopoietic cells.

We describe a new cystatin in both mice and humans, which we termed leukocystatin. This protein has all the features of a Class II secreted inhibitory cystatin but contains lysine residues in the normally hydrophobic binding regions. As determined by cDNA library Southern blots, this cystatin is expressed selectively in hematopoietic cells, although fine details of the distribution among these cell types differ between the human and mouse mRNAs. In addition, we have determined the genomic organization of mouse leukocystatin, and we found that in contrast to most cystatins, the leukocystatin gene contains three introns. The recombinant proteins corresponding to these cystatins were expressed in Escherichia coli as N-terminal glutathione S-transferase or FLAGTM fusions, and studies showed that they inhibited papain and cathepsin L but with affinities lower than other cystatins. The unique features of leukocystatin suggests that this cystatin plays a role in immune regulation through inhibition of a unique target in the hematopoietic system.

Amino Acid Sequence↗
PubMed1998

Identification and characterization of a constitutively active STAT5 mutant that promotes cell proliferation.

STAT (signal transducers and activators of transcription) proteins are transcription factors which are activated by phosphorylation on tyrosine residues upon stimulation by cytokines. Seven members of the STAT family are known, including the closely related STAT5A and STAT5B, which are activated by various cytokines. Except for prolactin-dependent beta-casein production in mammary gland cells, the biological consequences of STAT5 activation in various systems are not clear. We applied PCR-driven random mutagenesis and a retrovirus-mediated expression screening system to identify constitutively active forms of STAT5. By this strategy, we have identified a constitutively active STAT5 mutant which has two amino acid substitutions; one is located upstream of the putative DNA binding domain (H299R), and the other is located in the transactivation domain (S711F). The mutant STAT5 was constitutively phosphorylated on tyrosine residues, localized in the nucleus, and was transcriptionally active. Expression of the mutant STAT5 partially dispenses with interleukin 3 (IL-3) as a growth stimulant of IL-3-dependent cell lines. Further analyses of the mutant STAT5 have demonstrated that both of the mutations are required for nuclear localization, efficient transcriptional activation, and induction of IL-3-independent growth of an IL-3-dependent cell line, Ba/F3, and have indicated that a molecular basis for the constitutive activation is the stability of the phosphorylated form of the mutant STAT5.

Animals↗
PubMed1997

Actin plays a role in both changes in cell shape and gene-expression associated with Schwann cell myelination.

Schwann cell (SC) differentiation into a myelinating cell requires concurrent interactions with basal lamina and an axon destined for myelination. As SCs differentiate, they undergo progressive morphological changes and initiate myelin-specific gene expression. We find that disrupting actin polymerization with cytochalasin D (CD) inhibits myelination of SC/neuron co-cultures. Basal lamina is present, neurons are healthy, and the inhibition is reversible. Electron microscopic analysis reveals that actin plays a role at two stages of SC differentiation. At 0.75-1.0 microg/ml CD, SCs do not differentiate and appear as "rounded" cells in contact with axons. This morphology is consistent with disruption of actin filaments and cell shape changes. However, at 0.25 microg/ml CD, SCs partially differentiate; they elongate and segregate axons but generally fail to form one-to-one relationships and spiral around the axon. In situ hybridizations reveal that SCs in CD-treated cultures do not express mRNAs encoding the myelin-specific proteins 2',3'-cyclic nucleotide phosphodiesterase (CNP), myelin-associated glycoprotein (MAG), and P0. Our results suggest that at the lower CD dose, SCs commence differentiation as evidenced by changes in cell shape but are unable to elaborate myelin lamellae because of a lack of myelin-specific mRNAs. We propose that F-actin influences myelin-specific gene expression in SCs.

Actins↗
PubMed1997

Analysis of dendritic cells at the genetic level.

To increase our understanding of dendritic cell (DC) function we have used two approaches to search at the genetic level for molecules which are specifically expressed by these cells. First, we have performed random sequencing of cDNA libraries prepared from DC. Second, we have employed differential display PCR (DD-PCR). DD-PCR is a powerful technique for the identification at the RNA level of molecules which are expressed in a cell type-specific manner. In our study, we have compared RNA from DC with RNA from a panel of leukocyte cell lines. Here we present a summary of our findings using these two approaches, and show that both methods are complementary and can be used to identify molecules that are specific to DC.

Antigen Presentation↗
PubMed1996

The effect of carbon monoxide on oxygen metabolism in the brains of awake sheep.

Eight conscious chronically instrumented sheep were exposed to 1% inspired carbon monoxide (CO) for 35 min. In all sheep, carboxyhaemoglobin (COHb) levels at the end of the exposure were approximately 65%. Mean arterial blood pressure was unchanged with the exception of 2 sheep in which administration was stopped at 25 min following the sudden onset of hypotension. Oxygen delivery to the brain was sustained throughout the administration of CO due to a significant increase in cerebral blood flow (CBF). There was no evidence of either a metabolic acidosis or of lactate production by the brain suggesting the brain did not become hypoxic during the time-course of this study. Despite the apparent lack of hypoxia, oxygen consumption by the brain fell progressively and the sheep showed behavioural changes which varied from agitation to sedation and narcosis. The mechanism of these changes was therefore probably unrelated to hypoxia, but may have been due to raised intracranial pressure or a direct effect of CO on brain function. It is proposed that the time-course of progressive CO poisoning includes a phase in which CBF is elevated, blood pressure is unchanged and the brain is normoxic despite high COHb levels, but that this situation can rapidly evolve into a phase of haemodynamic collapse and severe hypoxia.

Administration, Inhalation↗
PubMed1996

Suicide by young men in Lothian 1993 and 1994.

OBJECTIVES: To examine the circumstances surrounding the suicides during 1993 and 1994 of young men aged 20-29 from the Lothian region. METHODS AND MATERIALS: The list of suicides for Lothian residents in this group was obtained from the General Registry Office and information relating to these people abstracted from records held in General Practice and at the Forensic Medicine Unit at the University of Edinburgh. RESULTS: Thirty-nine men met the selection criteria which gave a suicide rate of 28.7/100,000. Twenty-five had zero blood alcohol recorded post mortem and ten had blood alcohol concentrations above the legal driving limit of 80 mg/100 ml. Ten (26%) had seen their General Practitioner (GP) in the week and 13 (33%) in the month before suicide. Previous suicide attempts (seven within a year of death) were recorded in 19 men. Ten men left suicide notes. CONCLUSION: Using an overall rate to describe suicide hides the complexity of the issues involved: the inclusion or not of undetermined deaths in numerical targets also causes confusion. Targets should be interpreted carefully and suicide rates should not be considered as a proxy for the mental health status of a population. Prevention cannot be the domain of only the GP. Assessment of suicide risk should be integrated as part of improved mental health training for all health service staff.

Adult↗
PubMed1995

Problems in the modelling of inert gas kinetics.

The models used to describe the kinetics of inert gases during underwater diving are inadequate. Medical practitioners and scientists interested in such diving have attempted to quantitatively describe the behaviour of nitrogen in compressed air diving since 1908, with little success. The problems encountered during this diving research are relevant to anaesthesia theory and practice.

Air↗
PubMed1995

Multiculturalism and transcultural nursing in Australia.

The author looks at Australia's multicultural society and identifies the failure of the nursing profession to provide nursing services that meet the commitment of Australia to preserve the cultural backgrounds and meet the needs of the people nurses serve. The author suggests ways in which this problem can be addressed. It is argued that there is a need to ensure that transcultural nursing services are recognized and made accessible to people from diverse cultural backgrounds. Nurses need educational preparation to provide them with the knowledge, skills, and attitudes essential to work with people from different cultures. Moreover, the cultural profile of the nursing profession should approximate those served. Nurses today must recognize these critical needs and be committed to provide transcultural nursing care that is so essential in Australia's multicultural society.

Australia↗
PubMed1995

Audit of the support for breastfeeding mothers in Fife maternity hospitals using adapted 'Baby Friendly Hospital' materials.

BACKGROUND: The objective of this study was to assess the level of support given to breastfeeding mothers during their stay in maternity hospitals. The audit was carried out in maternity hospitals in Fife with the co-ordination of the Fife Joint Breastfeeding initiative. METHODS: The subjects consisted of ten maternity hospital staff (medical and midwifery), and 12 antenatal and 21 postnatal women. The design of the study consisted of an audit of hospital policies and practices in comparison with ten internationally recognized standards. This was carried out by adapting the external evaluation instruments from the WHO-UNICEF "Baby Friendly Hospital" materials. Methods relied not only on reported practices but also on direct observation and enquiry. RESULTS: Action was taken to address areas of practice which fell below the WHO-UNICEF standards: supplementary feeding of breastfed babies, particularly overnight, was reduced; discharge "bounty packs" advertising baby milk manufacturer products were discontinued; a hospital breastfeeding support group was established; the hypoglycaemia policy was revised; and the need for an orientation session on breastfeeding policies for medical staff was recognized. CONCLUSIONS: This audit approach using "Baby Friendly Hospital' materials has helped to define policy, measure performance against recognized standards, identify quality specifications for maternity service agreements and has improved hospital support for breastfeeding mothers. This approach is suitable for maternity hospitals whose breastfeeding rates make them ineligible for "Baby Friendly Hospital" accreditation, and has the potential to be extended to encompass wider "health-promoting hospital" issues such as promotion of infant car seats.

Adult↗