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Biomedical subjects

W Hurley

Publications and source records attributed to W Hurley.

8 recordsLinked to original sources
PubMed2005

Insulin-like growth factor binding proteins initiate cell death and extracellular matrix remodeling in the mammary gland.

We have demonstrated that insulin-like growth factor binding protein-5 (IGFBP-5) production by mammary epithelial cells increases dramatically during forced involution of the mammary gland in rats, mice and pigs. We proposed that growth hormone (GH) increases the survival factor IGF-I, whilst prolactin (PRL) enhances the effects of GH by decreasing the concentration of IGFBP-5, which would otherwise inhibit the actions of IGFs. To demonstrate a causal relationship between IGFBP-5 and cell death, we created transgenic mice expressing IGFBP-5, specifically, in the mammary gland. DNA content in the mammary glands of transgenic mice was decreased as early as day 10 of pregnancy. Mammary cell number and milk synthesis were both decreased by approximately 50% during the first 10 days of lactation. The concentrations of the pro-apoptotic molecule caspase-3 was increased in transgenic animals whilst the concentrations of two pro-survival molecules Bcl-2 and Bcl-x were both decreased. In order to examine whether IGFBP-5 acts by inhibiting the survival effect of IGF-I, we examined IGF receptor- and Akt-phoshorylation and showed that both were inhibited. These studies also indicated that the effects of IGFBP-5 could be mediated in part by IGF-independent effects involving potential interactions with components of the extracellular matrix involved in tissue remodeling, such as components of the plasminogen system, and the matrix metallo-proteinases (MMPs). Mammary development was normalised in transgenic mice by R3-IGF-I, an analogue of IGF-I which binds weakly to IGFBPs, although milk production was only partially restored. In contrast, treatment with prolactin was able to inhibit early involutionary processes in normal mice but was unable to prevent this in mice over-expressing IGFBP-5, although it was able to inhibit activation of MMPs. Thus, IGFBP-5 can simultaneously inhibit IGF action and activate the plasminogen system thereby coordinating cell death and tissue remodeling processes. The ability to separate these properties, using mutant IGFBPs, is currently under investigation.

Animals↗
PubMed1992

Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface.

Nonenzymatic glycosylation of proteins, as occurs at an accelerated rate in diabetes, can lead to the formation of advanced glycosylation end products of proteins (AGEs), which can bind to endothelial cells, thereby altering cellular function in a manner which could contribute to the pathogenesis of diabetic angiopathy. In this report, we describe the isolation of two endothelial cell surface-associated proteins which mediate, at least in part, the interaction of AGEs with endothelium. Based on pilot studies demonstrating AGE binding activity with comparable characteristics in bovine endothelial cell and lung extracts, the material from lung was sequentially subjected to chromatography on hydroxylapatite, fast protein liquid chromatography Mono S, and gel filtration. Two distinct polypeptides, approximately 35 and approximately 80 kDa, were purified to homogeneity, each of which bound AGEs as demonstrated by competitive binding assays using cellular binding proteins immobilized on a plastic surface. NH2-terminal sequence analysis indicated that the approximately 35-kDa protein was novel, whereas the NH2-terminal sequence of the approximately 80-kDa protein was identical to that of lactoferrin. Immunocytologic studies using polyclonal antibody prepared to each of the purified polypeptides demonstrated the presence of immunoreactive material on the surface of bovine endothelial cells maintained under serum-free conditions. Furthermore, immunoelectron microscopic studies with antibodies to the approximately 35- and approximately 80-kDa AGE-binding proteins conjugated to different size colloidal gold particles confirmed the presence of the target antigens on the cell surface and suggested that they were closely associated. IgG purified from polyclonal antisera to either the 35- or 80-kDa AGE-binding proteins blocked the binding of 125I-AGE-albumin to the cell surface. These results indicate that endothelial cells express specific cell surface molecules which mediate AGE-endothelial interaction. These polypeptides represent a novel class of cell surface acceptor molecules for glucose-modified proteins which may promote degradation and/or transcytosis of the ligand, and modulation of cellular function.

Amino Acid Sequence↗
PubMed1991

Psychological distress and psychiatric morbidity in women prisoners.

The population of a women's prison (n = 92) was screened for psychological distress and psychiatric morbidity with the 12-item General Health Questionnaire, the Hamilton Depression Rating Scale, a Recent Stressful Life Events questionnaire and the Structured Clinical Interview for DSM-III-R. High levels of symptoms of psychological distress were recorded. Distress was correlated with recent stressful life events and was more severe in women awaiting trial. Fifty-three per cent of the prisoners were diagnosed as current cases of a psychiatric disorder and the most frequent diagnoses were adjustment disorder with depressed mood and personality disorders. Lifetime prevalence of psychoactive substance use disorders was 54 per cent. Aboriginal women were over-represented in this prison population. A follow-up survey after 4 months showed no fall in the prevalence of psychological distress and psychiatric morbidity.

Adolescent↗
PubMed1991

Amiodarone-related postoperative adult respiratory distress syndrome.

Directed surgical intervention in patients with ventricular tachyarrhythmias who have experienced failure of amiodarone therapy is a common clinical scenario. Sixty-seven patients with malignant ventricular tachyarrhythmias received either an automatic implantable cardioverter-defibrillator (n = 43) or subendocardial resection (n = 24). Nineteen cardiothoracic procedures (automatic implantable cardioverter-defibrillator in six, endocardial resection in 13) were performed in 17 patients who received amiodarone before surgery. Eight received the drug acutely as a loading dose of 1,200 mg/day for 7-14 days; 11 patients were on chronic oral amiodarone at a mean dose of 362 +/- 74 mg/day. Eight patients were removed from amiodarone therapy a mean of 6.6 days before surgery. Adult respiratory distress syndrome (ARDS) developed after surgery in nine (50%) of 18 surgical survivors. ARDS was manifested by hypoxemia, pulmonary infiltrates, and prolonged intubation. Pulmonary capillary wedge pressure and cardiac output were measured before and after surgery and during ARDS. Pulmonary capillary wedge pressure and cardiac output remained constant after surgery at a time that the PaO2/FIO2 ratio fell significantly. By contrast, none of the remaining 44 patients who did not receive amiodarone developed ARDS despite similar preoperative and intraoperative clinical parameters. Patients with ventricular tachyarrhythmias who receive even a short course of amiodarone are at risk for postoperative ARDS.

Aged↗
PubMed1989

Suicides by prisoners.

In a consecutive series of 44 deaths of male prisoners in Brisbane Prison, a maximum-security prison, in the 15-year period 1973-1987, 20 deaths were a result of suicide. More than half the suicides occurred within the first two months in custody. Prisoners on remand were more prone to commit suicide than were sentenced prisoners. A history of psychiatric disorder was frequent, and more than one-third of the prisoners previously had received psychiatric inpatient treatment. In 40% of cases suicide had been attempted previously. Hanging was the usual method of suicide. The application of preventive measures in the presence of risk factors for suicide at the present level of knowledge are discussed.

Adult↗