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Biomedical subjects

C Patterson

Publications and source records attributed to C Patterson.

At least 91 records · Page 5Linked to original sources
PubMed1999

A study of postdiagnosis breast cancer concerns for women living in rural and remote Queensland. Part II: Support issues.

This paper presents the recent findings from a study on the postdiagnosis support needs of women with breast cancer living in rural and remote Queensland. The findings presented in this discussion focus on support needs from the perspective of the women experiencing breast cancer as well as health service providers. The tyranny of distance imposes unique hardships, such as separation from family and friends, during a time of great vulnerability for treatment, the need to travel long distances for support and follow-up services, and extra financial burdens, which can combine to cause strains on the marital relationship and family cohesion. Positive indications are, however, that the rural communities operate on strong, informal networks of support. This network of family, friends and community can, and does, play an active role in the provision of emotional and practical support.

Adult↗
PubMed1999

Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions.

The chaperone function of the mammalian 70-kDa heat shock proteins Hsc70 and Hsp70 is modulated by physical interactions with four previously identified chaperone cofactors: Hsp40, BAG-1, the Hsc70-interacting protein Hip, and the Hsc70-Hsp90-organizing protein Hop. Hip and Hop interact with Hsc70 via a tetratricopeptide repeat domain. In a search for additional tetratricopeptide repeat-containing proteins, we have identified a novel 35-kDa cytoplasmic protein, carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP is highly expressed in adult striated muscle in vivo and is expressed broadly in vitro in tissue culture. Hsc70 and Hsp70 were identified as potential interaction partners for this protein in a yeast two-hybrid screen. In vitro binding assays demonstrated direct interactions between CHIP and both Hsc70 and Hsp70, and complexes containing CHIP and Hsc70 were identified in immunoprecipitates of human skeletal muscle cells in vivo. Using glutathione S-transferase fusions, we found that CHIP interacted with the carboxy-terminal residues 540 to 650 of Hsc70, whereas Hsc70 interacted with the amino-terminal residues 1 to 197 (containing the tetratricopeptide domain and an adjacent charged domain) of CHIP. Recombinant CHIP inhibited Hsp40-stimulated ATPase activity of Hsc70 and Hsp70, suggesting that CHIP blocks the forward reaction of the Hsc70-Hsp70 substrate-binding cycle. Consistent with this observation, both luciferase refolding and substrate binding in the presence of Hsp40 and Hsp70 were inhibited by CHIP. Taken together, these results indicate that CHIP decreases net ATPase activity and reduces chaperone efficiency, and they implicate CHIP in the negative regulation of the forward reaction of the Hsc70-Hsp70 substrate-binding cycle.

Adenosine Triphosphatases↗
PubMed1999

Risk factors for suicide independent of DSM-III-R Axis I disorder. Case-control psychological autopsy study in Northern Ireland.

BACKGROUND: The vast majority of suicides suffer from at least one mental disorder at the time of death. AIMS: To identify risk factors for suicide, particularly those independent of current DSM-III-R Axis I disorder(s). METHOD: A case-control psychological autopsy study comparing suicides with matched community controls. RESULTS: Independent risk factors for suicide included: Axis II (personality) disorder (particularly antisocial, avoidant and dependent); at least one of 12 life events (from the List of Threatening Experiences) during the previous 52 or 4 weeks (in particular, a 'serious problem with close friend, neighbour or relative'); current unemployment; previous history of deliberate self-harm; and contact with a GP within 26 weeks. Relative to individuals with no current mental disorder, the estimated risk of suicide in those with Axis I-Axis II comorbidity (OR 346.0) was significantly greater than that in those with Axis I disorder(s) only (OR 52.4). CONCLUSIONS: Suicide risk assessment may be enhanced by enquiry about the aforementioned independent risk factors, and attention to Axis I-Axis II comorbidity.

Case-Control Studies↗
PubMed1999

Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group.

OBJECTIVE: To explore whether perinatal factors are associated with the development of childhood type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied hospital records from 892 cases of childhood type 1 diabetes compared with 2,291 population-based control subjects in seven study centers in Europe. RESULTS: In a pooled analysis incorporating stratification by center, we confirmed the previous findings that older maternal age, maternal preeclampsia, neonatal respiratory disease, and jaundice caused by blood group incompatibility are significant risk factors for type 1 diabetes, whereas being a firstborn child, having a low birth weight, or having a short birth length were protective. Cesarean section delivery and neonatal infectious diseases were not significantly associated with the risk of type 1 diabetes in this study. The strongest association was found for blood group incompatibility (AB0 and Rh factor) with an odds ratio (OR) of 2.96 (95% CI 1.88-4.65). AB0 incompatibility (OR = 3.92) was a more common and also a stronger risk factor than Rh incompatibility (OR = 1.62). The effect of AB0 blood group incompatibility was independent of treatment effects in logistical regression analysis. CONCLUSIONS: Different perinatal events are associated with an increased risk of type 1 diabetes. The effect of maternal-child blood group incompatibility is strong and indicates a true effect that must be further explored.

ABO Blood-Group System↗
PubMed1999

Gene regulation and arteriosclerosis: are developmental programs reactivated in vascular disease?

The molecular mechanisms regulating the development of vascular diseases such as atherosclerosis remain poorly understood at present. Similarities between genetic programs observed during the course of vascular disease with those observed during vascular development suggest that developmental processes are recapitulated in vascular disease. The earliest event in vascular development is the differentiation of endothelial cells from their mesodermally-derived hemangioblastic precursors. The receptor for vascular endothelial growth factor, KDR/flk-1, plays a critical role in these earliest stages of vascular development. During development and in the adult, expression of this receptor is restricted to vascular endothelial cells and their immediate precursors. We have therefore endeavored to determine the transcriptional events regulating KDR/flk-1 expression, with the hope of gaining insight into processes of vascular development that might also be important in vascular diseases of the adult.

Adult↗
PubMed1999

Prevention of restenosis after percutaneous coronary interventions: the medical approach.

Restenosis following successful percutaneous coronary revascularization continues to represent a major problem limiting the clinical efficacy of this procedure. The underlying mechanisms of restenosis are comprised of a combination of effects from vessel recoil, negative vascular remodeling, thrombus formation and neointimal hyperplasia. Indeed, there are important interactions among all of these mechanisms. For example, neointimal hyperplasia is stimulated by growth factors, which are released by local thrombi and the injured arterial segment itself, and act to enhance the expression of other growth-regulating proteins, in particular "second messengers", proto-oncogenes and other cell cycle controlling proteins. This results in an inflammatory and myofibroproliferative response, which may worsen vessel narrowing caused by recoil and result in the formation of a clinically significant restenotic lesion. A multitude of pharmacologic trials have been conducted in an attempt to prevent restenosis, but most have demonstrated little benefit. Studies in smaller numbers of patients have suggested a potential benefit for several classes of agents, including: 1) the antiproliferatives, angiopeptin, trapidil and tranilast; 2) selective elimination or alteration of proliferating cells; 3) enhancement of natural growth inhibitors; and 4) signal transduction blockade or inhibition of the gene expression for various growth-stimulating proteins. Finally, there have been advances in related areas, including development of antithrombotic catheters, novel polymers, and more efficient methods for transferring genes into the vessel wall. All of these offer the possibility of delivering agents (drugs, genes, or antisense oligonucleotides) locally at the site of intervention in a way that may optimize antiproliferative effects while minimizing systemic effects--ultimately leading to a more specific inhibition of the restenosis process.

Angioplasty, Balloon, Coronary↗
PubMed1998

Differential regulation of protease activated receptor-1 and tissue plasminogen activator expression by shear stress in vascular smooth muscle cells.

Recent studies have demonstrated that vascular smooth muscle cells are responsive to changes in their local hemodynamic environment. The effects of shear stress on the expression of human protease activated receptor-1 (PAR-1) and tissue plasminogen activator (tPA) mRNA and protein were investigated in human aortic smooth muscle cells (HASMCs). Under conditions of low shear stress (5 dyn/cm2), PAR-1 mRNA expression was increased transiently at 2 hours compared with stationary control values, whereas at high shear stress (25 dyn/cm2), mRNA expression was decreased (to 29% of stationary control; P<0.05) at all examined time points (2 to 24 hours). mRNA half-life studies showed that this response was not due to increased mRNA instability. tPA mRNA expression was decreased (to 10% of stationary control; P<0.05) by low shear stress after 12 hours of exposure and was increased (to 250% of stationary control; P<0.05) after 24 hours at high shear stress. The same trends in PAR-1 mRNA levels were observed in rat smooth muscle cells, indicating that the effects of shear stress on human PAR-1 were not species-specific. Flow cytometry and ELISA techniques using rat smooth muscle cells and HASMCs, respectively, provided evidence that shear stress exerted similar effects on cell surface-associated PAR-1 and tPA protein released into the conditioned media. The decrease in PAR-1 mRNA and protein had functional consequences for HASMCs, such as inhibition of [Ca2+] mobilization in response to thrombin stimulation. These data indicate that human PAR-1 and tPA gene expression are regulated differentially by shear stress, in a pattern consistent with their putative roles in several arterial vascular pathologies.

Aorta, Abdominal↗
PubMed1998

Induction of rat aortic smooth muscle cell growth by the lipid peroxidation product 4-hydroxy-2-nonenal.

BACKGROUND: Atherosclerotic lesion formation is a complex process, in part mediated by inflammatory and oxidative mechanisms including lipid peroxidation. To further characterize the potential role of lipid peroxidation products in atherogenesis, we studied the effects of 4-hydroxy-2-nonenal (HNE) on rat aortic smooth muscle cell growth. METHODS AND RESULTS: HNE, at concentrations of 1.0 and 2.5 micromol/L, significantly stimulated rat aortic smooth muscle cell growth as determined by cell counts, [3H]-thymidine uptake, and incorporation of bromo-deoxyuridine. To characterize the mechanism of HNE-induced mitogenesis, its effect on activation of intracellular growth signaling pathways was examined. Treatment with HNE resulted in activation of extracellular signal-regulated protein kinases ERK1 and ERK2, induction of c-fos and c-jun protein expression, and an increase in transcription factor AP-1 DNA binding activity. In addition, HNE induced expression of platelet-derived growth factor-AA (PDGF-AA) protein, and an anti-PDGF-AA antibody specifically inhibited HNE-mediated DNA synthesis, suggesting that growth factor induction may play a role in HNE-induced vascular smooth muscle cell growth. The role of redox-sensitive mechanisms in this process was further supported by the observation that HNE-induced DNA synthesis and AP-1 activation were inhibited by the antioxidants N-acetylcysteine and pyrrolidine dithiocarbamate. CONCLUSIONS: These data demonstrate that HNE, one of several important lipid peroxidation products, induces rat aortic smooth muscle cell growth through redox-sensitive mechanisms and growth factor expression. These observations are consistent with a role for lipid peroxidation products in vascular smooth muscle cell growth in atherogenesis.

Aldehydes↗
PubMed1998

Differential transcriptional regulation of the human thrombin receptor gene by the Sp family of transcription factors in human endothelial cells.

The mitogenic effects of thrombin are mediated by a G-protein-coupled receptor. Because the effects of thrombin are strongly influenced by the expression of its receptor, an understanding of its regulatory mechanisms is essential. To identify mechanisms of human thrombin receptor (HTR) gene regulation, a series of HTR-promoter-luciferase constructs were made and transfected into human microvascular endothelial cells for analysis. Deletion from bp -303 to -164 abolished reporter gene expression. Dimethyl sulphate treatment in vivo and DNase I footprinting in vitro demonstrated that a cluster of three GC box consensus sites was occupied, and electrophoretic mobility-shift assays established that Sp1 and Sp3 both bind to this 3' GC box cluster. We mutated each of the three GC boxes individually and all three collectively within this 3' cluster. Basal promoter activity was decreased to 46%, 78% and 29% of control for each of the GC boxes mutated individually, and to 6% when the three were mutated collectively. To test the individual abilities of Sp1 and Sp3 to activate or repress HTR transcription, we conducted co-transfection experiments with wild-type or mutated HTR-promoter-luciferase constructs. Co-transfection with Sp1 significantly augmented wild-type HTR promoter activity. Sp3 alone did not affect activity, and inhibited Sp1-mediated activation. Competition for shared binding sites by Sp1 and Sp3 might differentially regulate HTR expression in vascular endothelial cells.

Aorta↗
PubMed1998

Vascular endothelial growth factor induces heparin-binding epidermal growth factor-like growth factor in vascular endothelial cells.

Although several cytokines and growth factors have been shown to regulate vascular endothelial growth factor (VEGF) production, little is known about how VEGF may regulate growth factors that have known mitogenic and chemotactic actions on mesenchymal cells (which are involved in the maturation of the angiogenic process). We investigated the effect of VEGF on heparin-binding epidermal growth factor-like growth factor (HB-EGF) expression in human umbilical vein endothelial cells. HB-EGF mRNA was induced by 8-fold after 2 h of VEGF stimulation, and it returned to base line within 6 h. VEGF did not alter the half-life of HB-EGF mRNA (55 min). Nuclear run-on experiments showed a 4.9-fold increase in HB-EGF gene transcription within 2 h of VEGF stimulation, and Western analysis demonstrated an associated increase in cellular HB-EGF protein. We found that platelet-derived growth factor-BB (PDGF-BB) mRNA was also induced 3-fold after 5 h of VEGF stimulation, whereas neither endothelin 1 nor transforming growth factor-beta1 was regulated by VEGF. Finally, conditioned medium from VEGF-stimulated endothelial cells produced an increase in DNA synthesis in vascular smooth muscle cells, and this effect was blocked by a neutralizing antibody to PDGF. The induction of HB-EGF and PDGF-BB expression in endothelial cells may represent the mechanism by which VEGF recruits mesenchymal cells to form the medial and adventitial layers of arterioles and venules during the course of angiogenesis.

Cell Movement↗
PubMed1998

A crossover interaction between sex, sexual orientation, and handedness.

The distribution of handedness scores was analysed in 1414 heterosexual, bisexual, and homosexual men and women. Hand preference was assessed by a questionnaire that distinguishes consistently right-handed from partially or completely left-handed individuals, and sexual orientation was measured by the Kinsey scales. As expected from population-based studies, heterosexual men were, on average, more left-handed than heterosexual women. By contrast, gay men were more right-handed than lesbians or heterosexual men, and lesbians were more left-handed than gay men or heterosexual women. This crossover interaction suggests that a common variable influences sex, sexual orientation, and hand preference.

Journal Article↗
PubMed1998

Development and validation of a questionnaire designed to measure foot-health status.

The aim of this study was to apply the principles of content, criterion, and construct validation to a new questionnaire specifically designed to measure foot-health status. One hundred eleven subjects completed two different questionnaires designed to measure foot health (the new Foot Health Status Questionnaire and the previously validated Foot Function Index) and underwent a clinical examination in order to provide data for a second-order confirmatory factor analysis. Presented herein is a psychometrically evaluated questionnaire that contains 13 items covering foot pain, foot function, footwear, and general foot health. The tool demonstrates a high degree of content, criterion, and construct validity and test-retest reliability.

Adult↗
PubMed1998

Teenage mothers and their peers: a research challenge.

Recent reports have highlighted the adverse health experience of teenage mothers. The question of how these mothers' perceptions of their own health status and social networks differ from those of their nulliparous peers is explored in this pilot study, which highlights some practical problems associated with research in this important field.

Adolescent↗