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Biomedical subjects

Chris Jackson

Publications and source records attributed to Chris Jackson.

9 recordsLinked to original sources
PubMed2005

Leukocyte matrix metalloproteinase-9 is elevated and contributes to lymphocyte activation in type I diabetes.

Degradation of extracellular matrix proteins by matrix metalloproteinases (MMPs) is integral to cell migration and tissue remodeling in diabetes mellitus and its complications. MMPs also regulate the function of leukocytes via proteolytic processing of cytokines/chemokines. In this study, we measured the production of MMP-9 and its natural tissue inhibitor (TIMP)-1 by leukocytes isolated from human type I diabetic patients. MMP-9 was also detected in serum and splenocytes from non-obese diabetic (NOD) and BALB/c mice. MMP-9 was markedly elevated in leukocytes from diabetics compared to non-diabetic controls. TIMP-1 production was also enhanced in leukocytes from diabetics, but substantially less than MMP-9, with the MMP-9/TIMP-1 ratio being 1.6-fold higher in neutrophils and 3-fold higher in monocytes than controls. Interleukin (IL)-2 or lipopolysaccharide (LPS) treatment increased MMP-9 production in leukocytes from both diabetics and normal controls, whereas insulin decreased MMP-9 expression. Recombinant MMP-9 stimulated the proliferation of mouse splenocytes from NOD or BALB/c and a MMP-9 inhibitor dose-dependently inhibited splenocyte proliferation. In conclusion, our results demonstrate firstly that MMP-9 expression is elevated in leukocytes from type I diabetic patients and NOD mice and secondly, that MMP-9 elevates proliferation of mouse splenocytes. These data suggest that elevated leukocyte MMP-9 may contribute to the pathogenesis of type I diabetes and its associated complications.

Animals↗
PubMed2004

Activated protein C stimulates proliferation, migration and wound closure, inhibits apoptosis and upregulates MMP-2 activity in cultured human keratinocytes.

Activated protein C (APC) is a physiological serine protease that regulates blood clotting and inflammation. Keratinocytes are a major cell type of human skin and play a fundamental role in normal skin metabolism and cutaneous wound healing. In this study, we investigated the regulatory role of APC on the function of human primary cultured keratinocytes. In an in vitro wounding assay, APC accelerated wound closure which was due jointly to increased cell proliferation and migration. APC attenuated calcium-induced cell death via prevention of cell apoptosis, as indicated by a decrease in both active caspase-3 and morphologically apoptotic cells. APC dramatically enhanced the expression and activation of MMP-2 by keratinocytes, whilst having no effect on MMP-9. GM6001, a broad spectrum MMP inhibitor, abolished cell migration in a dose-dependent manner and delayed in vitro wound healing. APC also significantly increased the production of IL-6 and IL-8 and suppressed calcium- and LPS-stimulated NF-kappaB activity. These results demonstrate a central role for APC in promoting cell proliferation and migration, preventing apoptosis and increasing MMP-2 activity in cultured keratinocytes. This regulatory activity implicates APC as having potential to promote re-epithelialisation during wound healing.

Apoptosis↗
PubMed2004

The trauma of first episode psychosis: the role of cognitive mediation.

OBJECTIVE: First episode psychosis can be a distressing and traumatic event which has been linked to comorbid symptomatology, including anxiety, depression and PTSD symptoms (intrusions, avoidance, etc.). However, the link between events surrounding a first episode psychosis (i.e. police involvement, admission, use of Mental Health Act, etc.) and PTSD symptoms remains unproven. In the PTSD literature, attention has now turned to the patient's appraisal of the traumatic event as a key mediator. In this study we aim to evaluate the diagnostic status of first episode psychosis as a PTSD-triggering event and to determine the extent to which cognitive factors such as appraisals and coping mechanisms can mediate the expression of PTSD (traumatic) symptomatology. METHOD: Approximately 1.5 years after their first episode of psychosis, patients were assessed for traumatic symptoms, conformity to DSM-IV criteria for posttraumatic stress disorder (PTSD), and their appraisals of the traumatic events and coping strategies. Psychotic symptomatology was also measured. RESULTS: 31% of the sample of 35 patients who agreed to participate reported symptoms consistent with a diagnosis of PTSD. Although no relationship was found between PTSD (traumatic) symptoms and potentially traumatic aspects of the first episode (including place of treatment, detention under the MHA etc.), intrusions and avoidance were positively related to retrospective appraisals of stressfulness of the ward (i.e. the more stressful they rated it the greater the number of PTSD symptoms) and the patient's coping style (sealers were less likely to report intrusive re-experiencing but more likely to report avoidance). CONCLUSIONS: The results call into question whether it is possible to make claims for a simple causal link between psychosis and PTSD. Instead patients' appraisals of potentially traumatic events and their coping styles may mediate the traumatic impact of a first episode of psychosis.

Adaptation, Psychological↗
PubMed2004

Autobiographical memory and post-psychotic depression in first episode psychosis.

OBJECTIVES: In unipolar depression, the action of early life events has been shown to be linked to a deficit in accessing details of such autobiographical events ('overgeneral memory'). In this study, we test whether a similar deficit can be observed in post-psychotic depression (PPD) in first-episode psychosis. METHOD: A group of 29 patients were followed up during the 12 months after their first onset, and monitored for PPD. RESULTS: Of the sample group, 45% developed PPD, which was associated with overgeneral memory (p <.05; effect size = 1.05) and a heightened awareness of the diagnosis. CONCLUSIONS: Our findings raise the possibility that anomalies of psychosocial development may confer vulnerability to depression in psychosis.

Autobiographies as Topic↗
PubMed2003

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Animals↗
PubMed2003

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I.

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Acute Disease↗
PubMed2002

Matrix metalloproteinases and angiogenesis.

Angiogenesis is a prominent feature of numerous diseases, including cancer and arthritis, and appears to play an important role in kidney disease and hypertension. The matrix metalloproteinases, especially matrix metalloproteinase-2, play a vital role during angiogenesis by degrading the surrounding extracellular matrix and allowing endothelial cell invasion. Membrane type 1 matrix metalloproteinase directly degrades matrix components as well as activating matrix metalloproteinase-2 on the cell surface. The integrin receptors, particularly alpha(v)beta(3), can recruit and possibly activate matrix metalloproteinases to localized microdomains on the cell membrane. This restricts matrix metalloproteinase activity to the pericellular region, preventing excessive matrix degradation which would otherwise impede endothelial invasion. Inhibitors of matrix metalloproteinase activity may actually promote cell invasion by preventing uncontrolled matrix degradation. In addition to degrading the matrix, matrix metalloproteinases produce protein fragments that impede their angiogenic action. These multiple regulatory pathways permit fine control over cell invasion during angiogenesis and provide new, precise strategies for targeting abnormal angiogenesis, through control of matrix metalloproteinase activity.

Humans↗
PubMed2002

Duration of untreated psychosis and pathways to care in first-episode psychosis. Investigation of help-seeking behaviour in primary care.

BACKGROUND: Studies have consistently found that many individuals with first-episode psychosis experience significant delays before receiving treatment. Current research investigating treatment delays has focused on the relationship between demographic factors and duration of untreated psychosis (DUP). However, treatment-seeking behaviours in this group have not been investigated. AIMS: To examine psychological processes that influence the decision-making process to contact primary care, in individuals with emerging psychosis. METHOD: The influence of coping style, health locus of control and past health help-seeking behaviour on DUP was investigated in clients with a first episode of psychosis. This involved scrutiny of general practitioner (GP) records in an average of 6 years before the first treatment. RESULTS: Shorter DUP was associated with more frequent GP attendance in the 6 years before the onset of psychosis and lower health threat avoidant coping scores. CONCLUSIONS: Patients with short DUP have history of higher contact with their GP and, as a group, tend not to avoid health threats. The study underlines the importance of engaging young people and their families with primary care as one of a series of strategies to reduce DUP.

Adaptation, Psychological↗