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Biomedical subjects

Claire Thompson

Publications and source records attributed to Claire Thompson.

11 recordsLinked to original sources

Characterization of Foxp3+CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis.

CD4+CD25+ regulatory T cells can prevent and resolve intestinal inflammation in the murine T cell transfer model of colitis. Using Foxp3 as a marker of regulatory T cell activity, we now provide a comprehensive analysis of the in vivo distribution of Foxp3+CD4+CD25+ cells in wild-type mice, and during cure of experimental colitis. In both cases, Foxp3+CD4+CD25+ cells were found to accumulate in the colon and secondary lymphoid organs. Importantly, Foxp3+ cells were present at increased density in colon samples from patients with ulcerative colitis or Crohn's disease, suggesting similarities in the behavior of murine and human regulatory cells under inflammatory conditions. Cure of murine colitis was dependent on the presence of IL-10, and IL-10-producing CD4+CD25+ T cells were enriched within the colon during cure of colitis and also under steady state conditions. Our data indicate that although CD4+CD25+ T cells expressing Foxp3 are present within both lymphoid organs and the colon, subsets of IL-10-producing CD4+CD25+ T cells are present mainly within the intestinal lamina propria suggesting compartmentalization of the regulatory T cell response at effector sites.

Animals↗

Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology.

The CD40-CD154 pathway is important in the pathogenesis of inflammatory bowel disease. Here we show that injection of an agonistic CD40 mAb to T and B cell-deficient mice was sufficient to induce a pathogenic systemic and intestinal innate inflammatory response that was functionally dependent on tumor necrosis factor-alpha and interferon-gamma as well as interleukin-12 p40 and interleukin-23 p40 secretion. CD40-induced colitis, but not wasting disease or serum proinflammatory cytokine production, depended on interleukin-23 p19 secretion, whereas interleukin-12 p35 secretion controlled wasting disease and serum cytokine production but not mucosal immunopathology. Intestinal inflammation was associated with IL-23 (p19) mRNA-producing intestinal dendritic cells and IL-17A mRNA within the intestine. Our experiments identified IL-23 as an effector cytokine within the innate intestinal immune system. The differential role of IL-23 in local but not systemic inflammation suggests that it may make a more specific target for the treatment of IBD.

Animals↗

Plasma adiponectin levels are associated with insulin resistance, but do not predict future risk of coronary heart disease in women.

CONTEXT: Low adiponectin levels predict type 2 diabetes, and one prospective study in men reported its independent prediction of vascular events. Many observers thus already consider adiponectin to be a major part of the "common soil" underpinning diabetes and vascular disease. OBJECTIVE: The objective of this study was to assess the association between adiponectin and incident coronary heart disease (CHD) risk in the British Women's Heart and Health Study. DESIGN: This was a prospective (4 yr) case (n = 167) control (n = 334) study nested within the 4286 women in British Women's Heart and Health Study. SETTING: The study was performed in a primary care setting. PARTICIPANTS: The study consisted of women (n = 4286) randomly selected from 23 British towns between 1999 and 2001, who were 60-79 yr of age at baseline. MAIN OUTCOME MEASURES: Association of adiponectin with CHD risk factors and incident CHD events were the main outcome measures. RESULTS: Among both cases and controls, adiponectin positively correlated with age and high-density lipoprotein cholesterol and inversely correlated with waist to hip ratio, fasting insulin, fasting glucose, homeostasis model assessment of insulin resistance scores, C-reactive protein, and triglycerides. However, despite adequate power and these associations with CHD risk factors, adiponectin did not predict CHD events in unadjusted or adjusted analyses. The relative risk ratio for a doubling of adiponectin was 0.93 (95% confidence interval, 0.78, 1.11). CONCLUSIONS: It is premature to consider adiponectin as a root for vascular disease in women despite its association with insulin resistance and diabetes. Additional prospective studies are required to determine whether there is a true sex difference in the effect of adiponectin on CHD.

Adiponectin↗

Why caregivers of people with dementia and memory loss don't use services.

OBJECTIVES: To develop a typography of the characteristics of caregivers of community dwelling people with dementia or memory loss who do not use services and empirically investigate the reasons for service non-use. METHOD: The findings of a literature review were used to develop a typography of caregivers' non-use of services. This typography was applied to a sample of community-based caregivers. RESULTS: One in three caregivers were using no services and one in four only one service. Despite considerable proportions reporting low levels of life satisfaction and high levels of overload and resentment the main reasons caregivers gave for not using services were that they did not consider they needed the services. Other reasons for service non-use included care recipient reluctance to use services, lack of knowledge of services or being in the process of applying for services. Service availability or affordability were not identified as major impediments to service use. Presence of a physical disability and contact with a social worker were associated with service use. CONCLUSIONS: Caregivers of people with dementia incur significant strain and have substantial need for a variety of services. Nevertheless many caregivers were not using support services, mainly because of perceived lack of need or lack of awareness. Better public promotion of services, destigmatising dementia and encouraging referrals from health professionals could help overcome the barriers to service use.

Adult↗

Age and gender in the phenomenology of depression.

OBJECTIVE: Authors investigated the effects of current age, age at onset, and gender on the phenomenology of depression. METHODS: A mixed-age sample of 810 Mood Disorders Unit attendees with a diagnosis of unipolar major depressive episode at or near its nadir were interviewed by clinician-rated and self-report instruments assessing symptoms and severity of depression. RESULTS: Differences were found in depressive phenomenology according to current age but not age at onset, confirming previous findings. Age differences on several variables were found in women only. Subjective ratings of depression severity decreased with age, whereas objective, clinician-rated severity increased. CONCLUSIONS: The pattern and severity of depression change with increasing age. Longitudinal prospective studies would further elucidate this age-gender relationship. Clinicians should be aware of the decreased likelihood of older patients' reporting of depressive symptoms themselves.

Adolescent↗

The effects of additives on the growth and morphology of paracetamol (acetaminophen) crystals.

It is well known that the presence of impurities can dramatically affect the nucleation, morphology, and chemical properties of crystals. Although literature is replete with examples of impurity or additive-induced modifications of crystals, few have examined the interaction of these compounds with distinct growing faces. In this study, we utilize atomic force microscopy (AFM) and scanning electron microscopy (SEM) to investigate the influence of two structurally related additives of paracetamol (acetaminophen) on its crystal morphology. We also probe, in situ, the effects of these additives on the morphology and growth rate of steps on the (0 0 1) face of the crystal. This study, in conjunction with further investigations, aims to establish the specific mechanisms of inhibition of these additives on each face of paracetamol, and provide a means of overcoming the poor compaction behaviour of paracetamol.

Acetaminophen↗

Vulnerability to post-traumatic stress disorder and psychological morbidity in aged holocaust survivors.

OBJECTIVE: Although high rates of post-traumatic stress disorder (PTSD) and psychological morbidity have been consistently reported in Holocaust survivors (HS), reports are inconsistent about which factors are associated with psychological morbidity. In a study of the oldest HS cohort yet reported, we aim to clarify why this variability exists by examining factors associated with PTSD and psychological morbidity, including for the first time measures of personality and defense mechanisms. METHODS: One hundred HS randomly selected from a convenience sample of 309 respondents to a survey of Jewish persons aged 60 years and older living in the community in Sydney were assessed using the following instruments: demographics, severity of trauma experienced, General Health Questionnaire (GHQ-28), PTSD diagnosis (DSM-IV), Brief Psychiatric Rating Scale, Impact of Events Scale, Defense Style Questionnaire, modified Eysenck Personality Inventory. RESULTS: Older age, experience of more severe trauma, use of immature defense mechanisms and higher neuroticism were associated with significant PTSD and psychological morbidity; severity of trauma was associated with PTSD and with more severe psychological morbidity. CONCLUSIONS: A profile of survivors at-risk can be identified that may have application to survivors of more recent holocausts. Late life may be a period of vulnerability in the aftermath of severe trauma.

Female↗

Regulatory T cells.

Regulatory T (TR) cells are a subset of T cells that function to control immune responses. Different populations of TR cells have been described, including thymically derived CD4(+)CD25+ TR cells and Tr1 cells induced in the periphery through exposure to antigen. A transcription factor, Foxp3, has been identified that is essential for CD4(+)CD25+ TR cell development and function. There is now evidence that transforming growth factor-beta might play a role in this pathway. CD4(+)CD25+ TR cells proliferate extensively in vivo in an antigen-specific manner, and can respond to both self and foreign peptides. By suppressing excessive immune responses, TR cells play a key role in the maintenance of self-tolerance, thus preventing autoimmune disease, as well as inhibiting harmful inflammatory diseases such as asthma and inflammatory bowel disease.

Animals↗

CD40 ligand in pathogenesis of autoimmune ovarian disease of day 3-thymectomized mice: implication for CD40 ligand antibody therapy.

The blockade of CD40 ligand (CD40L) is effective in autoimmune disease prevention. Recently, a brief period of CD40L mAb treatment was reported to induce tolerance and enhancement of CD4(+)CD25(+) regulatory T cell activity. We therefore determined the efficacy of CD40L mAb treatment in autoimmunity that resulted from CD4(+)CD25(+) regulatory T cell deficiency. Autoimmune ovarian disease (AOD) and oocyte autoantibody response of day 3-thymectomized (d3tx) mice were inhibited by continuous CD40L mAb treatment from day 3, or from days 10-14, whereas CD40L mAb treatment confined to the neonatal week was ineffective. The enhanced expression of memory markers (CD44 and CD62L(low)) on CD4(+) T cells of the d3tx mice was unaffected by CD40L mAb treatment. In contrast, their increased T cell activation markers (CD69 and CD25) were eliminated by CD40L mAb treatment. Moreover, ex vivo activated T cells of d3tx mice expressed elevated intracellular IFN-gamma, and this was also blocked by CD40L mAb. The memory T cells, although nonpathogenic in CD40L mAb-positive environment, transferred severe AOD to CD40L mAb(-) neonatal recipients. Most importantly, CD40L mAb treatment inhibited AOD in recipients of T cells from d3tx donors with severe AOD and led to regression of AOD in d3tx mice documented at 4 wk. Therefore, 1) the continuous presence of CD40L mAb both prevents and causes regression of AOD in the d3tx mice; and 2) the multiple steps of the d3tx autoimmune disease, including T cell activation, cytokine production, T cell-mediated inflammation, and tissue injury, are CD40L dependent.

Adoptive Transfer↗

Health and safety issues pertaining to dental photographic mirrors and cheek and lip retractors.

This paper investigates the health and safety implications of using photographic dental mirrors and cheek retractors for photography of the intra-oral cavity. Medical photographers have moral and ethical responsibilities, and therefore should be aware of the diseases they are likely to encounter, and the possibility of cross infection when using these instruments. Although autoclaving is the safest way to remove infectious micro-organisms from contaminated instruments, that this may not be a practical method for small departments who only occasionally use these instruments. The alternative approach is to cold-sterilize the instruments using a chlorine- or alcohol-based disinfectant. The author provides information and guidelines for those who photograph the intra-oral cavity occasionally.

Bacterial Infections↗

Differential effect of neonatal thymectomy on systemic and organ-specific autoimmune disease.

Thymectomy on day 3 after birth (d3tx) depletes CD4+CD25+ regulatory T cells leading to multiple independent organ-specific autoimmune diseases. However, systemic autoimmune disease such as systemic lupus erythematosus has not been reported in d3tx mice. Herein, we investigate the effect of d3tx on spontaneous autoantibody response and immune complex glomerulonephritis (GN) in the lupus-prone (SWR x NZB)F1 (SNF1) mice. The d3tx SNF1 mice developed accelerated antibody responses to double-stranded DNA and DNA-histone complexes, and an increased frequency of activated CD4+ T cells. Unexpectedly, the renal histopathology and mortality from GN were significantly ameliorated in d3tx SNF1 mice, which concomitantly exhibited a Th2-biased antibody response. By 16 weeks, the d3tx mice had higher levels of total and autoantigen-specific IgG1, and at 12 months, the autoantigen-specific IgG2a was significantly below that of the sham thymectomized mice. These differences corresponded with reduction in total and autoantigen-specific IgG2a in the renal eluates of the d3tx mice. In addition, while all the mice had immune complex deposition in the mesangium and peripheral capillary loops of the glomeruli, IgG2a and C3 deposits restricted to the mesangial regions alone were more frequent in d3tx mice. D3tx SNF1 mice, protected from lupus-like GN, developed organ-specific autoimmune responses and diseases including prostatitis, orchitis and oophoritis, and antibodies to prostate, cardiac and skeletal muscle antigens. Therefore, d3tx paradoxically protects SNF1 mice from genetically prone lupus-like GN, yet promotes de novo organ-specific autoimmunity.

Animals↗