Biomedical subjects

A W Taylor

Publications and source records attributed to A W Taylor.

At least 19 recordsLinked to original sources

PubMed2006

The increasing prevalence of diabetes in South Australia: the relationship with population ageing and obesity.

OBJECTIVES: To use representative population surveillance data to monitor and project changes in the prevalence of diabetes for different age and body mass index (BMI) groups. STUDY DESIGN: Representative, annual, face-to-face South Australian Health Omnibus Surveys, 1991-2003 (n=3000 per year). METHODS: Trends in self-reported diabetes prevalence by age group and BMI were examined. Separate projections were made on the basis of predicted changes in population demography and diabetes prevalence. RESULTS: The age-sex standardized absolute prevalence of self-reported diabetes among people aged 15 years and over increased from 3.5% in 1991 to 6.7% in 2003. If this current trend continues, the prevalence is expected to increase to 10.5% by 2016. The prevalence of diabetes was significantly higher among those classified as obese (6.5% in 1991 to 12.2% in 2003) than those with normal BMI. The greatest relative percentage increase in prevalence between 1991 and 2003 (169%) was seen among people aged 15-39 years. Taking both age group and BMI classification into account, the greatest relative percentage increases over this time were seen among those with normal BMI aged 60 years or older (148%), and those who were obese and aged less than 60 years (139%). CONCLUSIONS: The prevalence of diabetes and obesity increased significantly between 1991 and 2003. Population ageing and an increase in diabetes prevalence in the future will further increase the burden of diabetes. Future increases in diabetes prevalence are not inevitable, however, if investments are made in public health prevention programmes, particularly those addressing obesity.

Adolescent↗

PubMed2006

Alpha-MSH regulates protein ubiquitination in T cells.

The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) suppresses IFN-gamma + T cells from mice. We discovered, however, that despite this significant production by DTH-mediating effector CD4 supression of IFN-gamma production, alpha-MSH-treated effector T cells had the same level of IFN-gamma mRNA expression and intracellular IFN-gamma protein as untreated activated T cells. In order to explain why IFN-gamma production was suppressed in the face of unchanged mRNA and intracellular IFN-gamma levels, we looked for mechanisms that could increase the degradation of IFN-gamma within the alpha-MSH-treated T cells. Among the known pathways of post-translational intracellular protein modification, the ubiquitin-proteosome system was examined in alpha-MSH-treated T cells to see if a post-translational protein modification occurred to prevent IFN-gamma secretion from the cell. Immunoblots from alpha-MSH-treated T cells showed higher levels of protein ubiquitination when compared to untreated T cells. Resting T cells treated with alpha-MSH also demonstrated enhanced protein ubiquitination. We found that IFN-gamma is one of the ubiquitinated proteins in the alpha-MSH-treated activated T cells. Our results demonstrate that one of the mechanisms by which alpha-MSH regulates T cell activity is through mediating a change in the pattern of protein ubiquitination in T cells.

Animals↗

PubMed2006

Melanocortin 5 receptor and ocular immunity.

The nervous system contributes to the mechanisms of ocular immune privilege by the constitutive presence of the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) in the eye. Alpha-MSH through the melanocortin 5 receptor (MC5r) mediates induction of CD4+ regulatory T cells that suppress in an antigen specific manner autoimmune disease. We investigated whether there was a role for MC5r expression in ocular immunity and the natural induction of regulatory T cells that emerged following resolution of experimental autoimmune uveoretinitis (EAU). Unlike wild type mice, EAU in MC5r-/- mice caused severe retinal damage, did mice expressed a not induce the emergence of ocular autoantigen regulatory immunity in the spleen, and the MC5r-/- classical memory immune response when reimmunized with ocular autoantigen. There was expression of MC5r in retinal pigment epithelial cells, in the ganglion cell and neural outer plexiform layers of healthy wild type mice retinas. The recovery of the ocular microenvironment from EAU was not dependent on the expression of MC5r, nor was the recovery dependent on the induction of CD4+ regulatory T cells (Treg cells) in the spleen. However, protection of the retina from the inflammatory damage of EAU and the induction of ocular autoantigen-responsive CD4+ Treg cells in the post EAU spleen requires expression of MC5r.

Animals↗

PubMed2006

A life-course approach to measuring socioeconomic position in population health surveillance systems.

Measuring socioeconomic position (SEP) in population chronic disease and risk factor surveillance systems is essential for monitoring socioeconomic inequalities in health over time. Life-course measures are an innovative way to supplement other SEP indicators in surveillance systems. A literature review examined the indicators of early-life SEP that could potentially be used in population health surveillance systems. The criteria of validity, relevance, reliability and deconstruction were used to determine the value of potential indicators. Early-life SEP indicators used in cross-sectional and longitudinal studies included education level, income, occupation, living conditions, family structure and residential mobility. Indicators of early-life SEP should be used in routine population health surveillance to monitor trends in the health and SEP of populations over time, and to analyse long-term effects of policies on the changing health of populations. However, these indicators need to be feasible to measure retrospectively, and relevant to the historical, geographical and sociocultural context in which the surveillance system is operating.

Confounding Factors, Epidemiologic↗

PubMed2005

The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages.

Since alpha-MSH suppresses endotoxin-induced inflammation by innate immunity, it is possible that alpha-MSH can suppress the interface between innate and adaptive immunity mediated by TLR4-stimulated macrophages. Endotoxin-stimulated macrophages treated with alpha-MSH are suppressed in nitric oxide and IL-12p70 production, and cannot enhance antigen-stimulated IFN-gamma production by Th1 cells. In macrophages treated with alpha-MSH, the inhibitory molecule IRAK-M is bound to IRAK-1, the proximal intracellular signal molecule of endotoxin-bound TLR4. These results further demonstrate the dynamic contribution of the nervous system, and the role of alpha-MSH in modulating the innate and adaptive immune interface in an inflammatory response.

Animals↗

PubMed2004

Hormone therapy use after the Women's Health Initiative.

OBJECTIVE: To continue surveillance of hormone therapy (HT) use in an Australian population and to assess the impact of the Women's Health Initiative (WHI) and associated reports on HT use 16 months after the results of the WHI were first reported. METHODS: Data were obtained from the 2003 South Australian Health Omnibus Survey, which involves a representative, population face-to-face interview survey. Data were compared to five surveys undertaken between 1991 and 2000, which had consistent methods and quality-control procedures. A total of 907 interviews were conducted with women over 40 years in their own homes by trained health interviewers. RESULTS: In association with the timing of media reporting of the WHI, current HT use rates dropped from 28% in women over 50 years in 2000 to an estimated 10.2% in 2002. By October 2003, current use rates had returned to 18.8% in this age group. The media had been the main influence in the women's decision-making. Half of those who restarted therapy changed to another type of HT. Only 2.8% changed to an alternative/complementary therapy. CONCLUSIONS: Nearly two-thirds (64%) of those currently using HT in 2002 stopped therapy, mostly in response to the media reporting of the WHI. Nearly half of those who stopped HT in 2002 have since restarted. Media reporting greatly influences the use of hormonal therapies.

Adult↗

PubMed2004

Psychological factors and asthma quality of life: a population based study.

BACKGROUND: Reports of psychological conditions in asthmatic subjects have been limited to certain population groups or convenience samples. A study was undertaken of the prevalence of psychological distress in asthma in the general population and its associations with quality of life. METHODS: The WANTS Health and Well-being Survey is a population household interview survey of adults (age > or =18) in Western Australia, the Northern Territory, and South Australia. Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to two questions: "Have you ever been told by a doctor that you have asthma?" and "Do you still have asthma?" determined current doctor-diagnosed asthma. Other items included the SF-12, the Kessler-10 index of psychological distress, questions on feelings of lack of control in different areas of life, and on mental health conditions. RESULTS: From the available sample of 10 080, 7619 interviews were completed (participation rate 74.8%), with 834 people reporting current doctor-diagnosed asthma (11.2%). Psychological distress was more frequent in those with asthma (17.9% v 12.2%, p<0.01) and a higher proportion with asthma were at higher risk for anxiety or depression (40.5% v 31.2%, p<0.01). Mental health conditions were also more common (16.2% v 10.8%, p<0.01), as was the frequency of those who sometimes or always felt a lack of control over their health (33.5% v 24.3%, p<0.01). People with both asthma and psychological distress had significantly lower scores on the SF-12 physical component summary (PCS) than those with either asthma or distress alone. Among those with psychological distress, mental component summary (MCS) scores did not differ between asthmatic and non-asthmatic respondents. In a multiple regression model the frequency of a feeling of lack of control over health-together with age, family's financial situation, education level, and number of days partially unable to work or perform usual duties-was significantly associated with scores on the PCS (r = 0.73, adjusted r2 = 0.54). CONCLUSION: These results, from a representative population sample, show that psychological distress and decreased feelings of control are common in asthma and are significantly associated with physical health status.

Adolescent↗

PubMed2003

Effect of diazepam treatment on metabolic indices in trained and untrained rats.

Exercise training, like diazepam, is commonly employed as a means of reducing anxiety. Both diazepam and exercise training have been shown to modify carbohydrate and lipid metabolism as well as influence calcium metabolism in skeletal muscle. As receptor binding and thereby efficacy of diazepam has been demonstrated to be modulated by the lipid environment of the receptor, and changes in calcium levels can affect a number of intracellular signalling pathways, we sought to determine if the interaction of both chronic diazepam and exercise training would modify selected metabolic indices in an animal model. For this purpose, muscle and liver glycogen, blood glucose and plasma free fatty acids (FFA) were measured in sedentary, exercise trained and exercise trained, acutely exhausted animals. Alterations in lipid and carbohydrate metabolism were observed in all experimental groups. Diazepam treatment alone exerts metabolic consequences, such as elevated muscle glycogen and plasma FFA and depressed blood glucose levels, which are similar to those observed with exercise training. When animals are acutely exercised to exhaustion, however, differences appear, including a reduced rise in plasma FFA, which suggests that long-term diazepam treatment does influence exercise metabolism, possibly as a result of effects on the sympatho-adrenal system.

Animals↗

PubMed2003

Modulation of regulatory T cell immunity by the neuropeptide alpha-melanocyte stimulating hormone.

Although many immunosuppressive factors have been identified in the eye, one of these factors, alpha-melanocyte stimulating hormone (alpha-MSH), both suppresses the activation of inflammatory activity by primed T cells and induces the activation of regulatory T cells (Treg cells). This neuropeptide alone at its ocular physiological concentration can account for most of the immunosuppressive activity of aqueous humor (the fluid filing the anterior chamber of the eye). Aqueous humor made devoid of alpha-MSH no longer suppresses IFN-gamma production by Th1 cells. It is alpha-MSH that mediates aqueous humor induction of regulatory T cells. What we have found is that alpha-MSH mediates the induction of C4+ CD25+ Treg cells, and that if the alpha-MSH Treg cells are specific to an autoantigen they can be used to suppress autoimmune disease. It is the objective of this review to demonstrate how we came to discover that alpha-MSH could have such an important role in the extreme regional immunity of the immune privileged eye and how this discovery could be applied to create or reestablish tolerance to prevent autoimmune disease.

Animals↗

PubMed2002

Hormone replacement therapy use over a decade in an Australian population.

OBJECTIVES: To describe the prevalence of hormone replacement therapy (HRT) during the 1990s in an Australian population and the length of time this therapy has been used. Design Data were obtained from five biennial representative population face-to-face interview surveys of the South Australian population from 1991 to 2000, and an additional telephone survey in 2001. The main surveys used consistent methods and quality control procedures. PARTICIPANTS: Over 3000 South Australian adults were interviewed in their own homes by trained health interviewers in each of the biennial surveys. RESULTS: In 2000, 28% of women aged over 50 were currently using HRT, and ever-use of HRT was 43%. Highest use of HRT was in the 55-59-year age group, where current use was 47% and ever-use was 70%. Among women 55 years and older there was a statistically significant increase in the prevalence of HRT use between 1991 and 2000. Mean length of use in women aged over 55 years increased from 5.4 years in 1991 to 9.6 years in 2000. CONCLUSIONS: Consistent surveillance of the population has shown that HRT use has not increased before age 55, but has greatly increased thereafter. Long-term effects may now be occurring, and further results of current long-term randomized trials are awaited to confirm the overall risk/benefit ratio suggested by observational studies and early results from long-term trials.

Adult↗

PubMed2001

Immune response to intragraft antigen in draining lymph nodes after corneal transplantation is mediated by interleukin-12.

To examine the molecular basis of immunity generated to intragraft antigens and determine whether it differs between acceptor and rejector hosts, we used a novel in vitro system to assay the T cell response to a specific antigen, ovalbumin (OVA), in the graft. OVA-containing corneas were orthotopically grafted into syngeneic or allogeneic hosts. Draining cervical lymph nodes (cLN) were assayed for OVA-specific T cell proliferation and cytokine production. In addition, cytokine production was assayed in cultures of antigen-presented cells (APC) isolated from cLN cultured with OVA-specific DO11.10 T cells and OVA. OVA-specific immunity was detected only in the draining cLN of mice following allogeneic, but not syngeneic, grafting, and this immunity was evident well before any demonstrable alloresponse in the graft. In addition, cLN cells from mice that accepted their corneal allografts produced significantly less interferon-gamma (IFN-gamma) when stimulated in culture than cells harvested from cLN of rejector hosts. Moreover, APC isolated from cLN of acceptor hosts produced significantly lower levels of IL-12. These data suggest that the induction of immunity to corneal antigens in the draining cLN occurs via an interleukin-12 (IL-12) and IFN-gamma-dependent mechanism. Targeting this process may serve as an effective immunomodulatory strategy in corneal transplantation.

Animals↗

PubMed2001

Determinants of oxygen uptake kinetics in older humans following single-limb endurance exercise training.

We hypothesised that the observed acceleration in the kinetics of exercise on-transient oxygen uptake (VO2) of five older humans (77 +/- 7 years (mean +/- S.D.) following 9 weeks of single-leg endurance exercise training was due to adaptations at the level of the muscle cell. Prior to, and following training, subjects performed constant-load single-limb knee extension exercise. Following training VO2 kinetics (phase 2, tau) were accelerated in the trained leg (week 0, 92 +/- 44 s; week 9, 48 +/- 22 s) and unchanged in the untrained leg (week 0, 104 +/- 43 s; week 9, 126 +/- 35 s). The kinetics of mean blood velocity in the femoral artery were faster than the kinetics of VO2, but were unchanged in both the trained (week 0, 19 +/- 10 s; week 9, 26 +/- 11 s) and untrained leg (week 0, 20 +/- 18 s; week 9, 18 +/- 10 s). Maximal citrate synthase activity, measured from biopsies of the vastus lateralis muscle, increased (P < 0.05) in the trained leg (week 0, 6.7 +/- 2.0 micromol x (g wet wt)(-1) x min(-1); week 9, 11.4 +/- 3.6 micromol x (g wet wt)(-1) x min(-1)) but was unchanged in the untrained leg (week 0, 5.9 +/- 0.5 micromol x (g wet wt)(-1) x min(-1); week 9, 7.9 +/- 1.9 micromol x (g wet wt)(-1) x min(-1)). These data suggest that the acceleration of VO2 kinetics was due to an improved rate of O2 utilisation by the muscle, but was not a result of increased O2 delivery.

Aged↗

PubMed2001

Telomerase activity is not altered by regular strenuous exercise in skeletal muscle or by sarcoma in liver of rats.

Telomerase is a specialized ribonucleoprotein enzyme complex which prevents the loss of the telomere. The activity of telomerase can be up- and down-regulated by various oxidative stresses but the effect of physical exercise is not known, whereas the modifying effect of cancer on telomerase activity is well documented. In the first study, we investigated the effect of mild and strenuous exercise training on telomerase activity, assessed by a PCR ELISA kit. No alteration in telomerase activity was detected. In the second investigation, solid sarcoma cells were transplanted to control, exercise trained or exercise trained and still exercising mice. On the 16th day after the transplantation, the size of tumors in the exercise trained group was 72% and in the exercising group 57% (P < 0.05) of that in the controls. Telomerase activity and 8-hydroxy-2'-deoxyguanosine levels in the liver were not significantly altered by exercise and/or sarcoma. We conclude that mild and strenuous exercise training does not significantly affect the activity of telomerase in the systems studied. Exercise training during sarcoma significantly retards the development of tumors and could possibly serve as a positive adjunct to treatment.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

Adaptation to exercise-induced oxidative stress: from muscle to brain.

Exercise increases the generation of reactive oxygen and nitrogen species (RONS) and by causing adaptation, could decrease the incidence of RONS-associated diseases. A single bout of exercise, depending upon intensity and duration, can cause an increase in antioxidant enzyme activity, decrease levels of thiols and antioxidant vitamins, and result in oxidative damage as a sign of incomplete adaptation. Increased levels of RONS and oxidative damage are initiators of a specific adaptive response, such as the stimulation of the activation of antioxidant enzymes, thiols, and enhanced oxidative damage repair. Regular exercise has the capability to develop compensation to oxidative stress, resulting in overcompensation against the increased level of RONS production and oxidative damage. Regular exercise causes adaptation of the antioxidant and repair systems, which could result in a decreased base level of oxidative damage and increased resistance to oxidative stress.

Adaptation, Biological↗

PubMed2000

Regular training modulates the accumulation of reactive carbonyl derivatives in mitochondrial and cytosolic fractions of rat skeletal muscle.

The oxygen flux into the mitochondria of skeletal muscle increases with exercise. However, the extent of oxidative damage to mitochondrial proteins of skeletal muscle has only been estimated. We studied the alteration of reactive carbonyl derivatives (RCD) in mitochondrial and cytosolic fractions of skeletal muscle following 9 weeks of swimming training in rats. The RCD content of mitochondria was significantly elevated compared with the cytosolic fraction of both control and exercised animals. Accumulation of RCD in muscle mitochondria of the exercised group was also significantly elevated (P < 0.05). On the other hand, alteration of the accumulation of RCD was not apparent in the cytosolic fraction of skeletal muscle. The activity of proteasome complex, however, was increased in the cytosolic fraction of exercised muscle (P < 0.05). The data suggest that mitochondria of skeletal muscle accumulate significantly larger amounts of RCD than the cytosolic fraction and the tendency of the accumulation varies in cell fractions. Exercise training increases the accumulation of protein damage in mitochondria of skeletal muscle but cytosolic proteins are protected by increased activity of proteasome complex and possibly by other antioxidant enzymes.

Animals↗

PubMed2000

Changes in urine 8-hydroxydeoxyguanosine levels of super-marathon runners during a four-day race period.

We have determined the urinary 8-hydroxydeoxyguanosine (8-OHdG) levels of five well trained supra-marathon runners during a four-day race. The daily running distances of the four-day race were the following; 93 km, 120 km, 56 km and 59 km, respectively. Pre-race and post-race urine samples were collected on each day and analyzed by a monoclonal antibody technique. The urinary 8-OHdG content increased significantly on the first day and tended to decrease from the third day. By the fourth day 8-OHdG content was significantly less than measured on the first three days. The serum creatine kinase activity changed in a similar fashion, showing a large increase (P<0.001) up to the third day when it decreased significantly from the peak value (P<0.05). We conclude that extreme physical exercise causes oxidative DNA damage to well trained athletes. However, repeated extreme exercise-induced oxidative stress does not propagate on increase of urinary 8-OHdG, but rather causes an adaptation leading to normalization of oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2000

Analysis of immunomodulatory activities of aqueous humor from eyes of mice with experimental autoimmune uveitis.

Aqueous humor (AqH) contains immunosuppressive factors, especially TGF-beta2, that contribute to the immune privileged status of the anterior chamber. However, this may not be true when the blood-ocular barrier is compromised by ocular inflammation. To determine the immunosuppressive status of AqH from murine eyes afflicted with experimental autoimmune uveitis, B10.A mice were immunized with interphotoreceptor retinoid-binding protein. AqH was collected from eyes of affected mice periodically after immunization and then evaluated for content of TGF-beta, proinflammatory cytokines, and the capacity to suppress anti-CD3-driven T cell proliferation. mRNA expression of selected cytokines in iris and ciliary body from inflamed eyes was analyzed by ribonuclease protection assay. We found that TGF-beta levels were significantly increased in AqH from EAU eyes on days 11, 17, and 28. AqH collected on day 11 (onset of disease) failed to suppress T cell proliferation and contained large amounts of locally produced IL-6 that antagonized TGF-beta. In contrast, AqH collected at 17 days (when ocular inflammation was progressively severe) re-expressed the ability to suppress T cell proliferation, in this case due to high levels of blood-derived TGF-beta1 and eye-derived TGF-beta2 in the absence of IL-6. Thus, during the onset of experimental autoimmune uveitis, the ocular microenvironment loses its immunosuppressive properties due to local production of IL-6. But as inflammation mounts, AqH IL-6 content falls, and the fluid reacquires sufficient TGF-beta eventually to suppress immunogenic inflammation. The paradoxical roles of IL-6 in antagonizing TGF-beta, while promoting TGF-beta accumulation during ocular inflammation, is discussed.

Adjuvants, Immunologic↗

PubMed2000

Prenylflavonoid variation in Humulus lupulus: distribution and taxonomic significance of xanthogalenol and 4'-O-methylxanthohumol.

The resins produced by either lupulin or leaf glands of over 120 plants of Humulus lupulus and one plant of H. japonicus (Cannabinaceae) were analyzed for the presence of prenylated flavonoids. The H. lupulus taxa investigated were H. lupulus var. lupulus from Europe, H. lupulus var. cordifolius from Japan, and H. lupulus from North America. Fifty-two of the plants examined were cultivars of European, American, and Japanese origin. Twenty-two flavonoids were detected in the glandular exudates of H. lupulus by HPLC-MS MS. Xanthohumol (3'-prenyl-6'-O-methylchalconaringenin) was the principal prenylflavonoid in all H. lupulus plants and was accompanied by 11 structurally similar chalcones. Ten flavonoids were identified as the flavanone isomers of these chalcones. Three other prenylchalcones were isolated from H. lupulus cv. 'Galena', one of which was identified as 3'-prenyl-4'-O-methylchalconaringenin (named 'xanthogalenol'). The distribution of three 4'-O-methylchalcones, i.e. xanthogalenol, 4'-O-methylxanthohumol, and 4',6'-di-O-methylchalconaringenin, was found to be limited to wild American plants from the Missouri-Mississippi river basin, H. lupulus var. cordifolius, and most of their descendents. These 4'-O-methylchalcones were absent from cultivars of European origin, and from wild hops from Europe and southwestern USA. The flavonoid dichotomy (presence versus absence of 4'-O-methylchalcones) indicates that there are at least two evolutionary lineages within H. lupulus (European and Japanese American), which is in agreement with morphological, molecular, and phytogeographical evidence. Leaf glands of H. japonicus from eastern Asia did not produce the H. lupulus prenylflavonoids.

Chromatography, High Pressure Liquid↗