Biomedical subjects

Erin Kelly

Publications and source records attributed to Erin Kelly.

10 recordsLinked to original sources

PubMed2006

Twist mediates suppression of inflammation by type I IFNs and Axl.

Type I interferons (IFNs) are pleiotropic cytokines with antiviral and immunomodulatory properties. The immunosuppressive actions of type I IFNs are poorly understood, but IFN-mediated suppression of TNFalpha production has been implicated in the regulation of inflammation and contributes to the effectiveness of type I IFNs in the treatment of certain autoimmune and inflammatory diseases. In this study, we investigated mechanisms by which type I IFNs suppress induction of TNFalpha production by immune complexes, Fc receptors, and Toll-like receptors. Suppression of TNFalpha production was mediated by induction and activation of the Axl receptor tyrosine kinase and downstream induction of Twist transcriptional repressors that bind to E box elements in the TNF promoter and suppress NF-kappaB-dependent transcription. Twist expression was activated by the Axl ligand Gas6 and by protein S and apoptotic cells. These results implicate Twist proteins in regulation of TNFalpha production by antiinflammatory factors and pathways, and provide a mechanism by which type I IFNs and Axl receptors suppress inflammatory cytokine production.

Animals↗

PubMed2006

The relationship between crystalline methamphetamine use and methamphetamine dependence.

BACKGROUND: The aim of the current study was to determine whether crystalline methamphetamine users are more dependent on methamphetamine than people who use other forms of the drug, and if so, whether this could be accounted for by their methamphetamine use history. METHOD: A structured face-to-face interview was used to assess drug use patterns and demographics among a convenience sample of 309 regular methamphetamine users from Sydney, Australia. Dependence on methamphetamine in the past year was measured using the Severity of Dependence Scale. The use of crystalline methamphetamine in the past year was confirmed using a photographic identification sheet. RESULTS: Participants who had used crystalline methamphetamine in the past year were significantly more likely to be dependent on methamphetamine than participants who took only other forms of methamphetamine during this time (61% versus 39%). Methamphetamine dependence was also associated with injecting or smoking methamphetamine (67% and 58%, respectively versus 30% for intranasal or oral use), using methamphetamine more than weekly (68% versus 34%), having used the drug for more than 5 years (61% versus 36%), and having used 'base' methamphetamine in the past year (59% versus 39%). Crystalline methamphetamine use remained significantly associated with methamphetamine dependence after adjusting for these patterns of methamphetamine use. CONCLUSIONS: Methamphetamine users who took crystalline methamphetamine in the past year were more likely to be dependent than methamphetamine users who had not taken the crystalline form of the drug during this time.

Adolescent↗

PubMed2006

Selective regulation of IL-10 signaling and function by zymosan.

Balanced activity of pro- and anti-inflammatory cytokines during innate immune responses is required to allow effective host defense while avoiding tissue damage and autoimmunity. Induction of cytokine production after recognition of pathogen-associated molecular patterns (PAMPs) by innate immune cells has been well demonstrated, but modulation of cytokine function by PAMPs is not well understood. In this study we show that stimulation of macrophages with zymosan, which contains PAMPs derived from yeast, rapidly extinguished macrophage responses to IL-10, a suppressive cytokine that limits inflammatory tissue damage but also compromises host defense. The mechanism of inhibition involved protein kinase Cbeta and internalization of IL-10R, and was independent of TLR2 and phagocytosis. Inhibition of IL-10 signaling and function required direct contact with zymosan, and cells in an inflammatory environment that had not contacted zymosan remained responsive to the paracrine activity of zymosan-induced IL-10. These results reveal a mechanism that regulates IL-10 function such that antimicrobial functions of infected macrophages are not suppressed, but the activation of surrounding noninfected cells and subsequent tissue damage are limited. The fate of individual cells in an inflammatory microenvironment is thus specified by dynamic interactions among host cells, microbes, and cytokines that determine the balance between protection and pathology.

Animals↗

PubMed2006

Effects of nicotine nasal spray on cognitive function in schizophrenia.

Schizophrenics have among the highest rates of cigarette smoking. Some studies indicate that cigarette smoking or nicotine may ameliorate some of the cognitive or theoretically related neurophysiological deficits seen in schizophrenic patients. This study investigated the effects of nicotine nasal spray on measures of attention, verbal memory, and visual-spatial memory in schizophrenic patients who were chronic smokers, using a double-blind placebo-controlled pre-post experimental design. Compared to placebo, active nicotine spray significantly decreased reaction time on the Conner's CPT and improved scores on a measure purported to reflect spatial working memory on a dot task. There were trends for the increased number of hits and decreased number of errors in pre-post comparisons on the CPT task in the active nicotine session. There were no effects of active nicotine nasal spray on verbal memory. Our results suggest that nicotine may modestly enhance attention and spatial working memory in schizophrenic patients who are cigarette smokers and have been abstinent overnight.

Adult↗

PubMed2005

Value orientation and forest management: the forest health debate.

Among both forest practitioners and the general public, "forest health" has become an issue of contention. Whereas the debate over which treatments will best achieve healthy forests has been framed largely by the popular media and politicians as a struggle between industry and environmentalists, the views of the general public remain unexplored. Survey results from Oregon and Washington residents were used to assess the relationships between respondents' self-described environmental or economic priorities and the following two variables: (1) acceptability of forest management practices and (2) perceived threats to forest health. Findings indicate that active management was generally accepted by a majority of respondents regardless of their environmental or economic orientation. Disagreement emerged, however, when the appropriateness of specific management practices within specific forest conditions was examined. Additionally, strong evidence was found for a relationship between self-described environmental or economic orientation and perceived threats to forest health. Those with an environmentally oriented viewpoint tended to perceive human-caused factors as the largest threats, whereas those with an economic orientation saw naturally occurring processes as the greatest threats. These findings suggest that the issue of contention is not active management per se. Rather, the major divisions in the forest health debate are defined by specific contexts and circumstances, as well as the management practices used.

Adult↗

PubMed2005

Characteristics of treatment provided for amphetamine use in New South Wales, Australia.

The purpose of this study was to examine the types of treatment services provided for amphetamine use, the characteristics of amphetamine treatment clients and the geographic areas most affected by amphetamine treatment provision within New South Wales (NSW), Australia. Data on completed amphetamine treatment episodes were extracted from the NSW Minimum Data Set for Alcohol and Other Drug Treatment Services for the year 2002/03 (n = 4,337). The geographic area of treatment presentations was based on the location of the treatment service, and was categorized as metropolitan, regional or rural. Treatment disproportionately affected regional and rural NSW, and treatment clients often presented with concurrent cannabis and/or alcohol problems. Clients were overwhelmingly injecting drug users with poor socio-demographic characteristics. Counselling was the most common treatment service provided, followed by detoxification and residential rehabilitation. Detoxification was usually provided in an in-patient setting, particularly within metropolitan NSW. Compliance with residential rehabilitation was notably poor. In conclusion, the development of appropriate interventions for amphetamine use needs to consider that the majority of treatment recipients will be based in a regional or rural setting, and treating amphetamine users will often involve treatment of concurrent cannabis and alcohol problems. The nature and appropriateness of treatment services provided for amphetamine use needs to be reviewed in detail, and further research is needed into the nature of problematic amphetamine use and factors affecting treatment demand in regional and rural NSW.

Adult↗

PubMed2005

Changes in response to insulin and the effects of varying glucose tolerance on whole-body protein metabolism in patients with cystic fibrosis.

BACKGROUND: Diabetes mellitus has been reported to increase whole-body protein breakdown and thus loss of lean body mass. Cystic fibrosis-related diabetes (CFRD) is associated with undernutrition and increased mortality. OBJECTIVE: We hypothesized that CFRD is associated with increased whole-body protein breakdown, which results in negative protein balance, and that correction of the glucose intolerance with insulin therapy would normalize whole-body protein metabolism. DESIGN: Rates of whole-body protein turnover and protein balance were measured in 28 adults with cystic fibrosis (17 M, 11 F). Subjects were assessed with a modified oral-glucose-tolerance test and categorized as having normal glucose tolerance, impaired glucose tolerance, or CFRD with and without fasting hyperglycemia; then they were compared with previously diagnosed CFRD adults already receiving insulin therapy. Indexes of protein turnover were calculated from [15N]glycine and 15N in urinary urea. RESULTS: Analysis of variance for the 28 subjects showed that whole-body protein breakdown was highest (P<0.05) in patients with CFRD. Whole-body protein synthesis was not significantly affected by impaired glucose tolerance. Significant (P<0.05) improvement in net protein synthesis occurred in the CFRD group 3 mo after insulin therapy was administered. Follow-up studies of 3 subjects with CFRD showed significant improvement in net protein synthesis after insulin therapy. Monitoring of the protein homeostasis of the impaired glucose tolerance group gave clues to the progression of their metabolic homeostasis. CONCLUSION: CFRD has an adverse effect on protein homeostasis by increasing net protein synthesis.

Adult↗

PubMed2004

Drug driving among injecting drug users in Sydney, Australia: prevalence, risk factors and risk perceptions.

AIMS: To examine the prevalence of drug driving, the prevalence of drug-related motor vehicle accidents, risk perceptions of drug driving and factors associated with drug driving among injecting drug users (IDU). DESIGN: Cross-sectional survey. SETTING: Sydney, Australia. PARTICIPANTS: Three hundred current IDU. FINDINGS: Ninety-five per cent had driven a vehicle, 74% in the previous 12 months ('current drivers'). Eighty-seven per cent of life-time drivers reported having drug driven, and 88% of current drivers had drug driven in the previous 12 months. There were no significant sex differences in life-time or recent drug driving. The most common drugs used before driving in the preceding year were: cannabis, heroin, amphetamines and cocaine. A third of life-time drivers reported having had a drug driving accident, with males more likely to have done so, and 9% of current drivers reported a drug driving accident in the previous year. The most common drugs that had been used before the most recent drug driving accident were heroin, cannabis and alcohol. Alcohol was perceived to be the most dangerous substance for driving performance and cannabis the least dangerous. Recent drug drivers perceived drug driving to be less dangerous than non-drug drivers. Recent drug drivers had driven more frequently over the preceding 12 months, had significantly higher levels of dependence, higher frequency of drug use, more extensive polydrug use and were more likely to have used and/or injected a drug in a car in the previous 12 months. CONCLUSIONS: Drug driving and drug-related accidents are large-scale public health problems among IDU. These behaviours pose serious risks to IDU themselves and to the broader community.

Accidents, Traffic↗

PubMed2004

A review of drug use and driving: epidemiology, impairment, risk factors and risk perceptions.

The existing literature on the prevalence of drug driving, the effects of drugs on driving performance, risk factors and risk perceptions associated with drug driving was reviewed. The 12-month prevalence of drug driving among the general population is approximately 4%. Drugs are detected commonly among those involved in motor vehicle accidents, with studies reporting up to 25% of accident-involved drivers positive for drugs. Cannabis is generally the most common drug detected in accident-involved drivers, followed by benzodiazepines, cocaine, amphetamines and opioids. Polydrug use is common among accident-involved drivers. Studies of impairment indicate an undeniable association between alcohol and driving impairment. There is also evidence that cannabis and benzodiazepines increase accident risk. The most equivocal evidence surrounds opioids and stimulants. It is apparent that drugs in combination with alcohol, and multiple drugs, present an even greater risk. Demographically, young males are over-represented among drug drivers. Although there is an association between alcohol use problems and drink driving, it is unclear whether such an association exists between drug use problems and drug driving. Evidence surrounding psychosocial factors and driving behaviour is also equivocal at this stage. While most drivers perceive drug driving to be dangerous and unacceptable, there is less concern about impaired driving among drug drivers and drink drivers than from those who have not engaged in impaired driving. Risk perceptions differ according to drug type, with certain drugs (e.g. cannabis) seen as producing less impairment than others (e.g. alcohol). It is concluded that drug driving is a significant problem, both in terms of a general public health issue and as a specific concern for drug users.

Automobile Driving↗

PubMed2002

IL-2 and related cytokines can promote T cell survival by activating AKT.

The regulated elimination of T cells serves to maintain normal immune function and prevents autoimmune responses. IL-2 family cytokines play an important role in controlling the survival of immature and mature T cells. These molecules activate the protein kinase, AKT/PKB. AKT has been shown to transduce an antiapoptotic signal in numerous cell types. In this study, we show that an active form of AKT can protect T cells from apoptosis following growth factor withdrawal and that IL-2 family cytokines can promote T cell survival by activating this kinase. We also provide evidence that AKT does not block death receptor-mediated killing of lymphocytes. These data suggest that AKT may serve as a common signaling element by which members of the IL-2 family of cytokines promote T cell survival.

Animals↗