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1.
Mucosal Immunol ; 11(3): 846-860, 2018 05.
Article in English | MEDLINE | ID: mdl-29186109

ABSTRACT

CD44 is a transmembrane molecule appearing in numerous isoforms generated by insertions of alternatively spliced variant exons (CD44v) and having various binding partners. CD44v7 on T cells was proposed to promote colitis by preventing T-cell apoptosis. Here we demonstrate that Cd44v7-deficient T cells - like Cd44 wild-type (Cd44WT) T cells - provoked disease in two different colitis models: the model induced by CD4+CD45RBhigh T-cell transfer into Rag2-deficient mice and a new model based on ovalbumin (OVA)-specific T-cell transfer into Rag-sufficient, OVA-challenged mice. In contrast, CD44v7 absence on macrophages in recipient mice prevented colitis. Prevention was associated with the downregulation of signal transducer and activator of transcription 3 (STAT3)-activating and Foxp3-counteracting interleukin-6 (IL-6), lower numbers of phospho-STAT3-containing lymphocytes, and higher Foxp3+ T-cell counts in the colon. Consequently, the protected colons showed lower IL-12, IL-1ß expression, and decreased interferon-γ levels. Importantly, stimulation of T cells by Cd44v7-deficient macrophages induced upregulation of Foxp3 in vitro, while cotransfer of Cd44WT macrophages into Cd44v7-deficient mice reduced Foxp3+ T-cell counts and caused colitis. Accordingly, the CD44v7 ligand osteopontin, whose levels were elevated in Crohn's disease, specifically induced IL-6 in human monocytes, a cytokine also increased in these patients. We suggest macrophage-specific targeting of the CD44v7 pathway as a novel therapeutic option for Crohn's disease.


Subject(s)
Colitis/immunology , Crohn Disease/immunology , Hyaluronan Receptors/metabolism , Macrophages/physiology , T-Lymphocyte Subsets/physiology , T-Lymphocytes, Regulatory/physiology , Adult , Alternative Splicing , Animals , Cells, Cultured , Coculture Techniques , Cytokines/metabolism , Disease Models, Animal , Exons/genetics , Female , Forkhead Transcription Factors/metabolism , Humans , Hyaluronan Receptors/genetics , Inflammation Mediators/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Knockout , Mice, Transgenic , Osteopontin/metabolism
2.
Sci Rep ; 7(1): 1506, 2017 05 04.
Article in English | MEDLINE | ID: mdl-28473710

ABSTRACT

Infection of bone is a severe complication due to the variety of bacteria causing it, their resistance against classical antibiotics, the formation of a biofilm and the difficulty to eradicate it. Antimicrobial peptides (AMPs) are naturally occurring peptides and promising candidates for treatment of joint infections. This study aimed to analyze the effect of short artificial peptides derived from an optimized library regarding (1) antimicrobial effect on different bacterial species, (2) efficacy on biofilms, and (3) effect on osteoblast­like cells. Culturing the AMP-modifications with Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus (including clinical isolates of MRSA and MSSA) and Staphylococcus epidermidis identified one candidate that was most effective against all bacteria. This AMP was also able to reduce biofilm as demonstrated by FISH and microcalorimetry. Osteoblast viability and differentiation were not negatively affected by the AMP. A cation concentration comparable to that physiologically occurring in blood had almost no negative effect on AMP activity and even with 10% serum bacterial growth was inhibited. Bacteria internalized into osteoblasts were reduced by the AMP. Taken together the results demonstrate a high antimicrobial activity of the AMP even against bacteria incorporated in a biofilm or internalized into cells without harming human osteoblasts.


Subject(s)
Antimicrobial Cationic Peptides/therapeutic use , Bone Diseases, Infectious/drug therapy , Bone Diseases, Infectious/prevention & control , Amino Acid Sequence , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/pharmacology , Biofilms/drug effects , Bone Diseases, Infectious/microbiology , Cells, Cultured , Drug Delivery Systems , Gentamicins/pharmacology , Humans , Microbial Sensitivity Tests , Osteoblasts/drug effects , Osteoblasts/microbiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Staphylococcus epidermidis/drug effects
3.
Anal Bioanal Chem ; 387(5): 1823-9, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17053919

ABSTRACT

The standard methods currently used to read out microarrays are fluorescent and chemiluminescent imaging techniques. These methods require labeling of a component with a marker and, usually, only the concentration of the marker molecule is detected. A label-free imaging method that also enables quantitative spectroscopic analysis of the composition and component interaction would be of great advantage. In this article it is shown for the first time that IR mapping ellipsometry enables label-free imaging of a biochip before and after incubation with peptide solution. The measurements prove that IR ellipsometry is a sensitive tool for laterally resolved identification of the different materials and determination of the composition of a biochip. The lateral resolution required was achieved by using radiation from an infrared synchrotron beamline.


Subject(s)
Luminescent Measurements/instrumentation , Optics and Photonics/instrumentation , Refractometry/instrumentation , Spectrophotometry, Infrared/instrumentation , Spectrum Analysis, Raman/instrumentation , Equipment Design , Equipment Failure Analysis , Reproducibility of Results , Sensitivity and Specificity
4.
J Paediatr Child Health ; 40(7): 353-5, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15228561

ABSTRACT

OBJECTIVE: To determine prevalence of, and trends in, overweight and obesity in South Australian children aged 4 years during the period 1995-2002. METHODS: Data from 114 669 children collected as part of Child and Youth Health 'preschool health assessments' of 4-year-olds throughout the state in the years 1995-2002 were analysed. Body mass index was calculated from height and weight data and prevalence of overweight and obesity for males and females determined using a standard world-wide definition. Yearly prevalence rates were compared for changes over time. RESULTS: Rates of overweight and obesity have increased over the period 1995-2002. In 1995, of females 12.8% were overweight or obese (obese 3.5%). Of males 10.2% were overweight or obese (obese 3.2%). The equivalent figures in 2002 were for females 21.4% (obese 5.8%) and males 17.3% (obese 4.1%). Rates of overweight and obesity were greater in females than males in all years (except obesity rate in 1995). CONCLUSION: Data from this large, consecutive yearly dataset of South Australian 4-year-old children show a significant increase in the rates of overweight and obesity. Much of this increase appears to have occurred in the mid-to-late 1990s. It is uncertain if these changes have plateaued at this time. These results reinforce rising obesity prevalence as a significant child health issue. They also indicate that obesity is seen as early as the preschool years; with implications for theories of causation and for prevention and treatment strategies.


Subject(s)
Obesity/epidemiology , Body Mass Index , Child, Preschool , Epidemiologic Methods , Female , Humans , Male , Prevalence , Sex Distribution , South Australia/epidemiology
5.
Arch Environ Health ; 56(5): 433-8, 2001.
Article in English | MEDLINE | ID: mdl-11777024

ABSTRACT

A South Australian preschool study carried out in 1993 showed that the prevalence of respiratory symptoms was significantly associated with use of unflued gas appliances for cooking and heating. The authors sought to determine an association between domestic exposure to nitrogen dioxide and the excretion of total urinary nitrate and nitrite, and their association with asthma prevalence. The results indicated that the geometric mean concentrations of nitrogen dioxide were much higher in homes that had natural gas appliance(s) and other types of appliances (i.e., electric and solid fuel). Higher levels of nitrogen dioxide were found in homes of suburban areas with higher prevalence of asthma and respiratory symptoms. Nitrogen dioxide levels were lower in the summer, and there was a higher level in kitchens than in bedrooms. Urinary nitrate excretion was evaluated in 1,335 preschool children from the same sampling areas. No association existed between nitrogen dioxide levels and urinary nitrates, nor was there a relationship between urinary nitrates and asthma prevalence. These findings confirm that there is a positive association between nitrogen dioxide exposure from gas appliances and the prevalence of respiratory symptoms, but urinary nitrate is not a useful biomarker of exposure at these levels.


Subject(s)
Air Pollution, Indoor/adverse effects , Asthma/epidemiology , Cooking , Inhalation Exposure , Nitrates/urine , Nitrites/urine , Nitrogen Oxides/adverse effects , Asthma/etiology , Biomarkers , Child, Preschool , Female , Humans , Male , Prevalence
6.
J Paediatr Child Health ; 33(6): 528-30, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9484686

ABSTRACT

OBJECTIVE: To evaluate the validity of a parental questionnaire used to screen preschool children for persistent hearing impairment. METHODOLOGY: Six-hundred and eighty-five children aged 4-5 years from a Metropolitan area of Adelaide, Australia, were enrolled. Each parent completed a questionnaire aimed at detecting parental concerns about hearing impairment. Screening audiometry was then performed. Children who failed the initial audiometry screening underwent repeat audiometry screening 6-8 weeks later. The audiometry and questionnaire data were then compared. RESULTS: Of the 657 children who successfully completed initial audiometry, 544 (83%) passed and 113 (17%) failed. Of the 84 children who had follow-up audiometry, 64 (76%) passed. Parental concerns were identified on questionnaire in 50% of all children. Neither individual questions nor the number of concerns were found to relate to audiometry results. Compared with audiometry results, the hearing screening questionnaire had a sensitivity of 56% and specificity of 52%. CONCLUSIONS: The hearing questionnaire used in this study and in several Australian states is an ineffective screening test for detecting persistent hearing loss.


Subject(s)
Hearing Disorders/diagnosis , Surveys and Questionnaires , Audiometry , Child, Preschool , Factor Analysis, Statistical , Female , Humans , Male , Mass Screening , Reproducibility of Results , Sensitivity and Specificity
7.
J Paediatr Child Health ; 31(2): 112-5, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7794610

ABSTRACT

OBJECTIVE: This study was designed to ascertain the prevalence of respiratory symptoms in South Australian preschool children and to investigate the relationship between prevalence rates and geographic location. METHODOLOGY: Data were collected from 14,124 families with a child aged 4 years 3 months to 5 years of age. This sample represents 73% of the State preschool population of that age. At the time of a routine preschool health check, parents completed a questionnaire regarding their child's respiratory health and place of residence (postcode). RESULTS: Results showed that the prevalence rates were as follows: (i) ever having chest wheezing 38.6%; (ii) chest wheezing within the preceding 12 months 25.2%; (iii) ever having asthma 22.5%; (iv) ever having a dry cough at night 33.7%; (v) ever having bronchitis or cough with sputum 55.3%; (vi) ever having hay fever 29.7%; (vii) prone to excessive head colds 32.6%; and (viii) ever having eczema 18.8%. Over 38% of parents claimed that winter was the season for the most frequent or severe attacks of wheezing and 31.7% claimed no seasonal difference. Winter was the season most associated with episodes of bronchitis (50.9%), with no seasonal difference in episodes for 29.8% of children. Prevalence rates differed by geographic location within South Australia and within the Adelaide metropolitan region. CONCLUSION: This population-based survey shows that over 22% of South Australian 4 to 5 year old preschool children have had (or continue to have) asthma. The study also documented the geographic distribution of respiratory symptom prevalence within South Australia.


Subject(s)
Respiration Disorders/epidemiology , Respiratory Hypersensitivity/epidemiology , Respiratory Tract Infections/epidemiology , Asthma/epidemiology , Child, Preschool , Humans , Prevalence , Residence Characteristics , Seasons , South Australia/epidemiology , Surveys and Questionnaires
8.
J Paediatr Child Health ; 31(2): 116-20, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7794611

ABSTRACT

OBJECTIVE: This study investigated the relationship between indoor air quality and the prevalence of respiratory symptoms in South Australian preschool children. METHODOLOGY: Data were collected from 14,124 families with a child aged 4 years 3 months to 5 years of age. This sample represents 73% of the targeted State preschool population. At the time of a routine preschool health check, parents completed a questionnaire regarding: their child's respiratory health and place of residence (postcode), parental smoking, type of fuel used for cooking and heating and method used for home cooling. RESULTS: For preschool children residing in the greater Adelaide region, logistic regression analyses found that having a natural gas stove compared to an electric stove was significantly associated with increased prevalence rates for: (i) asthma (odds ratio [OR] 1.24); (ii) wheezing in the preceding 12 months (OR 1.16); excessive colds (OR 1.14); and hay fever (OR 1.13). The use of a liquid petroleum gas stove compared to an electric stove was not associated with any respiratory symptoms. The use of a flueless gas heater compared to other forms of heating was significantly associated with increased prevalence rates for dry cough (OR 1.26), ever having wheezed (OR 1.15) and wheezing in the preceding 12 months (OR 1.18). The use of a wood fire/heater compared to other forms of heating was significantly associated with a reduced prevalence rate for dry cough (OR 0.84) and ever having wheezed (OR 0.82). Parental smoking was significantly associated with increased prevalence rates for bronchitis (OR 1.21) and ever having wheezed (OR 1.24). The form of home cooling used was not associated with prevalence rates, after accounting for geographic location. Socio-economic status (postcode level) was not generally associated with prevalence rates. CONCLUSIONS: These results suggest that respiratory symptom prevalence is related to the fuel used for cooking and heating and parental smoking. Prospective investigation regarding indoor air quality and respiratory symptoms is required.


Subject(s)
Air Pollution, Indoor , Respiration Disorders/epidemiology , Respiratory Hypersensitivity/epidemiology , Respiratory Tract Infections/epidemiology , Air Conditioning , Asthma/epidemiology , Child, Preschool , Heating , Humans , Logistic Models , Odds Ratio , Prevalence , Residence Characteristics , Social Class , South Australia/epidemiology , Surveys and Questionnaires , Tobacco Smoke Pollution
9.
J Paediatr Child Health ; 29(6): 438-44, 1993 Dec.
Article in English | MEDLINE | ID: mdl-8286160

ABSTRACT

After the first year of life, injury is the leading cause of mortality in children and adolescents in Australia and a major cause of morbidity and hospitalization. Studies from Europe and North American and more recently New Zealand have demonstrated that injury rates differ between different socio-economic groups, with a relatively consistent pattern of higher rates being found in lower socio-economic groups. To date, the pattern of child injury morbidity by socio-economic group has not been studied in Australia. Eighteen months of data from Brisbane and Melbourne collections of the National Injury Surveillance Unit data base were analysed and linked to census data from each postcode in the collecting area to calculate injury rates. Injury rates for each postcode were correlated with measures of disadvantage derived from the same census data. There was a consistent pattern of moderately strong statistically significant associations (Pearson correlation coefficients generally 0.30-0.60) found between measures of disadvantage and injury rate at the postcode level of aggregation. This association was present across cities, age groups, type of injury and for those hospitalized as well as those treated as outpatients. It is apparent that residence in a low income area is a significant predictor of child injury in Australia.


Subject(s)
Social Class , Wounds and Injuries/epidemiology , Adolescent , Australia/epidemiology , Child , Child, Preschool , Female , Humans , Infant , Male , Regression Analysis , Socioeconomic Factors
10.
J Paediatr Child Health ; 29(2): 150-3, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8489797

ABSTRACT

This study surveyed 313 parents to investigate how frequently parents used a parent-held child health record, and whether they saw the record as useful. Since 1981, The Child, Adolescent and Family Health Service has distributed a Personal Health Record (PHR) to the parents of all children in South Australia. The PHR has provided each family with an ongoing record that has been consistently used for immunization, child health checks and child health screening. However, little is known about how parents view the PHR, its usefulness, and how frequently the record is used. Previous studies, generally conducted prior to, or shortly after, a parent-held child health record was introduced, have shown a poor understanding of the uses of the PHR on the part of parents and a low level of use by health professionals such as general practitioners. In contrast, the results of this study show high levels of understanding of the health record on the part of parents, and an increase in the use of the health record by general practitioners over the 10 years since the record was introduced. Although moderated by the age of the child, the sections of the PHR seen as most useful (and the most frequently used) by parents were immunization, growth charts, progress notes and health checks.


Subject(s)
Forms and Records Control/methods , Medical Records , Parents , Age Factors , Child, Preschool , Family Practice , Health Knowledge, Attitudes, Practice , Humans , South Australia , Surveys and Questionnaires
11.
J Paediatr Child Health ; 28(5): 372-8, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1389449

ABSTRACT

This study investigated the factors influencing parental action on behalf of their child following a school entry health screening failure. It was predicted that compliance with recommendations to seek further assessment would be related to the screening process variables and the number of barriers to compliance parents faced and that these barriers, and hence compliance, would be influenced by the socio-economic status of the family. It was also expected that when schools were differentiated on adversity factors, the type of school attended would be related to compliance. Results from a sample of parents (n = 1231) showed that the parental non-compliance rate to a referral of their child for further assessment following health screening was 26.1%. Non-compliance was related to both screening process knowledge and satisfaction and the type of barriers to compliance parents experienced. Although the type and number of barriers experienced by parents was related to socio-economic status, the results of correlational and discriminant function analyses indicated that the barriers most strongly related to compliance (e.g. partner's views, time pressure, more serious problems to worry about) were not related to socio-economic status nor type of school attended. These findings provide valuable information for child health service providers as well as those involved in policy making and planning in the general area of community health services.


Subject(s)
Mass Screening , Parents , Referral and Consultation , School Health Services , Treatment Refusal , Child , Discriminant Analysis , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Socioeconomic Factors , South Australia
12.
J Pers Soc Psychol ; 55(2): 266-71, 1988 Aug.
Article in English | MEDLINE | ID: mdl-3171906

ABSTRACT

Eighty subjects from an introductory psychology course rated the desirability of eight course structures that differed according to all combinations of the presence or absence of effort required for success, time pressure, and the provision of feedback. Subjects also completed questionnaire measures of the Type A behavior pattern, test anxiety, and external locus of control. Results showed that the Type A behavior pattern was negatively related to external locus of control and that externals tended to have higher test anxiety scores than internals. Multiple regression analyses that involved the personality variables and age and gender showed that the Type A variable predicted preference for course structures that involved effort and feedback and that external control predicted preference for course structures that were independent of effort and provided little feedback. Test anxiety and desirability ratings were positively correlated for the course structure that was not dependent on effort, had little time pressure, and had little feedback. The results were consistent with the view that individuals seek out and prefer situations that are consistent with their personality characteristics.


Subject(s)
Anxiety/psychology , Internal-External Control , Type A Personality , Adolescent , Adult , Feedback , Female , Humans , Male , Middle Aged , Physical Exertion , Stress, Psychological/psychology , Time Factors
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