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1.
Sports Biomech ; : 1-9, 2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37114500

ABSTRACT

High elbow varus torque during baseball pitching has been identified as a potential cause of ulnar collateral ligament injury in baseball pitchers. In general, elbow varus torque increases as ball velocity increases across pitchers. However, studies incorporating within-subject analyses report that not all professional pitchers have a positive relationship between elbow varus torque and ball velocity (T-V relationship). It remains unknown whether collegiate pitchers show the same trend as professionals in their T-V relationships. The current study investigated the T-V relationship of collegiate pitchers focusing on both across and within pitchers. Division 1 collegiate pitchers (n = 81) were assessed for elbow torque and ball velocity during pitching. Both across- and within-pitcher T-V relationships were significant (p < 0.05) using linear regression. However, more variance in elbow varus torque was explained using the within-pitcher relationship (R2 = 0.29) than the across-pitcher relationship (R2 = 0.05). Of the 81 pitchers, nearly half (n = 39) had significant T-V relationships, while the other half (n = 42) did not. Our findings indicate that the T-V relationship should be assessed on an individual basis as T-V is pitcher-specific.

2.
Adv Clin Endocrinol Metab ; 2(1): 47-54, 2019.
Article in English | MEDLINE | ID: mdl-32699839

ABSTRACT

BACKGROUND: The current consensus guidelines for management of pediatric obesity recommend clinic-based, family-centered, multi-disciplinary interventions. It is well reported that these programs often only lead to modest improvements in BMI status. The individual factors that differentiate which patient's BMI status will improve vs. worsen remains understudied. A retrospective cohort study was conducted to evaluate the outcomes of EMPOWER clinic and identify the participant specific characteristics that predicted BMI status improvement in this population. METHODS: Youth who completed at least 6 visits in EMPOWER were included. Paired t-test was utilized to evaluate the mean change in zBMI, modified BMIz and %BMIp95 from baseline to 6th visit, and multivariate mixed effect models were utilized to analyze effect of baseline characteristics on change in BMI status. RESULTS: 92 participants were included in the analysis, 87% with severe obesity and 66% Hispanic. At the 6th visit, there was a significant reduction in zBMI (-0.09 SD, p <0.001) and modified BMIz (-0.0003 SD, p = 0.04) with a small reduction in %BMIp95 (-1.15 %, p = 0.20). Lower BMI status (p < 0.001) and absence of a comorbidity (p < 0.05) at baseline were predictors of BMI status improvement whereas age, gender, ethnicity, family history of obesity and insurance status were not significant predictors. CONCLUSIONS: Given that implementation of the current guidelines for management of obesity in pediatrics only results in modest BMI status reduction, further investigation is required to understand how the determinants of obesity-related health outcomes can guide development of more innovative, effective interventions for this high risk population.

3.
Pediatr Obes ; 14(2): e12464, 2019 02.
Article in English | MEDLINE | ID: mdl-30117309

ABSTRACT

BACKGROUND: Clinical approaches to treating childhood obesity can be expensive and poorly reimbursed, and often produce suboptimal results. It has been theorized that overeating may have addictive qualities, and a sizable number of adolescents with obesity endorse addictive habits. Interestingly, few weight management interventions have tested techniques founded in addiction medicine principles. We therefore performed a pilot study of an addiction model based mHealth weight loss intervention in adolescents. METHODS: Adolescents with obesity were recruited from an multidisciplinary weight management clinic (EMPOWER). Adolescents without significant obesity comorbidities, who exhibited signs of addictive eating, based on the Yale Food Addiction Scale, were enrolled in a pilot study of an interactive, addiction-based, weight loss smartphone app with coaching (http://clinicaltrials.gov: NCT02689154). The app was designed to help subjects omit problem foods, avoid snacking and reduce meal size. A contemporary cohort of adolescents who completed the EMPOWER program were evaluated. Feasibility of recruitment, adherence, retention rates, BMI change and cost of intervention were examined. RESULTS: Eighteen participants were recruited to app intervention. App participants had higher retention (100% vs. 37%) and lower total cost per patient ($855.15 vs. $1428.00) than the EMPOWER clinic participants. App participants exhibited a significant decrease in zBMI and %BMIp95 over the 6 months (p < 0.001 and p = 0.001), which was comparable to the age-matched EMPOWER program completers (p = 0.31 and p = 0.06). CONCLUSIONS: An addiction medicine-based mHealth intervention targeted for adolescents was feasible to implement, resulted in high retention and adherence rates, and reduced zBMI and %BMIp95 in a more cost-effective manner than an in-clinic intervention.


Subject(s)
Food Addiction/therapy , Pediatric Obesity/therapy , Telemedicine/methods , Weight Reduction Programs/methods , Adolescent , Body Mass Index , Child , Costs and Cost Analysis , Feasibility Studies , Female , Food , Humans , Mobile Applications/statistics & numerical data , Pilot Projects , Retrospective Studies , Telemedicine/economics , Treatment Adherence and Compliance/statistics & numerical data , Weight Loss , Weight Reduction Programs/economics
4.
Trop Biomed ; 33(2): 393-395, 2016 Jun 01.
Article in English | MEDLINE | ID: mdl-33579109

ABSTRACT

A study was carried out to investigate the presence of mites in human ear in 58 patients (113 ears). Ear scrapings were examined under the microscope by a parasitologist for the presence of house dust mites. Results showed the presence of house dust mites in 8 (7.1%) ears. We can conclude that mites are normal commensals of the external ears in tropical countries.

5.
Tropical Biomedicine ; : 393-395, 2016.
Article in English | WPRIM (Western Pacific) | ID: wpr-630782

ABSTRACT

A study was carried out to investigate the presence of mites in human ear in 58 patients (113 ears). Ear scrapings were examined under the microscope by a parasitologist for the presence of house dust mites. Results showed the presence of house dust mites in 8 (7.1%) ears. We can conclude that mites are normal commensals of the external ears in tropical countries.

6.
J Laryngol Otol ; 129 Suppl 1: S32-7, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25273837

ABSTRACT

OBJECTIVE: Coblation tonsillectomy can be controversial. This study assessed post-tonsillectomy haemorrhage outcomes for patients operated on by a single experienced coblation-trained ENT surgeon. STUDY DESIGN: A retrospective audit of coblation tonsillectomies was performed using the Flinders modification of Stammberger criteria for post-tonsillectomy haemorrhage. METHOD: Case note review, interview and database interrogation were utilised to obtain the dataset. Haemorrhage results were compared to reports in the current literature. RESULTS: Of those who underwent coblation tonsillectomy, 3.4 per cent were readmitted to hospital with haemorrhage and 1.3 per cent returned to the operating theatre (0.4 per cent primary haemorrhage and 0.9 per cent secondary haemorrhage). Younger children had a lower risk of returning to the operating theatre than older children or adults (0.3 per cent under the age of 12 years vs 2.0 per cent aged 12 years or older). CONCLUSION: Coblation can be a safe method for tonsillectomy with low complication rates when performed by an experienced ENT surgeon. The Flinders modification of the Stammberger criteria for post-tonsillectomy haemorrhage provides a simple system for data comparison.


Subject(s)
Postoperative Hemorrhage/etiology , Surgeons/standards , Tonsillectomy/adverse effects , Adolescent , Adult , Child , Child, Preschool , Clinical Competence , Employee Performance Appraisal , Humans , Postoperative Hemorrhage/classification , Retrospective Studies , Tonsillectomy/methods , Young Adult
7.
Med J Malaysia ; 68(2): 136-40, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23629559

ABSTRACT

Upper respiratory tract infection (URTI) is mostly viral in aetiology, but patients presenting with such complaints are frequently prescribed antibiotics. This may result in increased development of antimicrobial resistance. The objectives of this study are to determine the choice and proportion of oral antibiotics prescribed in patients with URTI, in a Sarawak district hospital setting. All outpatient prescriptions received in July 2011 in 10 hospitals with relevant diagnoses were analysed. A total of 6747 URTI prescriptions met the inclusion criteria, and 64.8% (95% CI 63.7%, 65.9%) had antibiotic prescribed. Medical Assistants (MAs) were significantly more likely to prescribe antibiotics compared to Medical Officers (MOs) (p < 0.001). Prescribers were significantly influenced by the patient's age and specific diagnosis when prescribing antibiotics for URTI (p < 0.001). Antibiotic choices differed between MOs and MAs, where some of the antibiotic choices were inappropriate. There is a need for multi-faceted interventions to improve antibiotic prescribing rate and choice.


Subject(s)
Hospitals, District , Practice Patterns, Physicians' , Anti-Bacterial Agents/therapeutic use , Humans , Malaysia , Respiratory Tract Infections
8.
Dis Esophagus ; 26(6): 628-35, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23163347

ABSTRACT

The epidemiology of esophageal adenocarcinoma demonstrates a strong gender bias with a sex ratio of 8-9:1 in favor of males. A potential explanation for this is that estrogen might protect against esophageal adenocarcinoma. Estrogen has previously been shown to stimulate apoptosis in esophageal squamous cancer cells. However, the effect of estrogen on esophageal adenocarcinoma cells has not been determined. We used immunoblotting analysis to determine the expression of estrogen receptors, cell adhesion marker E-cadherin, and proliferation marker Ki-67 in cell lines derived from esophageal adenocarcinoma (OE-19, OE-33) and Barrett's esophagus (QhTRT, ChTRT, GihTRT). Estrogen and selective estrogen receptor modulator (SERM)-dependent effects on cell growth were determined by the CellTiter-96 Aqueous Proliferation Assay. Apoptosis was determined by Annexin V/Propidium Iodide cell labeling and flow cytometry. We detected that physiological and supra-physiological concentrations of 17ß-estradiol and SERM decreased cell growth in esophageal adenocarcinoma cells. In Barrett's esophagus cells (QhTRT, ChTRT), decreased growth was also detected in response to estrogen/SERM. The level of estrogen receptor expression in the cell lines correlated with the level of anti-growth effects induced by the receptor agonists. Flow cytometry analysis confirmed estrogen/SERM stimulated apoptosis in esophageal adenocarcinoma cells. Estrogen/SERM treatments were associated with a decrease in the expression of Ki-67 and an increase in E-cadherin expression in esophageal adenocarcinoma cells. This study suggests that esophageal adenocarcinoma and Barrett's esophagus cells respond to treatment with selective estrogen receptor ligands, resulting in decreased cell growth and apoptosis. Further research to explore potential therapeutic applications is warranted.


Subject(s)
Adenocarcinoma/pathology , Esophageal Neoplasms/pathology , Estrogens/pharmacology , Apoptosis/drug effects , Barrett Esophagus/pathology , Cadherins/drug effects , Cell Count , Cell Culture Techniques , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Estradiol/pharmacology , Estrogen Receptor alpha/drug effects , Estrogen Receptor beta/drug effects , Female , Humans , Ki-67 Antigen/drug effects , Male , Raloxifene Hydrochloride/pharmacology , Receptors, Estrogen/drug effects , Selective Estrogen Receptor Modulators/pharmacology , Tamoxifen/pharmacology
9.
Biophys J ; 100(5): 1252-60, 2011 Mar 02.
Article in English | MEDLINE | ID: mdl-21354398

ABSTRACT

Mechanosensitive channels allow bacteria to respond to osmotic stress by opening a nanometer-sized pore in the cellular membrane. Although the underlying mechanism has been thoroughly studied on the basis of individual channels, the behavior of channel ensembles has yet to be elucidated. This work reveals that mechanosensitive channels of large conductance (MscL) exhibit a tendency to spatially cluster, and demonstrates the functional relevance of clustering. We evaluated the spatial distribution of channels in a lipid bilayer using patch-clamp electrophysiology, fluorescence and atomic force microscopy, and neutron scattering and reflection techniques, coupled with mathematical modeling of the mechanics of a membrane crowded with proteins. The results indicate that MscL forms clusters under a wide range of conditions. MscL is closely packed within each cluster but is still active and mechanosensitive. However, the channel activity is modulated by the presence of neighboring proteins, indicating membrane-mediated protein-protein interactions. Collectively, these results suggest that MscL self-assembly into channel clusters plays an osmoregulatory functional role in the membrane.


Subject(s)
Escherichia coli Proteins/chemistry , Escherichia coli Proteins/metabolism , Escherichia coli , Ion Channels/chemistry , Ion Channels/metabolism , Lipid Bilayers/metabolism , Cell Membrane/metabolism , Liposomes/metabolism , Microscopy, Atomic Force , Neutron Diffraction , Protein Binding , Scattering, Small Angle
10.
Mol Ecol ; 19(4): 775-84, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20074315

ABSTRACT

Body size often shows adaptive clines in many ectotherms across altitude and latitude, but little is known about the genetic basis of these adaptive clines. Here we identify a polymorphism in the Dca (Drosophila cold acclimation) gene in Drosophila melanogaster that influences wing size, affects wing:thorax allometry and also controls a substantial proportion of the clinal wing-size variation. A polymorphism in the promoter region of Dca had two common alleles showing strong reciprocal clinal variation in frequency with latitude along the east coast of Australia. The Dca-237 allele increased towards the tropics where wing size is smaller. A within-population association study highlighted that an increase in the frequency of this allele decreased wing size but did not influence thorax size. A manipulated increase in the level of expression of Dca achieved through UAS-GAL4 was associated with a decrease in wing size but had no effect on thorax size. This was consistent with higher Dca expression levels in family lines with higher frequency of the Dca-237 allele. Genetic variation in the promoter region of the Dca gene appears to influence adaptive size variation in the eastern Australian cline of Drosophila melanogaster and accounts for more than 10% of the genetic variation in size within and between populations.


Subject(s)
Adaptation, Physiological/genetics , Drosophila melanogaster/genetics , Genetics, Population , Polymorphism, Genetic , Wings, Animal , Alleles , Animals , Australia , Base Sequence , Body Size , Drosophila Proteins/genetics , Female , Gene Frequency , Genes, Insect , Genetic Association Studies , Genotype , Male , Molecular Sequence Data , Promoter Regions, Genetic
11.
Opt Lett ; 34(11): 1735-7, 2009 Jun 01.
Article in English | MEDLINE | ID: mdl-19488165

ABSTRACT

Titanium-diffused lithium niobate (Ti:LiNbO(3)) waveguides are widely used in current fiber optic networks because of their high-speed, electro-optic modulation, and low-loss integration with standard single-mode fibers. However, they cannot achieve small ring resonators owing to their lack of a high core-to-cladding index contrast. To overcome this challenge, we vertically integrate an emerging chalcogenide glass waveguide technology on well-established Ti:LiNbO(3) waveguides. We present, to our knowledge, the first arsenic trisulfide (As(2)S(3)) race-track ring resonator with a 290.8 microm bend radius in an all-pass filter configuration, integrated on a Ti:LiNbO(3) waveguide. Vertical coupling is achieved using a unique taper design. Experimental results are shown for 10.6% coupling, 2.08 dB roundtrip loss, and a 25.4 GHz free-spectral range.

12.
J Insect Physiol ; 55(6): 549-55, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19232407

ABSTRACT

Microarrays have been used to examine changes in gene expression underlying responses to selection for increased stress resistance in Drosophila melanogaster, but changes in expression patterns associated with increased resistance to cold stress have not been previously reported. Here we describe such changes in basal expression levels in replicate lines following selection for increased resistance to chill coma stress. We found significant up- or down-regulation of expression in 94 genes on the Affymetrix Genome 2.0 array. Quantitative RT-PCR was used to confirm changes in expression of six genes. Some of the identified genes had previously been associated with stress resistance but no previously identified candidate genes for cold resistance showed altered patterns of expression. Seven differentially expressed genes that form a tight chromosomal cluster and an unlinked gene AnnX may be potentially important for cold adaptation in natural populations. Artificial selection for chill coma resistance therefore altered basal patterns of gene expression, but we failed to link these changes to plastic changes in expression under cold stress or to previously identified candidate genes for components of cold resistance.


Subject(s)
Drosophila melanogaster/physiology , Gene Expression Regulation , Transcription, Genetic , Animals , Cold Temperature , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/genetics , Gene Expression Profiling , Molecular Sequence Data
13.
Insect Mol Biol ; 17(4): 351-60, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18651917

ABSTRACT

A cDNA-amplified fragment length polymorphisms approach was undertaken to screen for candidate genes associated with fenvalerate resistance in the AN02 strain of Helicoverpa armigera. Larvae and adults of this strain manifest approximately 50-fold resistance, which is suppressible by piperonyl butoxide and controlled by the semidominant gene RFen1 previously mapped to AFLP Linkage Group 13. Two cytochrome P450s (CYP337B1 and CYP4S1), one carboxylesterase-like protein and one glutathione transferase were found to be constitutively upregulated in resistant insects. Mapping of these potential detoxification genes showed that one of them, the novel P450 CYP337B1, was tightly linked to the resistance locus. This suggests that the RFen1(R) allele has a cis-acting effect on CYP337B1 expression, and possible trans-acting effects on expression of other genes.


Subject(s)
DNA, Complementary/genetics , Genes, Insect , Insecticide Resistance/genetics , Moths/drug effects , Moths/genetics , Nitriles/pharmacology , Pyrethrins/pharmacology , Amino Acid Sequence , Amplified Fragment Length Polymorphism Analysis , Animals , Down-Regulation , Gene Expression Profiling , Gene Expression Regulation/physiology , Genetic Linkage , Genetic Markers , Genotype , Insect Proteins/genetics , Insect Proteins/metabolism , Insecticides/pharmacology , Molecular Sequence Data , Up-Regulation
14.
Acta Paediatr ; 97(4): 414-9, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18363950

ABSTRACT

OBJECTIVES: (i) To compare original foetal brain ultrasound findings with a multidisciplinary expert opinion; (ii) to compare the multidisciplinary expert ultrasound opinion with foetal magnetic resonance imaging (MRI) findings and (iii) to determine in which circumstances foetal MRI gives additional information, and in how many cases management is changed by having information from MRI. STUDY DESIGN: Ultrasound scans of 51 consecutive foetuses where foetal brain MR had been performed were retrospectively reviewed by a panel consisting of maternal-foetal-medicine (MFM) consultants, a geneticist, neonatologists and MFM subspecialty trainees. The original ultrasound opinion was compared with the multidisciplinary opinion, which was then compared with MRI findings. In the cases where MRI gave additional information, an assessment was made as to whether this changed management. RESULTS: The multidisciplinary ultrasound opinion differed from the original opinion in 9 of 51 (17%) cases. In 19 patients (37%), the MRI gave additional information to the original ultrasound, in 7 (13%) cases, management, and in 7 (13%) cases, counselling was altered by additional information gained from MRI. The multidisciplinary ultrasound and MRI diagnoses were similar in 36 cases (71%). CONCLUSION: Multidisciplinary review of an apparently abnormal foetal brain ultrasound can provide additional diagnostic information. When compared with this level of ultrasound expertise, MRI gave additional information in 29% of cases, but only resulted in change in management in about 13%.


Subject(s)
Brain/embryology , Echoencephalography , Magnetic Resonance Imaging , Agenesis of Corpus Callosum , Brain/abnormalities , Cerebral Ventricles/abnormalities , Cerebral Ventricles/diagnostic imaging , Corpus Callosum/diagnostic imaging , Cysts/diagnostic imaging , Cysts/embryology , Female , Humans , Predictive Value of Tests , Pregnancy , Referral and Consultation , Retrospective Studies , Ultrasonography, Prenatal
16.
Emerg Med J ; 23(3): 206-9, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16498158

ABSTRACT

OBJECTIVE: To compare atropine with placebo as an adjunct to ketamine sedation in children undergoing minor painful procedures. Outcome measures included hypersalivation, side effect profile, parental/patient satisfaction, and procedural success rate. METHODS: Children aged between 1 and 16 years of age requiring ketamine procedural sedation in a tertiary emergency department were randomised to receive 0.01 mg/kg of atropine or placebo. All received 4 mg/kg of intramuscular ketamine. Tolerance and sedation scores were recorded throughout the procedure. Side effects were recorded from the start of sedation until discharge. Parental and patient satisfaction scores were obtained at discharge and three to five days after the procedure, with the opportunity to report side effects encountered at home. RESULTS: A total of 83 patients aged 13 months to 14.5 years (median age 3.4 years) were enrolled over a 16 month period. Hypersalivation occurred in 11.4% of patients given atropine compared with 30.8% given placebo (odds ratio (OR) 0.29, 95% confidence interval (CI) 0.09 to 0.91). A transient rash was observed in 22.7% of the atropine group compared with 5.1% of the placebo group (OR 5.44, 95% CI 1.11 to 26.6). Vomiting during recovery occurred in 9.1% of atropine patients compared with 25.6% of placebo patients (OR 0.29, 95% CI 0.09 to 1.02). There was a trend towards better tolerance in the placebo group. No patient experienced serious side effects. CONCLUSION: Ketamine sedation was successful and well tolerated in all cases. The use of atropine as an adjunct for intramuscular ketamine sedation in children significantly reduces hypersalivation and may lower the incidence of post-procedural vomiting. Atropine is associated with a higher incidence of a transient rash. No serious adverse events were noted.


Subject(s)
Adjuvants, Anesthesia/administration & dosage , Anesthetics, Dissociative/administration & dosage , Atropine/administration & dosage , Ketamine/administration & dosage , Pain/prevention & control , Adjuvants, Anesthesia/adverse effects , Adolescent , Anesthetics, Dissociative/adverse effects , Atropine/adverse effects , Child , Child, Preschool , Double-Blind Method , Drug Combinations , Female , Humans , Infant , Injections, Intramuscular , Ketamine/adverse effects , Male , Minor Surgical Procedures , Patient Satisfaction , Prospective Studies , Sialorrhea/chemically induced
17.
Conf Proc IEEE Eng Med Biol Soc ; 2005: 6203-6, 2005.
Article in English | MEDLINE | ID: mdl-17281682

ABSTRACT

Functional electrical stimulation (FES) has grown to be an effective and important element in the biomedical industry over the years. Due to this fact, it has become the basis of many researches. However, much work is focused on the theory and control technique with very few relating experiments. In this work, some key experiments were performed on the leg muscles during the leg movement. Some useful results were obtained with regards to muscle reaction, in terms EMG readings. The stimulus of the FES system was also applied to the muscles during the leg movement. The readings of experiments reveal some important muscle properties which are verified accordingly.

18.
Lancet ; 362(9391): 1192-7, 2003 Oct 11.
Article in English | MEDLINE | ID: mdl-14568741

ABSTRACT

BACKGROUND: Various lines of evidence suggest that antenatal factors are important in determining susceptibility to atopy and asthma. One possible mechanism is cytokines, production of which in the placenta is high throughout gestation and which protect placental integrity via control of local immunological homoeostasis. We investigated antenatal cytokine concentrations in a prospective birth cohort, intensively monitored for atopy and asthma outcomes at age 6 years. METHODS: Cryopreserved cord-blood serum samples from 407 children were assayed for interleukins 4, 5, 6, 10, 12, and 13, interferon gamma, and tumour necrosis factor alpha (TNFalpha). Associations between family, antenatal, and perinatal factors, cord-blood cytokine concentrations, and atopy or asthma outcomes were analysed by logistic regression. Causal effects of cytokines on outcomes were estimated by propensity scores based on family, antenatal, and perinatal factors. FINDINGS: Detectable cord-blood concentrations of interleukin 4 and interferon gamma were each associated with lower risk of physician-diagnosed asthma (adjusted odds ratios 0.60 [95% CI 0.37-0.99] and 0.60 [0.37-0.97] respectively), current asthma (0.59 [0.33-1.00] and 0.39 [0.22-0.71]), and current wheeze (0.55 [0.32-0.93] and 0.52 [0.31-0.90]) and atopy (sensitisation to some inhalant allergens) outcomes at 6 years. High concentrations of TNFalpha were associated with lower risk of atopy but not with asthma risk. These associations were broadly unaltered by propensity-score adjustment. Maternal smoking was associated with higher risk of both wheeze at 6 years and lower concentrations of interleukin 4 and interferon gamma in cord blood. INTERPRETATION: The mechanism underlying attenuated T-helper-1/T-helper-2 cytokine production in high-risk children also apparently operates in control of cytokine production in the fetoplacental unit. The finding that this mechanism is dysregulated by maternal smoking suggests it is a target for antenatal environmental factors relevant to asthma aetiology.


Subject(s)
Asthma/immunology , Cytokines/blood , Fetal Blood/metabolism , Hypersensitivity/immunology , Child , Child Development/physiology , Child, Preschool , Cohort Studies , Cytokines/immunology , Female , Fetal Blood/chemistry , Fetal Diseases/immunology , Humans , Hypersensitivity, Immediate/immunology , Infant , Infant, Newborn , Interferon-gamma/blood , Interferon-gamma/immunology , Interleukin-4/blood , Interleukin-4/immunology , Pregnancy , Prospective Studies , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/immunology
19.
Clin Exp Allergy ; 32(1): 97-106, 2002 Jan.
Article in English | MEDLINE | ID: mdl-12002746

ABSTRACT

BACKGROUND: T helper (Th)2 cytokines are considered to play a central role in the induction and expression of allergic disease. However, the relative importance of individual cytokines is unclear, and overall disease pathogenesis appears to involve the coordinate activities of a range of Th2 cytokines acting in sequence or in parallel. The present study examines an alternative approach to the study of cytokine gene function in atopy, focusing instead upon T cell transcription factors (TFs) which play a role in the regulation of multiple cytokine genes. OBJECTIVE: To investigate the allergen-induced expression of the TF GATA-3 and c-Maf in peripheral blood mononuclear cells (PBMCs) and in cytokine-driven Th polarization. METHODS: PBMC from house dust mite (HDM)-atopic and non-atopics were stimulated in vitro with allergen or anti-CD3/IL-2. TF expression was analysed by semiquantitative RT-PCR and major findings were validated by real-time PCR. Cell separations were performed to analyse the contribution of CD45RO+ cells. CD4+ cord blood cells were Th1 or Th2 polarized in vitro by exogenous cytokines and TF expression analysed by Northern blot and real-time PCR. Results We demonstrate for the first time that during differentiation of CD4+ CD45RA+ naïve human T cells towards Th2 commitment, and during allergen-specific reactivation of peripheral CD4+ CD45RO+ Th2 memory cells in established atopics, expression of the Th2-associated TF GATA-3 is rapidly up-regulated, whereas T cells from non-atopics display equally rapid GATA-3 down-regulation under identical conditions of allergen stimulation. CONCLUSION: These findings identify Th2-associated TFs as key determinants of the atopic phenotype, suggesting their unique potential as therapeutic targets for disease control.


Subject(s)
Allergens/pharmacology , DNA-Binding Proteins/blood , Dust , Hypersensitivity/blood , Mites/immunology , Monocytes/metabolism , Trans-Activators/blood , Adult , Animals , CD4-Positive T-Lymphocytes/metabolism , Cell Polarity/physiology , Cells, Cultured , Computer Systems , Cytokines/biosynthesis , DNA-Binding Proteins/metabolism , Female , GATA3 Transcription Factor , Humans , Male , Polymerase Chain Reaction , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-maf , Receptors, Interleukin-2/metabolism , Reference Values
20.
Allergy ; 56(11): 1042-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11703216

ABSTRACT

BACKGROUND: Atopic children show increased expression and production of the Th2-associated cytokines IL-4, IL-5, IL-13, and IL-9 from PBMCs after stimulation with allergen, but it has previously not been clearly determined whether the Th2-cytokine production is restricted to the inhalant allergen the child is sensitized to, and whether perennial or seasonal allergens induce different cytokine responses. Our purpose was to determine whether in vitro Th2 cytokine production is specific to the sensitizing allergen, and to compare the cytokine responses to a perennial and a seasonal allergen in monosensitized and polysensitized children. METHODS: Using semiquantitative RT-PCR, we analyzed the expression of the cytokines IL-4, IL-5, IL-13, IL-9, IL-10, and IFN-gamma after stimulation of PBMCs with house-dust-mite (HDM) or ryegrass allergen. The cells were sampled from groups of 6-year-old children sensitized to either HDM (n=20) or ryegrass (n=24), or to both allergens (n=20), as well as from a nonatopic group (n=20). RESULTS: After stimulation with HDM allergen, PBMCs from children sensitized only to HDM expressed increased mRNA levels of the Th2 cytokines, but not of IL-10 and IFN-gamma, whereas ryegrass stimulation did not result in increased cytokine expression. PBMCs from children sensitized to HDM and ryegrass expressed increased Th2 cytokines after stimulation with either of the two allergens. In contrast, PBMCs from children sensitized only to ryegrass did not express increased levels after stimulation with either of the allergens. CONCLUSIONS: The expression of Th2 cytokines after in vitro stimulation of PBMCs from atopic children is specific to the sensitizing allergen, indicating that atopic status per se does not affect the type of T-cell response. In addition, T cells specific to seasonal allergens circulate in the blood out of season only if the child is concomitantly sensitized to a perennial allergen.


Subject(s)
Allergens/adverse effects , Allergens/immunology , Cytokines/biosynthesis , Hypersensitivity, Immediate/etiology , Hypersensitivity, Immediate/immunology , Leukocytes, Mononuclear/immunology , Seasons , Animals , Antibody Specificity/immunology , Bystander Effect , Child , Child Welfare , Cohort Studies , Cytokines/immunology , Dust/adverse effects , Humans , Immunization , Immunoglobulin E/blood , Immunoglobulin E/immunology , Leukocytes, Mononuclear/metabolism , Lolium/adverse effects , Lolium/immunology , Mites/immunology , Skin Tests , Sweden/epidemiology
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