bluuebunny/crossref_metadata_2025 huggingface dataset:
No mutation in the KCNE3 potassium channel gene in Chinese thyrotoxic hypokalaemic periodic paralysis patients
Authors: Tang Nelson L. S. , Chow C. C. , Ko Gary T. C. , Tai Morris H. L. , Kwok Rachel , Yao X. Q. , Cockram Clive S.
Published: June 2004

objectives  Mutation in KCNE3 gene (Isk‐related family potassium voltage‐gated channel member 3 gene) was recently associated with the aetiology of thyrotoxic periodic paralysis (TPP). We studied 79 Chinese TPP patients by DNA sequencing of the entire coding sequence of KCNE3 to determine if this gene is the cause of TPP in Chinese patients.

design and measurements  A case–control genetic association study was carried out to determine the role of mutation/polymorphism in KCNE3 gene in the pathogenesis of TPP. Genomic DNA was extracted from peripheral blood samples. DNA sequencing was performed to cover the coding region of the KCNE3 gene for the TPP subjects. Restriction fragment length polymorphism was used to genotype specific sequence variants.

subjects  Seventy‐nine TPP patients (cases) and 111 male thyrotoxic patients without history of paralysis (controls) were identified from thyroid clinic and during acute admission in a teaching hospital.

results  No pathogenic mutation in KCNE3 was found in the TPP patients. The reported R83H mutation was also not found in the Chinese TPP patients. In addition, another silent polymorphism, 290T/C, was also not associated with TPP.

conclusion  The results indicate that mutation in KCNE3 is not a cause of TPP in Chinese patients.
Head circumference and linear growth during the first 3 years in treated congenital hypothyroidism in relation to aetiology and initial biochemical severity
Authors: Ng Sze May , Wong Sze Choong , Didi Mohammed
Published: June 2004

aims  To determine the head circumference and linear growth in children with congenital hypothyroidism (CH) during the first 3 years of life in relation to the aetiology of CH and initial biochemical severity of thyroid function.

methods  We examined the head circumference and linear growth of 125 patients with CH from diagnosis up to 3 years of age. All infants had radionuclide scans prior to treatment. Patients were categorized into athyreosis, ectopia and dyshormonogenesis. Occipito‐frontal circumference (OFC) SD, length SD, initial plasma TSH, initial plasma thyroxine (T4) and age of suppression of plasma TSH were compared between the groups. Multiple linear regression analysis was used to determine factors affecting OFC SD at 3 years of age.

results  There were 125 children in the study: athyreosis (n = 34), ectopia (n = 73) and dyshormonogenesis (n = 18). No difference was found in gestation, birth weight, age of starting L‐T4 and initial dose of L‐T4 in mcg/kg/day between groups. Confirmatory plasma total T4 at diagnosis was significantly lower for athyreosis when compared with ectopia and dyshormonogenesis. Median values for confirmatory TSH were significantly lower in dyshormonogenesis compared with the other two groups. At diagnosis, OFC were similar in all three groups. Children with athyreosis showed significantly larger OFCs compared with ectopia and dyshormonogenesis from 1 to 3 years. Length SD was within 1 SD of normal population standards at diagnosis and did not differ between the three groups throughout the 3 years. Spearman's correlation for OFC SD at 3 years of age showed a significant negative correlation with initial confirmatory plasma T4 (r = −0·35, P = 0·01). Multivariate analysis for OFC SD at 3 years of age showed confirmatory T4 as the only independent risk factor.

conclusion  Children with athyreosis showed significantly larger OFC from 1 to 3 years of age compared with ectopia and dyshormonogenesis, independent of linear growth. Our data shows that initial confirmatory T4 at diagnosis is an independent factor influencing head growth in the first 3 years of life.
Effects of Neurotensin on the Organization of Activity in Supraoptic Nucleus Cells in Virgin and Lactating Rats
Authors: Johnstone L. E. , Leng G. , Brown C. H.
Published: June 2004

Neurotensin increases the firing rate of supraoptic nucleus oxytocin and vasopressin neurones in vitro and induces Fos protein expression in the supraoptic nucleus in vivo. Here, we used extracellular single‐unit electrophysiological recording combined with local microdialysis administration of neurotensin (1 mM at 2 µl/min) to investigate the effects of locally applied neurotensin on the firing of oxytocin and vasopressin neurones in urethane‐anaesthetized virgin and lactating rats. Neurotensin decreased the mean firing rate of oxytocin cells in virgin, but not lactating, rats. In addition, neurotensin increased the index of dispersion (a measure of the variability of firing) in virgin, but not lactating, rats. By contrast to oxytocin cells, neurotensin increased the mean firing rate of vasopressin cells in both virgin and lactating rats, but did not alter the index of dispersion. The increase in firing of phasic vasopressin cells was achieved through an increase in intraburst frequency (rather than an increase in burst duration or decrease in interburst interval), which resulted from a reduction of the spike‐frequency adaptation that develops over the course of phasic bursts. Thus, neurotensin has differential effects on activity patterning in oxytocin and vasopressin cells and the effects on oxytocin cells, but not vasopressin cells, depend upon the physiological status of the animal. The increase in the variability of firing of oxytocin cells induced by neurotensin in virgin rats, but not in lactating rats, suggests that neurotensin (or other neurotransmitters/neuromodulators with similar actions) might establish conditions that predispose oxytocin cells to fire in milk‐ejection bursts in lactating rats.
Role of Leptin in Orexigenic Neuropeptide Expression During Lactation in Rats
Authors: Crowley W. R. , Ramoz G. , Torto R. , Kalra S. P.
Published: June 2004

The expression of neuropeptide Y (NPY) and agouti‐related peptide (AgRP), both of which are important neuropeptides involved in regulation of energy balance and hormone secretion, is up‐regulated in the arcuate nucleus during lactation in rodents. The present study tested whether reductions in circulating insulin and/or leptin that occur in lactation provide the critical signals to these systems. Lactating female rats received 3‐day infusions of either bovine insulin or recombinant rat leptin via Alzet Osmotic minipumps® implanted subcutaneously in regimens designed to restore serum concentrations of these hormones to the higher non‐lactating level. Compared to non‐lactating rats in diestrus, lactating rats displayed significantly lower serum concentrations of insulin and leptin, and significantly increased NPY peptide concentrations in the paraventricular nucleus (PVN) and median eminence, and AgRP mRNA in the arcuate nucleus. Infusion of leptin in lactating females significantly increased serum concentrations of leptin and significantly reduced NPY concentrations in the PVN and median eminence, and decreased NPY and AgRP mRNAs in the arcuate nucleus. The same effects were produced by infusion of insulin in lactating rats, which restored both insulin and leptin concentrations in serum. The levels of pro‐opiomelanocortin mRNA in the arcuate nucleus were not different in non‐lactating and lactating females, and were not altered by leptin or insulin treatment. These findings support the hypothesis that the reduction in circulating leptin during lactation contributes to increased expression of NPY and AgRP in hypothalamic systems involved in the behavioural and neuroendocrine adaptations to lactation.
A 5‐year follow‐up study on the prosthetic rehabilitation of the elderly in Helsinki, Finland
Authors: Nevalainen M. J. , Närhi T. O. , Ainamo A.
Published: June 2004

summary  In 1990, 364 elderly (76–86 years) inhabitants of Helsinki, Finland, attended a dental and oral examination study that was conducted as part of the Helsinki Aging Study. In spring 1996, these subjects were recalled for a 5‐year follow‐up. Between the baseline and follow‐up examinations, 114 (31%) subjects had deceased (86 women and 28 men), whereas 134 had either moved, were too ill, or refused to participate in the follow‐up. Follow‐up examination was conducted for 113 subjects (79 women and 34 men), with the participating rate being 46%. Five subjects became edentulous during the follow‐up. Of the subjects, 61% had 1–32 teeth at follow‐up. In these subjects, the mean number of teeth decreased from 14·9 (±8·3) to 13·5 (±8·6) (P < 0·0001). Prosthetic status changed in 40% of the elderly dentate people: 25% received new prostheses whereas 15% lost prostheses that were not replaced. New fixed partial dentures were made in five maxillae and in nine mandibles during the follow‐up. Acrylic removable partial dentures (ARPD) were most frequently used: 35% of dentate subjects had an ARPD. Subjects with removable prostheses had higher levels of salivary microbes and higher root caries incidence than those with natural teeth. Furthermore, the presence of removable prostheses at baseline, together with the male gender, was clearly associated with tooth loss during follow‐up. This study indicates that fixed rather than removable prostheses should be used in elderly patients. The need for a removable denture ought to be carefully considered.
The relationship between static and dynamic occlusion in 14–17‐year‐old school children
Authors: Al‐Hiyasat A. S. , Abu‐Alhaija E. S. J.
Published: June 2004

summary  This study investigated the relationship between static and dynamic occlusion in school children. A total of 447 subjects, within an age range of 14–17 years with no history of orthodontic treatment or trauma to the teeth were included in this study. Static occlusion was determined for both incisal and molar relationship. Dynamic occlusion was determined in lateral and protrusive movements of the mandible. The majority of the subjects had class I static occlusion for both incisor and molar relationship (45 and 54%, respectively). Canine‐guided occlusion was the dominant type of dynamic occlusion (57%) and most of the subjects had no posterior contact in protrusive movement (78%). There was an association between canine guidance with class II static occlusion. Statistically, a significant relationship was found between the dynamic and static occlusion of the incisor (P < 0·001) but not with the molar (P > 0·05).
Impact of Sjögren's syndrome on oral health‐related quality of life in southern Chinese
Authors: McMillan A. S. , Leung K. C. M. , Leung W. K. , Wong M. C. M. , Lau C. S. , Mok T. M. Y.
Published: June 2004

summary  The effect of oral symptoms of Sjögren's syndrome (SS) on health‐related quality of life is presently uncertain. This study aimed to investigate oral health‐related quality of life (OHRQOL) among southern Chinese people with SS. Twenty‐six primary SS cases, 25 secondary cases and 29 matched controls took part in this cross‐sectional study. Each participant completed a SF‐36 questionnaire, the Oral Health Impact Profile and a dry mouth measure, assisted by a trained interviewer. Data on socio‐demographic variables were also collected. The dry mouth measure revealed that people with primary and secondary SS had significant problems associated with subjective symptoms of dry mouth generally, and dry mouth when eating and speaking (P < 0·01). Sticky saliva and coughing were also problems in some primary SS cases. OHIP summary and sub‐scale scores did not reveal differences in negative impacts between groups. Mean SF‐36 sub‐scale scores were significantly different between groups (P < 0·05). In physical function, role‐physical and general health domains, primary and secondary SS sufferers had lower scores indicating poorer health. Oral symptoms of SS, notably xerostomia, had a negative effect on OHRQOL. Health‐related quality of life in general was also impaired in SS sufferers. The OHIP did not appear to discriminate oral problems of concern to SS sufferers.
Comparative strength of metal–ceramic and metal–composite bonds after extended thermocycling
Authors: Shimoe S. , Tanoue N. , Yanagida H. , Atsuta M. , Koizumi H. , Matsumura H.
Published: June 2004

summary  The relative strengths of ceramic‐to‐metal and composite‐to‐metal bonds were compared after prolonged thermocycling. A total of 104 cast discs were produced from a gold alloy (Pontor LFC). A ceramic material (Duceragold) was fused to 24 discs to assess the strength of the metal–ceramic bond. An indirect composite material (New Metacolor Infis) was bonded to the remaining discs after surface preparation by Rocatec tribochemical coating, tin plating and priming with a phosphate conditioner [10‐methacryloyloxydecyl dihydrogen phosphate (MDP), Cesead II], priming with a thione conditioner (V‐Primer) or no treatment (unprimed control). Shear bond strengths were determined before and after thermocycling at 20 000 and 100 000 cycles. Pre‐thermocycling bond strengths were ranked in the order: metal–ceramic (40·5 MPa); Rocatec treatment (33·1 MPa) and tin plating–MDP (31·0 MPa); V‐Primer (20·9 MPa); and control (11·9 MPa). The bond strengths of the first three groups were not significantly different after 20 000 thermocycles, whereas those of the V‐Primer and control groups were significantly reduced. After extended thermocycling (100 000 cycles) the metal–ceramic group had the highest mean shear bond strength (28·5 MPa; P < 0·05), followed by the Rocatec (23·9 MPa) and tin plating–MDP (22·1 MPa) groups. The metal–ceramic bond was the most durable, although its strength was reduced by 29·6% after extended thermocycling. On the basis of these results, we recommend the Rocatec and tin plating–MDP systems for composite‐to‐metal bonding. Metal–ceramic bonding, however, is superior to metal–composite bonding within the limitation of the current experiment.
Reduction of shrinkage on heat‐activated acrylic denture base resin obtaining gradual cooling after processing
Authors: Kobayashi N. , Komiyama O. , Kimoto S. , Kawara M.
Published: June 2004

summary  Heat‐activated acrylic denture base resin is widely used for its many good attributes, although it does show polymerization shrinkage. Although several processing methods have been developed for the purpose of minimizing polymerization shrinkage, some warpage after processing is inevitable. The purpose of this study was to examine the development of residual stress relaxation in resin denture base samples in the region where shrinkage was restricted, in order to clarify how cooling variations in the stone mould influenced the shrinkage. Flat, dumbbell‐shaped specimens were used. Thermocouples and strain gauges were embedded in the resin for measuring temperature and strain during the dough‐stage of resin packing. To clarify stress relaxation in the stone mould, specimens were removed from the stone mould by de‐flasking 4 h after the start of cooling at room temperature (control), and 12 and 24 h from the start of gradual cooling in a water bath. The strain differences between before and after removing from the stone mould for the control, and 12‐ and 24‐h experimental groups were 1793, 1354 and 1093 μɛ, respectively. Our results suggest that a gradual cooling course for 12 h or more after processing a heat‐activated acrylic denture base is effective for lessening deformation of the prosthesis.
Update on human cytomegalovirus in destructive periodontal disease
Authors: Slots J.
Published: June 2004

Aim:  Human cytomegalovirus (HCMV), a herpesvirus, is discussed in this review as it relates to destructive periodontal disease in humans.

Results:  HCMV genomic sequences, detected by polymerase chain reaction identification, occur with elevated frequency in severe adult periodontitis, localized and generalized aggressive (juvenile) periodontitis, Papillon–Lefèvre syndrome periodontitis, acute necrotizing ulcerative gingivitis, and periodontal abscesses.

Discussion:  Herpesviruses establish lifelong persistent infections. HCMV infection involves an asymptomatic latent phase interrupted by periods of recrudescence where viral replication and possibly clinical disease become manifest. HCMV reactivation is triggered by a number of immunosuppressive factors, some of which have been shown also to be risk factors/indicators of periodontitis. HCMV periodontal infection may cause release of tissue‐destructive cytokines, overgrowth of pathogenic periodontal bacteria, and initiation of cytotoxic or immunopathologic events.

Conclusions:  A growing body of data supports the concept that HCMV contributes to severe types of periodontal disease. HCMV infection of the periodontium may alter the immune control of resident microorganisms and be important in a multistage pathogenesis of periodontitis involving viral activation, periodontopathic bacteria, and host immune responses. Understanding the significance of HCMV and other herpesviruses in the development of periodontal disease may have important therapeutic implications. Vaccines against HCMV, which are in various stages of development, need to be evaluated for their ability to decrease the incidence of destructive periodontal disease.
Efficacy of ozone on survival and permeability of oral microorganisms
Authors: Nagayoshi M. , Fukuizumi T. , Kitamura C. , Yano J. , Terashita M. , Nishihara T.
Published: June 2004

In the present study, we examined the effect of ozonated water on oral microorganisms and dental plaque. Almost no microorganisms were detected after being treated with ozonated water (4 mg/l) for 10 s. To estimate the ozonated water‐treated Streptococcus mutans, bacterial cells were stained with LIVE/DEAD®BacLightTM Bacterial Viability Kit. Fluorescence microscopic analysis revealed that S. mutans cells were killed instantaneously in ozonated water. Some breakage of ozonated water‐treated S. mutans was found by electron microscopy. When the experimental dental plaque was exposed to ozonated water, the number of viable S. mutans remarkably decreased. Ozonated water strongly inhibited the accumulation of experimental dental plaque in vitro. After the dental plaque samples from human subjects were exposed to ozonated water in vitro, almost no viable bacterial cells were detected. These results suggest that ozonated water should be useful in reducing the infections caused by oral microorganisms in dental plaque.
Transcriptional analysis of mutacin I (mutA) gene expression in planktonic and biofilm cells of Streptococcus mutans using fluorescent protein and glucuronidase reporters
Authors: Kreth J. , Merritt J. , Bordador C. , Shi W. , Qi F.
Published: June 2004

Streptococcus mutans is implicated as the primary pathogen involved in the development of dental caries. The production of specific bacteriocins (called mutacins) by S. mutans is one of the major virulence factors which facilitate the dominance of the bacterium within dental plaque. While much has been revealed about the biochemical structures of mutacins, little is known about the expression and regulation of mutacin genes, largely due to the lack of proper methods to monitor mutacin gene expression, especially under biofilm conditions. In this study, a set of reporter systems with the green fluorescent protein (gfp), the monomeric red fluorescent protein (mrfp1), and the glucuronidase (gusA) are introduced to S. mutans to study the transcriptional activities of the mutacin I gene (mutA). Although the mutA‐reporter fusions are in single copy on the chromosome, these reporter systems display strong signals that allow us to effectively monitor mutA gene expression in S. mutans. Using these reporter systems, we show that mutA is expressed in both planktonic and biofilm cells, even though mutacin activities are normally detected only in biofilm cells. Furthermore, we confirm that mutR, the gene upstream of the mutacin operon, is required for mutacin I gene expression. The success of this study validates the feasibility of using these reporter systems to study gene expression and regulation in S. mutans.
Role of gene E2f1 in susceptibility to bacterial adherence of oral streptococci to tooth surfaces in mice
Authors: Matsumoto N. , Salam M. A. , Watanabe H. , Amagasa T. , Senpuku H.
Published: June 2004

Dental plaque is composed of a biofilm community of microorganisms on teeth that coats the oral cavity, including attaching to the teeth, and provides a protective reservoir for oral microbial pathogens, which are the primary cause of persistent and chronic infectious diseases. Oral streptococci are pioneering organisms that play an important role in biofilm formation on tooth surfaces as well as being primary causative agents of dental caries. The purpose of this study was to clarify the role of the E2f1 gene in susceptibility to dry mouth and bacterial adherence of oral streptococci to tooth surfaces in animal model experiments. A mutation of the E2f1 gene in mice is known to cause enhanced T‐lymphocyte proliferation, leading to testicular atrophy, splenomegaly, salivary gland dysplasia, and other systemic and organ‐specific autoimmunity. We found a decreased volume of saliva production and protein production rate, along with increased amylase activity, IgA concentration, and mucin 1 concentration in E2F‐1–/– mice as compared with the control C57BL/6 mice. Further, we quantified the recolonization of oral streptococci in E2F‐1–/– mice and found that a higher number of some oral streptococci were colonized on the teeth of these mice. In particular, following oral ingestion of 1% sucrose in water, the colonization of Streptococcus mutans increased in comparison with other streptococci. Our results suggest that the E2f1 gene may affect susceptibility for oral biofilm formation by streptococci in humans with dry mouth.
Serum thrombomodulin in systemic lupus erythematosus and juvenile idiopathic arthritis
Authors: El‐Gamal Yehia M. , Heshmat Nahla M. , El‐Kerdany Tahany H. , Fawzy Arwa F.
Published: June 2004

Thrombomodulin is a thrombin receptor on the vascular endothelial cell surface which is likely released upon endothelial cell damage. Serum soluble thrombomodulin (sTM) was assessed and investigated as a parameter of disease activity in children and adolescents with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA). Patients included in this study were regularly attending the Allergy and Immunology Clinic, Children's Hospital, Ain Shams University. They were 38 (76%) females and 12 (24%) males, their ages ranged between 5 and 18 years with a mean of 14.3 ± 4.84 years and median of 13 years. They were divided into two groups: SLE group which included 20 patients and JIA group which included 30 patients; and the control group which included 30 healthy age and sex‐matched individuals for comparison. Disease activity in SLE patients was evaluated by systemic lupus erythematosus disease activity index (SLEDAI) score, while in JIA patients disease activity was determined by number of joints with active arthritis, erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP). Serum levels of sTM were determined by enzyme‐linked immunosorbent (ELISA) assay. Serum levels of sTM were significantly higher in SLE and JIA patients in comparison with the control group; there was no significant difference between SLE and JIA patients. In SLE patients, a highly significant correlation was found between sTM and SLEDAI score (r = 0.99, p < 0.001). In JIA patients, a highly significant correlation was found between sTM and number of joints with active arthritis as well as ESR (r = 0.85, p < 0.001; r = 0.93, p < 0.001, respectively). Levels of sTM were significantly higher in CRP‐positive than CRP‐negative JIA patients. Serum sTM is a useful serologic marker of disease activity in SLE and JIA. It may prove to be a potential indicator for early and more aggressive treatment. Furthermore, sTM may prove to be an important marker for vasculitis in general.
Perennial rhinitis in the under 4s: A difficult problem to treat safely and effectively? A comparison of intranasal fluticasone propionate and ketotifen in the treatment of 2–4‐year‐old children with perennial rhinitis
Authors: Fokkens W. J. , Scadding G. K.
Published: June 2004

To compare the safety and efficacy of fluticasone propionate aqueous nasal spray (FPANS) and oral ketotifen in children aged 2–4 years with perennial rhinitis. A randomized, multicentre, double‐blind, double dummy, placebo‐controlled study. Paediatric patients between the ages of 2–4 years with perennial rhinitis. Rhinitis symptoms score (parent‐rated), clinical evaluation of symptoms (investigator‐rated) and adverse event profiles during the treatment period. Patients treated with FPANS had a significant reduction in both the total night‐time rhinitis symptom assessment for weeks 4–6 (p‐value 0.036), and the total daytime rhinitis symptom score over the same period (p‐value 0.049). Generally, except for nasal itching/rubbing over weeks 1–3, the patients taking FPANS had lower recorded symptom scores for all individual symptoms measured. Nasal blockage, in particular, was significantly reduced over the 4–6 week period (p‐value 0.027). The overall investigator‐rated clinical evaluation showed substantial improvement or improvement in nine of 12 of the children taking FPANS compared with four of 14 taking ketotifen. Finally, there were no reports of serious adverse events, the incidence of drug‐related adverse events was low and there was no statistical difference between the groups. FPANS may be an appropriate treatment to control the symptoms of rhinitis in children between 2 and 4 years old.
Low vitamin D status is associated with low cord blood levels of the immunosuppressive cytokine interleukin‐10
Authors: Zittermann Armin , Dembinski Jörg , Stehle Peter
Published: June 2004

The cytokine interleukin‐10 (IL‐10) plays a pivotal regulatory role in tolerizing exogenous antigens. Experimental data indicate that low cellular availability of the vitamin D hormone 1,25‐dihydroxyvitamin D [1,25(OH)2D] results in a down‐regulation of IL‐10 concentrations. The tissue production of an adequate amount of 1,25(OH)2D depends on a high circulating 25‐hydroxyvitamin D (25‐OHD) level. The present study was thus aimed at evaluating the associations between season of birth, vitamin D status, and the allergy risk markers IL‐10 and total immunoglobulin (IgE) in newborns. Cord blood was obtained from 49 infants born during the summer half year (mid‐April to mid‐October, geographic latitude 51°N) and from 47 infants born during the winter half year (mid‐October to mid‐April, geographic latitude of 51°N). Serum levels of 25‐OHD were 99% higher, and IL‐10 levels were 43% higher in the summer half year compared with the winter half year (p < 0.001 and p = 0.018). Moreover, the ratio of IL‐10 to total IgE was 124% higher in the summer half year compared with the winter half year (p = 0.039). Serum levels of 25‐OHD were correlated with IL‐10 levels (r = +0.22; p < 0.05). Mothers’ age, gestational ages, birth weights and serum 1,25(OH)2D levels did not differ between study groups. We conclude that the low vitamin D status of infants born in winter may at least in part adversely affect biomarkers of allergy risk.
Value of a shortened questionnaire in the description of asthma in 10–12‐year‐old pupils
Authors: Hublet Anne , Bacquer Dirk De , Vereecken Carine , Maes Lea
Published: June 2004

Asthma is a common and severe chronic disease in children influencing their quality of life and functioning at school. A 5‐item asthma‐screening instrument was developed and tested in 1052 children aged 10–12 years. Questionnaires were completed by parents and children separately and data were compared. Children reported less to be diagnosed by a medical doctor as having asthma compared with their parents, although children reported more to have certain asthma symptoms. No difference in prevalence of asthma was found between children and parents’ answers. The absolute agreement for the scale was 92% and a good kappa agreement was found. Recoding the ‘don't know’‐answers in ‘no’‐answers resulted in a 4% misclassification. The short 5‐item asthma screening tool can be valuable in the categorization of a subgroup of children likely to suffer from asthma in a survey. Recoding ‘don't know’‐answers to ‘no’‐answers is justified in large samples.
Natural history of atopic dermatitis and its relationship to serum total immunoglobulin E in a population‐based birth cohort study
Authors: Perkin Michael R. , Strachan David P. , Williams Hywel C. , Kennedy Cameron T. C. , Golding Jean ,   the ALSPAC Study Team
Published: June 2004

We investigated the natural history of atopic dermatitis (AD) in a population‐based birth cohort and assessed whether children at risk of visible eczema at 5 years of age can be identified from total immunoglobulin E (IgE) levels measured at 8, 12 and 18 months. AD data collected included a whole body examination for visible eczema at 49 months (4 years) and 61 months (5 years) of age and parent completed questionnaire data throughout their early lives. Children were divided into four groups based on their natural history of early AD: persistent (AD at 1, 6, 18, 30 and 42 months, n = 34), intermittent early onset (before 18  months of age, n = 495), intermittent late onset (18–42 months of age, n = 273) and unaffected (n = 429). Visible eczema at 5 years of age was present in 12.2% (117/957) (95% confidence interval [CI] 10.1–14.3%) of the children. Levels of total IgE at 8, 12 and 18 months of age were associated with early onset of AD, but not with AD of later onset. For all four natural history groups, the geometric mean total IgE at 12 months was higher in those who subsequently had visible eczema than those who did not. However, the degree of overlap was such that total IgE at 12 months of age was a poor predictor of eczema at age five. A cutoff point of 78 kU/l had the highest positive predictive value for visible eczema at 5 years of age of 28.6%, with a sensitivity of 12% and specificity of 95%.
Recurrent parotitis in selective IgA deficiency
Authors: Shkalim Vered , Monselise Yehudit , Mosseri Ronen , Finkelstein Yaron , Garty Ben Zion
Published: June 2004

Recurrent parotitis is an uncommon condition in children. In most cases the etiology is unknown, although the disease is occasionally associated with viral infections, autoimmune disorders and immunodeficiency. We describe, for the first time, a child with recurrent parotitis and isolated immunoglobulin A (IgA) deficiency, without autoimmune disease. As IgA is the main immunoglobulin secreted into the mucosal surfaces, including that of the respiratory and gastrointestinal tracts, and into the saliva, the lack of IgA may be involved in the pathogenesis of recurrent parotitis. We recommend that IgA and other immunoglobulins be tested in all cases of recurrent parotitis.
Breast milk substitutes in Hong Kong
Authors: Nelson EAS , Chan CW , Yu CM
Published: June 2004

Objective:  In 1981 the World Health Assembly (WHA) adopted the International Code of Marketing of Breast Milk Substitutes (the Code) to support breastfeeding. Despite improving trends, Hong Kong has low rates of breastfeeding compared to other developed countries.

Methods:  We surveyed companies marketing breast milk substitutes in Hong Kong to determine self‐reported adherence to the Code. Companies were informed that individual responses would not be published and seven of nine companies responded to the questionnaire.

Results:  The majority of respondents promoted infant and follow‐on formula in hospitals and provided free supplies of infant formula to hospitals. Follow‐on formula and weaning foods were promoted in shops and to the general public and free samples were given to mothers reflecting a belief that, despite WHA resolutions, follow‐on formula is not a breast milk substitute.

Conclusions:  Transnational companies should follow the Code and subsequent WHA resolutions equally in all countries.
Motor Performance Checklist for 5‐year‐olds: A tool for identifying children at risk of developmental co‐ordination disorder
Authors: Gwynne K , Blick B
Published: June 2004

Objective: The aim of this study was to further evaluate the ‘Motor Performance Checklist for 5‐year‐olds’, an instrument which had been piloted with some success and reported via this journal in 1996.

Method: Both validity and reliability in identifying children in most need of paediatric occupational therapy services was assessed. The Motor Performance Checklist was compared against a chosen ‘gold standard’ test, The Bruininks‐Oseretsky test of Motor Proficiency, in a group of 141 5‐year‐old children.

Results: Correlations of 0.72 and 0.85 were found between the tests. The checklist was found to have a sensitivity of 83% and a specificity of 98%. Positive predictive validity was found to be 72% and negative predictive validity 99%. Interrater reliability ranged between 0.79 and 0.99 and intrarater reliability was 0.77.

Conclusions: These results indicate that the Motor Performance Checklist has the potential to assist in identifying children in most need of referral to community occupational therapy services.
Comparison of selected reasons for hospitalization of children among children’s/tertiary hospitals, Australia, 1996−97 and 1997−98
Authors: Ford JB , Henry RL , Sullivan EA
Published: June 2004

Objectives:  To describe the major characteristics of admissions to children’s/tertiary hospitals (compared to other hospitals) and to compare characteristics of local and non‐local admissions to specialist children's hospitals.

Methods:  A cross‐sectional analysis of a routinely collected data set of hospitalizations in Australia in 1996−97 and 1997−98.

Results:  Hospital‐specific proportions of asthma and bronchitis, tonsillectomy and/or adenoidectomy and gastroenteritis varied considerably. Multivariate analysis comparing the characteristics of admitted patients by locality showed that non‐local admissions of patients with asthma and bronchitis and gastroenteritis to selected children's hospitals were significantly more likely to be Indigenous children and/or children who had been transferred from another hospital. Non‐local admissions of tonsillectomy and/or adenoidectomy patients to selected hospitals were significantly more likely to be public patients.

Conclusions:  Differences in the characteristics of admitted patients to children's hospitals by locality raise issues about equality of access and availability of appropriate services for these children and their families.
De novo interstitial duplication 4(q28.1q35) associated with choanal atresia
Authors: Lin S , Kirk EPE , McKenzie F , Francis C , Shalhoub C , Turner AM
Published: June 2004

Abstract:  We report a case of direct interstitial duplication of chromosome 4 from 4q28.1 to 4q35 associated with bilateral choanal atresia. The child also had dysmorphic features including a broad nasal bridge, telecanthus, downward slanting palpebral fissures, prominent ears, mild bilateral clinodactyly of the 5th fingers and bilateral hypoplasia of the 2nd−5th toenails. There was also a slightly dilated renal collecting system. At the age of 2.5 years, he had moderate global developmental delay, short, wide and tapering fingers, and short toes with hypoplastic toenails. To our knowledge, this is the second report of choanal atresia in a patient with trisomy 4q involving this region.
Epitope Structure of the
Bordetella pertussis
Protein P.69 Pertactin, a Major Vaccine Component and Protective Antigen
Authors: Hijnen Marcel , Mooi Frits R. , van Gageldonk Pieter G. M. , Hoogerhout Peter , King Audrey J. , Berbers Guy A. M.
Published: June 2004

Bordetella pertussis
is reemerging in several countries with a traditionally high vaccine uptake. An analysis of clinical isolates revealed antigenic divergence between vaccine strains and circulating strains with respect to P.69 pertactin. Polymorphisms in P.69 pertactin are mainly limited to regions comprised of amino acid repeats, designated region 1 and region 2. Region 1 flanks the RGD motif, which is involved in adherence. Although antibodies against P.69 pertactin are implicated in protective immunity, little is known about the structure and location of its epitopes. Here we describe the identification by pepscan analysis of the locations of mainly linear epitopes recognized by human sera and mouse monoclonal antibodies (MAbs). A total of 24 epitopes were identified, and of these only 2 were recognized by both MAbs and human antibodies in serum. A number of immunodominant epitopes were identified which were recognized by 78 to 93% of the human sera tested. Blocking experiments indicated the presence of high-avidity human antibodies against conformational epitopes. Human antibodies against linear epitopes had much lower avidities, as they were unable to block MAbs. Pepscan analyses revealed several MAbs which bound to both region 1 and region 2. The two regions are separated by 289 amino acids in the primary structure, and we discuss the possibility that they form a single conformational epitope. Thus, both repeat regions may serve to deflect the immune response targeted to the functional domain of P.69 pertactin. This may explain why the variation in P.69 pertactin is so effective, despite the fact that it is limited to only two small segments of the molecule.
Mycobacterium aviumsubsp.paratuberculosisFibronectin Attachment Protein Facilitates M-Cell Targeting and Invasion through a Fibronectin Bridge with Host Integrins
Authors: Secott T. E. , Lin T. L. , Wu C. C.
Published: June 2004

Efficient attachment and ingestion ofMycobacterium aviumsubsp.paratuberculosisby cultured epithelial cells requires the expression of a fibronectin (FN) attachment protein homologue (FAP-P) which mediates FN binding byM. aviumsubsp.paratuberculosis. Invasion of Peyer's patches byM. aviumsubsp.paratuberculosisoccurs through M cells, which, unlike other intestinal epithelial cells, express integrins on their luminal faces. We sought to determine if the interaction between FAP-P ofM. aviumsubsp.paratuberculosisand soluble FN enabled targeting and invasion of M cells byM. aviumsubsp.paratuberculosisin vivo via these surface integrins. Wild-type and antisense FAP-P mutantM. aviumsubsp.paratuberculosisstrains were injected alone or coinjected with blocking peptides or antibodies into murine gut loops, and immunofluorescence microscopy was performed to assess targeting and invasion of M cells byM. aviumsubsp.paratuberculosis. NonopsonizedM. aviumsubsp.paratuberculosispreferentially invaded M cells in murine gut loops. M-cell invasion was enhanced 2.6-fold whenM. aviumsubsp.paratuberculosiswas pretreated with FN. Invasion of M cells by the antisense FAP-P mutant ofM. aviumsubsp.paratuberculosiswas reduced by 77 to 90% relative to that observed for the control strains. Peptides corresponding to the RGD and synergy site integrin recognition regions of FN blockedM. aviumsubsp.paratuberculosisinvasion of M cells by 75 and 45%, respectively, whereas the connecting segment 1 peptide was noninhibitory. Antibodies against the α5, αV, β1, and β3 integrin subunits inhibited M-cell invasion by 52 to 73%. The results indicate that targeting and invasion of M cells byM. aviumsubsp.paratuberculosisin vivo is mediated primarily by the formation of an FN bridge formed between FAP-P ofM. aviumsubsp.paratuberculosisand integrins on M cells.
Zipper-Like Internalization of Dr-PositiveEscherichia coliby Epithelial Cells Is Preceded by an Adhesin-Induced Mobilization of Raft-Associated Molecules in the Initial Step of Adhesion
Authors: Kansau Imad , Berger Cédric , Hospital Maxime , Amsellem Raymonde , Nicolas Valérie , Servin Alain L. , Bernet-Camard Marie-Françoise
Published: June 2004

We undertook a study of the mechanism by which Dr-positive bacteria invade epithelial cells. Our findings show that Dr-positive bacteria enter via a zipper-like mechanism that is independent of the Dr-induced mobilization of F-actin and of the signaling molecules that control Dr-induced F-actin rearrangements. We also observed that Dr-positive IH11128 bacteria entered cells that were positive for the caveola marker VIP21/caveolin (HeLa and Caco-2/Cav-1 cells) to the same extent as those that were not (parental Caco-2 cells). Using fluorescence labeling and confocal laser scanning microscopy, we provide evidence that during the adhesion step, the α5β1 integrin, which plays a pivotal role in Afa/Dr diffusely adheringEscherichia colibacterial entry, is mobilized around adhering Dr-positive bacteria. We show that the receptor for Afa/Dr adhesins, glycosylphosphatidylinositol-anchored CD55; the raft marker, ganglioside GM1; and VIP21/caveolin are all recruited around adhering Dr-positive bacteria. We also observed that extracting membrane cholesterol with methyl-β-cyclodextrin (MBCD) did not affect the recruitment of CD55, GM1, or β1 integrin to adhering Dr-positive bacteria. In contrast, extracting or changing membrane-bound cholesterol by means of drugs that modify lipid rafts (MBCD, filipin III, or mevalonate plus lovastatin plus MBCD) inhibited the entry of Dr-positive IH11128 both into cells that expressed VIP21/caveolin (HeLa and Caco-2/Cav-1 cells) and into those that did not (parental Caco-2 cells). Finally, restoring cholesterol within the cell membrane of MBCD-treated cells restored Dr-positive IH11128 internalization.
Isolation of a Chromosomal Region ofKlebsiella pneumoniaeAssociated with Allantoin Metabolism and Liver Infection
Authors: Chou Huei-Chi , Lee Cha-Ze , Ma Li-Chen , Fang Chi-Tai , Chang Shan-Chwen , Wang Jin-Town
Published: June 2004

Klebsiella pneumoniaeliver abscess with metastatic complications is an emerging infectious disease in Taiwan. To identify genes associated with liver infection, we used a DNA microarray to compare the transcriptional profiles of three strains causing liver abscess and three strains not associated with liver infection. There were 13 clones that showed higher RNA expression levels in the three liver infection strains, and 3 of these 13 clones contained a region that was absent in MGH 78578. Sequencing of the clones revealed the replacement of 149 bp of MGH 78578 with a 21,745-bp fragment in a liver infection strain, NTUH-K2044. This 21,745-bp fragment contained 19 open reading frames, 14 of which were proven to be associated with allantoin metabolism. The K2044 (ΔallS) mutant showed a significant decrease of virulence in intragastric inoculation of BALB/c mice, and the prevalence of this chromosomal region was significantly higher in strains associated with liver abscess than in those that were not (19 or 32 versus 2 of 94;P= 0.0001 [χ2test]). Therefore, the 22-kb region may play a role inK. pneumoniaeliver infection and serve as a marker for rapid identification.
Oral Tolerance in T Cells Is Accompanied by Induction of Effector Function in Lymphoid Organs after Systemic Immunization
Authors: Parameswaran Neetha , Samuvel Devadoss John , Kumar Ramesh , Thatai Sangeeta , Bal Vineeta , Rath Satyajit , George Anna
Published: June 2004

The physiological ramifications of oral tolerance remain poorly understood. We report here that mice fed ovalbumin (OVA) exhibit oral tolerance to subsequent systemic immunization with OVA in adjuvant, and yet they clear systemic infection with a recombinant OVA-expressing strain ofSalmonella entericaserovar Typhimurium better than unfed mice do. Mice fed a sonicated extract ofS. entericaserovar Typhimurium are also protected against systemic bacterial challenge, and the protection is Th1 mediated, as feeding enhances clearance in interleukin-4-null (IL-4−/−) and IL-10−/−mice but not in gamma interferon-null (IFN-γ−/−) mice. When T-cell priming in vivo is tracked temporally in T-cell receptor-transgenic mice fed a single low dose of OVA, CD4 T-cell activation and expansion are restricted largely to mucosal lymphoid organs. However, T cells from spleens and peripheral lymph nodes of fed mice proliferate and secrete IFN-γ when restimulated with OVA in vitro, indicating the presence of primed T cells in systemic tissues following oral exposure to antigen. Nonetheless, oral tolerance can be observed in the fed mice as reduced recall responses following subsequent systemic immunization with OVA in adjuvant. Soluble OVA administered systemically has similar effects in vivo, and the “tolerance” seen in both cases can be partially reversed if the initial priming is made more immunogenic. Together, the results indicate that antigen exposure under poor adjuvantic conditions, whether oral or systemic, may lead to T-cell commitment to effector rather than proliferative capabilities, necessitating a reassessment of therapeutic modalities for induction of oral tolerance in allergic or autoimmune states.
Infection withToxoplasma gondiiReduces Established and Developing Th2 Responses Induced byNippostrongylus brasiliensisInfection
Authors: Liesenfeld Oliver , Dunay Ildiko R. , Erb Klaus J.
Published: June 2004

Oral infection of C57BL/6 mice with 100 cysts of the protozoan parasiteToxoplasma gondiiresults in the development of small intestinal Th1-type immunopathology. In contrast, infection with intestinal helminths results in the development of protective Th2-type responses. We investigated whether infection with the helminthNippostrongylus brasiliensisinfluences the development ofT. gondii-induced Th1 responses and immunopathology in C57BL/6 mice infected withT. gondii. Prior as well as simultaneous infection of mice withN. brasiliensisdid not alter the course of infection with 100 cysts ofT. gondii. Coinfected mice produced high levels of interleukin-12 (IL-12) and gamma interferon (IFN-γ), developed small intestinal immunopathology, and died at the same time as mice infected withT. gondii. Interestingly, local and systemicN. brasiliensis-induced Th2 responses, including IL-4 and IL-5 production by mesenteric lymph node and spleen cells and numbers of intestinal goblet cells and blood eosinophils, were markedly lower in coinfected than inN. brasiliensis-infected mice. Similar effects were seen when infection with 10T. gondiicysts was administered following infection withN. brasiliensis. Infection of C57BL/6 mice with 10T. gondiicysts prior to coinfection withN. brasiliensisinhibited the development of helminth-induced Th2 responses and was associated with higher and prolongedN. brasiliensisegg production. In contrast, oral administration ofToxoplasmalysate prior toN. brasiliensisinfection had only a minor and short-lived effect on Th2 responses. Thus,N. brasiliensis-induced Th2 responses fail to alterT. gondii-induced Th1 responses and immunopathology, most likely because Th1 responses develop unchanged in C57BL/6 mice with a prior or simultaneous infection withN. brasiliensis. Our findings contribute to the understanding of immune regulation in coinfected animals and may assist in the design of immunotherapies for human Th1 and Th2 disorders.