bluuebunny/crossref_metadata_2025 huggingface dataset:
Apical endocytosis in outer hair cells of the mammalian cochlea
Authors: Griesinger C. B. , Richards C. D. , Ashmore J. F.
Published: July 2004

Outer hair cells (OHCs), the sensory–motor cells of the mammalian cochlea, contain an endocytic tubulovesicular compartment below their apical stereocilia. We have used two‐photon imaging of FM1‐43 in the intact epithelium to show that these cells take up membrane in a Ca2+‐dependent manner from a distinct apical site. The uptake rate was 0.8 µm2/s and internalized membrane was trafficked rapidly to a compartment along the lateral wall and distinct intracellular compartments. Double labelling with FM1‐43 and DiOC6, an endoplasmic reticulum (ER) marker, showed that these compartments are part of the tubulovesicular endoplasmic reticulum of OHCs. Labelling with a lysosomal marker showed that OHC lysosomes are restricted to the apex. Using the protein marker wheat germ agglutinin (WGA‐FITC) we demonstrate that apical protein internalization and trafficking is about eight times slower than membrane internalization. Using double labelling with FM1‐43 and WGA‐FITC, we show that membrane and protein internalization are apically colocalized but that patterns of protein and membrane traffic differ. Protein was targeted only to the most apical third of the lateral wall. In control conditions, OHCs displayed only weak WGA‐FITC surface labelling at the site of endocytosis. Lowering the rate of apical endocytosis increased this surface signal. The results suggest that OHCs endocytose membrane and membrane proteins with a high turnover rate and that these cells may use apical endocytosis to sort proteins via an indirect pathway to the lateral membrane.
Brain hyperthermia induced by MDMA (‘ecstasy’): modulation by environmental conditions
Authors: Brown P. Leon , Kiyatkin Eugene A.
Published: July 2004

Drugs of abuse, such as 3,4‐methylenedioxymethamphetamine (MDMA), often have more powerful effects during states of increased activation and under specific environmental conditions. Because hyperthermia is a major complication of MDMA use and a factor potentiating neurotoxicity, we examined the effects of this drug (9 mg/kg, sc; approximately one‐fifth of the known LD50 in rats) on brain [nucleus accumbens (Nacc) and hippocampus (Hippo)] and muscle (musculus temporalis) temperatures in male rats under conditions that either model human drug use (social interaction with female, warm temperature) or restrict heat dissipation from the brain (chronic occlusion of jugular veins). Under quiet resting conditions at 23 °C, MDMA induced a moderate but prolonged hyperthermia. Both NAcc and Hippo showed more rapid and stronger temperature increases than muscle, suggesting metabolic neural activation as a primary cause of brain hyperthermia. During social interaction with a female, brain hyperthermia induced by MDMA was significantly potentiated (+89%). Brain hyperthermia induced by MDMA was also strongly potentiated (+188%) in animals with chronically occluded jugular veins, suggesting impaired cerebral outflow enhances intrabrain heat accumulation. At 29 °C, MDMA pushed temperatures in the brain to its biological limits (>41 °C; +268%), resulting in fatalities in most (83%) tested animals. Therefore, by inducing metabolic brain activation and restricting heat dissipation, MDMA use under ‘party’ conditions may be much more dangerous than under standard laboratory conditions.
Dendritic excitability and localization of GABA‐mediated inhibition in spider mechanoreceptor neurons
Authors: Gingl Ewald , French Andrew S. , Panek Izabela , Meisner Shannon , Torkkeli Päivi H.
Published: July 2004

GABAergic inhibition of mechanosensory afferent axon terminals is a widespread phenomenon in vertebrates and invertebrates. Spider mechanoreceptor neurons receive efferent innervation on their peripherally located axons, somata and sensory dendrites, and the dendrites have recently been shown to be excitable. Excitability of the spider sensory neurons is inhibited by muscimol and GABA, agonists of ionotropic GABA receptors. Here we asked where in the neurons this inhibition occurs. We found no evidence for inhibition of action potentials in the sensory dendrites, but axonal action potentials were rapidly suppressed by both agonists. Earlier work showed that metabotropic GABAB receptors are located on the dendrites and distal somata of the spider sensory neurons, where they modulate voltage‐activated conductances and may provide slower, prolonged inhibition. Therefore, GABA released from single peripheral efferents may activate both ionotropic and metabotropic receptor types, providing rapid suppression of axonal activity followed by slower inhibition that eventually prevents action potential initiation in the distal dendrites.
Synchronization of oxytocin neurons in suckled rats: possible role of bilateral innervation of hypothalamic supraoptic nuclei by single medullary neurons
Authors: Moos Françoise , Marganiec Arleta , Fontanaud Pierre , Guillou‐Duvoid Anne , Alonso Gérard
Published: July 2004

We have previously shown that oxytocin neurons located in the four hypothalamic magnocellular nuclei display synchronous bursts of action potentials before each milk ejection. The mechanisms involved in such a synchronization have, however, not yet been elucidated. In this study, we test the hypothesis of an extranuclear synchronization arising from a common extrahypothalamic input innervating bilateral magnocellular nuclei. First, two different retrograde tracers were injected into the right and left supraoptic nuclei of rats that were fixed 5–7 days later. Each tracer labelled numerous neurons in various brain regions ipsilateral or contralateral to the injection site, but colocalization of the two tracers within the same cell body could only be detected bilaterally in neurons in the ventromedial regions of the medulla oblongata. The axonal projections of these medullary neurons were then visualized by the unilateral microinjection of an anterograde tracer (BDA) within the ventromedial medulla oblongata. BDA‐labelled axons afferent to the hypothalamus were found to branch towards both supraoptic nuclei through medial portions of the optic chiasma. Finally, in anaesthetized lactating rats, surgical lesions were placed medially through the optic chiasma and the electrical activity of oxytocin neurons in bilateral supraoptic nuclei was pair‐recorded during suckling. The incidence of synchronous bursts in oxytocin neurons located within bilateral supraoptic nuclei were dramatically altered only when the medial portions of the optic chiasma were totally lesioned. Taken together, these data suggest that medullary neurons afferent to bilateral supraoptic nuclei are involved in the recruitment and synchronization of bursting in oxytocin neurons during suckling.
Abnormalities of presynaptic protein CDCrel‐1 in striatum of rats reared in social isolation: relevance to neural connectivity in schizophrenia
Authors: Barr Alasdair M. , Young Clint E. , Sawada Ken , Trimble William S. , Phillips Anthony G. , Honer William G.
Published: July 2004

Post‐weaning social isolation‐rearing of rats leads to behavioural and neurochemical sequelae that model aspects of schizophrenia, and it may be useful to test hypotheses related to putative molecular mechanisms of the illness. In humans, the presynaptic protein CDCrel‐1 represents an interesting candidate molecule for the mechanism and aetiology of schizophrenia. CDCrel‐1 modulates dopamine neurotransmission, binds to the SNARE protein syntaxin and maps onto a region of chromosome 22q11 deleted in velo‐cardio–facial and DiGeorge syndromes, which are associated with increased prevalence of schizophrenia. Using the isolation‐rearing model, we measured immunoreactivity of the synaptic proteins CDCrel‐1, synaptophysin and syntaxin. Male, Sprague–Dawley rats were raised in groups or in isolation for 12 weeks from weaning. Synaptic protein immunoreactivities were measured in striatal and hippocampal homogenates, using a sensitive enzyme‐linked immunoadsorbent assay with monoclonal antibodies. Isolation‐rearing produced region‐ and protein‐specific effects. CDCrel‐1 immunoreactivity was significantly lower in the striatum and marginally higher in the hippocampus of isolation‐reared compared with socially reared animals. There were no statistically significant differences in synaptophysin immunoreactivity in either region. Confocal microscopy demonstrated a high degree of colocalization between the two presynaptic proteins. In striatum, a robust relationship between CDCrel‐1 and syntaxin immunoreactivities was observed in socially reared rats, this was lost in the isolation‐reared animals. Altered levels of the septin CDCrel‐1 in isolation‐reared rats may contribute to changes in neuronal connectivity and neurotransmission, and suggest a potential role for CDCrel‐1 in schizophrenia related to chromosome 22q11 deletion syndrome.
Amygdala central nucleus function is necessary for learning but not expression of conditioned visual orienting
Authors: McDannald Michael , Kerfoot Erin , Gallagher Michela , Holland Peter C.
Published: July 2004

When exposed to pairings of a visual stimulus with food delivery, rats normally acquire both conditioned orienting responses directed toward the visual stimulus and conditioned food‐related responses. Consistent with the results of previous lesion studies, reversible inactivation of amygdala central nucleus function before each conditioning session prevented the acquisition of conditioned orienting responses, whereas food‐related behaviors were acquired normally. By contrast, neither inactivation nor neurotoxic lesions of central nucleus affected the expression of previously acquired conditioned orienting responses. Thus, the central nucleus is apparently not critical to the maintenance of information required for conditioned orienting, but instead is necessary for memory storage elsewhere. Specialized roles for components of a circuit for conditioned orienting, which includes the central nucleus, the substantia nigra, and dorsolateral striatum, are discussed.
Oral administration of desloratadine prior to sensitization prevents allergen‐induced airway inflammation and hyper‐reactivity in mice
Authors: Blümchen K. , Gerhold K. , Thorade I. , Seib C. , Wahn U. , Hamelmann E.
Published: July 2004

Background
Histamine‐1‐receptor (H1R)‐antagonists were shown to influence various immunological functions on different cell types and may thus be employed for immune‐modulating strategies for the prevention of primary immune responses.

Objective
The aim of this study was to investigate the effects of an H1R‐antagonist on allergen‐induced sensitization, airway inflammation (AI) and airway hyper‐reactivity (AHR) in a murine model.

Methods
BALB/c mice were systemically sensitized with ovalbumin (OVA) (six times, days 1–14) and challenged with aerosolized allergen (days 28–30). One day prior to the first and 2 h prior to every following sensitization, mice received either 1 or 0.01 μg of desloratadine (DL) or placebo per os.

Results
Sensitization with OVA significantly increased specific and total IgE and IgG1 serum levels, as well as in vitro IL‐5 and IL‐4 production by spleen and peribronchial lymph node (PBLN) cells. Sensitized and challenged mice showed a marked eosinophilic infiltration in broncho‐alveolar lavage fluids and lung tissues, and developed in vivo AHR to inhaled methacholine. Oral treatment with DL prior to OVA sensitization significantly decreased production of OVA‐specific IgG1, as well as in vitro Th2‐cytokine production by spleen and PBLN cells, compared with OVA‐sensitized mice. Moreover, eosinophilic inflammation and development of in vivo AHR were significantly reduced in DL‐treated mice, compared with sensitized controls.

Conclusion
Treatment with H1R‐anatagonist prior to and during sensitization suppressed allergen‐induced Th2 responses, as well as development of eosinophilic AI and AHR. This underscores an important immune modulating function of histamine, and implies a potential role of H1R‐anatagonists in preventive strategies against allergic diseases.
Kiwi fruit is a significant allergen and is associated with differing patterns of reactivity in children and adults
Authors: Lucas J. S. A. , Grimshaw K. E. C. , Collins K. , Warner J. O. , Hourihane J. O'B.
Published: July 2004

Background
Allergy to kiwi fruit appears increasingly common, but few studies have evaluated its clinical characteristics, or evaluated methods of investigating the allergy.

Objective
To characterize the clinical characteristics of kiwi fruit allergy and to study the role of double‐blind placebo‐controlled food challenge (DBPCFC), skin tests and specific IgE in the diagnosis of this food allergy.

Methods
Two‐hundred and seventy‐three subjects with a history suggestive of allergy to kiwi completed a questionnaire. Forty‐five were investigated by DBPCFC, prick‐to‐prick skin testing with fresh kiwi pulp, and specific IgE measurement. Nineteen subjects were also skin tested using a commercially available solution.

Results
The most frequently reported symptoms were localized to the oral mucosa (65%), but severe symptoms (wheeze, cyanosis or collapse) were reported by 18% of subjects. Young children were significantly more likely than adults to react on their first known exposure (P<0.001), and to report severe symptoms (P=0.008). Twenty‐four of 45 subjects (53%) had allergy confirmed by DBPCFC. Prick‐to‐prick skin test with fresh kiwi was positive in 93% of subjects who had allergy confirmed by DBPCFC, and also in 55% of subjects with a negative food challenge. The commercial extract was significantly less sensitive, but with fewer false‐positive reactions. CAP sIgE was only positive in 54% of subjects who had a positive challenge.

Conclusions
Kiwi fruit should be considered a significant food allergen, capable of causing severe reactions, particularly in young children. DBPCFC confirmed allergy to kiwi fruit in 53% of the subjects tested, who had a previous history suggestive of kiwi allergy. Skin testing with fresh fruit has good sensitivity (93%), but poor specificity (45%) in this population. CAP sIgE and a commercially available skin test solution were both much less sensitive (54%; 75%) but had better specificity (90%; 67%).
Asymptomatic atopy is associated with increased indoleamine 2,3‐dioxygenase activity and interleukin‐10 production during seasonal allergen exposure
Authors: Von Bubnoff D. , Fimmers R. , Bogdanow M. , Matz H. , Koch S. , Bieber T.
Published: July 2004

Background
Indoleamine 2,3‐dioxygenase (IDO) is a tryptophan (TRP)‐catabolizing enzyme with regulatory effects on T cells. T cell inhibition is achieved through both TRP depletion and TRP metabolite accumulation in specific local tissue microenvironments. The expression of IDO activity by different types of antigen‐presenting cells (APCs) has been shown to play a role in many instances of immunoregulation and tolerance induction. Induction of IDO after the engagement of the high‐affinity receptor for IgE, FcɛRI, on atopic monocytes has been suggested to regulate T cell responses in atopic disorders. Interleukin‐10 (IL‐10), a cytokine known for its down‐regulatory functions in the immune system, has recently been associated with the stable expression of IDO in mature tolerogenic dendritic cells.

Objective
This study was devised to understand the role of systemic IDO and IL‐10 in the prevention of clinical apparent allergy.

Methods
The concentration of TRP and the break‐down product kynurenine were measured by high‐performance liquid chromatography in‐ and off‐season in sera from patients with seasonal allergic rhinitis (n=12) and from clinically asymptomatic atopic patients sensitized to specific aeroallergens (n=12). Non‐atopic (NA) individuals (n=12) served as control. The concentration of plasma IL‐10 was determined in parallel from these donors by ELISA in‐ and off‐season.

Results
In clinically unresponsive but aeroallergen‐sensitized atopic individuals significantly higher systemic activity of IDO and increased plasma IL‐10 levels were found during allergen exposure but not off‐season compared to symptomatic atopic individuals with allergic rhinitis and NA individuals.

Conclusion
Enhanced systemic IDO activity as well as increased systemic levels of IL‐10 may contribute to the containment of allergic T cell responses and could be involved in the maintenance of a state of clinical unresponsiveness.
Interleukin‐5 receptors on human lung eosinophils after segmental allergen challenge
Authors: Julius P. , Hochheim D. , Böser K. , Schmidt S. , Myrtek D. , Bachert C. , Luttmann W. , Virchow J. C.
Published: July 2004

Background
IL‐5 is a specific cytokine for eosinophil accumulation, activation and prolongation of survival and can be recovered in elevated concentrations from the bronchoalveolar compartment in atopic asthma following allergen challenge.

Objective
The action of IL‐5 is mediated via the specific IL‐5 receptor‐α (IL‐5Rα). Although in vitro data suggest that IL‐5R expression is regulated by cytokines such as IL‐3, IL‐5 and GM‐CSF, IL‐5R regulation in vivo and its kinetics following allergen provocation are incompletely understood.

Methods
We investigated IL‐5R regulation in vivo following segmental allergen provocation (SAP) with an individually standardized dose of allergen in 12 patients with atopic asthma. Lavage was performed 10 min and 18 h (eight patients) and 10 min and 42 h (eight patients) after allergen challenge. In addition to differential cell counts, IL‐5Rα was measured by flow cytometry and IL‐5 concentrations in bronchoalveolar lavage (BAL) fluid were determined by ELISA.

Results
IL‐5Rα expression decreased significantly on peripheral blood and on BAL eosinophils 18 and 42 h after SAP. In contrast, IL‐5 concentrations increased significantly in BAL fluid 18 and 42 h after SAP. In four and two patients, respectively, there were detectable IL‐5 concentrations in serum 18 or 42 h after allergen exposure.

Conclusions
Although there was no correlation between IL‐5 concentrations and IL‐5Rα expression on eosinophils in BAL, our data support previous in vitro and in vivo findings of a negative feedback mechanism between IL‐5 concentrations and IL‐5Rα expression on eosinophils.
Nerve growth factor induces increased airway inflammation via a neuropeptide‐dependent mechanism in a transgenic animal model of allergic airway inflammation
Authors: Quarcoo D. , Schulte‐Herbrüggen O. , Lommatzsch M. , Schierhorn K. , Hoyle G.W. , Renz H. , Braun A.
Published: July 2004

Background
Nerve growth factor (NGF) exerts an important functional impact on the pathogenesis of allergic diseases. Data obtained in animal models of allergic bronchial asthma indicate that NGF alters sensory nerve function and promotes allergic inflammation, bronchial hyper‐reactivity, and airway obstruction.

Objective
To further delineate the effects of NGF on airway inflammation, we employed a transgenic (tg) animal model of allergic inflammation and asthma.

Methods
NGF‐tg mice, which overexpress NGF in Clara cells of the airways, were compared with wild‐type (wt) littermates regarding their ability to mount IgE‐related airway inflammatory responses. Mice were sensitized intraperitoneally to ovalbumin (OVA) and locally challenged via the airways according to established protocols.

Results
NGF‐tg mice displayed enhanced levels of OVA‐specific IgE antibody titres after repeated OVA aerosol exposure. In the airways, increased numbers of eosinophils were detected. These results were confirmed to be NGF specific, because similar results were obtained following local application of NGF into the airways of wt mice. The effect of NGF was partly mediated via neuropeptides, as treatment of OVA‐sensitized NGF‐tg mice with the dual neurokinin (NK) receptor NK‐1/NK‐2 antagonist partly prevented enhanced airway inflammation.

Conclusion
The present data indicate an important functional role of NGF in allergic airway inflammation and point to an involvement of tachykinins as mediators of NGF effects.
Antibiotic use in the first year of life and asthma in early childhood
Authors: Celedón J.C. , Fuhlbrigge A. , Rifas‐Shiman S. , Weiss S.T. , Finkelstein J.A.
Published: July 2004

Background
An association between antibiotic use in early life and asthma in childhood has been reported in five retrospective studies and one longitudinal study.

Objective
To examine the relation between the use of oral antibiotics in the first year of life and asthma in early childhood.

Methods
Longitudinal follow‐up of 4408 children enrolled in a health maintenance organization (HMO) from birth to the age of 5 years.

Results
After adjusting for sex and illnesses of the lower respiratory tract (LRIs), we found a significant association between antibiotic use in the first year of life and asthma between the ages of 1 and 2 years (odds ratio (OR) for 1–2 vs. no courses of antibiotics=1.9, 95% confidence interval (CI)=1.3–2.7; OR for 3–4 vs. no courses of antibiotics=1.6, 95% CI=1.1–2.4; OR for at least 5 vs. no courses of antibiotics=2.1, 95% CI=1.5–3.2). After adjustment for sex and LRIs in the first year of life, there was no significant association between antibiotic use in the first year of life and asthma that was initially diagnosed between the ages of 2 and 5 years and that persisted up to the age of 5 years (OR for 1–2 vs. no courses of antibiotics=1.1, 95% CI=0.8–1.4; OR for 3–4 vs. no courses of antibiotics=1.3, 95% CI=0.9–1.8; OR for at least 5 vs. no courses of antibiotics=1.0, 95% CI=0.7–1.4).

Conclusions
Our findings do not support the hypothesis that antibiotic use in early life is associated with the subsequent development of asthma in childhood but rather suggest that frequent antibiotic use in early life is more common among asthmatic children.
Assessment of histamine‐releasing activity of sera from patients with chronic urticaria showing positive autologous skin test on human basophils and mast cells
Authors: Asero R. , Lorini M. , Chong S. U. , Zuberbier T. , Tedeschi A.
Published: July 2004

Background
All previous studies agree that only a proportion of sera from patients with chronic urticaria (CU) positive on the autologous serum skin test (ASST) are able to induce histamine release in vitro. A non‐specific release of bradykinins during clotting of blood samples has been suggested; however, ASST seems rather specific and some data point to the existence of a mast cell‐specific histamine‐releasing factor.

Objective
To assess whether, and to what extent, the use of both human basophils and mast cells increases the sensitivity of in vitro histamine release assays (HRAs) in ASST‐positive patients with CU.

Methods
The histamine‐releasing activity of sera from 93 patients with CU selected on the basis of strong skin reactivity on ASST was assessed in vitro on basophils from 1 (n=86), 2 (n=31), or 3 (n=20) normal donors, and on mast cells from 1 (n=3), 2 (n=3), or 3 (n=87) normal donors.

Results
Sera from 88/93 (95%) patients induced significant histamine release from mast cells or basophils on at least one HRA. 76/93 (82%), 45/90 (50%), 22/80 (28%), and 6/12 (50%) sera were able to induce significant histamine release from cells of 2/5, 3/5, 4/5 and 5/5 donors, respectively.

Conclusion
Sera from nearly all ASST‐positive patients with CU are able to induce histamine release in vitro. However, the serum from each single patient seems to show its maximal activity on autologous mast cells in vivo, and functional in vitro tests show much variability and seem less sensitive than ASST in the detection of patients with histamine‐releasing factors in their blood.
Effect of anti‐immunoglobulin E on nasal inflammation in patients with seasonal allergic rhinoconjunctivitis
Authors: Bez C. , Schubert R. , Kopp M. , Ersfeld Y. , Rosewich M. , Kuehr J. , Kamin W. , Berg A. V. , Wahu U. , Zielen S.
Published: July 2004

Background
Binding of allergens to IgE on mast cells and basophils causes release of inflammatory mediators in nasal secretions.

Objective
The combined effect of specific immunotherapy (SIT) and omalizumab, a humanized monoclonal anti‐IgE antibody, on release of eosinophilic cationic protein (ECP), tryptase, IL‐6, and IL‐8 in nasal secretion was evaluated.

Methods
Two hundred and twenty five children (aged 6–17 years) with a history of seasonal allergic rhinoconjunctivitis induced by birch and grass pollen were randomized into four groups: either birch‐ or grass‐pollen SIT in combination with either anti‐IgE or placebo. Complete sets of nasal secretion samples before treatment Visit 1 (V1), during birch‐ (V2) and grass (V3)‐pollen season and after the pollen season (V4) were collected from 53 patients.

Results
A significant reduction in tryptase only was seen in the anti‐IgE‐treated group at V2 (P<0.05) and V4 (P<0.05) compared with the placebo group. During the pollen season, patients with placebo showed an increase of ECP compared with baseline (V2: +30.3 μg/L; V3: +134.2 μg/L, P< 0.005; V4: +79.0 μg/L, P< 0.05), and stable levels of tryptase, IL‐6 and IL‐8. Treatment with anti‐IgE resulted in stable ECP values and a significant decrease of tryptase compared with V1 (baseline): V2: −80.0 μg/L (P< 0.05); V3: −56.3 μg/L, which persisted after the pollen season with V4: −71.6 μg/L (P< 0.05). After the pollen season, a decrease of IL‐6 was observed in both groups (V4 placebo group: −37.5 ng/L; V4 anti‐IgE group: −42.9 ng/L, P< 0.01).

Conclusion
The combination of SIT and anti‐IgE is associated with prevention of nasal ECP increase and decreased tryptase levels in nasal secretions.
β2 adrenoceptor Arg16Gly polymorphism, airway responsiveness, lung function and asthma in infants and children
Authors: Turner S. W. , Khoo S.‐K. , Laing I. A. , Palmer L. J. , Gibson N. A. , Rye P. , Landau L. I. , Goldblatt J. , Le Souëf P. N.
Published: July 2004

Background
We have previously reported a relationship between increased airway responsiveness (AR) in infancy and reduced childhood lung function.

Objective
The current study aimed to determine whether the Arg16Gly polymorphism of the β2 adrenoceptor (β2AR) gene was important to this relationship.

Methods
A cohort that initially numbered 253 individuals underwent assessments of AR and lung function aged 1 month, 6 and 11 years; genotyping for polymorphisms of the β2AR was performed.

Results
At 1 month of age, the genotype homozygous Arg16 (n=24) was associated with a mean increase in log dose–response slope (AR) of 0.27 [95% confidence interval (CI) 0.07, 0.49] compared with the genotype homozygous Gly16 (n=58), P=0.01. At 11 years of age, the genotype homozygous Arg16 (n=35) was associated with a mean reduction in the percentage of forced expiratory volume in 1 s of 5.3% [95% CI 0.3, 10.2] compared with the genotype homozygous Gly16 (n=65), P=0.03. There was no association between the Arg16Gly polymorphism and atopy or diagnosed asthma. However, nine of 69 individuals with the genotype homozygous Gly16 were admitted to hospital with asthma compared with five out of 111 individuals with the remaining genotypes (P<0.05).

Conclusion
The Arg16Gly polymorphism may be important to the association between increased AR in infancy and reduced lung function in childhood and may also be a determinant of asthma severity in children but not asthma per se.
The remodelled tracheal basement membrane zone of infant rhesus monkeys after 6 months of recovery
Authors: Evans M. J. , Fanucchi M. V. , Baker G. L. , Van Winkle L. S. , Pantle L. M. , Nishio S. J. , Schelegle E. S. , Gershwin L. J. , Miller L. A. , Hyde D. M. , Plopper C. G.
Published: July 2004

Background
In previous studies, we showed that repeated exposure to (1) house dust mite allergen (HDMA) (Dermatophagoides farinae) caused thickening of the basement membrane zone (BMZ) and (2) HDMA+ozone (O3) caused depletion of BMZ perlecan and atypical development of BMZ collagen (irregular thin areas<2.0 μm in width).

Objective
The purpose of this study was to determine if these remodelling changes were reversible after 6 months of recovery.

Methods
Rhesus monkeys were exposed to a regimen of HDMA and or O3 or filtered air (FA) for 6 months. After the exposure protocol was completed FA and O3 groups were allowed to recover in FA for 6 months. The HDMA and HDMA+O3 exposure groups recovered in a modified environment. They were re‐exposed to HDMA aerosol for 2 h at monthly intervals during recovery in order to maintain sensitization for pulmonary function testing. To detect structural changes in the BMZ, collagen I and perlecan immunoreactivity were measured and compared to data from the previous papers.

Results
The remodelled HDMA group had a significantly thicker BMZ and after 6 months of recovery the width had not regressed. In the remodelled BMZ of the HDMA+O3 group, perlecan had returned to the BMZ after 6 months of the recovery protocol, and the thin, irregular, collagen BMZ had been resolved.

Conclusion
In summary, this study has shown that: (1) The width of the remodelled HDMA BMZ did not regress during a recovery protocol that included a sensitizing dose of HDMA. (2) The atypical collagen BMZ in the HDMA+O3 BMZ was resolved in the absence of O3. (3) Depletion of perlecan from the BMZ by O3 was reversed by recovery in the absence of O3.
Talon cusp associated with other dental anomalies: a case report
Authors: DASH J. K. , SAHOO P. K. , DAS S. N.
Published: July 2004

Talon cusp is an uncommon dental anomaly referring to an accessory cusp projecting from the cingulum area, or cemento‐enamel junction of maxillary or mandibular anterior teeth, in both the primary and permanent dentition. This paper reports a rare case of talon cusp affecting the mandibular right central incisor and maxillary right lateral incisor, together with other dental abnormalities, viz. an inverted impacted migrating mandibular right second premolar; complete agenesis of the maxillary and mandibular third molars, the maxillary right second permanent molar, and the mandibular left permanent central incisor; severe crowding; deep bite; hypoplastic teeth; bilateral reverse cross‐bite in the premolar region; and a retrognathic mandible. The presence of this number of dental anomalies in a single patient is rare.
Papillon–Lefèvre syndrome: a report of two cases
Authors: PATEL S. , DAVIDSON L. E.
Published: July 2004

Papillon–Lefèvre syndrome is a rare disease characterized by skin lesions caused by palmar‐plantar hyperkeratosis, and severe periodontal destruction involving both the primary and permanent dentitions. It is transmitted as an autosomal recessive condition and consanguinity of parents is evident in about one‐third of cases. This paper describes two preschool children who presented at the Paediatric Dentistry Department, Sheffield, UK, with progressively loosening teeth and discomfort during eating. The medical history revealed scaling on the hands and feet, which had been medically diagnosed as eczema. Papillon–Lefèvre syndrome was diagnosed in both cases.
Nevoid basal cell carcinoma syndrome: a review of the literature and a report of a case
Authors: BAKAEEN G. , RAJAB L. D. , SAWAIR F. A. , HAMDAN M. A. M. , DALLAL N. D.
Published: July 2004

The purpose of this paper is to report the development of multiple odontogenic keratocysts (OKCs) in a 15‐year‐old female with nevoid basal cell carcinoma syndrome (NBCCS) and review the literature pertinent to NBCCS. Although more than 100 abnormalities have been reported in NBCCS, the development of OKCs is one of its principle features. In view of this, the patient was subjected to further medical, dermatological and radiographic investigation. Multiple basal cell naevi and skeletal anomalies associated with NBCCS were found. Because of the autosomal dominant inheritance of this syndrome, the patient's family was then investigated. The patient's father was found to have multiple OKCs. The report highlights the need for vigilance in considering the diagnosis of NBCCS in all cases of OKCs, particularly those affecting young patients.
The modulating effect of culture on the expression of dental anxiety in children: a literature review
Authors: FOLAYAN M. O. , IDEHEN E. E. , OJO O. O.
Published: July 2004

The experience of anxiety is a universal human phenomenon. Studies have shown a world‐wide variation in the prevalence of dental anxiety with estimates ranging between 3% and 43%. The aetiology of dental anxiety is multifactorial, with factors acting in synergy to affect its expression. For children, age and gender play fundamental roles in its expression. However, these two factors are modulated by other variables such as culture which may influence the context in which anxiety is experienced, the interpretation of its meaning and responses to it. The modulating effect of culture in synergy with other variables may be one of the reasons why reports on dental anxiety have varied from region to region. This paper attempts to identify the interrelating roles of culture, age and gender, and how these relationships may affect variability in the expression and measurement of dental anxiety in children.
Microleakage assessment of pit and fissure sealant with and without the use of pumice prophylaxis
Authors: ANSARI G. , OLOOMI K. , ESLAMI B.
Published: July 2004

Objectives. This study evaluated the effect of pumice prophylaxis on the level of microleakage around and between the sealant and enamel.

Materials and methods. A total of 32 freshly extracted sound upper first premolars, assigned as suitable for sealant application, were chosen and divided randomly into two groups: (1) a test group, without prophylaxis; and (2) a control group, with prophylaxis. Sealant was applied to all teeth using the same conventional technique, with prophylaxis being omitted in the test group. The sealed teeth were thermocycled (120 × 30 s, 5 and 55 °C cycles) and then immersed in 2% Basic Fuchsin solution for 72 h. Each tooth was sectioned and examined for dye penetration under a stereomicroscope (× 60 magnification).

Results. No dye penetration was seen in 19 (29·6%) of the teeth in the test group and 36 (56·2%) of the teeth in the control group. Dye had penetrated to the base of the fissure in 31 (48·4%) of the teeth in the test group and 23 (35·9%) of the teeth in the control group. Using a chi‐square test for trend, the frequency of microleakage was significantly higher in the test group compared to the controls (P < 0·016).

Conclusion. Prophylaxis has a role in improving sealant retention. Removing this step may cause an increase in microleakage.
Special Care Dentistry: attitudes of Specialists in Paediatric Dentistry practising in the UK to the creation of a new specialty
Authors: HUNTER M. L. , HUNTER B. , THOMPSON S. A. , MCLAUGHLIN W. S.
Published: July 2004

Objectives. This study was designed to examine the attitudes of Specialists in Paediatric Dentistry (SPDs) practising in the UK towards the creation of a specialty of Special Care Dentistry (SCD).

Design. Data were collected by postal questionnaire.

Sample and methods. Two hundred and eleven dentists whose names were entered on the General Dental Council's Specialist List in Paediatric Dentistry, and who were resident and practising in the UK, were asked to complete a questionnaire consisting of both open and closed questions.

Results. Questionnaires were returned by 167 (79·2%) of the eligible SPDs. One hundred and sixty respondents (95·8%) expressed an opinion in relation to the creation of a specialty of SCD. One hundred and forty‐three respondents (85·6%) stated that they supported such a proposal. However, slightly fewer (n = 149) respondents were prepared to indicate what they considered to be the remit of the proposed specialty. Ninety‐two respondents (55·1%) considered that it should be restricted to the provision of specialist care for adults with ‘special needs’; the remaining 57 respondents felt that it should provide specialist care across the entire age spectrum.

Conclusions. Among SPDs, there is overwhelming support for the creation of a specialty of SCD, the majority view being that this should be dedicated to the provision of specialist care for adults with ‘special needs’.
Patterns of parental relatedness and pup survival in the grey seal (Halichoerus grypus)
Authors: BEAN K. , AMOS W. , POMEROY P. P. , TWISS S. D. , COULSON T. N. , BOYD I. L.
Published: July 2004

Levels of parental relatedness can affect offspring survival and susceptibility to disease. We investigated parental relatedness of live and deadHalichoerus grypuspups between and within island populations and between possible causes of mortality. Nine microsatellites were used to calculate internal relatedness (IR) and standardized meand2.We find that pups with higher than average levels of IR have significantly lower survival and that this varied between island populations and that certain loci contributed to the effect more than others. Although, there were no significant differences between causes of mortality, peritonitis, infection and stillborn had the highest levels of IR. These results provide evidence that parental relatedness is an important determinant of pre‐weaning pup survival in the grey seal and that this may vary with cause of mortality given a larger sample size.
Spatial genetic structure in two congeneric epiphytes with different dispersal strategies analysed by three different methods
Authors: SNÄLL T. , FOGELQVIST J. , RIBEIRO P. J. , LASCOUX M.
Published: July 2004

Three different approaches were used to assess the kinship structure of two epiphytic bryophytes, Orthotrichum speciosum and O. obtusifolium, that have different dispersal strategies. The two species were sampled in a 200 ha landscape where species occurrence and host trees had been mapped previously. Local environmental conditions at sampled trees were recorded and kinship between individuals was calculated based on amplified fragment length polymorphism (AFLP)‐marker data. We did not detect any association between AFLP‐markers and investigated environmental conditions. In both species, significant kinship coefficients were found between individuals up to 300–350 m apart which shows that both species have a restricted dispersal range. The spatial kinship structure was detected with both autocorrelation analysis and generalized additive models (GAMs), but linear regression failed to detect any structure in O. speciosum. Although the dioecious O. obtusifolium is currently the more common species it may, none the less, due to its restricted dispersal range and reproduction mode, become threatened in the future by current silvicultural practices which enhance the distance between host trees and decrease their life span. Finally, GAMs seem most appropriate for analysing spatial genetic structure because the effects of local environmental conditions and spatial structure can be analysed simultaneously, no assumption of a parametric form between kinship coefficient and distance is required, and spatial data resolution is not lost in the arbitrary choice of distance classes characterizing autocorrelation analysis.
Population genetics after fragmentation: the case of the endangered Spanish imperial eagle (Aquila adalberti)
Authors: MARTÍNEZ‐CRUZ B. , GODOY J. A. , NEGRO J. J.
Published: July 2004

The highly endangered Spanish imperial eagle,Aquila adalberti, has suffered from both population decline and fragmentation during the last century. Here we describe the current genetic status of the population using an extensive sampling of its current distribution range and both mitochondrial control region sequences and nuclear microsatellite markers. Results were evaluated in comparison to those obtained for the Eastern imperial eagle,Aquila heliaca, its nearest extant relative. Mitochondrial haplotype diversity was lower in the Spanish than in the Eastern species whereas microsatellite allelic richness and expected heterozygosity did not differ. Both allelic richness and expected heterozygosity were lower in the small Parque Nacional de Doñana breeding nucleus compared to the remaining nuclei. A signal for a recent genetic bottleneck was not detected in the current Spanish imperial eagle population. We obtained low but significant pairwiseFSTvalues that were congruent with a model of isolation by distance.FSTand exact tests showed differentiation among the peripheral and small Parque Nacional de Doñana population and the remaining breeding subgroups. The centrally located Montes de Toledo population did not differ from the surrounding Centro, Extremadura and Sierra Morena populations whereas the latter were significantly differentiated. On the other hand, a Bayesian approach identified two groups, Parque Nacional de Doñana and the rest of breeding nuclei. Recent migration rates into and from Parque Nacional de Doñana and the rest of breeding nuclei were detected by assignment methods and estimated as 2.4 and 5.7 individuals per generation, respectively, by a Bayesian approach. We discuss how management strategies should aim at the maintenance of current genetic variability levels and the avoidance of inbreeding depression through the connection of the different nuclei.
Red to Mediterranean Sea bioinvasion: natural drift through the Suez Canal, or anthropogenic transport?
Authors: SHEFER SIGAL , ABELSON AVIGDOR , MOKADY OFER , GEFFEN ELI
Published: July 2004

The biota of the eastern basin of the Mediterranean Sea has experienced dramatic changes in the last decades, in part as a result of the massive invasion of Red Sea species. The mechanism generally hypothesized for the ‘Red‐to‐Med’ invasion is that of natural dispersal through the Suez Canal. To date, however, this hypothesis has not been tested. This study examines the mode of invasion, using as a model the mussel Brachidontes pharaonis, an acclaimed ‘Lessepsian migrant’ that thrives along the eastern Mediterranean coast. Our findings reveal two distinct lineages of haplotypes, and five possible explanations are discussed for this observation. We show that the genetic exchange among the Mediterranean, Gulf of Suez and the northern Red Sea is sufficiently large to counteract the build up of sequential genetic structure. Nevertheless, these basins are rich in unique haplotypes of unknown origin. We propose that it is historic secondary contact, an ongoing anthropogenic transport or both processes, that participate in driving the population dynamics of B. pharaonis in the Mediterranean and northern Red Sea.
Living with uncertainty: genetic imprints of climate shifts in East Pacific anchovy (Engraulis mordax) and sardine (Sardinops sagax)
Authors: LECOMTE F. , GRANT W. S. , DODSON J. J. , RODRÍGUEZ‐SÁNCHEZ R. , BOWEN B. W.
Published: July 2004

In the upwelling zone of the northeastern Pacific, cold nutrient‐rich conditions alternate with warm nutrient‐poor intervals on timescales ranging from months to millennia. In this setting, the abundances of Pacific sardine (Sardinops sagax) and northern anchovy (Engraulis mordax) fluctuate by several orders of magnitude, with sardine dominating during warm conditions and anchovy dominating during cool conditions. Two population models can explain the response of these fishes to adverse conditions. Under the basin model, species distributions contract to a central (optimal) range during population crashes. Expectations of this model may include a single range‐wide population with a decline in genetic diversity on both sides of a central refuge. In contrast, the self‐recruitment model invokes a series of local oceanographic domains that maintain semi‐isolated subpopulations. During adverse conditions, some subpopulations cannot complete the life cycle within the local environment and are extirpated. Expectations of this model include some degree of population genetic structure and no clear gradient in genetic diversity. We examined mitochondrial DNA cytochrome bsequences to assess these competing models for anchovy (N = 196; 539 bp) and sardine (N = 107; 425 bp). The mitochondrial DNA gene genealogies are shallow but diverse for both species. Haplotype frequencies are homogeneous among subpopulations, but genetic diversities peak for both species along Baja California and adjacent southern California. Mismatch distributions and Tajima'sD‐values reveal distinctive signatures of population bottlenecks and expansions. Sardine haplotypes coalesce at ~241 000 yearsbp, with an initial female effective population sizeNf0 = 0 followed by exponential growth toNf1 = 115 million. Anchovy haplotypes coalesce at ~282 000 yearsbp, with an initial population size ofNf0 = 14 000, followed by exponential growth toNf1 = 2.3 million. These results indicate a founder event for sardine and a severe population decline for anchovy in the California Current during the late Pleistocene. Overall, these data support the basin model on decadal timescales, although local recruitment may dominate on shorter timescales.
Identity and diversity of coral endosymbionts (zooxanthellae) from three Palauan reefs with contrasting bleaching, temperature and shading histories
Authors: FABRICIUS K. E. , MIEOG J. C. , COLIN P. L. , IDIP D. , H. VAN OPPEN M. J.
Published: July 2004

The potential of corals to associate with more temperature‐tolerant strains of algae (zooxanthellae, Symbiodinium) can have important implications for the future of coral reefs in an era of global climate change. In this study, the genetic identity and diversity of zooxanthellae was investigated at three reefs with contrasting histories of bleaching mortality, water temperature and shading, in the Republic of Palau (Micronesia). Single‐stranded conformation polymorphism and sequence analysis of the ribosomal DNA internal transcribed spacer (ITS)1 region was used for genotyping. A chronically warm but partly shaded coral reef in a marine lake that is hydrographically well connected to the surrounding waters harboured only two single‐stranded conformation polymorphism profiles (i.e. zooxanthella communities). It consisted only of Symbiodinium D in all 13 nonporitid species and two Porites species investigated, with the remaining five Porites harbouring C•. Despite the high temperature in this lake (> 0.5° above ambient), this reef did not suffer coral mortality during the (1998) bleaching event, however, no bleaching‐sensitive coral families and genera occur in the coral community. This setting contrasts strongly with two other reefs with generally lower temperatures, in which 10 and 12 zooxanthella communities with moderate to low proportions of clade D zooxanthellae were found. The data indicate that whole coral assemblages, when growing in elevated seawater temperatures and at reduced irradiance, can be composed of colonies associated with the more thermo‐tolerant clade D zooxanthellae. Future increases in seawater temperature might, therefore, result in an increasing prevalence of Symbiodinium phylotype D in scleractinian corals, possibly associated with a loss of diversity in both zooxanthellae and corals.