CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation of Rap1.

CD98 is a multifunctional heterodimeric membrane protein involved in the regulation of cell adhesion as well as amino acid transport. We show that CD98 cross-linking persistently activates Rap1 GTPase in a LFA-1-dependent manner and induces LFA-1/ICAM-1-mediated cell adhesion in lymphocytes. Specific phosphatidylinositol-3-kinase (PI3K) inhibitors suppressed both LFA-1 activation and Rap1GTP generation, and abrogation of Rap1GTP by retroviral over-expression of a specific Rap1 GTPase activating protein, SPA-1, totally inhibited the LFA-1/ICAM-1-mediated cell adhesion. These results suggest that CD98 cross-linking activates LFA-1 via the PI3K signaling pathway and induces accumulation of Rap1GTP in a LFA-1-dependent manner, which in turn mediates the cytoskeleton-dependent cell adhesion process.

Distinct aggregation of beta- and gamma-chains of the high-affinity IgE receptor on cross-linking.

The high-affinity IgE receptor (FcepsilonRI) on mast cells and basophils consists of a ligand-binding alpha-chain and two kinds of signaling chains, a beta-chain and disulfide-linked homodimeric gamma-chains. Crosslinking by multivalent antigen results in the aggregation of the bound IgE/alpha-chain complexes at the cell surface, triggering cell activation, and subsequent internalization through coated pits. However, the precise topographical alterations of the signaling beta- and gamma-chains during stimulation remain unclarified despite their importance in ligand binding/signaling coupling. Here we describe the dynamics of FcepsilonRI subunit distribution in rat basophilic leukemia cells during stimulation as revealed by immunofluorescence and immunogold electron microscopy. Immunolocalization of beta- and gamma-chains was homogeneously distributed on the cell surfaces before stimulation, while crosslinking with multivalent antigen, which elicited optimal degranulation, caused a distinct aggregation of these signaling chains on the cell membrane. Moreover, only gamma- but not beta-chains were aggregated during the stimulation that evoked suboptimal secretion. These findings suggest that high-affinity IgE receptor beta- and gamma-chains do not co-aggregate but for the most part form homogenous aggregates of beta-chains or gamma-chains after crosslinking.

[Recent pollen sensitization and its possible involvement in allergic diseases among children in a pediatric allergy clinic].

We studied the rate of sensitization to several pollen allergens as well as to house dust mites in 226 children visiting our pediatric allergy clinic during the past 3 years (from April 1996 to March 1999). The allergens studied were Sugi (Japanese cedar pollen, Cryptomeria japonica), Kamogaya (Dactylis gromerata), Butakusa (ragweed, Ambrosia artemisiifolia), and Der f (house dust mite, Dermatophagoides farinae). The presence of nasal symptoms (either seasonal and perenial) was checked in 97 children visiting the clinic in March 1999. Overall average sensitization rates were 82.3% for Der f, 53.1% for Sugi, 38.5% for Kamogaya, and 17.1% for Butakusa. Among children aged 12 or more, sensitization rates for Sugi and Kamogaya were much higher (68.8%, 56.3%, respectively). Those who had seasonal nasal symptoms showed significantly higher rates of sensitization to the pollens. However, more than half of patients without nasal symptoms, 62.8% of whom had only atopic dermatitis (AD), also showed sensitization to the pollens. Several possible factors accounting for pollen sensitization in children with only AD and no sasal symptoms, such as existence of occult allergic rhinitis, future onset of allergic rhinitis, or pollen as directly aggravating factor of AD, need to be evaluated by careful follow-up of these cases.

[Re-evaluation of multi-allergen skin prick test for infants with atopic dermatitis--clinical relevance and evaluation by mothers].

We performed skin-prick tests (SPT) for 8 food and inhalant allergens on 55 infants (between 3 months and 2 years of age) with atopic dermatitis (AD) at their initial visit to our allergy clinic. SPT results were compared with those of radioallergosorbent tests (RAST) and the severity of AD symptoms. We also administered a questionnaire-based survey of 46 patients mothers to see how they evaluated SPT compared to blood tests. SPT for egg white had the highest positive rate (91%) and far exceeded that for other allergens. More than two allergens showed positive in more than half of the patients, and about 30% of them showed positive reactions to more than three allergens. Concordance rate between SPT and RAST was 78.6%. Patients showing positive reactions to multi-allergens tended to have more severe AD symptoms. Mothers appreciated the SPT test and felt that quick results for multi-allergens was the greatest advantage of SPT. More than 90% of the mothers wanted the allergic status of their next children to be evaluated with SPT. Especially, more than 30% of the mothers preferred SPT than RAST as initial screening test. As SPT is harmless, easy to administer even in infancy, and has different advantages for those of RAST, this method deserves further re-evaluation as a means of identifying allergic status especially among infants.

Soft laser irradiation effects on pain reduction in orthodontic treatment.

The effects of soft laser (low reactive level laser) on reduction of pain while undergoing orthodontic treatment was examined in this study. These patients were randomly separated into 3 groups: non-treated control group (CG), blind irradiation group (BG), and laser irradiated group (LG). The effect of laser irradiation on reduction in pain was analyzed by a questionnaire given to patients who had been wired with an edgewise appliance of a multi-bracket system for orthodontic therapy. Just after application of the initial wire, LG patients were irradiated with the soft laser from the labial and lingual sites for a total of one minute. Reduction in pain was found in some patients who had been irradiated. In particularly, delay in the pain appearance was noted as compared to the other two control groups.

An electromyogram study on mandibular movement in unilateral cleft lip and palate patients before and after orthodontic treatment.

The purpose of this study is to investigate masticatory muscle function in subjects with unilateral cleft lip and palate compared with normal occlusion and the extents of improvement before and after orthodontic treatment. Subjects were twenty pretreatment patients, thirty posttreatment patients and ten controls. Electromyograms were recorded from their masticatory muscles during masticatory movement and tapping movement. Reduction of duration/stroke ratio (D/S) was observed in electromyograms obtained during masticatory movement after orthodontic treatment. The reduction was especially notable in the masseter muscle. In spite of a significant reduction in coefficient of variation (CV) values, a significant difference between the posttreatment group and the control group indicated some persisting irregularity in masticatory movement. Electromyograms taken during tapping movement showed no change in latency in the posttreatment group, but duration of the silent period (SP) was shortened and SP appearance increased. The findings outlined above reveal electromyographically clear improvements in masticatory muscle functions and jaw reflex mechanisms after orthodontic treatment. Nevertheless, parameters for subjects with cleft lip and palate still differed from those for controls with normal occlusion. The influence of plastic surgery in subjects with the defects discussed here causes maxillary retrusion, which in turn results in skeletal malocclusion. Orthodontic treatment should be designed to compensate this dentally and alveolarly. This design and the need to improve masticatory functions would contribute to eliminate the extreme difficulty of the therapeutic process.

Soft laser irradiation induced pain reduction in orthodontic treatment.

It has been emphasized that pain reduction without analgesic drugs is necessary in orthodontic treatment. Especially, needed is reduction after the initial wire application. Soft laser irradiation has been applied in dental clinics, and we reported its effectiveness in pain reduction in orthodontic treatment. In this study, we evaluated the continuous effects of the laser irradiation by questionnaire and pulp sensitization measured by pulp electrodiagnosis. The laser irradiation time required for pain reduction was also examined. We confirmed that soft laser irradiation produced an effective pain reduction in orthodontic treatment.

Effect of weak electric current on reducing oral bacteria in vitro.

The ions generated by weak electric current may be used for removal of dental plaque. Also, it has been judged from changes in the viable bacterial cell count and the amount of adenosine triphosphate (ATP) in the saliva that the passage of such a current also has a bactericidal effect on the oral microflora. We confirmed in vitro that 0.5 and 1.0 mA currents that passed for 10 min through phosphate buffered saline containing salivary bacteria were effective in killing the bacteria.

The Nd-YAG laser is useful in prevention of dental caries during orthodontic treatment.

Plaque control during the course of orthodontic treatment is not an easy task, and dental caries are not an unlikely complication. We examined the possibility of controlling dental caries with Nd-YAG laser irradiation in orthodontic patients. As a preliminary experiment, we used the Nd-YAG laser to irradiate an extracted tooth and then left it to soak in lactic acid. The decay of the tooth was evaluated with a scanning electron microscope (SEM); tooth decay was inhibited by the action of the laser. Twenty patients undergoing orthodontic treatment for early decalcification of the teeth (white spot lesions) were selected, and photographs were taken of their oral cavities. White spot lesions on the four incisors and two canines of the maxilla were traced on tracing paper, and their areas were calculated by computer. Ten of the patients received laser treatment and acidulated phosphate fluoride solution (APF); the other ten acted as the control group. Between 11 and 12 months later, we photographed the oral cavity as we had previously; the white spot lesions were again traced and their areas calculated. The changes in the areas of the white spots of the laser-irradiated and control groups showed the following increases: laser-irradiated group, 1.41 times; controls, 2.87 times. The difference was statistically significant. These results demonstrate that Nd-YAG laser irradiation with application of APF acts as an effective method of caries control during orthodontic treatment.

A lip seal study of Japanese children with malocclusion.

The purpose of this study was to clarify the relationship between lip seal and malocclusion in Japanese children. Fifty-three patients aged 7 to 14 years (mean 10.24 +/- 1.93) were selected randomly, and compared with 20 subjects with normal occlusion aged 7 to 14 years (mean 10.50 +/- 2.56). The subjects were divided into a good lip seal group and poor lip seal group by observing the distance between the upper and lower lip at rest. The variables that were analyzed for morphological evaluation included model analysis and cephalometric analysis. Noted for functional evaluation were tongue position, the size of the tonsils and adenoids and the oral muscle force measured by button pulling. In the evaluation of the degree of lip seal, there was no statistical difference between subjects with malocclusion and those with normal occlusion. Within the group with malocclusions, however, there were significant differences in overbite (p < 0.01), overjet (p < 0.01), and oral muscle force by button pulling (p < 0.05) between the good lip seal and poor lip seal groups. These results suggest that there is a need not only to correct malocclusion but also to be aware of lip sealing so that it may be improved in Japanese children.

Comparison of skin prick test with serially diluted wild-type and genetically engineered recombinant Der f2.

BACKGROUND: C8/119S, a genetically engineered less allergenic mutant of group II allergen (Der f2) of house dust mite, Dermatophagoidesfarinae, was constructed in order to reduce the risk of anaphylactic reactions of allergen specific immunotherapy. OBJECTIVE: To further evaluate, with a larger number of mite-allergic patients, the safety of C8/119S for the treatments of humans. METHOD: We tested the dose-dependent responses of 20 mite-allergic volunteers to a skin prick test with C8/119S and wild-type recombinant Der f2 and compared the biologic potentials of these allergens to induce type I allergic reactions. In a separate experiment, we compared IgE binding capacities to C8/119S and to wild-type recombinant Der f2 in individual sera from 34 mite-allergic donors. RESULTS: The concentration of C8/119S needed to induce positive skin prick test (SPT) reaction was at least 100 times more than that of recombinant Der f2 in 95% of the volunteers tested. Consistent with this result, IgE binding data showed that 85% of the mite-allergic donors had little or no detectable IgE bound to C8/119S. Our data also shows that a minority of mite-allergic patients responded in a similar manner to both C8/119S and wild-type recombinant Der f2. CONCLUSION: Our data confirms that C8/119S is much less allergenic and thus can be used safely for immunotherapy of most of mite-allergic patients. Care should still be taken because, in a minority of patients, C8/119S may cause similar type I allergic reactions as does wild-type recombinant Der f2.

Month of birth and prevalence of atopic dermatitis in schoolchildren: dry skin in early infancy as a possible etiologic factor.

BACKGROUND: Month of birth has been shown to affect later development of allergic diseases. OBJECTIVE: We sought to evaluate the relationship between month of birth and the prevalence of atopic dermatitis (AD) in a large-scale general population of schoolchildren and to elucidate the possible mechanism for this relationship. METHODS: Questionnaire data on the prevalence of allergic diseases were obtained for 33,725 schoolchildren aged 7 to 15 years. In a separate study the water-holding capacity of "uninvolved" skin was compared for children with and without AD. RESULTS: We found striking differences in the prevalence of AD according to the month of birth (chi2 = 34.9, P <.0001). Overall, those born in autumn showed the highest (7.5%), and those born in spring showed the lowest (5.5%), prevalence of AD. There was little or no such tendency for the prevalence of bronchial asthma (chi2 = 17.2, P =.103) and allergic rhinitis (chi2 = 24, P =.01). We found no statistical variation across birth month in the ratio of AD with no other allergic disease/total AD, indicating that this deviation was observed whatever the allergic predisposition of the subjects. In a separate study a significantly lower water-holding capacity of uninvolved skin was observed in children with AD even from early infancy. CONCLUSION: These findings lead us to speculate that the climate in early infancy affects the skin condition and that those born in autumn have dry skin in early infancy, which may ultimately result in a higher prevalence of AD among young schoolchildren. This might be at least one of the "nonallergic" etiologic factors of this complex disease.

Relationships between atopy and lung function: results from a sample of one hundred medical students in Japan.

BACKGROUND: The prevalence of allergic diseases has been increasing dramatically and several studies have shown that atopy is related to asthmatic symptoms and bronchial hyperresponsiveness. OBJECTIVE: To observe the relationships between atopic status and asthmatic predisposition (obstructive change in lung function) in apparently healthy young adults in Japan. METHODS: A sample of 100 healthy Japanese medical students were subjected to a skin prick test for 11 common aeroallergens and food allergens, and their spirometric lung function was measured. RESULTS: Surprisingly, 90% of them showed a positive prick test result for at least one of the 11 allergens tested, and 59% of them showed allergic responses to more than three allergens. The positive rate for Dermatophagoidesfarinae (Der) was the highest (71.0%), followed by house dust (57.0%), Dactylois gloinerata (42.0%), Cryptomeria gromerata (Cry) (40.0%), and cat fur (39.0%). Furthermore, there was no statistical difference in the positive rates for Der and Cry between groups with and without either the present illness or past history of any of the three major allergic diseases: bronchial asthma (BA), atopic dermatitis (AD), or allergic rhinitis (AR). Compared with the positive rates for these aeroallergens, those for food allergens were much lower (4% to 9%). Several lung function parameters, including the levels of FEV1% and %V50 which reflect obstructive pulmonary changes, showed significant negative correlation to the number of skin prick test-positive allergens. The same correlation was observed for groups without either the present illness or past history of BA. CONCLUSION: These data suggest that those who are multi-allergic tend to feature subclinical asthma-like changes in their lung functions. Further studies are needed to determine whether this multi-allergic status can lead to future onset of asthma or other allergic diseases.