Design Characteristics for the Tissue Engineering of Cartilaginous Tissues

Tissues like the temporomandibular joint (TMJ) disc and the knee meniscus are often mistakenly viewed as a tantamount to hyaline cartilage, largely due to the absence of a comprehensive understanding of the distinguishing properties of cartilaginous tissues. Because of this confusion, fibrocartilaginous tissue engineering attempts may not be based on suitable experimental designs. Fibrocartilaginous tissues are markedly different than hyaline cartilage; however, the dearth of knowledge related to their cellular and biochemical composition, as well as their biomechanical characteristics, is stunning. Hyaline articular cartilage is exclusively composed of chondrocytes that produce primarily type II collagen, whereas the TMJ disc and the knee meniscus have a mixed cell population of fibroblasts and cells similar to chondrocytes, which predominantly secrete type I collagen. Additionally, fibrocartilaginous tissues have a low glycosaminoglycan content, a low compressive modulus, and a high tensile modulus when compared to hyaline cartilage. Therefore, it is crucial for fibrocartilaginous tissue engineering attempts to be tissue-specific, utilizing the knowledge of the distinct and unique properties of these tissues. At the same time, advances and insights related to the science and engineering aspect of hyaline cartilage regeneration must be carefully considered for the in vitro engineering of fibrocartilaginous tissues.     

Different pattern of risk factors for atopic and nonatopic asthma among children – report from the Obstructive Lung Disease in Northern Sweden Study

BACKGROUND: A cross-sectional study was performed among 78-year-old schoolchildren during the winter of 1996 in three municipalities in the most northern province of Sweden, Norrbotten. The study was the starting point of a longitudinal study of asthma, rhinitis, eczema, and type-1 allergy, and provided data on prevalence and risk factors for these conditions. The aim of the present study was to validate the classification of asthma based on a parental questionnaire, and to examine risk factors for atopic and nonatopic asthma. METHODS: The ISAAC questionnaire with additional questions was distributed by the schools to the parents. The response rate was 97%, and 3431 completed questionnaires were returned. The children in Kiruna and Lule? were also invited to be skin tested, and 2149 (88%) were tested with 10 common airborne allergens. A structured interview was administered by pediatricians in stratified samples of the children to test the validity of the diagnosis of asthma based on the questionnaire. RESULTS: After the validation study, the prevalence of "ever asthma" was estimated to be 8.0%. The specificity of the question, "Has your child been diagnosed as having asthma by a physician?", was high, >99%, while the sensitivity was around 70%. The strongest risk factor for "ever asthma" was a positive skin test (OR 3.9). Risk factors for asthma in the asthmatics who were not sensitized were family history of asthma, OR 3.6; breast-feeding less than 3 months, OR 1.8; past or present dampness at home, OR 1.8; smoking mother, OR 1.7; and male sex, OR 1.6. Among the sensitized asthmatics, only a family history of asthma was a significant risk factor (OR 3.0), while breast-feeding less than 3 months was not associated with an increased risk (OR 1.0). A synergistic effect between genetic and environmental factors was found especially in the nonatopic asthmatics; the children with a family history of asthma who had a smoking mother and past or present dampness at home had an OR for "ever asthma" of 13. CONCLUSIONS: Different risk-factor patterns were found for asthma and type-1 allergy. In addition, the risk factors for atopic or allergic asthma diverged from those for nonatopic asthma.     

Medical treatment reverses cytokine pattern in allergic and nonallergic chronic rhinosinusitis in asthmatic children

A Th2 cytokine pattern has recently been reported both in allergic and nonallergic chronic rhinosinusitis in asthmatic children. The aim of the study was to evaluate the cytokine pattern in chronic rhinosinusitis in allergic and nonallergic asthmatic children before and after medical treatment. Thirty asthmatic children were evaluated, 18 males and 12 females (mean age 9.1 years). Sixteen were allergic and 14 were nonallergic. All children were asthmatic and suffered from chronic rhinosinusitis, whose diagnosis was confirmed by endoscopy. All of them were treated with amoxicilline-clavulanate (20 mg/kg b.i.d.) and fluticasone propionate aqueous nasal spray (100 µg daily) for 14 days; a short course of oral corticosteroid was also prescribed (deflazacort 1 mg/kg daily for 2 days, 0.5 mg/kg daily for 4 days and 0.25 mg/kg daily for 4 days). Rhinosinusal lavage and nasal cytology were performed in all subjects before and after medical treatment. IL4 and IFNγ were measured by immunoassay and inflammatory cells were counted by conventional staining. Thirteen allergic children and 12 nonallergic children showed a negative endoscopy after the treatment. Allergic subjects showed a significant decrease of IL4 (p = 0.0002) and a significant increase of IFNγ (p = 0.03) after the treatment. Nonallergic children showed a significant decrease of IL4 (p = 0.0007) and a nonsignificant increase of IFNγ. A significant reduction of the inflammatory infiltrate was detected in all asthmatic children (p < 0.05). This study confirms a Th2 polarization in chronic rhinosinusitis both in allergic and nonallergic asthmatic children. Moreover, the medical treatment of chronic rhinosinusitis reversed the cytokine pattern from a Th2 towards a Th1 profile both in allergic and nonallergic children.     

Anaphylaxis to sheep's milk cheese in a child unaffected by cow's milk protein allergy

A 5-year-old atopic boy unaffected by cow's milk protein allergy experienced several anaphylactic reactions after eating food containing “pecorino” cheese made from sheep's milk. Prick-prick tests were strongly positive to sheep's buttermilk curd and `pecorino' sheep's cheese. Skin prick tests to fresh sheep's milk and to goat's milk were also positive, whereas they were negative to all cow's milk proteins, to whole pasteurized cow's milk and to cheese made from cow's milk. Specific IgE antibodies were negative to all cow's milk proteins. Conclusion Sheep's milk and cheese derived from sheep's milk may cause severe allergic reactions in children affected and, as we report, in children not affected by cow's milk protein allergy. Received: 14 January 1997 and in revised form: 20 June 1997 / Accepted: 8 July 1997     

Natural rubber latex allergy: prevalence and risk factors in patients with spina bifida compared with atopic children and controls

Type 1 allergy against natural rubber latex is an increasing problem in health care workers and children with spina bifida or urogenital malformations. The aim of our study was to evaluate the prevalence of latex IgE antibodies and cross-reacting fruit antibodies in patients with spina bifida compared with atopic and non-atopic controls. Risk factors for sensitization should be determined. Sera of 148 patients with spina bifida and 98 controls (44 with atopy) were screened for IgE antibodies against latex, banana and kiwi by fluorescence enzyme immunoassay (CAP system). Atopies, allergic symptoms after latex contacts and the number of operations were compiled by a questionnaire. Patients with spina bifida developed latex IgE antibodies (≥0.7 kU/l) more frequently (40.5%) than atopic children (11.4%) or healthy controls (1.9%). All 18 symptomatic patients belonged to the spina bifida group and had high values of latex antibodies. The risk for developing latex antibodies increases with the number of operations. There was no difference in the history of atopic diseases and in a screening test of IgE antibodies against inhalative allergens between latex sensitized and not sensitized children with spina bifida. Antibodies against banana were more frequent in the latex sensitized children with spina bifida. (18.3% vs 3.4%, P = 0.002). Conclusion The high prevalence of latex antibodies in children with spina bifida justifies a primary prophylaxis by avoiding latex contacts, especially during anaesthesia and surgery, a correlation between the number of operations and the development of latex antibodies exists. Received: 30 March 1996 and in revised form: 19 March 1997 / Accepted: 20 March 1997     

The effect of the H2 antagonist cimetidine on the numbers of CD4+ and CD8+ cells in the nasal mucosa of patients with allergic rhinitis

This paper reports the effects of the H₂ antagonist cimetidine on the number of CD4⁺ and CD8⁺ cells in nasal mucosa and the IgE level of nasal secretions in patients with allergic rhinitis. The results showed the numbers of CD4⁺ cells were greater than the numbers of CD8⁺ cells in nasal mucosa, both in the patients with allergic rhinitis and normal subjects, but the ratio of CD4⁺ : CD8⁺ cells was much higher in the patients with allergic rhinitis. After treatment with cimetidine locally for 4 weeks, the numbers of CD4⁺ cells fell and the numbers of CD8⁺ cells increased in the patients with allergic rhinitis. The high IgE level of nasal secretion of the patients with allergic rhinitis was much reduced after treatment with cimetidine. The results suggest that there are high numbers of CD4⁺ cells and lower numbers of CD8⁺ cells in the nasal mucosa and a high level of IgE in the nasal secretions of the patients with allergic rhinitis. Treatment with cimetidine locally may be of some value to relieve the clinical symptoms of allergic rhinitis.     

Molekulare Aspekte und diagnostische Wertigkeiten von Pilzallergenen

Zusammenfassung. Die Klonierung, Sequenzierung und Produktion von hochreinen Allergenen bietet die Möglichkeit, perfekt standardisierte Allergenpräparate herzustellen. Die Entwicklung eines neuen Klonierungssystems, das auf filamentösen Phagen basiert, führte zu einer schnellen Isolierung und Charakterisierung von Aspergillus fumigatus-Allergenen. Die auf diesem Weg rekombinant hergestellten Proteine wurden serologisch und klinisch geprüft und ihr routinemä-ßiger Einsatz im ImmunoCAP-System evaluiert. Es gelang eine quantitative Übereinstimmung zwischen Hauttestergebnissen und Serologie nachzuweisen, welche das Potential rekombinanter Allergene in der Diagnostik allergischer Krankheiten aufzeigt. Darüber hinaus trägt die Charakterisierung der Pilzallergene wesentlich zum Verständnis der moiekularen Natur der allergieauslösenden Komponenten bei Zum jetzigen Zeitpunkt können, abgesehen von Proteinen mit unbekannten biologischen Funktionen, die Pilzallergene in zwei Klassen eingeteilt werden: 1. Spezies-spezifische sezcrnierte Allergene und 2. cytoplasmatische, hoch konservierte Proteine. Diese letztgenannten Pilzallergene zeigen auch zu Proteinen aus phylogenetisch weit entfernten Organismen weitreichende Sequenzhomologien. Neben der daraus zu erwartenden IgE-Kreuzreaktivität findet man in einigen Fällen auch eine Kreuzreaktivität mit den homologen humanen Proteinen, was auf Autoimmunreaktionen, bei Pilzalleigien hindeutet. Summary. Cloning, sequencing and production of highly pure recombinant allergens allows to produce perfectly standardised allergen preparations. The development of a new cloning system based on filamentous phage allowed the fast isolation and characterisation of allergens from the fungus Aspergillus fumigatus. The produced recombinant allergens were tested in serological and clinical studies as well as for their performance for routine assessments in the ImmunoCAP-system. Thereby, a perfect correlation between skin test results and serology was found showing the potential of recombinant allergens for the diagnosis of allergic diseases. Moreover, the characterisation of fungal allergens substantially contributes to our understanding of the molecular nature of proteins involved in the elication of allergic reactions. Apart from allergenic proteins with unknown biological function, fungal allergens can be subdivided into two classes: 1. Species-specific, secreted proteins and 2. cytoplasmic, even in phylogenetically distant organisms, well conserved proteins. These fungal allergens show extended sequence similarity, a high level of IgE cross-reactivity and in some cases also cross-reactivity with homologous human proteins indicating autoimmune reactions involved in fungal allergy.     

药物导致的变态反应、过敏反应及超敏反应

复杂的药物不良反应如变态反应、过敏反应及超敏反应出现频率较多,而且这3种反应有其共性,也有其差异,不易区 别,以致常有交叉替用,本文拟予探讨。     

Low vitamin D status is associated with low cord blood levels of the immunosuppressive cytokine interleukin-10

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 degrees N) and from 47 infants born during the winter half year (mid-October to mid-April, geographic latitude of 51 degrees 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.