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21.
Kinnunen T Buhot C Närvänen A Rytkönen-Nissinen M Saarelainen S Pouvelle-Moratille S Rautiainen J Taivainen A Maillère B Mäntyjärvi R Virtanen T 《European journal of immunology》2003,33(6):1717-1726
We have proposed earlier that the poor capacity of the lipocalin allergen Bos d 2 to stimulate highly allergic subjects' peripheral blood mononuclear cells could be ascribed to endogenous lipocalins and could be related to the allergenic potential of the molecule. Here, we have characterized the proliferative and cytokine responses of human T cell clones against the immunodominant epitope of Bos d 2. We observed, for clone F1-9, that a substitution of aspartic acid for asparagine in the core region of the epitope increased the stimulatory capacity of the peptide about 100-fold in comparison with the natural peptide. For clone K3-2, from a different patient, the substitution of lysine for glutamine or isoleucine for leucine in the core region resulted in about 30-fold and 10-fold increases in the stimulatory capacity of the peptides, respectively. The clones also recognized self-protein-derived peptides but not the peptides derived from other lipocalins. We suggest that the poor recognition of the immunodominant epitope of Bos d 2 can be a factor accounting for Bos d 2-allergic subjects' weak cellular responses. Suboptimal recognition of self and allergen epitopes by T cells may be of significance for the allergenicity of proteins. 相似文献
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As transdermal patches become more widely prescribed, it is important that clinicians understand: (a) the common causes of
skin reactions with these medications; (b) how to minimize these reactions; and (c) how to manage the signs and symptoms.
Here we review published data for skin reactions with patch medications approved within the past decade. Overall, the most
common application site signs and symptoms appear to be localized redness (erythema) or itching, sometimes accompanied by
swelling (edema). Typically, these are mild to moderate in severity, transient in nature, and occur in 20% to 50% of patients.
Most are localized to the area of application, and resolve spontaneously within several days following patch removal. Discontinuations
due to these types of event are infrequent, ranging from 1.7% to 6.8% in the 6-month trials reviewed here. Based on expert
opinion, the majority of these skin reactions would be a form of irritant contact dermatitis, with infrequent cases of allergic
contact dermatitis. These types of reactions usually cause minimal pain or discomfort to the patient, and are unlikely to
be of medical concern. Signs and symptoms of irritant contact dermatitis may be minimized by rotation of the application site,
careful removal of the patch, and appropriate use of moisturizers and topical corticosteroids. In conclusion, the potential
advantages of transdermal patches usually outweigh any additional skin issues; however, further research into treatment and
management strategies is required. 相似文献
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Ale Laukeviciene Stephan Brecht Egidijus Kevelaitis Thomas Herdegen 《European journal of pharmaceutical sciences》2006,29(5):335-339
The c-Jun N-terminal kinases (JNKs) form a subfamily of the mitogen-activated protein kinases (MAPK). These signalling pathways regulate various processes such as mitosis, cellular differentiation, stress response or apoptosis in multicellular organisms. There is rising evidence about the role of JNKs activities in neurodegenerative and metabolic diseases as well as in immunological disorders. The physiological functions of JNKs, however, remain to be elucidated. Recent data have demonstrated an essential role of JNKs in the cardiovascular system and the regulation of carbon hydrate and glucose metabolism. Therefore, we have investigated the contractility of blood vessels in mice with genetically deleted JNK1, JNK2, JNK3 and JNK2+3 isoforms and their respective wildtypes. The contractility of the isolated segments from A. carotis communis was measured by small blood vessel wire myograph. Contraction induced by 80 mM KCl was significantly increased in arteries from JNK2+3 double knockout compared to controls and single knockouts. The maximal contraction generated by the -agonists phenylephrine or noradrenaline (10 μM) was significantly enhanced in JNK2+3 knockout arteries compared with arteries from the remaining strains. Inhibition of NOS by Nw-nitro-l-arginine did not change the pattern of vasoconstriction, but vasoconstriction by noradrenaline following NOS inhibition was significantly enhanced in the arteries from JNK2+3 double knockout mice.
In conclusion, genetic deletion of JNK2+3 in mice results in altered contractility of carotid arteries and this might depend on the function of the smooth muscles rather than on the endothelium. These findings have implications for the long-term treatment with pharmacological JNK inhibitors for neurodegenerative or metabolic diseases such as stroke or diabetes. 相似文献
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