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排序方式: 共有450条查询结果,搜索用时 15 毫秒
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3.
Analysis of IFN-kappa expression in pathologic skin conditions: downregulation in psoriasis and atopic dermatitis. 总被引:3,自引:0,他引:3
Claudia Scarponi Bernardetta Nardelli David W Lafleur Paul A Moore Stefania Madonna Ornella De Pità Giampiero Girolomoni Cristina Albanesi 《Journal of interferon & cytokine research》2006,26(3):133-140
Interferon-kappa (IFN-kappa) is a type I IFN expressed by keratinocytes, monocytes and dendritic cells (DCs). In human keratinocytes, it is produced in response to double-stranded RNA (dsRNA) and other IFNs and protects from viral infections. In monocytes and DCs, IFN-kappa induces tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) and inhibits lipopolysaccharide (LPS)-induced IL-12. In this study, we evaluated IFN-kappa expression in skin lesions of patients with common immune-mediated inflammatory disorders using immunohistochemical techniques. IFN-kappa was not detectable in healthy skin but was strongly expressed in allergic contact dermatitis and lichen planus-affected skin. IFN-kappa was localized mainly in basal and suprabasal keratinocytes and in some leukocytes infiltrating the dermis. In contrast, IFN-kappa expression in psoriatic or atopic dermatitis (AD) pidermis was weak and detectable in only 2 of 5 patients examined. Consistently, cultured keratinocytes and monocytes obtained from psoriatic and AD patients expressed null or low levels of IFN-kappa in response to IFN-gamma, which strongly upregulates IFN-kappa in normal keratinocytes. IFN-kappa accumulated in keratinocyte cytoplasm and plasma membrane, and only limited amounts were released extracellularly. Soluble IFN-kappa did not influence keratinocyte proliferation or chemokine and membrane molecule expression, and only its membrane-associated form activated IFN-stimulated response element (ISRE) signaling. Given the difference in IFN-kappa expression levels in the skin disorders examined, IFN-kappa presence or deficiency might have different pathogenetic consequences depending also on other disease-specific intrinsic alterations. 相似文献
4.
Burchill MA Nardelli DT England DM DeCoster DJ Christopherson JA Callister SM Schell RF 《Infection and immunity》2003,71(6):3437-3442
We showed that Borrelia burgdorferi-vaccinated interferon gamma-deficient (IFN-gamma(0)) mice challenged with the Lyme spirochete developed a prominent chronic severe destructive osteoarthropathy. The immune response underlying the development of the severe destructive arthritis involves interleukin-17 (IL-17). Treatment of vaccinated IFN-gamma(0) mice challenged with B. burgdorferi with anti-IL-17 antibody delayed the onset of swelling of the hind paws but, more importantly, inhibited the development of arthritis. Histopathologic examination confirmed that treatment with anti-IL-17 antibody prevented the destructive arthropathy seen in vaccinated and challenged IFN-gamma(0) mice. Similar preventive results were obtained when vaccinated and challenged IFN-gamma(0) mice were treated with anti-IL-17 receptor antibody or sequentially with anti-IL-17 antibody followed by anti-IL-17 receptor antibody. By contrast, treatment of vaccinated and challenged IFN-gamma(0) mice with recombinant IL-17 (rIL-17) did not alter the development and progression of arthritis found in vaccinated and challenged IFN-gamma(0) mice without treatment with rIL-17. Therapeutic intervention may be a realistic approach to prevent arthritis, especially if IL-17 is involved in the perpetuation of chronic or intermittent arthritis. 相似文献
5.
乳腺管状小叶癌(Tubulolobular carcinoma,TLC)最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征,并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁(中位年龄60岁)。1例双侧乳腺受累,5例病变为多灶性。肿瘤直径0.5-2.5cm,色灰褐,质硬。组织学观察:TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂,且两者比例相当(统称为管状小叶模式)。 相似文献
6.
An IFN-beta-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates. 总被引:6,自引:0,他引:6
Cynthia Sung Bernardetta Nardelli David W LaFleur Erich Blatter Marta Corcoran Henrik S Olsen Charles E Birse Oxana K Pickeral Junli Zhang Devanshi Shah Gordon Moody Solange Gentz Lisa Beebe Paul A Moore 《Journal of interferon & cytokine research》2003,23(1):25-36
The long half-life and stability of human serum albumin (HSA) make it an attractive candidate for fusion to short-lived therapeutic proteins. Albuferon (Human Genome Sciences [HGS], Inc., Rockville, MD) beta is a novel recombinant protein derived from a gene fusion of interferon-beta (IFN-beta ) and HSA. In vitro, Albuferon beta displays antiviral and antiproliferative activities and triggers the IFN-stimulated response element (ISRE) signal transduction pathway. Array analysis of 5694 independent genes in Daudi-treated cells revealed that Albuferon beta and IFN-beta induce the expression of an identical set of 30 genes, including 9 previously not identified. In rhesus monkeys administered a dose of 50 microg/kg intravenously (i.v.) or subcutaneously (s.c.) or 300 microg/kg s.c., Albuferon beta demonstrated favorable pharmacokinetic properties. Subcutaneous bioavailability was 87%, plasma clearance at 4.7-5.7 ml/h/kg was approximately 140-fold lower than that of IFN-beta, and the terminal half-life was 36-40 h compared with 8 h for IFN-beta. Importantly, Albuferon beta induced sustained increases in serum neopterin levels and 2',5' mRNA expression. At a molar dose equivalent to one-half the dose of IFN-beta, Albuferon beta elicited comparable neopterin responses and significantly higher 2',5'-OAS mRNA levels in rhesus monkeys. The enhanced in vivo pharmacologic properties of IFN-beta when fused to serum albumin suggest a clinical opportunity for improved IFN-beta therapy. 相似文献
7.
Germline mutations of the CDKN2 gene in UK melanoma families 总被引:4,自引:1,他引:4
Harland M; Meloni R; Gruis N; Pinney E; Brookes S; Spurr NK; Frischauf AM; Bataille V; Peters G; Cuzick J; Selby P; Bishop DT; Bishop JN 《Human molecular genetics》1997,6(12):2061-2067
Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin
D kinase inhibitor p16, and more rarely, mutations in the gene coding for
CDK4, the protein to which p16 binds, underlie susceptibility in some
melanoma families. We have sequenced all exons of CDKN2 and analysed the
CDK4 gene for mutations in 27 UK families showing evidence of
predisposition to melanoma. Five different germline mutations in CDKN2 were
found in six families. Three of the mutations (Met53Ile, Arg24Pro and
23ins24) have been reported previously. We have identified two novel CDKN2
mutations (88delG and Ala118Thr) which are likely to be associated with the
development of melanoma, because of their co-segregation with the disease
and their likely functional effect on the CDKN2 protein. In binding assays
the protein expressed from the previously described mutation, Met53Ile, did
not bind to CDK4/CDK6, confirming its role as a causal mutation in the
development of melanoma. Ala118Thr appeared to be functional in this assay.
Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were
detected in exon 2 of CDK4, suggesting that causal mutations in this gene
are uncommon. The penetrance of these mutant CDKN2 genes is not yet
established, nor is the risk of non-melanoma cancer to gene carriers.
相似文献
8.
Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg
TPA) protocols were found to be under multigenic control. Eighty- one N2
mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were
either solidly resistant (no papillomas) or highly susceptible (> or = 7
papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite
markers to check for associations with susceptible and resistant
phenotypes. A locus on Chr 5 (Skts4) was found to control the
susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to
papilloma formation. In addition, higher than expected linkage scores were
seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is
required to establish whether genes determining papilloma formation are
located in these regions of the genome. In general, no evidence was seen
for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in
17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.
相似文献
9.
S Di Paolo V Lattanzi E Guastamacchia C Vincenti A M Balice N Montanaro G M Nardelli R Giorgino 《Diabetes research and clinical practice》1990,9(1):65-73
A 59-year-old woman with systemic lupus erythematosus was found to have marked hyperglycemia, extreme insulin resistance and abnormally high plasma immunoreactive insulin. Her circulating erythrocytes displayed a dramatic decrease of 125I-labeled insulin binding. Both the whole serum and purified IgG fraction strongly inhibited the binding of radiolabeled insulin to control erythrocytes. These results suggested, although indirectly, the existence of antibodies to insulin receptors in the serum of the patient. To directly investigate this issue, we used an enzyme-linked solid-phase immunoassay which allows the detection and enumeration of lymphocytes secreting antibodies towards insulin receptors. Peroxidase-conjugated anti-human immunoglobulin is used to reveal the binding of antibodies to insulin receptor-coated dishes. We demonstrated that the patient's mononuclear cells, when briefly incubated in Petri dishes with partially purified insulin receptor, were able to secrete immunoglobulins of G class specifically directed to the antigen. Moreover, only a fraction of the whole population of anti-insulin receptor antibodies was directed towards the insulin binding region of the receptor, seemingly corresponding to the auto-antibodies detected with conventional binding-inhibition assay. 相似文献
10.
Luigia Di Francesco Melania Dovizio Annalisa Trenti Emanuela Marcantoni Ashleigh Moore Peadar O’Gaora Cathal McCarthy Stefania Tacconelli Annalisa Bruno Sara Alberti Salvatore Gizzo Giovanni Battista Nardelli Genny Orso Orina Belton Lucia Trevisi Dan A Dixon Paola Patrignani 《British journal of pharmacology》2015,172(18):4575-4587