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51.
Background There is strong evidence to suggest that alopecia areata (AA) is a tissue‐specific, T cell‐mediated autoimmune disease, which is usually characterized by patchy areas of hair loss on the scalp. Tyrosine hydroxylase (TH) is a known B‐cell autoantigen in patients with autoimmune polyendocrine syndrome type 1 (APS1) associated with the presence of AA. In addition, melanocyte‐specific proteins, gp100 and MelanA, are putative T‐cell autoantigens in AA and so may also represent targets of the humoral immune response. Objective To analyse the sera of patients with AA for the presence of antibodies against TH and the melanocyte‐specific proteins tyrosinase, tyrosinase‐related protein (TRP)‐1, TRP‐2, gp100 and MelanA. Methods Radioimmunoassays were used to detect the relevant antibodies in sera from patients with AA (n = 32) and in sera from healthy individuals (n = 28). Results Of 32 patients with AA, six (19%) were positive for TH antibodies. A significant increase in the frequency of TH antibodies in the AA patient group was evident when compared with controls (P = 0·03). Only three of 32 (9%) patients exhibited antibody responses to tyrosinase, TRP‐1, TRP‐2 and gp100. No immunoreactivity against MelanA was detected in any patient with AA. Conclusion Antibodies against TH can be present in patients with AA unrelated to APS1. Humoral immune responses against tyrosinase, TRP‐1, TRP‐2, gp100 and MelanA are not prevalent in patients with AA. Overall, a dominant melanocyte‐specific B‐cell autoantigen in AA has yet to be identified. 相似文献
52.
Akhtar S Gavalas NG Gawkrodger DJ Watson PF Weetman AP Kemp EH 《Archives of dermatological research》2005,297(2):94-98
Vitiligo is an acquired hypomelanotic skin disorder characterised by circumscribed depigmented macules resulting from the
loss of functional melanocytes from the cutaneous epidermis and autoimmunity has been suggested to play a role in the pathogenesis
of the disease. Recently, an insertion/deletion (I/D) polymorphism of a 287-base pair repetitive sequence in intron 16 of
the angiotensin converting enzyme (ACE) gene has been associated with autoimmune disease and with the development of vitiligo.
In this study, the distribution of ACE gene I/D genotypes was investigated in a population of 106 English patients with generalised
(non-segmental) vitiligo and 174 ethnically matched healthy controls using a restriction fragment length polymorphism-polymerase
chain reaction genotyping method. No significant difference in the frequencies of II, ID and DD genotypes was detected between
vitiligo patients and control subjects (P=0.35). The same result was evident for the genotype distribution in vitiligo patients with an autoimmune disease and for
those without when compared with controls (P=0.33 and P=0.53, respectively). In addition, the results indicated that the D allele was not significantly over-represented in the group
of patients with vitiligo compared with controls (P=0.42) and that this was also the case for patients with and without associated autoimmunity (P=0.40 and P=0.62, respectively). 相似文献
53.
Hedley Gawkrodger Weetman Morandini Boeynaems Ghanem & Mac Neil 《The British journal of dermatology》1998,138(3):536-543
α-Melanocyte stimulating hormone (α-MSH) was found significantly to reduce tumour necrosis factor-α (TNF-α) stimulated upregulation of intercellular adhesion molecule-1 (ICAM-1) in normal adult cutaneous melanocytes. The maximum inhibitory response to α-MSH was obtained at around 10−10 mol/L α-MSH when cells were coincubated with α-MSH and TNF-α for 24 h. α-MSH had little or no effect on basal ICAM-1 expression in melanocytes and the effects of α-MSH could be mimicked with 3-isobutyl-1-methylxanthine (IBMX). Preliminary data in three human melanoma cell lines also showed α-MSH and forskolin to be effective in significantly reducing TNF-α stimulated ICAM-1 expression over 24 h. The extent of the inhibition varied from cell line to cell line and was greatest in those cells with the highest number of α-MSH receptors. These data suggest that α-MSH has the ability to oppose the action of the pro-inflammatory cytokine TNF-α on melanocytes and melanoma cells. 相似文献
54.
Green DM Cotton CA Malogolowkin M Breslow NE Perlman E Miser J Ritchey ML Thomas PR Grundy PE D'Angio GJ Beckwith JB Shamberger RC Haase GM Donaldson M Weetman R Coppes MJ Shearer P Coccia P Kletzel M Macklis R Tomlinson G Huff V Newbury R Weeks D 《Pediatric blood & cancer》2007,48(5):493-499
PURPOSE: NWTS-5 was a multi-institutional clinical trial for patients less than 16 years of age at diagnosis with specific renal neoplasms who were diagnosed between August 1, 1995 and May 31, 2002. A uniform approach to the treatment of patients with relapse was employed. PATIENTS AND METHODS: Seventy-two patients who relapsed after immediate nephrectomy (stages I and II), initial chemotherapy with vincristine (VCR) and actinomycin D and no radiation therapy were registered on stratum B of the NWTS-5 relapse protocol. Four patients were not evaluable: one due to insufficient data and three due to major protocol violations. Among the 68 remaining patients, one who was 19 years of age at initial diagnosis of Wilms tumor, five with bilateral Wilms tumor at diagnosis, three who developed a contralateral relapse, and one with persistent disease were not included in this analysis. Relapse treatment included surgical excision, when feasible, radiation therapy and alternating courses of VCR, doxorubicin and cyclophosphamide and etoposide and cyclophosphamide. RESULTS: The outcomes of 58 patients were analyzed. The lung was the only site of relapse for 31 patients. Event-free survival 4 years after relapse was 71.1% and 4-year overall survival was 81.8% for all patients and were 67.8 and 81.0% for those who relapsed only to their lungs. The most frequent toxicities were hematological. CONCLUSIONS: These results demonstrate that a significant proportion of children with Wilms tumor who relapse after initial treatment with VCR and actinomycin D can be successfully re-treated. 相似文献
55.
56.
Growth characteristic and acid production of oral isolates of Candida albicans and Candida glabrata in glucose supplemented and glucose-free, pooled, human whole saliva were examined. Both Candida species exhibited sigmoidal growth curves in batch cultures of mixed saliva, supplemented with glucose. The growth of Candida in saliva was accompanied by a rapid decline in pH from 7.5 to 3.2 over 48 h and the major acidic components initiating and sustaining this pH drop were pyruvates and acetates. These acidic metabolites may play an important role in the pathogenesis of oral Candida infections. 相似文献
57.
应用新型单克隆抗体T_8/S_6F_1和流体细胞测定仪双色荧光程序检测了15例Graves病和8例Hashimoto甲状腺炎患者循环和甲状腺内的细胞毒性T细胞(cytotoxic T ceils,Tc)的分布。传统的单克隆抗体CD_8(OKT_8或Leu_2)仅能检测含有两个次亚群——抑制性T细胞(Ts)和细胞毒性T细胞(Tc)的Ts/TcT细胞亚群,不能将它们区别开来。本文应用的单克隆抗体T_8/S-6F_1首次能够单独测定Tc亚群。Graves病和Hashimoto甲状腺炎患者的循环Tc亚群分别为27.6±11.2%和27.5%±12.2%,与正常对照组差异无显著性。两组患者甲状腺内的Tc亚群数目也未见增加。Graves病患者甲状腺内Te细胞为16.45±4.7%。本文结果提示:AITD患者循环内和甲状腺内的细胞毒性T细胞亚群的数目未见增加。 相似文献
58.
Suppressive role of NK cells in pokeweed mitogen-induced immunoglobulin synthesis: effect of depletion/enrichment of Leu 11b+ cells. 总被引:1,自引:0,他引:1
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Natural killer (NK) cells probably have immunoregulatory effects. However, the evidence to date is mainly based on the suppressive effect of enrichment with relatively impure NK populations (large granular lymphocytes, LGL, Leu 7a+ cells). Here we report on the effect of enrichment and depletion of Leu 7a+ and Leu 11b+ cells (the latter containing virtually all NK activity in freshly prepared lymphocytes) on pokeweed mitogen (PWM)-induced immunoglobulin (Ig) synthesis. Enrichment suppressed Ig synthesis to a degree dependent on the number of cells added, and was not enhanced further by their pretreatment with interferon. Furthermore, depletion of Leu 11b+ cells from peripheral blood lymphocytes (PBL) led to marked enhancement (2-25-fold increase) of Ig synthesis, suggesting these cells may normally exert a suppressive effect. The possible underlying mechanisms were investigated further. Enhanced Ig synthesis by Leu 11b-depleted cultures was associated with an increased number of Ig-secreting cells by plaque assay, but with no change in numbers of CD4+ or CD8+ cells. Treatment of PBL with monoclonal antibodies (anti-Leu 7a/Leu 11b) alone suppressed PWM-induced immunoglobulin synthesis. We conclude that NK cells play a role in the regulation of Ig production, at least in part by an effect on activation/differentiation of B cells, but independent of altered T-cell subpopulations. The effect may be unrelated to their cytotoxic function (being unaffected by interferon, IFN), although the direct effects of anti-Leu 11b and Leu 7a in enhancing the suppressive effect suggest an alternative activation pathway. 相似文献
59.
E Helen Kemp Nikos G Gavalas Samia Akhtar Kai JE Krohn J Carl Pallais Edward M Brown Philip F Watson Anthony P Weetman 《Journal of bone and mineral research》2010,25(1):132-140
Previously, we have demonstrated the presence of anti‐calcium‐sensing receptor (CaSR) antibodies in patients with autoimmune polyglandular syndrome type 1 (APS1), a disease that is characterized in part by hypoparathyroidism involving hypocalcemia, hyperphosphatemia, and low serum levels of parathyroid hormone. The aim of this study was to define the binding domains on the CaSR of anti‐CaSR antibodies found in APS1 patients and in one patient suspected of having autoimmune hypocalciuric hypercalcemia (AHH). A phage‐display library of CaSR peptides was constructed and used in biopanning experiments with patient sera. Selectively enriched IgG‐binding peptides were identified by DNA sequencing, and subsequently, immunoreactivity to these peptides was confirmed in ELISA. Anti‐CaSR antibody binding sites were mapped to amino acid residues 41–69, 114–126, and 171–195 at the N‐terminal of the extracellular domain of the receptor. The major autoepitope was localized in the 41–69 amino acid sequence of the CaSR with antibody reactivity demonstrated in 12 of 12 (100%) APS1 patients with anti‐CaSR antibodies and in 1 AHH patient with anti‐CaSR antibodies. Minor epitopes were located in the 114–126 and 171–195 amino acid domains, with antibody reactivity shown in 5 of 12 (42%) and 4 of 12 (33%) APS1 patients, respectively. The results indicate that epitopes for anti‐CaSR antibodies in the AHH patient and in the APS1 patients who were studied are localized in the N‐terminal of the extracellular domain of the receptor. The present work has demonstrated the successful use of phage‐display technology in the discovery of CaSR‐specific epitopes targeted by human anti‐CaSR antibodies. © 2010 American Society for Bone and Mineral Research 相似文献
60.