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1.
遗传性血管性水肿C1INH基因1440V变异及其对结构的影响 总被引:1,自引:0,他引:1
目的 通过基因测序了解遗传性血管性水肿(HAE)患者C1酯酶抑制剂(C1INH)基因第八外显子的变异情况.方法 从HAE患者外周血白细胞中提取基因组DNA,PCR扩增第八外显子片段后插入pUC19质粒载体冉转化入感受态大肠杆菌TG1菌株,培养扩增质粒DNA,提取纯化后进行基因测序.将患者血清进行SDS-PAGE及Westem印迹,以了解该变异对CIINH结构的可能影响.结果 在1例I型HAE患者的第八外显子中发现一个变异位点,16776A>G,致440位的异亮氨酸突变成缬氨酸(1440V),SDS-PAGE及Westem印迹显示该患者血清中C1INH全部表现为96 000片段而非正常的105 000片段.结论 1440v是一个新的C1INH基因变异,位于C1INH反应中心环的P4位,变异可能导致C1INH分子构象发生改变. 相似文献
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Iwamoto K Tanaka A Kawai M Ishii K Mihara S Hide M 《Clinical and experimental dermatology》2012,37(1):20-23
C1 inhibitor (C1-INH) deficiency [hereditary or acquired angio-oedema (HAE or AAE)] is characterized by recurring episodes of subcutaneous or submucosal oedema. Many different mutations in the C1-INH gene have been identified as a cause of HAE. We investigated the molecular basis of the disease in a Japanese woman with sporadic HAE. Direct sequencing of genomic DNA revealed no point mutation in the C1-INH gene. Quantitative real-time PCR showed that the copy number of the C1-INH gene in the patient was half that of a healthy control. Furthermore, we identified a 650-kbp deletion on the chromosome, which included the C1-INH gene. We evaluated the correlation between the patient's attacks and her coagulation activity. The levels of D-dimer were high during the angio-oedema attacks, and often exceeded the normal range even during remission, thus the level of D-dimer reflected the activity of HAE in this patient. 相似文献
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A 25‐year‐old woman presented to our clinic with a history of recurrent swelling and abdominal symptoms for > 20 years. The patient's father was similarly affected. The patient was diagnosed with hereditary angio‐oedema (HAE) due to C1 inhibitor deficiency. This was initially managed with systemic androgens, but the symptoms of hyperandrogenism eventually became intolerable. Treatment with icatibant (an antagonist of bradykinin B2 receptors) was partially successful. We changed the therapy to prophylactic treatment with C1 inhibitor. Although the patient became completely symptom‐free under this regimen, she found the repeated intravenous injections unacceptable. Therefore, we changed the route of administration to subcutaneous injections of C1 inhibitor 1000 U in 10 mL twice weekly, using a subcutaneous infusion kit. Since that time (December 2013), she has remained completely free of symptoms under this regimen. To our knowledge, this is the first report documenting the efficacy and safety of subcutaneous injections of C1 inhibitor in a patient with HAE. 相似文献
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Anete S. Grumach Marina T. Henriques Maine L.D. Bardou Daniele A. Pontarolli Jaco Botha Mariangela Correa 《Anais brasileiros de dermatologia》2022,97(4):448-457
BackgroundHereditary angioedema can be caused by C1-Inhibitor (C1-INH) deficiency and/or dysfunction (HAE-1/2) or can occur in patients with normal C1-INH (HAE nC1-INH).MethodsThe Icatibant Outcome Survey (IOS; NCT01034969) registry monitors the safety and effectiveness of icatibant for treating acute angioedema.ObjectivePresent findings from Brazilian patients with HAE-1/2 and HAE nC1-INH participating in IOS.Results42 patients were enrolled (HAE-1/2, n = 26; HAE nC1-INH, n = 16). Median age at symptom onset was significantly lower with HAE-1/2 vs. HAE nC1-INH (10.0 vs. 16.5y, respectively; p = 0.0105), whereas median age at diagnosis (31.1 vs. 40.9y; p = 0.1276) and the median time between symptom onset and diagnosis (15.0 vs. 23.8y; p = 0.6680) were numerically lower vs. HAE nC1-INH, respectively. One icatibant dose was used for > 95% of HAE attacks. Median (range) time-to-event outcomes were shorter for patients with HAE nC1-INH vs. HAE-1/2, including time to first administration (0.5 [0–96.0] vs. 1.0 [0–94.0]h, respectively), time from first administration to complete resolution (1.0 [0–88.0] vs. 5.5 [0–96.0]h, respectively), and total attack duration (7.0 [0.3–99.0] vs. 18.5 [0.1–100.0]h, respectively). Mean (SD) time from attack onset to resolution was significantly shorter for patients with HAE nC1-INH vs. HAE-1/2 (9.8 [18.7] vs. 19.6 [24.0]h, respectively; p = 0.0174). 83 adverse events (AEs) in 42 patients were reported; most were mild (66.3%) or moderate (13.3%) and non-serious (75.9%). The most common icatibant-related AE was injection site erythema (HAE-1/2, 34.6%; HAE nC1-INH, 18.8%).Study limitationsThis was an observational study without a treatment comparator and that relied on patient recall.ConclusionsFindings demonstrate effectiveness and tolerability of icatibant in Brazilian HAE patients. 相似文献
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Risa Konishi Ryota Tanaka Sae Inoue Yuki Ichimura Toshifumi Nomura Naoko Okiyama 《The Journal of dermatology》2022,49(1):118-123
Dermatomyositis, an idiopathic inflammatory myopathy, is characterized by cutaneous itchy manifestations, which are frequently refractory and recurrent even after intensive immunosuppressive treatments. To evaluate the effectiveness and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in treating skin-dominant dermatomyositis in which myositis and interstitial lung disease are absent or in remission, we performed this prospective, single-arm, interventional study. A total of five Japanese patients (one male and four females, median [range] age, 64 [37–71] years) with refractory dermatomyositis-associated cutaneous manifestations were recruited and treated with a 12-week course of oral apremilast. Among five enrolled patients, three experienced diarrhea with full-dose apremilast (30 mg twice daily), two of whom withdrew from the study and recovered quickly afterwards. A total of three evaluable female patients (median [range] age, 65 [64–71] years) received apremilast treatment for 12 weeks. A 39.4% reduction from baseline Cutaneous Dermatomyositis Disease Area and Severity Index total activity score, but not the damage score, at week 12 was observed in all three patients. Visual analog scale of itching, and quality of life by Dermatology Life Quality Index were slightly improved in one and two apremilast-treated patients, respectively. As apremilast was effective, with expected and recoverable digestive adverse events (diarrhea), in patients with refractory and recurrent dermatomyositis-associated cutaneous manifestations in this first phase Ib study, it can be suggested as a possible treatment when aggressive immunosuppressive therapies with high-dose systemic corticosteroid and/or immunosuppressive agents for other manifestations, myositis, and interstitial lung disease, are not required. 相似文献
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Hailey-Hailey disease: molecular and clinical characterization of novel mutations in the ATP2C1 gene 总被引:6,自引:0,他引:6
Dobson-Stone C Fairclough R Dunne E Brown J Dissanayake M Munro CS Strachan T Burge S Sudbrak R Monaco AP Hovnanian A 《The Journal of investigative dermatology》2002,118(2):338-343
Hailey-Hailey disease is an autosomal dominant skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. Mutations in ATP2C1, the gene encoding a novel, P-type Ca2+-transport ATPase, were recently found to cause Hailey-Hailey disease. In this study, we used conformation-sensitive gel electrophoresis to screen all 28 translated exons of ATP2C1 in 24 Hailey-Hailey disease families and three sporadic cases with the disorder. We identified 22 different mutations, 18 of which have not previously been reported, in 25 probands. The novel mutations comprise three nonsense, six insertion/deletion, three splice-site, and six missense mutations and are distributed throughout the ATP2C1 gene. Six mutations were found in multiple families investigated here or in our previous study. Haplotype analysis revealed that two of these are recurrent mutations that have not been inherited from a common ancestor. Comparison between genotype and phenotype in 23 families failed to yield any clear correlation between the nature of the mutation and clinical features of Hailey-Hailey disease. The extensive interfamilial and intrafamilial phenotypic variability observed suggests that modifying genes and/or environmental factors may greatly influence the clinical features of this disease. 相似文献
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L. DUBERTRET C. CHASTANG† C. BEYLOT‡ J. BAZEX§ C. ROGNIN¶ R. TOURAINE 《The British journal of dermatology》1985,113(3):323-330
Extensive lesions on 36 patients with psoriasis were treated by Tigason, I mg/kg/day plus PUVA until skin clearance. A clinical score was calculated for each body area, and erythema, scaling, thickness and pruritus of the lesions were scored from 0 to 3. Skin clearing was defined as a clinical score less than 10% of the initial score. Double-blind maintenance treatment was then started. This was Tigason at half of the maximal dose tolerated during the clearing phase of the treatment v. placebo. Relapse of the disease was defined as the occurrence of a clinical score greater than 50% of the initial score. Among the 36 patients randomized, 20 received placebo and 16 received Tigason. Relapses increased quickly in the patients on placebo, but occurred in few patients treated by Tigason with 60% remaining clear after 1 year (P less than 0.05). Surprisingly, the kinetics of disappearance of the most frequent side effect, cheilitis, was the same in the Tigason group and in the placebo group. This double-blind randomized clinical trial shows that Tigason at low doses is an efficient and well-tolerated maintenance treatment of psoriasis. 相似文献
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Treatment of gonorrhoea with cefotiam: activity in vitro and clinical results of a 1-gram single-dose regimen 总被引:1,自引:0,他引:1
Cefotiam is clearly more active against Neisseria gonorrhoeae in vitro than penicillin. This applies especially to strains producing beta-lactamase but also to those which do not. No strain requires more than 0.25 micrograms/ml for inhibition. 1 g of cefotiam dissolved in 3 ml of 1% lidocaine solution cures 90.0% of patients suffering from uncomplicated genital gonorrhoea if injected once intramuscularly. Tolerance of this regimen is very good, no major side-effect being found. 相似文献
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S Gangemi† RA Merendino‡ F Guarneri§ PL Minciullo† G DiLorenzo¶ M Pacor SP Cannavò§ 《Journal of the European Academy of Dermatology and Venereology》2003,17(1):42-46
OBJECTIVE: To find new aspects of the systemic involvement of the Immune System in psoriasis, we determined serum levels of interleukin-18 (IL-18) (Th1-inducing factor cytokine), CD30 (Th2 marker) and sICAM-1 (adhesion molecule). In addition we evaluated the correlation between these molecules and psoriasis area and severity index (PASI). BACKGROUND: Psoriasis is associated to an overexpression of Th1 cytokines and a relative underexpression of Th2 cytokines. IL-18 plays an important role in inducing Th1 response because it is a potent inductor of synthesis of IFN-gamma, TNF and other mediators. The two major sources of IL-18 are monocytes and macrophages but also human keratinocytes constitutively synthesized IL-18. SUBJECTS AND METHODS: We selected two groups of subjects: 16 healthy donors (HD) and 16 patients affected by psoriasis, matched for sex and age. Serum IL-18, CD30 and sICAM-1 levels were assayed by immunoenzymatic method with commercial kits. RESULTS: IL-18 and sICAM-1 levels in the patients were significantly higher than in the HDs (385.94 +/- 193.89 vs. 227.38 +/- 92.76 pg/mL, P = 0.005 and 445.00 +/- 152.67 vs. 317.88 +/- 107.20 ng/mL, P = 0.02, respectively). On the contrary, no significant difference was found between serum sCD30 levels of patients in respect to those of HDs. A significant correlation was found between serum IL-18 and PASI (Rho = 0.695, P = 0.0071), serum IL-18 and sICAM-1 (Rho = 0.543, P = 0.0356) and between sICAM-1 and PASI (Rho = 0.659, P = 0.0107). 相似文献
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B P Leroy J M Lachapelle M Jacquemin J M Saint-Remy 《Dermatology (Basel, Switzerland)》1992,184(4):271-274
This study describes the long-term follow-up of the clinical response of 10 adult patients suffering from atopic dermatitis (AD) who were treated by administration of complexes made of Dermatophagoides pteronyssinus (Dpt) allergens and autologous antibodies specific to that allergen. We have already described the clinical improvement observed after 1 year of treatment involving regular injections of complexes; this improvement was maintained throughout a second year, even though the number of injections was greatly reduced. At the end of the second year of treatment, 5 patients were completely free of disease, and 3 had had a short-lasting recurrence of low-severity dermatitis. Using a disease intensity index the mean improvement for these 8 patients was 83% compared to baseline values. One patient showed a significant recurrence of symptoms, and 1 patient left the study for personal reasons when she was in good clinical condition. A significant reduction of specific anti-Dpt IgE antibody titers was observed in 7 out of the 8 patients in clinical remission, while the level of total IgE antibodies was unchanged until the very end of the study. This study not only confirms that clinical benefit can be obtained from the treatment of AD patients hypersensitive to Dpt by injections of allergen-antibody complexes but also indicates that the therapy induces a suppression of IgE antibody production that is specific for the particular allergen. 相似文献
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目的 报道一个家族性良性天疱疮家系并对其致病基因ATP2C1进行突变筛查。方法 对先证者及其家族4代成员进行临床调查。采集每一成员静脉血标本,同时采集50例健康人血液标本作为对照。提取外周血基因组DNA,分别对 ATP2C1基因的所有28个外显子及其侧翼内含子序列进行PCR扩增,再对每一扩增产物进行直接测序,最后将测序结果分别与基因库(NM_014382.2和NC_000003.9)的编码序列和基因组序列进行逐一比对分析。结果 调查该家系4代24个成员,共有8例患者。基因筛查显示先证者和该家族其他患者的ATP2C1基因第17号外显子上发生一单核苷酸碱基置换,即c(1696C→T);同时该家族中第2代、第3代正常成员和50例健康对照均未检测到这一碱基变化。第4代4个成员中,仅有1个成员,即Ⅳ3,亦检测到这一变化。结论 该家系患者ATP2C1基因发生c(1696C→T)无义突变,可能是家族性良性天疱疮的致病突变;Ⅳ3携带该突变,但到目前为止,其未发生家族性良性天疱疮的相关临床症状,有必要对其进行密切随访。 相似文献
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Raiko L Siljamäki E Mahoney MG Putaala H Suominen E Peltonen J Peltonen S 《Experimental dermatology》2012,21(8):586-591
Mutations in the ATP2C1 gene encoding Ca2+/Mn2+ ATPase SPCA1 cause Hailey–Hailey disease (HHD, OMIM 16960). HHD is characterized by epidermal acantholysis. We attempted to model HHD using normal keratinocytes, in which the SPCA1 mRNA was down‐regulated with the small inhibitory RNA (siRNA) method. SiRNA inhibition significantly down‐regulated the SPCA1 mRNA, as demonstrated by qPCR, and decreased the SPCA1 protein beyond detectable level, as shown by Western analysis. The expression of selected desmosomal, adherens and tight junction (TJ) proteins was then studied in the SPCA1‐deficient and control keratinocytes cultured in low (0.06 mm ) or high (1.2 mm ) calcium concentration. The mRNA and protein levels of most TJ components were up‐regulated in non‐treated control keratinocyte cultures upon switch from low to high calcium concentration. In contrast, SPCA1‐deficient keratinocytes displayed high levels of TJ proteins claudins 1 and 4 even in low calcium. ZO‐1 did not, however, follow similar expression patterns. Protein levels of occludin, beta‐catenin, E‐cadherin, desmoplakin, desmogleins 1–3, desmocollin 2/desmocollin 3 and plakoglobin did not show marked changes in SPCA1‐deficient keratinocytes. Indirect immunofluorescence labelling revealed delayed translocation of desmoplakin and desmoglein 3 in desmosomes and increased intracellular pools of TJ and desmosomal components in SPCA1‐inhibited keratinocytes. The results show that SPCA1 regulates the levels of claudins 1 and 4, but does not affect desmosomal protein levels, indicating that TJ proteins are differently regulated. The results also suggest a potential role for claudins in HHD. 相似文献
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M Maticic† M Poljak‡ T Lunder§ K Rener-Sitar¶ L Stojanovic 《Journal of the European Academy of Dermatology and Venereology》2008,22(7):779-788
Background Several controversies exist regarding the relationship between hepatitis C virus (HCV) infection and some cutaneous manifestations, lichen planus (LP) in particular. Objectives To determine the prevalence of LP and other cutaneous manifestations in a cohort of patients infected with HCV from low HCV endemic area of Slovenia, to correlate findings with chosen biological variables and to assess the role of interferon (IFN)‐based treatment of HCV infection in cutaneous manifestations. Methods A total of 171 consecutive HCV‐seropositive patients and 171 HCV‐seronegative age‐ and gender‐matched controls were studied prospectively. Prevalence of cutaneous manifestations, comparison between study patients and controls and correlation of skin findings with demographic, biochemical, virological and liver histologic findings as well as IFN‐based therapy were assessed. Results Overall presence of LP in HCV‐seropositives was 2.3%; although LP was not found in controls, the difference was not statistically significant (P = 0.123). Significantly higher than in controls was the prevalence of pruritus (31.0%, P < 0.001), dry skin (16.4%, P < 0.001) and hair loss (9.9%, P < 0.001). In IFN‐based treatment naïves, skin findings were more frequent compared with controls, but not significantly, with no correlation to chosen biological variables. Current IFN‐based treatment was significantly connected to pruritus (P < 0.001) and dry skin (P < 0.001). Compared with treatment naïves, in post‐treated patients pruritus (odds ratio, 19.13; 95% confidence interval, 6.85–53.42; P < 0.001), dry skin (odds ratio, 4.21; 95% confidence interval, 1.44–12.31; P < 0.001) and hair loss (P < 0.001) were significantly more common. Conclusions LP was not significantly related to HCV infection. Prevalence of pruritus, dry skin and hair loss was significantly higher in post‐compared with pre‐treated patients. The role of IFN in post‐treatment persistence of skin manifestations needs to be assessed. 相似文献
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Ota's nevus is a dermal melanocytic disease which causes serious cosmetic problems for affected individuals. Recently Q-switched lasers with a pulse duration of 100 nsec or less became available for patient treatment. We evaluated the clinical efficacy of the Q-switched alexandrite laser (755 nm, 100 nsec) in relation to the histopathological findings. Fifty-five Korean patients with Ota's nevus were treated with a Q-switched alexandrite laser for three sessions (7.5 J/cm2) at three month intervals. Skin biopsies were taken in all of the patients before treatment and immediately after treatment in five patients. Clinical effectiveness and side effects were evaluated by direct observation and photographs. Pigment clearing was excellent in 27 patients (49%), good in 17 patients (31%), fair in 7 patients (13%) and poor in 4 (7%) patients. Postinflammatory hyperpigmentation developed in 30 patients (55%) which resolved within four months. But there were no serious complications including scarring or textural change. The therapeutic outcome was not affected by color but by depth of the nevus. Nevi of Ota with depth of 1 mm or less were associated with excellent or good results. Q-switched alexandrite laser is a very effective and safe tool for treating Ota's nevus. Depth of 1 mm or less of dermal melanocytes was a good prognostic marker. 相似文献