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Two Approaches to the Study of a Controversial Relationship: Cutaneous Photosensitivity and Anti-Ro/SS-A Autoantibodies

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Open Journal of Rheumatology and Autoimmune diseases 2014年第1期4卷 1-12页

作者： Mariela L. Paz Eliana M. Cela Alejandro Ferrari Adrián d. Friedrich Juliana Leoni daniel H. González Maglio Immunology department Pharmacy and Biochemistry School University of Buenos Aires Buenos Aires Argentina.

Background: Autoantibodies (Aabs) are the hallmark of numerous systemic autoimmune pathologies (SAPs), for instance anti-Ro/SS-A Aabs are usually found in Systemic Lupus Erythematosus (SLE) and Sjogren’s Syndrome. Cutaneous photosensitivity (CP) is found in most forms and subsets of LE and consists of a skin rash as a result of unusual reaction to sunlight. There are many theories which relate specifically the presence of circulating anti-Ro/SS-A Aabs with the CP phenomenon, though there are several studies which are in disagreement. Results: In this study we analyzed the relationship between CP and anti-Ro Aabs by means of two approaches. The first one included an in vitro model where we evaluated by flow cytometry the binding capacity of affinity-purified Aabs to autoantigens relocalized on apoptotic keratinocyte’s surface. We found that there was no relationship between the binding capacity of serum from 10 selected patients or their corresponding purified anti-Ro52 and anti-Ro60 Aabs, and the presence or absence of CP, neither with the SAPs. The in vivo model consisted of Hairless SKH:1 mice which were induced to produce anti-murine Ro52 and/or Ro60 Aabs and were subsequently irradiated with UVB light. We evaluated the skin histology and also the epidermal production of TnF-α. We found no differences between the groups in neither of the parameters evaluated. Conclusions: These results agree with some studies on the role of the Aabs in CP, considering anti-Ro Aabs not as the only responsible for the manifestation;and disagree with many other authors, who believe in the strong association between these two events.

关键词： Cutaneous Photosensitivity Purified Anti-Ro/SS-A Autoantibodies SKH-1 Hairless Mice UVB Irradiation TnF-α

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氟伐他汀诱发的皮肌炎(法语)

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世界核心医学期刊文摘（皮肤病学分册） 2006年第4期2卷 28-29页

作者： Thual n. Penven K. Chevallier J.-M. d. Leroy 李晓莉 Service de dermatologie Centre Hospitalier Universitaire Avenue Georges Clé menceau 14033 Caen Cedex

Background. dermatomyositis is a rare inflammatory dermatosis for which an iatrogenic origin has been described in very few cases. We report a case of dermatomyositis occurring after fluvastatin intake. Case report. A 76-year-old male patient sought medical attention for a photodistributed rash and considerable muscular weakness present for one month. Two months earlier, fluvastatin had been introduced following the discovery of dyslipidemia. Serum creatine phosphokinase levels were elevated. Histological examination of a muscle biopsy was consistent with a diagnosis of dermatomyositis. Investigation for neoplasia and associated autoimmune disease proved negative. All clinical and laboratory abnormalities diminished spontaneously without recourse to corticosteroids with in one month of the final intake of fluvastatin. After a follow-up period of three years, no recurrence was observed and no signs of neoplasia or connectivitis were found. discussion. Iatrogenic dermatomyositis has only been reported in rare cases. Certain drugs have been incriminated, notably d-penicillamine. Six cases of drug-induced dermatomyositis have been described with statins: simvastatin, atorvastatin, pravastatin and lovastatin. Of these cases, only one resolved spontaneously after withdrawal of the drug alone without use of corticosteroids. Our case concerns intake of fluvastatin, an HMG-CoA reductase inhibitor with rare though well-known muscular side effects: elevated serum CPK, myalgia and rhabdomyolysis. Six cases of polymyositis have also been reported. Ours is the first case of dermatomyositis described with this category of statins. It is also the second reported case showing improvement after withdrawal of the lipid-lowering agent and without corticosteroids. Thus in cases of dermatomyositis, this iatrogenic picture should be sought routinely.

关键词：皮肌炎氟伐他汀药物诱发多发性肌炎横纹肌溶解他汀药物结缔组织病自身免疫疾病降脂药肌痛

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Prediction of Functional Outcome in Post-Hospital Brain Injury Rehabilitation

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Journal of Behavioral and Brain Science 2019年第12期9卷 406-416页

作者： Frank d. Lewis Gordon J. Horn neuroRestorative Research Institute Medical College of Georgia at Augusta University Augusta GA USA neuroRestorative Research Institute College of Medicine Florida State University Tallahassee FL USA

Post-hospital brain injury rehabilitation programs are afforded limited time to reduce chronic disability resulting from acquired brain injury. Therefore, the purpose of this study was to identify deficit areas resulting from acquired brain injury that have the greatest impact on functional outcomes to enable greater efficiency in rehabilitation programming. Study participants were 1717 persons with acquired brain injury treated in residential post-hospital rehabilitation programs. Participants were assessed at admission and discharge on the MPAI-4. Functional status at discharge was evaluated based on T-scores derived from MPAI-4 discharge participation index items: Initiation, self-care and residence. The data base of 1717 was randomly divided into two subsets. Items from admission Abilities Index and select person variables were entered into stepwise multiple regression on subset one and then in a hierarchical multiple regression on subset two. rash analysis demonstrated satisfactory construct validity and internal consistency of admission and discharge MPAI-4 evaluations (Person reliability > 0.90, Item reliability = 0.99). Both regression analyses revealed that Mobility and novel Problem Solving accounted for 40% of the variance in functional outcome, p d brain injury results in a myriad of cognitive and physical impairments. Of the many possible deficits, the greatest gains in overall functional outcomes may be achieved by allocating additional treatments aimed at reducing disability in mobility and novel problem solving.

关键词： Brain Injury Mayo Portland Adaptability Index Version-4 Rasch Analysis Outcome Post-Hospital Brain Injury Rehabilitation

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The Adverse Event Profile in Patients Treated with Transferon<sup>TM</sup>(dialyzable Leukocyte Extracts): A Preliminary Report

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Pharmacology & Pharmacy 2015年第2期6卷 65-74页

作者： Toni Homberg Violeta Sáenz Jorge Galicia-Carreón Iván Lara Edgar Cervantes-Trujano Maria C. Andaluz Erika Vera Oscar Pineda Julio Ayala-Balboa Alejandro Estrada-García Sergio Estrada-Parra Mayra Pérez-Tapia Maria C. Jiménez-Martínez Clinical Trials Branch and Clinical Immunology Service Unit of External Services and Clinical Research (USEIC) National School of Biological Sciences National Polytechnic Institute Mexico City Mexico Unit of Pharmacovigilance Unit of External Services and Clinical Research (USEIC) National School of Biological Sciences National Polytechnic Institute Mexico City Mexico department of Immunology National School of Biological Sciences National Polytechnic Institute Mexico City Mexico Unit of R&d in Bioprocesses (UdIBI) National School of Biological Sciences National Poly-technic Institute Mexico City Mexico department of Biochemistry Faculty of Medicine National Autonomous University of Mexico Mexico City Mexico

Background: dialyzable leukocyte extracts (dLE) are heterogeneous mixtures of peptides less than 10 kda in size that are used as immunomodulatory adjuvants in immune-mediated diseases. TransferonTM is dLE manufactured by national Polytechnic Institute (IPn), and is registered by Mexican health-regulatory authorities as an immunomodulatory drug and commercialized nationally. The proposed mechanism of action of TransferonTM is induction of a Th1 immunoregulatory response. despite that it is widely used, to date there are no reports of adverse events related to the clinical safety of human dLE or TransferonTM. Objective: To assess the safety of TransferonTM in a large group of patients exposed to dLE as adjuvant treatment. Methods: We included in this study 3844 patients from our Clinical Immunology Service at the Unit of External Services and Clinical Research (USEIC), IPn. Analysis was performed from January 2014 to november 2014, searching for clinical adverse events in patients with immune-mediated diseases and treated with TransferonTM as an adjuvant. Results: In this work we observed clinical nonserious adverse events (AE) in 1.9% of patients treated with TransferonTM (Md 1.9, IQR 1.7 - 2.0). AE were 2.8 times more frequently observed in female than in male patients. The most common AE were headache in 15.7%, followed by rash in 11.4%, increased disease-related symptomatology in 10%, rhinorrhea in 7.1%, cough in 5.7%, and fatigue in 5.7% of patients with AE. 63% of adverse event presentation occurred from day 1 to day 4 of treatment with TransferonTM, and mean time resolution of adverse events was 14 days. In 23 cases, the therapy was stopped because of adverse events and no serious adverse events were observed in this study. Conclusion: TransferonTM induced low frequency of nonserious adverse events during adjuvant treatment. Further monitoring is advisable for different age and disease groups of patients.

关键词： dialyzable Leukocyte Extracts Adverse Events Monitoring drug Safety Adjuvant Therapy Immunoregulation Guidelines Transfer Factor Pharmacovigilance

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联合应用沙利度胺和脂质体阿霉素治疗复发性卵巢上皮性癌和腹膜癌的初步研究

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现代妇产科进展 2008年第2期17卷 109-112页

作者：郭红燕 nelson n. Teng John K. Chan Amreen Husain deirdre Stieglitz Jonathon S Bereck 北京大学第三医院妇产科北京100083 美国斯坦福大学肿瘤妇科

目的：评价联合应用沙利度胺与脂质体阿霉素治疗复发性卵巢上皮性癌和腹膜癌的疗效和毒副作用。方法：将9例经手术和术后泰素＋卡铂化疗后复发患者纳入本研究。每4周予以脂质体阿霉素30～50mg／m^2化疗，共3～8个疗程；同时每日予以沙... 详细信息

目的：评价联合应用沙利度胺与脂质体阿霉素治疗复发性卵巢上皮性癌和腹膜癌的疗效和毒副作用。方法：将9例经手术和术后泰素＋卡铂化疗后复发患者纳入本研究。每4周予以脂质体阿霉素30～50mg／m^2化疗，共3～8个疗程；同时每日予以沙利度胺100～300mg，其剂量从100mg／d开始，此后每2周增加50～100mg。通过体检、影像学检查和测定CA125水平评价治疗效果。结果：9例患者的中位年龄为56岁（35～81岁），FIGO分期为ⅢB～Ⅳ期。本次化疗的中位疗程数是6个疗程。中位随访时间为18．5个月。最常见的不良反应为疲劳（55．6％）和神经系统症状（55．6％）。3例患者出现Ⅲ度副反应，1例为无力、1例过敏性皮疹和1例末梢神经感觉异常。根据RECIST标准评价有病灶的6例患者疗效，2例部分缓解，2例治疗中疾病无进展，1例病情进展，1例失访。另有2例CA125升高的患者，在联合化疗3～4个疗程后CA125水平降低50％以上。1例二次肿瘤细胞减灭术后化疗的患者治疗后随访36个月无肿瘤复发迹象。在随访的8例患者中，中位疾病无进展时间为6．5个月（0～36个月）；中位总的生存时间为20．5个月（8～36个月）。结论：联合应用沙利度胺与脂质体阿霉素治疗复发性卵巢上皮性癌具有可接受的毒副作用，同时具有一定的治疗效果。

关键词：复发性卵巢上皮性癌沙利度胺脂质体阿霉素药物疗法,联合

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MSH1 Is a Plant Organellar dnA Binding and Thylakoid Protein under Precise Spatial Regulation to Alter development

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Molecular Plant 2016年第2期9卷 245-260页

作者： Kamaldeep S. Virdi Yashitola Wamboldt Hardik Kundariya John d. Laurie Ido Keren K.R. Sunil Kumar Anna Block Gilles Basset Steve Luebker Christian Elowsky Philip M. day Johnna L. Roose Terry M. Bricker Thomas Elthon Sally A. Mackenzie School of Biological Sciences department of Agronomy and Horticulture University of nebraska Lincoln NE 68588 USA Center for Biotechnology University of Nebraska Lincoln NE 68588 USA department of Biological Sciences Louisiana State University Baton Rouge LA 70803 USA These authors contributed equally to this article

As metabolic centers, plant organelles participate in maintenance, defense, and signaling. MSH1 is a plant- specific protein involved in organeUar genome stability in mitochondria and plastids. Plastid depletion of MSH1 causes heritable, non-genetic changes in development and dnA methylation. We investigated the rash I phenotype using hemi-complementation mutants and transgene-null segregants from RnAi suppres- sion lines to sub-compartmentalize MSH1 effects. We show that MSH1 expression is spatially regulated, specifically localizing to plastids within the epidermis and vascular parenchyma. The protein binds dnA and localizes to plastid and mitochondrial nucleoids, but fractionation and protein-protein interactions data indicate that MSH1 also associates with the thylakoid membrane. Plastid MSH1 depletion results in variegation, abiotic stress tolerance, variable growth rate, and delayed maturity. depletion from mitochon- dria results in 7%-10% of plants altered in leaf morphology, heat tolerance, and mitochondrlal genome sta- bility. MSH1 does not localize within the nucleus directly, but plastid depletion produces non-genetic changes in flowering time, maturation, and growth rate that are heritable independent of MSH 1. MSH1 deple- tion alters non-photoactive redox behavior in plastids and a sub-set of mitochondrially altered lines. Ectopic expression produces deleterious effects, underlining its strict expression control. Unraveling the complexity of the MSH1 effect offers insight into triggers of plant-specific, transgenerational adaptation behaviors.

关键词： Thylakoid protein Organellar dnA binding MSH1 Epigenetic variation

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用抗雌激素药物改善皮肌炎皮疹

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世界核心医学期刊文摘（皮肤病学分册） 2006年第3期2卷 31-32页

作者： Sereda d. Werth V.P. 刘艳 2 Rhoads Pavilion Department of Dermatology 36th and Spruce Streets Philadelphia PA19104United States Dr

Background: dermatomyositis (dM) is an autoimmune disorder that occurs more often inwomen than men and causes highly symptomatic and inflammatory cutaneous and proximal muscle disease. Corticosteroids have been the treatment of choice for myositis in dM, and antimalarial agents for the skin disease of dM, with methotrexate sodium, azathioprine, mycophenolate mofetil, cyclosporine, and intravenous immunoglobulin used as steroid-sparing agents. Recently, reports supporting a role for anti-tumor necrosis factorα (TnF-α ) therapy in the treatment of dM have emerged. Observations: We describe 2 women who experienced an improvement in their dM-associated skin eruptions while taking antiestrogen medication. The first patient was taking tamoxifen, a selective estrogen receptor modulator that has been found to have anti-TnF-α properties. The second was taking anastrozole, an aromatase inhibitor. When tamoxifen therapy was discontinued after 4 years of use in the first patient, her dM rash worsened and remained difficult to control with conventional immunosuppressant medication. Conclusions: With the limited number of therapies available to manage dM skin eruptions, the discovery of novel agents effective in treating this disease is vital. Using antiestrogen medication in women with dM may result in a significant improvement in their rash, possibly via the inhibition of TnF-α production by immune or other cells. Further investigation into the use of antiestrogen therapy in dM is merited to evaluate longterm risks and benefits.

关键词：抗雌激素药物皮肌炎肿瘤坏死因子-α(TnF-α) 选择性雌激素受体调节剂静脉注射免疫球蛋白自身免疫性疾病皮疹女性患者抗TnF-α 皮肤损害

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经表皮试验及淋巴细胞转化试验证实由A组皮质类固醇激素诱发的口服泼尼松龙后出现急性泛发性发疹性脓疱病

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世界核心医学期刊文摘（皮肤病学分册） 2006年第9期2卷 49-50页

作者： Buettiker U. Keller M. PichlerW.J. n. Yawalkar 吴佳纹 department of dermatology Inselspital CH- 3010 Berne Switzerland Dr.

Background: Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption which is often provoked by drugs. Case Report: We report 2 cases of AGEP which showed rapidly spreading pustular eruptions accompanied by malaise, fever and neutrophilia after the administration of systemic prednisolone (corticosteroid of group A, hydrocortisone type). The histological examination showing neutrophilic subcorneal spongiform pustules was consistent with the diagnosis of AGEP. In both cases the rash cleared within a week upon treatment with topical steroids (corticosteroid of group d1, beta-methasonediprop-ionate type and corticosteroid of group d2, hydrocortisone-17-butyrate type). Three months after recovery, the sensitization to corticosteroids of group A was confirmed by epicutaneous testing and positive lymphocyte transformation tests. Conclusion: These cases show that systemic corticosteroids can induce AGEP and demonstrate that epicutaneous testing and lymphocyte transformation tests may be helpful in identifying the causative drug. Our data support previous reports indicating an important role for drug-specific T cells in inducing neutrophil inflammation in this disease.

关键词：急性泛发性发疹性脓疱病淋巴细胞转化试验皮质类固醇激素泼尼松龙激素诱发皮试验丁酸氢化可的松嗜中性粒细胞

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原发性人疱疹病毒6型感染的群体调查研究

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世界核心医学期刊文摘（儿科学分册） 2005年第7期1卷 2-3页

作者： Zerr d.M. Meier A.S. Selke S.S. 李开 Children's Hospital 4800 Sand Point Way NE Seattle WA 98105 United States Dr.

BACKGROUnd: Serologic studies indicate that human herpesvirus 6 (HHV-6) infects 90 percent of children by two years of *** is known about the acquisition, virologic course, and clinical manifestations of HHV-6 ***: We prospectively studied a cohort of 277 children from birth through the first two years of life to define the pattern of acquisition of *** children’s saliva was tested weekly for HHV-6 dnA with the use of the polymerase chain *** maintained a daily log of signs and symptoms of illness in their ***: Primary HHV-6 infection occurred in 130 children, with cumulative percentages of 40 percent by the age of 12 months and 77 percent by the age of 24 *** peak age of acquisition was between 9 and 21 *** acquisition of HHV-6 was associated with female sex (adjusted hazard ratio, 1.7; 95 percent confidence interval, 1.2 to 2.4) and having older siblings (adjusted hazard ratio, 2.1; 95 percent confidence interval, 1.4 to 2.9).Among 81 children with a well-defined time of acquisition of HHV-6, 93 percent had symptoms, and 38 percent were seen by a *** had *** compared with children who had other illnesses, those with primary HHV-6 infection were more likely to have fever (P=0.003), fussiness (P=0.02), diarrhea (P=0.03), rash (P=0.003), and roseola (P=0.002) and were more likely to visit a physician (P=0.003).COnCLUSIOnS: The acquisition of HHV-6 in infancy is usually symptomatic and often results in medical *** occurs in a minority of patients, and febrile seizures are infrequently associated with primary HHV-6 *** siblings appear to serve as a source of HHV-6 transmission.

关键词：疱疹病毒群体调查高峰年龄感染方式病毒感染过程多聚酶链式反应前瞻性队列研究热性惊厥易激惹血清学

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肝移植后急性移植物抗宿主病的早期指征:皮疹和全血细胞减少

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世界核心医学期刊文摘(皮肤病学分册) 2005年第9期 61-62页

作者： Whalen J.G. Jukic d.M. English III J.C. 焦婷 department of dermatology University of Pittsburgh 145 Lothrop Hall 190 Lothrop St Pittsburgh PA 15213 United States Dr.

Acute graft-versus-host disease is mainly a complication of allogeneic bone-marrow transplantation, and rarely seen after transplantation of solid organs. We describe a 68-year-old man who developed a maculopapular eruption and fever approximately 15 days after orthotopic liver transplantation for cryptogenic cirrhosis. At day 19, the patient developed abrupt neutropenia and diarrhea. Skin biopsy was performed and the specimen revealed basal cell layer vacuolization, necrotic keratinocytes, and satellite cell necrosis. Bone-marrow aspiration performed after the patient became pancytopenic revealed aplastic marrow with scattered lymphocytes and rare megakaryocytes. A diagnosis of acute graft-versus-host disease was made and an immunosuppressive drug regimen was initiated. Unfortunately, the patient died after support was withdrawn because of total ablation of his bone marrow and multiorgan failure. This report describes the rare presentation of acute graft-versus-host disease after solid organ transplantation, and that skin manifestations may be an early presenting sign.

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