BACKGROUND & AIMS: :There are several reports in the literature describing the coexistence of features of pemphigus vulgaris and pemphigoid in the same patient. We describe 15 patients with clinical, histological, and immunopathological features of mucous membrane (cicatricial) pemphigoid at the time of initial diagnosis. All 15 patients failed to respond clinically to conventional systemic agents over a mean period of 7.2 years. Hence, IVIg therapy was used. Prior to initiating IVIg therapy, features of mucous membrane pemphigoid and pemphigus vulgaris were demonstrated by various serological tests. Different assays were performed to identify molecular characteristics of these two autoantibodies. Twenty-five healthy normal individuals, 22 patients with mucous membrane pemphigoid, 17 patients with pemphigus vulgaris, and 12 patients with pemphigus foliaceus served as controls for comparison of serological studies. On indirect immunofluorescence, using monkey esophagous as substrate, sera of all 15 patients had demonstrable levels of anti-intercellular cement substance (ICS) or anti-keratinocyte cell surface antibody. Sera of 14 patients on salt split skin bound to the epidermal side of the split, which was consistent with mucous membrane pemphigoid. Sera of all 15 patients demonstrated binding to a 205-kDa protein (human B4 integrin) and a 130-kDa protein (desmoglein 3) on immunoblot. In a sample of sera from each of the 6 patients with mucous membrane pemphigoid and pemphigus vulgaris, the anti-ICS antibody was of the IgG4 subclass. The IgG4 subclass is a characteristic feature associated with pathogenic autoantibodies in pemphigus vulgaris. Hence, in such patients, a dual diagnosis should be considered and confirmed by various serological assays. It is possible that the presence of two pathogenic autoantibodies in these patients could have contributed to the lack of response to conventional immunosuppressive therapy.

背景与目标： : 文献中有几篇报道描述了同一患者中寻常型天疱疮和类天疱疮的特征并存。我们描述了15例在最初诊断时具有粘膜 (瘢痕性) 类天疱疮的临床，组织学和免疫病理特征的患者。在7.2年的平均时间内，所有15名患者对常规全身性药物均没有临床反应。因此，使用了IVIg疗法。在开始IVIg治疗之前，通过各种血清学测试证明了粘膜类天疱疮和寻常型天疱疮的特征。进行了不同的测定以鉴定这两种自身抗体的分子特征。25名健康正常人，22例粘膜类天疱疮患者，17例寻常型天疱疮患者和12例叶状天疱疮患者作为血清学研究的对照。在间接免疫荧光上，以猴食道为底物，所有15例患者的血清均具有明显水平的抗细胞间骨水泥物质 (ICS) 或抗角质形成细胞表面抗体。14例盐裂皮肤上的血清与裂口的表皮侧结合，与粘膜类天疱疮一致。在免疫印迹上，所有15名患者的血清均显示出与205 kDa蛋白 (人B4整联蛋白) 和130 kDa蛋白 (desmoglein 3) 结合。在6例粘膜类天疱疮和寻常型天疱疮患者的血清样本中，抗ICS抗体属于IgG4亚类。IgG4亚类是与寻常型天疱疮中的致病性自身抗体相关的特征。因此，在此类患者中，应考虑并通过各种血清学检测来确认双重诊断。这些患者中存在两种致病性自身抗体可能导致对常规免疫抑制疗法缺乏反应。

BACKGROUND & AIMS: :Detection of anti-desmoglein-1 (anti-DSG-1) and anti-DSG-3 autoantibodies is widely used in the diagnosis of pemphigus. Two validated scoring systems, Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), are used for the evaluation of clinical severity. The aim of this cross-sectional study was to interpret the titres of pemphigus autoantibodies in correlation with either total or location-dependent PDAI scores and ABSIS. A total of 35 pemphigus patients were selected and evaluated at 3 time points. Total PDAI and ABSIS seemed useful in pemphigus with cutaneous lesions or in the mucocutaneous form, while location-dependent PDAI and ABSIS scores were useful in the mucosal form. Anti-DSG-1 autoantibodies titres better showed the disease extent in pemphigus with cutaneous only or with mucocutaneous lesions. Anti-DSG-3 autoantibodies titres did not correlate to disease activity.

背景与目标： : anti-desmoglein-1 (anti-DSG-1) 和anti-DSG-3自身抗体的检测被广泛用于天疱疮的诊断。两种经过验证的评分系统，即天疱疮疾病面积指数 (PDAI) 和自身免疫性大疱性皮肤病强度评分 (ABSIS)，用于评估临床严重程度。这项横断面研究的目的是解释天疱疮自身抗体的滴度与总或位置依赖性PDAI评分和ABSIS相关。共选择35例天疱疮患者，并在3个时间点进行评估。总PDAI和ABSIS似乎在具有皮肤病变或粘膜皮肤形式的天疱疮中有用，而位置依赖性的PDAI和ABSIS评分在粘膜形式中有用。Anti-DSG-1自身抗体滴度更好地显示了仅皮肤或皮肤粘膜病变的天疱疮的疾病程度。Anti-DSG-3自身抗体滴度与疾病活动无关。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :The nephrotic syndrome complicating malignancy in the absence of renal vein thrombosis, amyloid or neoplastic infiltration of the kidney is an unusual occurrence. A case of diffuse, well differentiated, lymphocytic lymphoma and lipoid nephrosis documented by light microscopy, electron microscopy and immunofluorescent studies is reported. A review of the literature revealed 76 case reports in which the nephrotic syndrome was associated with neoplasia. The most frequently associated neoplasms are Hodgkin's disease, various carcinomas, nonHodgkin's lymphoma and leukemia in descending order. The most frequent renal lesion in patients with the nephrotic syndrome associated with various carcinomas is membranous glomerulonephritis (81 per cent) as opposed to patients with lymphomas or leukemias who have predominantly lipoid nephrosis (60 per cent). The evidence is reviewed suggesting that the lesions in membranous nephropathy are immunologically mediated by tumor or viral antigen-antibody complexes and in lipoid nephrosis perhaps by a defect in t-lymphocyte function.

背景与目标： : 在没有肾静脉血栓形成，肾脏淀粉样蛋白或肿瘤性浸润的情况下，肾病综合征并发恶性肿瘤是不常见的。报道了通过光学显微镜，电子显微镜和免疫荧光研究记录的弥漫性，高分化，淋巴细胞淋巴瘤和类脂性肾病的病例。对文献的回顾揭示了76例肾病综合征与肿瘤相关的病例报告。最常见的肿瘤是霍奇金病，各种癌，非霍奇金淋巴瘤和白血病。与各种癌相关的肾病综合征患者相比，最常见的肾脏病变是膜性肾小球肾炎 (81%)，而淋巴瘤或白血病患者主要患有类脂性肾病 (60%)。审查的证据表明，膜性肾病的病变是由肿瘤或病毒抗原-抗体复合物免疫介导的，而类脂性肾病可能是由t淋巴细胞功能缺陷介导的。

BACKGROUND & AIMS: :Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration [PCD]) were evaluated using neuropsychological tests and 18F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a "reverse cerebellar diaschisis."

背景与目标： : 使用神经心理学测试和18f-氟脱氧葡萄糖/正电子发射断层扫描对11例获得性小脑变性患者 (其中10例患有副肿瘤性小脑变性 [PCD]) 进行评估，以 (1) 量化运动，认知和代谢异常; (2) 确定葡萄糖区域脑代谢率 (rCMRGlc) 的特征性改变是否与PCD相关; (3) 将疾病严重程度的行为和代谢指标相关联。18名志愿者作为正常对照。尽管某些PCD神经心理学测试分数异常，但这些结果通常无法与构音障碍和共济失调的影响分离。除脑干外，所有区域的PCD患者 (与正常对照组相比) 的rCMRGlc均降低。使用区域代谢相互作用的数学模型对患者和对照rCMRGlc数据进行分析，揭示了两个代谢模式描述符SSF1和SSF2，将PCD患者与正常对照组区分开来; SSF2，描述了小脑，楔形和后颞，外侧额叶和中央旁皮质之间的代谢耦合，与小脑功能障碍的定量指标相关。我们无法证明10例PCD患者中有7例存在实质性的智力障碍，这与先前研究者报告的PCD中痴呆的50% 发生率形成了对比。PCD rCMRGlc的广泛减少可能是由于小脑传出到丘脑和前脑结构的丧失，即 “反向小脑困难”。

BACKGROUND & AIMS: :Esophageal involvement of pemphigus vulgaris (PV) had been considered an exceptional event. We present the case of a woman with PV who developed esophageal involvement while being treated with azathioprine and resolved after steroid therapy. This case highlights that esophageal involvement of PV might be resistant to immunosuppressive therapy other than steroids.

背景与目标： : 食管受累寻常天疱疮 (PV) 被认为是一个特殊事件。我们介绍了一名患有PV的妇女，该妇女在接受硫唑嘌呤治疗时出现食道受累，并在类固醇治疗后消退。该病例突出表明，PV的食道受累可能对类固醇以外的免疫抑制疗法具有抵抗力。

BACKGROUND & AIMS: :Adult-onset Still's disease is a systemic disorder without specific histological feature. Diagnosis requires to rule out any other disorder including neoplasia. Nevertheless, patients with paraneoplastic adult-onset Still's disease have been reported. We report a patient with an adult-onset Still's disease who presented with a liver involvement at onset. Two years later, a liver angiosarcoma was diagnosed. This report underlines the difficulty of the diagnosis of the adult-onset Still's disease even in the presence of Yamaguchi et al.'s [J Rheumatol 19 (1992) 424-30] and Fautrel et al.'s [Medicine 81 (2002) 194-200] classification criteria and may suggest a link between the initial clinical picture and the discovery nearly two years later, of a liver angiosarcoma.

背景与目标： : 成人型斯蒂氏病是一种全身性疾病，没有特定的组织学特征。诊断需要排除任何其他疾病，包括肿瘤。尽管如此，已经报道了患有副肿瘤性成人斯蒂里氏病的患者。我们报告了一名成人Still病患者，该患者在发病时表现为肝脏受累。两年后，诊断出肝脏血管肉瘤。该报告强调了即使在存在Yamaguchi等人的 [J风湿病19 (1992) 424-30] 和Fautrel等人的 [医学81 (2002) 194-200] 分类标准的情况下，成人发病的斯蒂尔病的诊断困难，并且可能建议最初的临床情况和近两年后的发现，肝脏血管肉瘤。

BACKGROUND & AIMS: A 54-year-old woman with clinically diagnosed paraneoplastic limbic encephalitis secondary to adenocarcinoma of the lung is described. Neuropsychological evaluation revealed intact visual perception, visual construction, language, speeded processing, and verbal abstract reasoning in the presence of a severe anterograde amnesia for both verbal and visual information. A profound consolidation problem is discussed in view of other diseases of the mesial temporal lobes resulting in impaired consolidation of new material.

背景与目标： 描述了一名54岁的女性，其临床诊断为继发于肺腺癌的副肿瘤性边缘性脑炎。神经心理学评估显示，在存在严重的顺行性遗忘的口头和视觉信息的情况下，完整的视觉感知，视觉构造，语言，快速处理和口头抽象推理。鉴于中颞叶的其他疾病导致新材料的巩固受损，讨论了一个深刻的巩固问题。

BACKGROUND & AIMS: This report describes a case of paraneoplastic neurological syndrome associating a subacute sensory neuronopathy and an intestinal pseudo-obstruction in a 64-year old man with a small cell lung cancer. Various paraneoplastic neurological syndromes have been described in association with small cell lung cancer. In our patient anti-Hu antibodies were identified by indirect immunohistochemistry and western-blot analysis. This antibody constitutes an informative tool in assessing the paraneoplastic origin of neurologic symptoms when the etiological inquiry is negative. Its positivity is important in promoting the search for an underlying malignancy and should lead to repeat investigations if the first investigations are normal.

背景与目标： 本报告描述了一例副肿瘤神经系统综合症，该病例与一名64岁的小细胞肺癌患者的亚急性感觉神经病和肠假性梗阻有关。已经描述了与小细胞肺癌相关的各种副肿瘤神经综合征。在我们的患者中，通过间接免疫组织化学和western印迹分析鉴定了抗Hu抗体。当病因询问为阴性时，该抗体构成了评估神经症状的副肿瘤起源的有用工具。它的阳性对于促进寻找潜在的恶性肿瘤很重要，如果首次调查正常，则应导致重复调查。

BACKGROUND & AIMS: :The onset and course of pemphigus are often the result of an interaction between predisposing genetic factors and environmental triggering agents. The latter are heterogeneous, numerous and increasing, ranging from drug intake (the commonest cause of pemphigus induction) to the exposure to physical agents (heat, UV and ionizing rays, surgical and cosmetic procedures), viral infections (especially by herpesvirus), contact dermatitis, certain diet ingredients and even emotional stress. Alerting physicians and pemphigus patients to the effects that unsuspected precipitating factors may have on the progression of the disease is an important task. In fact, avoiding or limiting deleterious habits (e.g. overindulging in unnecessary drugs) and suggesting alternative ways (e.g. substituting potentially pemphigus-inducing drugs with others considered harmless in this respect) may be a useful precaution in the management of pemphigus patients, since it can improve the efficacy of conventional treatments, reduce the risks of relapses and sometimes result in a cure.

背景与目标： : 天疱疮的发作和病程通常是易感遗传因素和环境触发因素之间相互作用的结果。后者是异质的，数量众多且不断增加，从药物摄入 (天疱疮诱导的最常见原因) 到暴露于物理试剂 (热，紫外线和电离射线，外科手术和美容手术)，病毒感染 (尤其是疱疹病毒)，接触性皮炎，某些饮食成分甚至情绪压力。提醒医师和天疱疮患者注意未怀疑的诱发因素可能对疾病进展的影响是一项重要任务。事实上，避免或限制有害习惯 (例如过度沉迷于不必要的药物) 和建议替代方法 (例如用在这方面被认为无害的其他可能诱发天疱疮的药物替代) 可能是治疗天疱疮患者的有用预防措施，由于它可以提高常规治疗的疗效，降低复发的风险，有时可以治愈。

BACKGROUND & AIMS: OBJECTIVE:To analyze the clinical feature, efficacy of treatment and prognosis in familial benign chronic pemphigus (FBCP). METHODS:Sixty-nine cases of FBCP were retrospectively analyzed. RESULTS:The ratio of male to female is 3.93:1 in 69 patients (55 males, 14 females). The mean age at the onset was 29.09 years (3-60 years). There was familial history in 27 families in all of the cases. The lesion usually involved in genital area, neck, axillae and popliteal fossa. Erythemas and vesicles on the soles were seen only in 1 case. Histopathologically 44 cases had special features of FBCP, and immunopathologically 8 cases were direct immunofluorescence (DIF) negative, in which one case had C3 linear deposition along dermoepidermal junction. The combined regimen was more effective. The low-dose X-ray could improve the effect. CONCLUSION:The disease is transmitted as an irregular autosomal dominant trait. The condition in males is more frequent than that in females, probably owing to the different level of female hormone in both sexes. Our patients have the same clinical features as those reported in the literature, but the erythema, vesicle lesions on sole have not been documented in the literature. The combined therapy should be adopted in this condition.

背景与目标：

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :A not well-appreciated but clinically important aspect of malignant tumours is their effects on distantly located host cells. The effects, termed paraneoplastic syndromes, also pose an intriguing mechanistic problem: how do malignant cells influence properties of host cells not in contact with them? Erythrocytes from the circulation of rats bearing intraperitoneal Yoshida ascites sarcoma exhibit higher agglutinability with concanavalin A (Con A) than the cells from normal animals. Since the tumour and the red cells are not in contact, the enhanced agglutinability of the latter is a paraneoplastic effect. The mechanism by which the tumour brings about this effect is investigated as a model for paraneoplastic syndromes. The cell-free ascites fluid is able to impart high agglutinability on cells from normal animals in vitro. Also, when injected intraperitoneally in normal animals, the ascites fluid is able to enhance the agglutinability of erythrocytes in circulation. Apparently the tumour produces a substance(s) that appears in the ascites fluid and is able to diffuse into circulation, explaining the mechanism by which it can reach distant sites. From the cell-free ascites fluid three fractions have been isolated that are active in vitro. Of these, only one showed activity in vivo. From this fraction, a glycoprotein has been purified to homogeneity that confers maximal Con A-agglutinability on normal erythrocytes at 8 x 10(-7)M, at which concentration 6,400 molecules bind per cell. The protein has a molecular weight of 600 kDa in the native state and a pI of 5.35. It is made up of 4 identical subunits of Mr 170,000. It is detected in the plasma of tumour-bearing but not normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： : 恶性肿瘤的一个不被重视但临床上重要的方面是它们对遥远定位的宿主细胞的影响。这种效应被称为副肿瘤综合征，也带来了一个有趣的机制问题: 恶性细胞如何影响不与它们接触的宿主细胞的特性？腹膜内携带吉田腹水肉瘤的大鼠循环中的红细胞与刀豆球蛋白A (Con A) 相比，其凝集性高于正常动物的细胞。由于肿瘤和红细胞不接触，因此后者的凝集能力增强是一种副肿瘤作用。研究了肿瘤引起这种作用的机制，作为副肿瘤综合征的模型。无细胞腹水能够在体外对正常动物的细胞赋予高度凝集性。同样，当在正常动物中腹膜内注射时，腹水能够增强循环中红细胞的凝集能力。显然，肿瘤会产生一种物质，这种物质会出现在腹水中，并能够扩散到循环中，从而解释了它可以到达远处的机制。从无细胞的腹水液中分离出三个在体外具有活性的部分。其中，只有一个在体内显示出活性。从该级分中，糖蛋白已被纯化至同质，其在8 × 10(-7)M的正常红细胞上赋予最大的Con-凝集性，在该浓度下6,400分子结合每个细胞。该蛋白质在天然状态下具有600 kDa的分子量和5.35的pI。它由Mr 170,000的4个相同的亚基组成。它是在荷瘤大鼠的血浆中检测到的，但不是正常大鼠。(摘要截短于250字)

BACKGROUND & AIMS: :Desmoplakin I and II are important components of the attachment plaque of the desmosome which mediates cell to cell adhesion, in epithelial cells. In this study we used well-characterized antibody against desmoplakin I and II immunohistochemically and immunoelectron microscopically on two cases of pemphigus vulgaris and one case of pemphigus erythematosus and two cases each of Hailey-Hailey's disease and Darier's disease. In the normal human epidermis the desmosomes were demonstrated in a dotted pattern along cell periphery. In pemphigus vulgaris and pemphigus erythematosus acantholytic cells and the perilesional cells exhibited normal dotted pattern along the cell periphery. In Hailey-Hailey's disease and Darier's disease, the dotted pattern is lost in acantholysed and perilesional areas and anti-desmoplakin I + II positive proteins were observed diffusely in the cytoplasm. Immunoelectron microscopical findings correspond to these light microscopical observations. It is concluded that in autoimmune acantholytic disease such as pemphigus vulgaris and pemphigus erythematosus, desmoplakins are intact even in acantholytic cells, whereas in genodermatoses such as vulgaris and pemphigus erythematosus, desmoplakins are intact even in acantholytic cells, whereas in genodermatoses such as Hailey-Hailey's disease and Darier's disease primary or secondary abnormalities abnormalities of desmosomes may be involved in their pathogenesis.

背景与目标： : Desmoplakin I和II是上皮细胞中介导细胞与细胞粘附的桥粒附着斑块的重要组成部分。在这项研究中，我们对2例寻常型天疱疮和1例红斑天疱疮以及2例Hailey-Hailey病和Darier病各2例进行了免疫组织化学和免疫电子显微镜下的抗desmoplakin I和II抗体。在正常人表皮中，桥粒沿细胞外围以虚线显示。在寻常型天疱疮和红斑天疱疮中，棘层分解细胞和周围细胞沿细胞外围显示出正常的点状模式。在Hailey-Hailey病和Darier病中，在棘突和周围区域失去了点状图案，并且在细胞质中广泛观察到抗desmoplakin I II阳性蛋白。免疫电子显微镜检查结果与这些光学显微镜观察结果相对应。结论在自身免疫性棘皮病如寻常型天疱疮和红斑天疱疮中，即使在棘层分解细胞中，结膜蛋白也是完整的，而在寻常型和红斑天疱疮等遗传性皮肤病中，结膜蛋白即使在棘层分解细胞中也是完整的，而在遗传皮肤病中，例如Hailey-Hailey病和Darier病，桥粒的原发性或继发性异常可能与其发病机理有关。

BACKGROUND & AIMS: :Pemphigus vulgaris (PV) is an autoimmune blistering skin disease characterized by suprabasal acantholysis produced as a consequence of desmoglein (Dsg) and non-Dsg autoantibodies binding to several targeting molecules localized on the membrane of keratinocytes. Nitric oxide (NO) may exert a pathogenic function in several immunological processes. We have previously demonstrated that neural nitric oxide synthase (nNOS) plays part in PV acantholysis. Also, our group has described a relevant role for HER [human epidermal growth factor receptor (EGFR) related] isoforms and several kinases such as Src (Rous sarcoma), mammalian target of rapamycin (mTOR) and focal adhesion kinase (FAK), as well as caspases in PV development. Using a passive transfer mouse model of PV, we aimed to investigate the relationship between the increase in nNOS and EGFR, Src, mTOR and FAK kinase upregulation observed in PV lesions. Our results revealed a new function for nNOS, which contributes to EGFR-mediated PV acantholysis through the upregulation of Src, mTOR and FAK. In addition, we found that nNOS participates actively in PV at least in part by increasing caspase-9 and caspase-3 activities. These findings underline the important issue that in PV acantholysis, caspase activation is a nNOS-linked process downstream of Src, mTOR and FAK kinase upregulation.

背景与目标： : 寻常型天疱疮 (PV) 是一种自身免疫性水疱性皮肤病，其特征是由于desmoglein (Dsg) 和非Dsg自身抗体结合到位于角质形成细胞膜上的几种靶向分子而产生的基底上棘皮溶解。一氧化氮 (NO) 可能在几个免疫过程中发挥致病功能。我们以前已经证明神经一氧化氮合酶 (nNOS) 在PV棘层分解中起作用。此外，我们的小组还描述了HER [人表皮生长因子受体 (EGFR) 相关] 亚型和几种激酶的相关作用，例如Src (Rous肉瘤)，雷帕霉素的哺乳动物靶标 (mTOR) 和粘着斑激酶 (FAK)，以及PV开发中的caspase。使用PV的被动转移小鼠模型，我们旨在研究在PV病变中观察到的nNOS增加与EGFR，Src，mTOR和FAK激酶上调之间的关系。我们的结果揭示了nNOS的新功能，它通过Src，mTOR和FAK的上调促进了EGFR介导的PV棘皮分解。此外，我们发现nNOS至少部分通过增加caspase-9和caspase-3活动来积极参与PV。这些发现强调了一个重要问题，即在PV棘层分解中，caspase激活是Src，mTOR和FAK激酶上调下游的nNOS连接过程。