肾淀粉样变的发病机制及病理特点的研究进展

淀粉样变是由异常折叠的蛋白聚集形成淀粉样物并沉积于器官组织所导致的一类疾病,常累及肾。近年来有关淀粉样原纤维形成的机制、其在肾脏内特异性沉积并致组织损伤的作用机制及肾病理特点均有了进一步的了解。     

皮肤异色病样淀粉样变病一家系

先证者(Ⅲ5)男,20岁,因背部、四肢皮肤色素沉着伴色素减退9年,于2006年8月来我科就诊。患者自述从11岁时起无明显诱因双前臂伸侧、双小腿、背部皮肤颜色逐渐变深,其间出现点状色素减退斑,皮损随着年龄增长逐年增多,并出现苔藓样丘疹。至青春期皮损明显加重,延及双上臂伸侧、双大腿、整个背部和臀部。夏季日晒后,暴露部位皮损加重,色素沉着更明显。未出现过水疱,无明显自觉症状。查体:各系统检查无异常。皮肤科检查:双上肢伸侧、双下肢、背部和臀部皮肤颜色较深,呈淡褐色,其间夹杂米粒至黄豆大形状不规则的乳白色色素减退斑,分布较均匀对称。…     

原发性胆汁性肝硬化发病机制研究进展

原发性胆汁性肝硬化（Pimary biliary　crrhosis,PBC）以破坏肝内小及中等大小胆管为主的器官特异性自身免疫性肝病,表现为肝门脉区炎症导致纤维化,肝硬化甚至功能性衰竭。PBC患者90％以上为女性,年龄一般为30至65岁之间。自身免疫病可见少儿患者,但PBC是唯一例外,随年龄增长期发病率呈上升趋势。     

老年性痴呆症发病机制及其防治措施的研究进展

老年性痴呆症是严重影响老龄人口健康帕中枢神经系统退行性疾病，目前有许多有关老年性痴呆症发病机制的学说，其中β淀粉样蛋白级联学说是目前最广为接受的学说之一。此学说认为淀粉样蛋白多肽异常分泌和沉积是老年性痴呆症的核心环节，减少淀粉样蛋白多肽的产生、抑制其沉积是预防和治疗老年性痴呆症的根本途径。本综述重点介绍和评述了β淀粉样蛋白级联学说以及老年性痴呆症预防和治疗措施的研究进展。     

一个常染色体显性遗传先天性皮肤淀粉样变家系

摘 要：为寻找疾病相关基因,通过调查、体检、病理检查等手段,发现了一皮肤淀粉样变家系,到目前4代中有12人患有皮肤淀粉样变病,主要表现斑状淀粉样变的特征,其特点是由点状色素斑点聚集成波纹状或网状褐色色素斑,对称分布于背部肩胛区、小腿、臂部、乳房和臀部,中等度瘙痒.遗传分析表明,该疾病属常染色体显性遗传.该家系可作为寻找眼外肌纤维化疾病相关基因的宝贵资源。     

原发性干燥综合征发病机制的研究进展

原发性干燥综合征（pSS）是一种慢性自身免疫性疾病,其发病机制尚未明确,也无较好的治疗方法。随着分子生物学技术日趋成熟,pSS研究已逐步向分子水平深入,本文就目前国内外pSS发病机制研究进行综述,以期为明确其发病机制及探究其治疗方法提供参考。     

原发性皮肤B细胞淋巴瘤研究进展

皮肤的Ｂ细胞淋巴瘤曾被认为是淋巴造血系统结内淋巴瘤的一个结外表现 ,且提示预后差。目前认为原发性皮肤Ｂ细胞淋巴瘤 (ｐｒｉｍａｒｙｃｕｔａｎｅｏｕｓＢｃｅｌｌｌｙｍｐｈｏｍａｓ ,ＰＣＢＣＬｓ)是一组细胞形态学高度异质 ,临床表现独特 ,起源于皮肤并常常只局限于皮肤的独立疾病[1,2 ] 。大部分患者的临床表现是非进展性的 ,与同类结内淋巴瘤相比 ,预后较好。近年来 ,虽然对该病的认识在不断提高 ,但对其分类仍存在着分歧。我们对目前ＰＣＢＣＬｓ的分类方案、主要临床类型、病理特点及其与皮肤的淋巴组织增生性疾病的鉴别进行了回…     

原发性硬化性胆管炎发病机制的研究进展

原发性硬化性胆管炎（Primary sclerosing cholangitis，PSC）最早于1924年由法国学者Delbet提出，是以肝内外胆管进行性炎症、阻塞和纤维化为特征的慢性胆汁淤积性肝病。其自然发病过程个体差异比较大，典型的症状是黄疸和瘙痒症，其他非特异性症状有腹部不适、乏力、体重减轻等。病情呈进行性发展，最终出现肝硬化和肝衰竭，8％～30％的病人可发展为胆管癌，平均生存时间为12～17年。     

老年性痴呆症发病机制及其防治措施的研究进展

老年性痴呆症是严重影响老龄人口健康的中枢神经系统退行性疾病,目前有许多有关老年性痴呆症发病机制的学说,其中β淀粉样蛋白级联学说是目前最广为接受的学说之一。此学说认为淀粉样蛋白多肽异常分泌和沉积是老年性痴呆症的核心环节,减少淀粉样蛋白多肽的产生、抑制其沉积是预防和治疗老年性痴呆症的根本途径。本综述重点介绍和评述了β淀粉样蛋白级联学说以及老年性痴呆症预防和治疗措施的研究进展。     

FAP患者心脏组织淀粉样变形成机制分析

目的 探讨转甲状腺素蛋白(transthyretin,TTR)在家族性淀粉样变多发性神经性损害(familial amyloidotic polyneuropathy,FAP)中的淀粉样变形成机制.方法 (1)利用质量分析装置法(matrix assisted laser desorption ionisation time-of-flight mass spectrometry,MALDI-TOF/MS)测定TTR基因突变类型.(2)刚果红染色(Congo red,CR)结合偏振光显微镜检查鉴定心脏组织是否发生淀粉样变沉积.(3)免疫组化染色鉴定淀粉样变沉积蛋白类型.(4)组织形态学分析确定TTR淀粉样变沉积程度及其分布特点.结果 (1)MALDI-TOF/MS分析结果说明基因突变类型为ATTRVal30Met.(2)FAP患者心脏组织CR染色与偏振光显微镜检查确定淀粉样变沉积阳性,且心肌纤维间隙存有明显淀粉样变沉积.(3)免疫组化染色结果显示淀粉样变沉积前蛋白为TTR.结论 FAP ATTRVal30Met患者心肌间隙与疏松间质处,淀粉样变沉积明显,提示机体内TTR的载体运输或蛋白化学修饰等因素在淀粉样变形成机制中,可能具有重要作用.     

The pathogenesis and biochemistry of amyloidosis

The transformation of serum proteins into Congo red-sensitive fibrillar material is requisite for the onset and progression of amyloid disease. All the mechanisms which lead to the disease itself have not been elucidated, but our knowledge has increased significantly. It is apparent that in all types of amyloid fibrils, three common features are displayed by the major protein constituents. These are that the fibril protein has a serum precursor, a high degree of anti-parallel beta-sheet conformation and a distinctive ultrastructure on electron microscopy. In the AL and AA forms of amyloidosis, the putative precursors appear to undergo limited degradation to form the protein component of amyloid fibrils. It has been suggested that there may be certain primary structural characteristics inherent in precursor molecules which make them amyloidogenic, thus predisposing them to amyloid fibril formation. This would include certain subtypes of immunoglobulin light chains, possibly kappa I and lambda VI, in the AL type of amyloidosis and one of the polymorphic SAA species, SAA2, which has been identified as the predominating isotype found in AA amyloid fibrils. In AH amyloidosis, the mechanism of amyloid fibril formation appears to be simply a concentration phenomenon where elevated concentrations of B2-M are not handled normally and amyloid deposition is the result. Amyloidogenesis in the hereditary form of systemic amyloidosis may involve other factors in addition to the presence of a variant precursor prealbumin as indicated by the delayed onset of the disease. It is evident that the elucidation of the mechanism(s) which governs the onset and progression of the amyloidoses will allow future regulation and treatment of these all too often complex disorders.     

Localized amyloidosis of the uterine cervix

Summary Localized amyloidosis of the uterine cervix was found in a 56-year-old woman. The firm enlarged cervix showed massive tumorous amyloid deposition. In the amyloid deposits there were foci of ossification and calcification. An infiltrate of multinucleated giant cells, histiocytes, lymphocytes, and plasma cells was seen adjacent to the amyloid deposits. Immunohistochemically, the amyloid reacted with antisera against A-lambda, amyloid protein of immunoglobulin lambda light chain origin. This indicated that the amyloid protein was of immunoglobulin origin in this rare case of localized amyloidosis of the uterine cervix.     

Proteoglycans in the pathogenesis of amyloidosis

Glycosaminoglycans, which occur in most organisms from bacteria to vertebrates, appear to be present in all amyloid deposits regardless of the protein involved. This, their early appearance, and their likely interaction with specific proteins imply that they play an essential role in the pathogenesis of amyloidosis.     

On the pathogenesis of amyloidosis

Summary The information submitted makes it possible to speak of the participation of immunological reactions in the pathogenesis of amyloidosis, which, in all probability, come about by a mechanism of auto-aggression. Furthermore, two stages may be distinguished in the development of amyloidosis: First stage, the formation of auto-antigens and of corresponding auto-antibodies, this appearing as a result of a deranged protein-synthetizing function of the reticulo-endothelium. Second stage, association of auto-antigens with auto-antibodies followed by the formation of specific complexes and their fixation in tissues in the form of an amyloid substance.

---

Über die Pathogenese der Amyloidose

Zusammenfassung Auf Grund von Untersuchungen über experimentelle Amyloiderzeugung mit Kasein wird die Amyloidose als Autoimmunkrankheit gedeutet, die in zwei Phasen abläuft. In der ersten Phase erfolgt die Bildung von körpereigenen Antigenen und entsprechenden Antikörpern. Die Antigene gehen aus einer veränderten Proteinsynthese durch das retikuloendotheliale Gewebe hervor. In der zweiten Phase führt die Antigen-Antikörperreaktion zur Bildung spezifischer Verbindungen mit geweblicher Fixation derselben in Form von Amyloid.

     

Reelin在阿尔茨海默病小鼠发病中的作用

目的探讨阿尔茨海默病(AD)小鼠病理改变、Reelin和Notch1的表达变化及DNA甲基化状态的改变,为深入了解阿尔茨海默病的发病机制提供理论依据。方法以淀粉样蛋白前体(APP)/早老素-1(PS1)双转基因小鼠为AD模型、同窝野生型小鼠为对照组,两组小鼠共计184只,利用高尔基染色、透射电子显微镜、免疫荧光染色、免疫印迹等技术检测AD模型鼠病理改变、Reelin和Notch1的表达变化及DNA甲基化状态的改变。结果AD小鼠在约6个月时开始出现淀粉样斑沉积、神经元纤维出现缠结等病理改变;AD小鼠发病后,星形胶质细胞和小胶质细胞在淀粉样斑周围聚集增多,随病情加重逐渐增加;Reelin在淀粉样斑周围聚积形成斑块,随病情加重逐渐增多;全长Notch1受体和其活性Notch细胞内片段(NICD)在AD鼠脑部表达减少;AD小鼠脑部甲基化状态减弱,淀粉样斑中有DNA片段,但甲基化状态消失,DNA甲基转移酶1(Dnmt1)和Dnmt3a在AD小鼠中表达减少。结论 AD小鼠脑内淀粉样斑沉积,促使胶质细胞聚集、Reelin聚积形成斑块、Notch1受体表达下降及甲基化状态减弱,进一步加剧AD神经功能紊乱。     

An ultrastructural study of nodular amyloidosis of the tongue

We have treated a patient with a nodular amyloidosis in the center of the dorsum of the tongue. Ultrastructural observations of human amyloidosis have been reported by many investigators, but there have been few reports of nodular amyloidosis of the tongue. Ultrastructural investigation showed a number of amyloid fibrils around and in the plasmocytoid cells, and severe pressure atrophy was found in many stromal cells, especially in endothelial cells.This study was presented at the 27th Annual Meeting of the Clinical Electron Microscopy Society of Japan, Kurashiki, September 28–30, 1995.     

Age-related amyloidosis outside the brain: A state-of-the-art review

Inside and outside the brain, accumulation of amyloid fibrils plays key roles in the pathogenesis of fatal age-related diseases such as Alzheimer’s and Parkinson’s diseases and wild-type transthyretin amyloidosis. Although the incidence of all amyloidoses increases with age, for some types of amyloidosis aging is known as the main direct risk factor, and these types are typically diseases of elderly people. More than 10 different precursor proteins are known to cause age-associated amyloidosis; these proteins include amyloid β protein, α-synuclein, transthyretin, islet amyloid polypeptide, atrial natriuretic factor, and the newly discovered epidermal growth factor-containing fibulin-like extracellular matrix protein 1. Except for intracerebral amyloidoses, most age-related amyloidoses have been little studied. Indeed, in view of the increasing life expectancy in our societies, understanding how aging is involved in the process of amyloid fibril accumulation and the effects of amyloid deposits on the aging body is extremely important. In this review, we summarize current knowledge about the nature of amyloid precursor proteins, the prevalence, clinical manifestations, and pathogenesis of amyloidosis, and recent advances in our understanding of age-related amyloidoses outside the brain.     

Two cases of limited cutaneous nodular amyloidosis with primary Sj?gren's syndrome]

We described two female patients with primary Sj?gren's syndrome associated with localized cutaneous nodular amyloidosis (LCNA), in which amyloid protein was derived from immunoglobulin light chain. Case 1; a 70-year-old female had complained with polyarthralgia, low-grade fever and parotid gland swelling. She was diagnosed as primary Sj?gren's syndrome. Three years later she noticed brown color small tumor on the thigh and yellow to brown nodules on the bilateral calves of legs. Skin biopsy from the left thigh revealed amyloid L protein deposition, which was positive for anti-lambda light chain staining, in almost entire dermis. Infiltration of lymphocytes and plasma cells around the amyloid deposit were prominent. Case 2; a 51-year-old female had noticed increasing eruption on the hip. Skin biopsy revealed amyloid L protein deposition in the dermis, which was negative for anti-lambda nor kappa light chain staining. When she was refereed to our hospital, she complained of xerostomia and xerophthalmia. She was diagnosed as primary Sj?gren's syndrome. In both cases, histological examination of a minor salivary gland biopsy revealed infiltration of lymphocytes and plasma cells but not amyloid deposit. Serum M protein and urine Bence-Jones protein were not detected. These cases represent localized amyloidosis without systemic involvement. It is widely recognized that Sj?gren's syndrome is frequently accompanied by B cell lymphoproliferative disorders. In LCNA, infiltration of plasma cells around the amyloid deposits was frequently prominent. The relation between these two disorders is discussed.