Ehlers—Danlos综合征1例

报告１例Ｅｈｌｅｒｓ－Ｄａｎｌｏｓ综合征，患者男性，１４岁。其临床特五为皮肤弹性增加，关节活动过度，皮肤血管脆性增加，此外尚伴有指甲，骨及肾脏的病变。     

Ehlers-Danlos syndrome Type II: Importance of recognition

We report a case of Ehlers-Danlos syndrome Type II presenting with subtle clinical features and discuss the importance of early recognition of this disorder. A 16 year old Caucasian schoolgirl presented with soft tissue swellings on her fingers. There was a history of poor wound healing and prematurity and a family history of miscarriages. Clinical examination revealed hypermobile joints, hyperelastic skin and a ‘cigarette paper’ scar at the site of a previous minor surgical excision. Management consisted of genetic counselling and advice concerning career choice, recreational activities, as well as future pregnancy and surgery. This subtype of Ehlers-Danlos syndrome is probably fairly common in the community. While it may present with subtle clinical features, recognition is important so that counselling can be offered at a young age in order to avoid the major consequences that may arise during pregnancy and surgery.     

Ehlers-Danlos syndrome type VI: lysyl hydroxylase deficiency due to a novel point mutation (W612C)

Received: 10 July 1997     

Cutaneous metaplastic synovial cyst in Ehlers-Danlos syndrome

Classic Ehlers-Danlos syndrome (EDS) is a connective tissue disorder characterized by laxity. The skin, as one of the organs involved, shows hyperextensibility, which makes it prone to trauma. In this context, it would seem logical for cutaneous synovial metaplasia, which is considered a form of repair, to be commonly found in cases of EDS. However, there are only two previously published cases of synovial metaplasia in EDS. We present a third case in a 56-year-old woman with painful redundant skin in both elbows and knees for whom a skin fold of the left elbow was removed to relieve her symptoms. The biopsy showed preservation of the elastic and collagen fibers. The main alteration was the evidence of dermal cystic spaces lined by fibrinoid rests with focal pseudopapillary projections. However, in some zones the cellular lining was preserved, and it was composed of vimentin-positive, fibroblast-like flat, elongated cells, as well as CD68-positive macrophages. No birefringent particles were found in an examination under polarized light.     

Collagen metabolism in granulating wounds of rat skin

Summary Collagen metabolism in granulating wounds of rat skin was studied with biochemical, isotopic and electron microscopical methods. Deposition of collagen in rat skin wounds was not only the result of an increase in collagen synthesis but it was also caused by a decrease in collagen degradation.Our investigations showed significant differences in the collagen turnover at different times of wound healing. Decreased collagen catabolism at the early stages of wound healing contributed decisively to collagen accumulation in the wound area. At later stages, during wound contraction and remodelling of the scar, the rate of collagen degradation rose.The above-mentioned results are discussed in the context of general criteria of scar formation.     

长波紫外线对成纤维细胞胶原合成的影响

目的 探讨皮肤光老化的发生机理,并建立细胞水平的光老化模型。方法 应用正常人来源的单层培养皮肤成纤维细胞,长波紫外线照射２天后,用ＭＭＴ法检测其细胞增殖情况,＾３Ｈ－脯氨酸检测其胶原合成情况。结果 照射组与非照射组增殖差异无显著性意义（Ｐ〉０．０５）,而照射组细胞胶原合成比非照射组显著降低（Ｐ〈０．００１）。结论 在体外培养情况下,短期、小剂量长波紫外线对人成纤维细胞胶原生物合成有显著的抑制作用。     

系统性硬皮病患者皮肤克隆成纤维细胞胶原代谢的异质性

目的在克隆水平上研究系统性硬皮病(SSc)和正常皮肤成纤维细胞(FB)胶原代谢异质性的特点。方法以皮肤克隆FB作为研究对象,采用实时荧光定量RT-PCR法检测其Ⅰ,Ⅲ型前胶原和基质金属蛋白酶(MMP-1,MMP-3)mRNA水平;采用酶联免疫吸附法检测其细胞培养上清中Ⅰ型胶原蛋白的表达,筛选出具有不同胶原合成能力的异质性克隆,分析其胶原代谢的特点。结果 SSc和正常皮肤克隆FB的胶原代谢均具有异质性,SSc患者克隆FBⅠ,Ⅲ型前胶原mRNA水平的异质性较正常人大(F=20.540,P=0.000;F=6.822,P=0.012),SSc患者Ⅰ型前胶原mRNA高表达克隆的比例高于正常人(48.0%vs14.3%);SSc和正常皮肤克隆FB细胞培养上清中Ⅰ型胶原蛋白水平与其mRNA水平均存在正相关关系(r=0.873,P=0.000;r=0.538,P=0.039)。结论 SSc和正常皮肤克隆FB的胶原代谢均具有异质性。     

Biochemical and immunological studies of fibroblasts derived from a patient with Ehlers-Danlos Syndrome Type IV

Summary Fibroblasts derived from a skin biopsy of a patient with the Ehlers-Danlos syndrome (EDS) type IV were cultured in monolayer. The amount of collagen synthesized during a 24-h pulse was not different from that found with normal fibroblasts. Chromatographic procedures and immunofluorescence staining showed a normal synthesis of type I procollagen and collagen but a deficiency in synthesis of type III procollagen and collagen. This could be corroborated by radioimmuno assays showing a reduction in type III procollagen by about 90%. The secretion and degradation of collagens was not altered. The results demonstrate that the molecular defect in this particular patient is due to an impairment of the mechanism controlling the gene expression for type III procollagen.

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Abbreviations BAPN -aminopropionitrile - CM carboxy-methyl - DEAE diethylaminoethyl - EDS Ehlers-Danlos syndrome - EDTA ethylendiaminetetracetate - S.C. subcutaneous     

Case report and study of collagen metabolism in Ehlers-Danlos syndrome type II

A case report on a 41-year-old Japanese woman with prominent features of Ehlers-Danlos syndrome is presented. At birth, the patient was noted to have moderate hyperlastic skin and hypermobility of the joints, especially those of the hands and fingers. She bruised easily, formed purpura, and had cigarette paper scars. From the age of 38, she became aware of palpitation, dyspnea and easy fatigue on exertion; examination showed mitral insufficiency. Mitral-valve prolapse was revealed by echocardiogram and CT echogram. Upper G-I series of X-ray revealed duodenum diverticula. At the age of 42, she was operated for mitral valve replacement. From the clinical features she was dignosed as having Ehlers-Danlos syndrome type II. Tissue sections stained with H-E showed a few, fine, disorderly arranged collagen fibers. Electron microscopically, the diameter of individual collagen fibrils was rather more varied than that in normal skin, but the average diameter was within the normal range. In longitudinal sections, no apparent abnormal findings could be observed. Cultured dermal fibroblasts from the patient synthesized pro alpha 1 trimer of type I collagen but failed to secrete type III procollagen or pro alpha 2 chain of type I collagen. Affected cells were stained with antibodies against type I and type III collagen. Specific fluorescences against type I collagen were observed and very faint positive results against type III collagen were seen. These studies indicate that secreted altered type I procollagens that are synthesized can result in the clinical syndrome of our case.     

The effect of reactive oxygen species on the biosynthesis of collagen and glycosaminoglycans in cultured human dermal fibroblasts

The purpose of this study was to evaluate the possibility that the biological changes observed in connective tissue matrix components of photoaging skin may be induced by an alteration of biosynthesis in fibroblasts damaged by reactive oxygen species (ROS). We investigated the effect of ROS induced by xanthine and the xanthine oxidase system on the biosynthesis of connective tissue matrix components, collagen and glucosaminoglycans (GAGs) in cultured human dermal fibroblasts. ROS decreased collagen production and increased GAGs synthesis. Interestingly, these changes were consistent with the biological alterations of connective tissue matrix components observed in photoaging skin. Moreover, catalase and alpha-tocopherol completely prevented the ROS-induced alterations of collagen and GAGs biosynthesis, whereas superoxide dismutase had no effect on the ROS-induced changes. These results suggest that ROS may be one of the factors which cause the biological changes of connective tissue matrix components observed in photoaging skin.     

Pachydermodactyly: Report of a case

We report a case of pachydermodactyly, a rare entity characterized by acquired diffuse swelling of the lop and sides of the fingers.     

Collagen biosynthesis in a case of epidermolysis bullosa dystrophica recessiva

Collagen metabolism was studied in fibroblast cultures from a patient presenting an epidermolysis bullosa dystrophica recessiva (EBDR) syndrome characterized, in particular, by blistering below the basal lamina observed by electron microscopy. The previously described increase in collagen production was confirmed and several other qualitative modifications of the secreted collagen were observed, including an underhydroxylation of lysine, a decrease in the type III/type I collagen ratio, and an increase in the rapidly degraded collagen. On the other hand, these fibroblasts were able to organize and contract collagen to form a dermal equivalent like normal fibroblasts. Normal keratinocytes can grow and form an epidermal sheet on the surface of these dermal equivalents including normal or pathological fibroblasts.     

Collagen and lipid biosynthesis in a case of epitheliogenesis imperfecta in cattle

An analysis of the dermis and a study of collagen and lipid biosynthesis by fibroblast cultures were carried out in one case of epitheliogenesis imperfecta in a new born calf. This was found to be not only an epidermal disease with fissures and blisters within basal cells on the basement membrane but also a metabolic disease affecting the dermal fibroblasts. These fibroblasts showed a significant decrease in collagen biosynthesis with an increase in the percentage of type III collagen and also a decrease in the biosynthesis of lipids, especially glycerides and cholesterol.     

瘢痕疙瘩Ⅰ、Ⅲ型胶原基因表达研究

目的：为研究瘢痕疙瘩Ⅰ、Ⅲ型胶原基因表达情况。方法：采用cDNA-mRNA原位杂交法观察正常皮肤、瘢痕疙瘩祛炎舒松—A(TA—A)治疗前及治疗后Ⅰ、Ⅲ型胶原基因表达情况，并进行Ⅰ型胶原天狼星红特异性染色，观察Ⅰ型胶原的分布和含量。结果：研究表明瘢痕疙瘩中Ⅰ、Ⅲ型胶原表达增加，经TA治疗后降低。结论：瘢痕疙瘩中胶原堆积是胶原基因表达增加所致，TA—A能抑制胶原基因表达，从而抑制胶原合成。