Acrometageria: A spectrum of “premature aging” syndromes

A child with manifestations of acrogeria and metageria, two “premature aging” syndromes, is presented. Because of his indistinct phenotype and because the question has been previously raised as to whether these conditions are separate, we propose the designation of acrometageria to describe this phenotypic continuum. As there is much in common clinically between acrometageria and the syndrome of type III procollagen deficiency (Ehlers-Danlos type IV), it might be presumed that a similar pathogenesis for acrometageria exists. This possibility has been tested previously, without demonstrating specific quantitative or qualitative deficits, but with some indirect evidence that collagen metabolism is deranged in these patients. One such crude indicator is the elevation of urinary hyaluronic acid levels, demonstrated in our patient and also observed in the phenotypically distinct Werner and Hutchinson-Gilford premature aging syndromes. On one hand, it could be argued that this supports the concept that premature aging syndromes exist as a biological continuum. On the other hand, it is equally valid to argue that syndromes of premature aging are so described merely because they include recognizable changes of normal aging and that the demonstration of an underlying mutation in a collagen gene, for example, invalidates their study as models of accelerated normal aging. © Wiley-Liss, Inc.     

Activation of mRNA expression of collagen,collagenase and its inhibitor on renal biopsy specimens in patients with IgA nephropathy

Summary: In situ hybridization of mRNA for collagen IV, collagen VI, stromelysin (MMP-3) and TIMP1 was examined in renal biopsy specimens from patients with IgA nephropathy (IgAN) or diabetic nephropathy with various degrees of tissue damage. The majority of cells in the glomeruli expressed these mRNA almost simultaneously, but a few cells demonstrated positive expression for only one of these probes. There was a parallel relationship between the degree of tissue damage and that of mRNA expressions of these probes in patients with IgAN, while patients with diabetic nephropathy showed a reverse relationship between these two parameters. It is concluded that patients with mesangial proliferative glomerulonephritis expressed mRNA for collagen collagenase and its inhibitor in the glomeruli in parallel with the progress of tissue damage. In contrast, glomerular samples from patients with diabetic nephropathy showed that there was an inverse relationship between tissue damage and expression of mRNA. It is concluded that expression of collagen, collagenase and its inhibitor parallels the progression of glomerular changes in IgAN, but such parallel expression was not observed in patients with diabetic nephropathy.     

Induction of type II collagen-specific antibody production in blood lymphocyte cultures of rhesus monkeys (Macaca mulatta) with collagen-induced arthritis using the immobilized native antigen.

Peripheral blood mononuclear cells (PBMC) from Rhesus monkeys previously immunized with bovine type II collagen to induce arthritis were cultured with the same antigen. Because the native protein is poorly soluble in culture medium a heating step is often used. The antigen in this form induced PBMC proliferation, but epitopes for the induction of antibody production and arthritis were lost. To keep the native protein intact it was coated on affigel beads. With the immobilized antigen specific antibody production could be induced.     

Regional gene therapy for full-thickness articular cartilage lesions using naked DNA with a collagen matrix.

A novel gene therapy approach for treating damaged cartilage is proposed that involves placing endotoxin-free cDNA containing the gene for bone morphogenetic protein-2 (BMP-2) in type I collagen sponges and then transferring the naked plasmid DNA construct to the injury site. A full-thickness cartilaginous defect in rabbits implanted with plasmid containing a marker gene (beta-galactosidase) showed expressed protein as detected by immunostaining. At 1 week postimplantation, mesenchymal cells subjacent to the defect had incorporated the implanted naked plasmid DNA and, once transfected, served as local bioreactors, transiently producing the gene product. Plasmids containing the gene for BMP-2 implanted in collagen sponges in cartilage lesions stimulated hyalinelike articular cartilage repair at 12 weeks postimplantation, nearly equivalent in quality to that induced by collagen sponges with recombinant BMP-2 protein. Our approach circumvents the risks of inflammation and immunogenic response associated with the use of viral vectors. Naked plasmid DNA as a vehicle for transferring therapeutic genes has been shown to be effective in a therapeutic model within rabbit articular cartilage and appears to be safe and cost effective.     

S-nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair

BACKGROUND: Nitric oxide (NO) plays a key role in wound repair and S-nitrosothiols like S-nitrosoglutathione (GSNO) are well known NO donors. METHODS: Animals were separated in two groups and submitted to excisional wounds on the dorsal surface at the first day. GSNO (100 microm)-containing hydrogels were topically applied on the wound bed in the GSNO group, daily, during the first 4 days. Control group was topically treated with hydrogel without GSNO for the same period. Wound contraction and re-epithelialization were measured. Animals were sacrificed 21 days after wounding. Samples of lesion and normal tissue were formalin-fixed, paraffin embedded for histological analysis. RESULTS: Wound contraction, measured 14 and 21 days after wounding, was greater in the GSNO group than in the control group (P<0.05 for both). The re-epithelialized wound area, measured 14 days after wounding, was higher in the GSNO group than in the control group (P<0.05). A higher amount of inflammatory cells was observed in superficial and deep areas of the granulation tissue of the control group compared to the GSNO group. Twenty-one days after wounding, thin red-yellow collagen fibers arranged perpendicularly to the surface were found in the granulation tissue of the control group, whereas in the GSNO-treated group collagen fibers were thicker and arranged parallel to the surface. Increased number of mast cells was observed in the GSNO group compared with that in the control group. Vascularization and myofibroblast distribution were similar in both groups. CONCLUSION: Topical application of GSNO-containing hydrogel during the early phases of rat cutaneous wound repair accelerates wound closure and re-epithelialization and affects granulation tissue organization.     

Some investigations into the nature and cause of massive fibrosis (MF) in the lungs of South African gold, coal, and asbestos mine workers

Samples from fibrotic lung lesions greater than 1 cm in diameter macroscopically (by definition, massive fibrosis; MF) were taken from the lungs of 9 randomly selected post-mortem cases of mine workers all showing a background of a pneumoconiosis. These samples were studied histologically, biochemically, and by X-ray diffraction and electron microscopy. As controls for the biochemical and X-ray diffraction investigations, nonfibrosed lung tissue was taken from the same specimens. The findings suggest that the higher quartz content may be the primary cause responsible for the MF formation in this series of cases, while other factors such as tuberculosis may play a part according to some relevant literature on MF. Although an area of MF appears macroscopically to be a solid lesion, on microscopy this is not the case and the lesion is composed of dense and sparse collagen bundles and cellular elements.     

枳鳖胶囊抗大鼠肝纤维化形态学及肝组织Ⅲ型胶原mRNA表达的实验研究

目的:观察枳鳖胶囊抗肝纤维化形态学和Ⅲ型胶原mRNA表达的变化。方法:选择66只健康清洁级SD大鼠,雌雄各半,随机分为:正常对照组,模型组,秋水仙碱组,枳鳖胶囊大、中、小剂量组。以40%四氯化碳花生油皮下注射结合高脂饲料、酒水饮料复合因素诱导大鼠肝纤维化模型。造模结束后,除正常组不予处理外,其他组分别以蒸馏水,秋水仙碱混悬液,高、中、低浓度枳鳖胶囊溶液灌胃,疗程36d。疗程结束后,观察大鼠新鲜肝脏的表面情况、色泽、质地等大体形态,测定肝组织Ⅲ型胶原mRNA的表达,光镜观察肝组织HE染色和网状纤维染色的病理形态学改变。结果:模型组大鼠肝细胞损害、肝脏脂肪变性和胶原纤维增生的程度最显著,Ⅲ型胶原mRNA的表达最强。枳鳖胶囊组上述改变明显减轻,且可抑制Ⅲ型胶原mRNA的表达,疗效优于秋水仙碱组。结论:枳鳖胶囊可较好地保护肝细胞,并能阻止肝纤维化进程甚或逆转肝纤维化病理改变,抑制胶原基因表达,抑制胶原基因表达可能是其抗肝纤维化的作用机理之一。     

ELISA测定血清Ⅱ型胶原抗体对类风湿性关节炎的诊断意义

应用ELISA测定了54例类风湿性关节炎患者、99例非类风湿性关节炎患者以及100例正常人的血清Ⅱ型胶原抗体,结果阳性率分别为90.7%、0、0.54例类风湿性关节炎患者中有7例血清类风湿因子为阴性而Ⅱ型胶原抗体为阳性,且病程均在半年之内。结果表明:Ⅱ型胶原抗体的检测对类风湿性关节炎具有特异性诊断和早期诊断的临床意义。     

纤维结合素在实验性肝纤维化中动态变化研究

本实验研究了血浆纤维结合素和肝组织中纤维结合素的动态变化规律。结果显示F_n在肝中的沉积与肝纤维化的严重程度有关。在肝纤维化早期血浆F_n增高,当胶元在肝中沉积达最高峰时,血浆F_n反而下降低于正常。这提示F_n可能参予胶元在肝中的沉积并对肝纤维化的早期诊断有一定意义。