Lung Transplant Metalloproteinase Levels Are Elevated Prior to Bronchiolitis Obliterans Syndrome

Parenchymal disease in the allograft lung is associated with interstitial remodeling believed to be mediated by matrix metalloproteinases (MMPs). Recent studies suggest high levels of MMP-9 are associated with bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Since BOS occurs late in the posttransplant period and may be preceded by episodes of acute rejection or infection, which are associated with interstitial remodeling, we examined MMP profiles in allograft bronchoalveolar lavage (BAL) fluid in the early posttransplant period (preceding BOS). Gelatin zymography, protein array analysis and specific ELISA on BAL fluids from transplanted lungs indicated that MMP-8, MMP-9 and TIMP-1 were strongly expressed in allograft BAL fluid from stable patients, or those with infection or rejection compared to BAL fluid from normal volunteers. Elevated expression of MMP-8, MMP-9 and TIMP-1 occurred early, and was sustained for the 3.2 years covered in this study. Elevations of MMP-8, MMP-9 and TIMP-1 in the first 2 years posttransplant appear to be associated with lung transplantation itself, and not infection or rejection. These data suggest that ongoing and clinically silent MMP activity could perpetuate progressive disease in the allograft lung.     

瘢痕疙瘩形成机制的研究进展

瘢痕疙瘩是烧伤外科研究的重要课题，其形成机制尚未完全明确，本文就其在遗传机制、免疫作用、细胞增殖与胶原代谢、细胞因子等方面的研究进展进行综述。     

Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific modes revealed by immunohistochemistry and in situ hybridization

BACKGROUND: Oral submucous fibrosis (OSF) is a chewing habit-related pre-cancerous condition of the oral mucosa affecting predominantly south Asians. It is histopathologically characterized by epithelial atrophy and fibrosis of the subepithelial connective tissue. Fibrosis extends all the way into the muscle layer, leading to difficulty in mouth opening. However, the dynamics of extracellular matrix (ECM) remodeling with OSF progression is largely unknown. METHODS: Forty biopsy specimens of OSF and 10 of normal buccal mucosa were examined for expression/deposition modes of eight ECM molecules by histochemistry, immunohistochemistry, and in situ hybridization. RESULTS: In the early stage of OSF, tenascin, perlecan, fibronectin, collagen type III were characteristically enhanced in the lamina propria and the submucosal layer. In the intermediate stage, the ECM molecules mentioned above and elastin were extensively and irregularly deposited around muscle fibers. In the advanced stage, such ECM depositions decreased and were entirely replaced with collagen type I only. Their gene expression levels varied with progression of fibrosis, but the mRNA signals were confirmed in fibroblasts in the submucosal fibrotic areas. CONCLUSIONS: The results indicate that the ECM remodeling steps in OSF are similar to each phase of usual granulation tissue formation. Restricted mouth opening may be a result of loss of variety of ECM molecules including elastin into the homogeneity of collagen type I replacing muscle fibers.     

Contact urticaria from protein hydrolysates in hair conditioners

Protein hydrolysates (PHs) are added to hair-care products (to "repair" broken hair), soaps, bath gels, creams, etc. From one to 22 PHs used in hair-care products (collagen, keratin, elastin, milk, wheat, almond, and silk) were tested in three patient groups: A) 11 hairdressers with hand dermatitis B) 2160 consecutive adults with suspected allergic respiratory disease subjected to routine skin prick tests C) 28 adults with atopic dermatitis.
In group A, all the 22 PHs were tested with scratch and patch tests. In groups B and C, one to three PHs were tested with prick tests. Positive scratch/prick test reactions were seen in 12 patients from three PHs altogether. All were women with atopic dermatitis, and all reacted to at least hydroxypropyl trimonium hydroly:ed collagen (Crotein Q"). In three patients, prick and open tests with a hair conditioner containing Crotein Q were performed with positive results. One patient reported contact urticaria on her hands, and two reported acute urticaria on their head, face, and upper body from a hair conditioner containing Crotein Q. In seven of the eight studied sera, specific IgE to Crotein Q was detected. In conclusion, PHs of hair cosmetics can cause contact urticaria, especially in patients with atopic dermatitis.     

组织扩张术皮肤胶原的代谢改变

目的：研究常规扩张（ＩＴＥ）和持续快速扩张（ＣＴＥ）对皮肤胶原代谢的影响。方法用白色小家猪制作组织扩张术动物模型，用Ｇｏｒｄｅｌａｄｚｅ法测定血清和扩张组织的羟脯氨酸（ＨＰ）含量，藻酸盐印模材膜片法测量标记区面积；光镜测量真皮厚度。结果：ＩＴＥ组血清ＨＰ含量升高，０．８倍，ＣＴＥ组升高１．２倍，ＩＴＥ和ＣＴＥ组皮肤含量与正常皮肤相同，组织中ＨＰ总量均明显升高，持续扩张皮瓣组（ＣＴＥＦ）术后４ｗｋ皮     

Expression of collagen and elastic fibers in duct-ligated submandibular glands of mice

Atrophy of salivary glands may occur by ductal obstruction caused by calculus, infection or neoplastic processes, or as consequence of systemic diseases and aging. In the present work, we have used histochemical methods to study the expression of elastic and collagen fibers during experimental atrophy of the submandibular gland of mice. Glandular atrophy was accompanied by a rapid increase in collagen deposition in both septal and intralobular regions. The expression of elastic fibers was not significantly altered during atrophy; a discrete increase of elastic fibers was noted only around ductal structures. The results showed that experimental ductal obstruction is a useful in vivo model to study molecular events that take part in the remodeling of the extracellular matrix during atrophy of salivary glands.     

骨髓间质干细胞体外预构组织工程化肌腱的实验研究

目的探讨骨髓间质干细胞与胶原-聚羟基乙酸的细胞相容性,为构建组织工程化肌腱寻求理想方法.方法以贴壁法分离、培养骨髓间质干细胞,并检测CD44.在实验组中将骨髓间质干细胞置入含胶原-聚羟基乙酸的DMEM培基中培养:在对照组中将骨髓间质干细胞置入DMEM培基中培养.通过MTT方法比较两组的细胞活性和生长情况,并对实验组进行超微观察.以骨髓间质干细胞为种子细胞,以胶原-聚羟基乙酸为支架在体外预构组织工程化肌腱.结果以贴壁法原代培养骨髓间质干细胞,11天细胞即汇合成片,检测CD44示阳性.骨髓间质干细胞接种于胶原-聚羟基乙酸中混合培养后14天生长良好,始终保持89%以上的细胞活力,与对照组比较无显著差别;实验组细胞数未发生明显改变,而对照组从第4天开始即发生增殖.透射电镜示实验组细胞培养14天后仍保持旺盛的分泌功能.体外预构的组织工程化肌腱具有良好的形态,细胞伸展成梭形,沿聚羟基乙酸缝线大致平行排列.结论骨髓间质干细胞与胶原-聚羟基乙酸的细胞相容性好.以骨髓间质干细胞为种子细胞,以胶原-聚羟基乙酸为支架可在体外初步预构组织工程化肌腱.     

氟对体外培养人牙乳头间充质细胞合成I型胶原的影响

目的:明确氟对人牙乳头细胞合成 I型胶原的影响。 方法:对人牙乳头细胞进行体外培养 ,分别给予0 .0、0 .2× 10 - 6、1.0× 10 - 6、5 .0× 10 - 6、2 5 .0× 10 - 6 g/ L 氟处理 ,采用免疫细胞化学方法染色 ,图象分析氟对细胞合成 I型胶原的影响。 结果:I型胶原在对照组和 4种氟浓度处理组细胞表达均为阳性。图象分析结果表明 ,4种氟浓度对体外培养的人牙乳头细胞合成 I型胶原量与对照组相比差异无统计学意义 (P>0 .0 5 )。结论:过量氟对牙本质基质 型胶原的影响可能不是通过影响成牙本质细胞内合成实现的     

Viscoelastic properties of acid- and alkaline-treated human dermis: a correlation between total surface charge and elastic modulus

BACKGROUND: One of the major mechanical functions of collagenous tissues is the storage, transmission and dissipation of elastic energy during mechanical deformation. In skin, mechanical energy is stored during loading and then is transmitted and dissipated, which protects skin from mechanical failure. Thus energy storage (elastic properties) and dissipation (viscous properties) are important characteristics of extracellular matrices. METHODS: A uniaxial incremental stress relaxation test method has been used to characterize the time-dependent (viscous) and time-independent (elastic) properties of human dermis. Viscoelasticity was investigated in processed human dermis that was equilibrated at pHs of 3.0, 7.4 and 11.0 in an effort to study the link between electrostatic interactions within the collagen matrix and macroscopic tissue properties. RESULTS: Our results show that the solution pH and the charge on collagen significantly affected the high-strain elastic behavior of dermis; the elastic behavior of skin has previously been shown to be directly correlated with axial stretching of the collagen triple helix in crosslinked collagen fibrils. A positive linear correlation existed between the high-strain elastic modulus and both pH (R(2)=0.96) and the total number of charged residues on collagen (R(2)=0.93). These results provide in vitro/ex vivo evidence that charged groups on the surface of collagen molecules in processed human skin influence the high-strain elastic properties of dermis and are likely to be involved in elastic energy storage. CONCLUSION: It is proposed that the pH and charged residue dependency of the elastic modulus suggests that charged pair interactions and repulsions within and between collagen molecules are involved in elastic energy storage during stretching at high strains. It is hypothesized that elastic energy storage is associated with the stretching of pairs of charged amino acid residues that are found primarily in the flexible regions of collagen molecules.