ABSTRACT
Dermatomyositis, a common autoimmune disease in clinical practice, often involves muscles and lungs, and can be complicated by malignant tumors, and the lung involvement can be fatal. Therefore, early diagnosis and treatment of dermatomyositis is of great benefit for the reduction of muscle and lung injury, early recognition and management of malignant tumors, and improvement of prognosis and survival rate of patients. However, the heterogeneity and various clinical manifestations of dermatomyositis pose challenges to early diagnosis. This article describes risk factors for dermatomyositis complicated by rapidly progressive pulmonary interstitial fibrosis, dysphagia or malignant tumors, and proposes a mode of "rashes + nailfold capillary abnormalities + myositis antibodies" for the early diagnosis of dermatomyositis, early recognition of important visceral injury and tumors, and early management, in order to improve overall survival rate of patients.
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Pseudoangioedema, a new type of skin lesions of dermatomyositis, is characterized by localized or diffused, non-pitting, non-pruritic edema on the face, lips, and limbs, with or without erythema. Most dermatomyositis patients with pseudoangioedema are positive for anti-transcriptional intermediary factor 1γ antibodies, and experience severe muscle injuries, increase of serum creatine kinase levels, and refractory dysphagia. A small number of dermatomyositis patients with pseudoangioedema are positive for anti-melanoma differentiation-associated gene 5 antibodies, and have lung involvement. Therefore, high attention should be paid to the occurrence of pseudoangioedema in patients with dermatomyositis, and the screening of specific antibodies can facilitate early diagnosis and differential treatment, as well as improvement in symptoms and survival rates.
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Seborrheic dermatitis-distributed dermatomyositis, a special type of dermatomyositis, is characterized by facial seborrheic dermatitis-distributed rashes, usually accompanied by Gottron papules, inverse Gottron papules, mechanic′s hands and skin ulcers, seldom accompanied by muscle involvement. Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive patients with seborrheic dermatitis-distributed dermatomyositis are prone to interstitial lung disease/rapidly progressive interstitial lung disease. Early diagnosis of seborrheic dermatitis-distributed dermatomyositis can be made through the combination of rashes and antibody detection, and early and active combined treatment with glucocorticoids and immunosuppressors can improve the survival rate of patients.
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Under laboratory condition, the compound materials of Poly (DL-lactic-co-glycolic acid)/Tricalcium phosphate [PLGA/TCP(L), with component ratio of 7:3] were fabricated by combining the thermally induced phase separation (TIPS) with solvent-casting particulate-leaching (SCPL) approach. On the other hand, rapid prototyping (RP) technique manufactured PLGA/TCP scaffolds [PLGA/TCP(RP)] were obtained. These two kinds of carriers were coated with collagen type I (Col I). The extracted bovine bone morphogenetic protein (bBMP) was loaded into carriers to establish biomimetic synthetic bones. PLGA/TCP(L) scaffolds, demineralized bone matrices (DBM) of bovine cancellous bone, PLGA/TCP(L) scaffolds, biomimetic synthetic bones and OsteoSet bone graft substitutes were investigated. Scanning electron microscopy revealed that the microarchitecture of PLGA/TCP(RP) scaffolds was much better than that of PLGA/TCP(L) scaffolds. The diameter of macropore of PLGA/TCP(RP) scaffold was 350 microm. The porosities of PLGA/ TCP(L) scaffolds, DBM, PLGA/TCP(RP) scaffolds and OsteoSet bone graft substitutes were 21.5%, 70.4%, 58.6% and 0%, respectively (P<0.01). Modification of PLGA/TCP scaffolds with collagen type I [PLGA/TCP(L)-Col I and PLGA/TCP(RP)-Col I] essentially increased the affinity of the carriers to bBMP. Among these synthetic materials, PLGA/TCP(RP)-Col I-bBMP composite is promising as a novel bone graft substitute due to its advanced fabrication technique, good tri-dimensional microarchitecture and ideal components.
Subject(s)
Humans , Biocompatible Materials , Chemistry , Bone Morphogenetic Proteins , Chemistry , Bone Substitutes , Chemistry , Calcium Phosphates , Chemistry , Lactic Acid , Chemistry , Microscopy, Electron, Scanning , Polyglycolic Acid , Chemistry , Porosity , Surface Properties , Tissue Engineering , MethodsABSTRACT
0.05),but all statistically distinguishable from fresh allografts(P
ABSTRACT
Tri-dimensional poly (DL-lactic-co-glycolic acid) (PLGA) scaffolds were fabricated using a rapid prototyping (RP) technique and the gene of human bone morphogenetic protein 2 (hBMP-2) was transferred into rabbit bone marrow stromal cells (MSCs) via recombinant adeno-associated virus vectors (rAAV-hBMP-2). Thirty-two PLGA scaffolds, size (4 mm X 4 mm X 4 mm), were coated with collagen type I and equally divided into 2 groups. In group A, each scaffold was loaded with 2 X 10(4) hBMP-2 (+) MSCs to establish a hBMP-2 (+) MSCs/PLGA composite. In group B, each scaffold was loaded with 2 X 10(4) hBMP-2 (-) MSCs to establish a hBMP-2 (-) MSCs/PLGA composite. The composites in both groups were cultured for subcutaneous implantation in nude mice. All animals were killed 30 days after implantation and the differentiation of composites was evaluated. As a result, MSCs infected with rAAV-hBMP-2 efficiently expressed hBMP-2 protein. RP-based PLGA scaffolds had ideal microarchitecture. The diameters of macropore and micropore of the scaffolds were 300 microm and 3-5 microm, respectively. At 3-5 days after culture, a number of seeding cells well grew on the scaffolds of both groups. The composites in group A had chondrogenesis ability in vivo and the expression of collagen type II was positive. In group B, however, only polymers and fiber tissues were predominantly found. The percentage of polymer remnant area was significantly lower in group A than in group B (P<0.01). Our results therefore indicate that RP-based PLGA scaffolds efficiently coated with collagen type I have good biocompatibility with hBMP-2 (+) MSCs and the techniques developed in this study may favor cartilage tissue engineering.
Subject(s)
Animals , Humans , Male , Mice , Rabbits , Biocompatible Materials , Bone Marrow Cells , Cell Biology , Bone Morphogenetic Protein 2 , Bone Morphogenetic Proteins , Genetics , Cell Differentiation , Cells, Cultured , Chondrogenesis , Guided Tissue Regeneration , Methods , Implants, Experimental , Lactic Acid , Mice, Nude , Polyglycolic Acid , Polymers , Stromal Cells , Cell Biology , Tissue Engineering , Methods , Transfection , Transforming Growth Factor beta , GeneticsABSTRACT
BACKGROUND: For xenogeneic bone transplantation, immune rejection is the major problem that affects the prognosis. However, the understanding about the expression and regulation of the immune factors in heterogenic bone transplantation is limited. Interleukin-1 (IL-1), interleukin-6 (IL-6)and tumor necrosis factor alpha (TNF-α) are important immune factors, and are closely related with post-transplantation rejection.OBJECTIVE: To observe the regional expressions of mRNA and protein of IL-1α, IL-6 and TNF-α in xenogeneic bone transplantation, and to in vestigate the effect of transforming growth factor (TGF)-β on these immune factors.DESIGN: A randomized controlled experiment. SETTING: The Orthopaedic Institute of Xijing Hospital of the Fourth Military Medical University of Chinese PLA MATERIALS: Totally 72 male Balb/c mice, with a body mass of 20 to 25 g, were randomly divided into 3 groups: combined bovine cancellous bone (bCB) granule group (Group A), simple bCB granule group (Group B) and blank control group (Group C) with 24 mice in each group.INTERVENTIONS: This experiment was conducted at the Institute of Orthopaedics, Xijing Hospital, Fourth Military Medical Univessity of Chinese PLA from June 2003 to June 2004. In Group A, one bCB combined TGF-β was implanted into the muscles of left thigh of each mouse. In Group B, one bCB alone was implanted, and in Group C, no bCB was implanted. The number of proliferation of cells in bone implantation area or adjacent tissues of the operated area was observed at postoperative 4, 7, 14 and 21 days; and the regional expressions of several immune factors in im plants were detected with in situ hybridization and immunocytochemistry methods.MAIN OUTCOME MEASURES: Histological observation and detection of regional cellular density of the implants of the mice in each group; the regional expressions of mRNA and protein of IL-1α,IL-6 and TNF-α in the implants RESULTS: ①) Histological observation and detection of regional cellular density of the implants of the mice in each group: on day 7, the cellular density of the proliferated tissues was significantly higher in the Group A than in the Group B [(470.63±132.89), (311.46±93.69)/field,P < 0.01];But on days 14 and 21, there was no significant difference. ②The regional expressions of mRNA and protein of IL-lα, IL-6 and TNF-α of the im plants of the mice in each group. On days 7 and 14 after xenografts were implanted, the regional expressions of IL-1α, IL-6 was respectively lower the xenografts combined with TGF-βthan in the simple xenogeneic bone (day 7: IL-1α 42.55±9.65 vs 67.95±17.82,IL-6 48.26±11.17 vs 77.21±15,16;day 14: IL-1α mRNA 84.77 ±7.42 vs 112.94±7.02,78.1 ±17.22 vs 121.18±15.44,P < 0.01) ,but for the TNF-α, there was no significant difference (P > 0.05).CONCLUSION: In the region of bone xenograft, a variety of cells express mRNAs and proteins of IL-1α, IL-6 and TNF-α, and their expressions are regulated by TGF-β. It may imply a kind of regulation of the immunity of bone xenograft by TGF-β.
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BACKGROUND: Bone morphogenetic protein(BMP) is one of the most important cytokines that induce and promote seed cells to be transformed into osteocytes. Insoluble natural BMP can hardly affect the life of cultured seed cells. The expensive soluble recombinant BMP is also hard to work on the seed cells at the appropriate time and dose. Therefore, gene therapy technique provides us with a brand new idea of using gene-modified seed cells.OBJECTIVE: To transfect exogenous BMP-3 gene into the fibroblasts and screen the positive fibroblast clones that can express BMP-3 stably.DESIGN: Simple sample study.SETTING: Orthopaedic Research Institute, Xijing Hospital, Fourth Military Medical University of Chinese PLA.MATERIALS: The fibroblasts(NIH3T3) were kindly presented by Professor Situ Zhen-qiang of the Stomatological College of Fourth Military Medical University of Chinese PLA.METHODS: This experiment was conducted in the Key Laboratory of Chinese PLA, which belongs to the Orthopaedic Research Institute of Fourth Military Medical University. BMP-3 gene was transfected into the fibroblasts through lipofectamin. The transfected cells were screened by G418. The separated cloned cells were identified through immunohistochemistry. The positively stained cells were the clones of BMP-3 expressing fibroblasts.MAIT OUTCOME MEASURES: The screening concentration of NIH3T3 cells, screening of positive transfected cells, and expression of BMP-3 in screened cells.RESULTS: BMP-3 gene was successfully transfected into the fibroblasts. BMP-3 expressing fibroblast clones were creened and identified through immunohistochemistry. Fibroblast strains with stable BMP-3 expression were obtained.CONCLUSION: The transfection of BMP-3 gene eukaryonic expression vector into the fibroblasts and obtaining of fibroblast strains with BMP-3 expression have laid foundation for the usage of gene-modified seed cells in future research of bone tissue engineering.
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Aim To investigate the possible roles of age, bodyheight, mass and body mass index(BMI) in Lumbar1-4 bone mineralcontent (L1-4BMC), L1-4 areal bone mineral density(L1-44BMD) and L1-4volumetric bone mineral apparent density(L1-4BMAD) of Chinese adoles-cents with early ankylosing spondylitis (AS). Methods Thirty-one maleChinese adolescent outpatients with early AS were included. Age (y),total body mass (kg), height(cn) and body mass index (BMI, kg/m2)of subjects were obtained. L1-44BMC(g) and L1-4 BMD(g/cm2) were e-valuated by using DEXA, and L1-4 BMAD(L1-44BMC/Area3/2, g/cm3)was subsequently calculated. Correlation and multiple regression analyseswere performed. Results Multiple regression revealed that height ( P =0.000) and BMI(P=0.009) were significantly positively related toL1-44BMC (R=0.759, Radj2=0.545, P=0.000 <0.01), and heightplayed the pivotal roles in significant correlation with L144BMC(R =0. 676 Radj2 = 0. 439, P = 0. 000) . Body mass significantly positivelycorrelated with both L-44BMD ( R = 0. 657, Radj2 = 0. 412, P = 0. 000)and L1-4BMAD (R=0.551, Radj2=0.280, P=0.001) .Therefore,height as well as BMI significantly positively correlated with L144BMC andmass was definitely associated with both L1-4BMD and L1-4BMAD in ado-lescents with early AS in this study. Conclusion Height and mass couldhave significantly positive effects on axial bone mass and densities ofadolescents with early AS.