Ullrich's disease is a congenital muscular dystrophy clinically characterized by generalized muscle weakness, multiple contractures of the proximal joints, and hyperextensibility of the distal joints. All the patients develop rigidity of spine, often assoicated with scoliosis, failure to thrive, and early and severe respiratory involvement, irrespective of their levels of motor function. Intellectual development is normal. The biopsied muscles show dystrophies including remarkable variation in the fiber size, notably proliferated endomysial connective tissues, and a lot of degenerated and regenerated fibers. The expression of merosin and dytrophin is normal. Recent studies have demonstrated that collagen VI is deficient in the muscles of the patients with Ullrich's disease, and some result from recessive mutations of the collagen VIalpha 2 gene(COL6A2). And a marked reduction of fibronectin receptors in the extracellular matrix of skin and cultured fibroblasts of these patients is also reported. These results suggest that collagen VI deficiency may lead to the reduction of fibronectin receptors and that any abnormalities of cell adhesion may be involved in the pathogenesis of the disease. A case of Ullrich's disease has not been reported yet in Korea. So, we describe a male patient with Ullrich's disease with a brief review of the literature.
Cell Adhesion ; Collagen ; Connective Tissue ; Contracture ; Extracellular Matrix ; Failure to Thrive ; Fibroblasts ; Humans ; Integrin alpha5beta1 ; Joints ; Korea ; Laminin ; Male ; Muscle Weakness ; Muscles ; Muscular Dystrophies ; Receptors, Fibronectin ; Scoliosis ; Skin ; Spine

Anodic spark deposition method(ASD) surface treated titanium implant possesses a considerable osteoconductive potential that promoting a high level of implant osseointegration in normal bone. The purpose of this study was to observe the ASD implant's osseointegration in the osteoporosis-induced animal model. Twenty four rats, 10 weeks of age, were ovarectomized and 5 weeks later divided into two groups : ASD implant group and control implant group. Titanium screw implants (diameter; 2.0 mm, length, 3.5 mm; pitch-height, 0.4 mm) were designed for this study. Experimental implants were ASD treated and no treatment on control implants. ASD implants and control implants were placed in to left tibiae of rats. The rats were sacrificed at different time interval(1, 2, 4 and 8 weeks after implantation) for histopathologic observation and immunohisto -chemistrical observation, with collagen type I, fibronectin, integrin alpha2beta1 and integrin alpha5beta1 antibodies. The results obtained from this study were as follow: 1. Histopathologic findings, overall tissue response and the pattern of bone formation in both groups were similar. In ASD group, more newly formed bone was seen at 1 week and 2weeks than control group. 2. The levels of type I collagen and fibronectin expression were the most abundant at 2weeks and decreased gradually in both groups. Fibronectin and type I collagen expression in ASD group were stronger than control group but no significance. 3. The levels of integrin alpha2beta1 and Integrin alpha5beta1 expression were most abundant at 2 weeks and decreased gradually in both groups. No significant difference was observed in both groups. From this results, anodic oxidized titanium implants were more advantages in early stage of bone formation than control group, but have no significance in tissue responses and late bone formations. It could be stated that although anodic oxidized titanium implant possesses considerable osteoconductive potential but in osteoporotic bone condition dental implant procedure should performed after improving or treating the osteoporotic bone condition.
Animals ; Antibodies ; Collagen Type I ; Dental Implants ; Fibronectins ; Implants, Experimental ; Integrin alpha2beta1 ; Integrin alpha5beta1 ; Models, Animal ; Osseointegration ; Osteogenesis ; Osteoporosis ; Rats ; Tibia ; Titanium

OBJECTIVE: The adhesion molecule that mediate cell-cell and cell-extracellular matrix adhes.ion provides very important role in growth and differentiation of cells and tissue. VLA integrin is a prototype of adhesion molecule which participate in cell-cell and cell-extracellular matrix interacton, especially for collagen, laminin and fibronectin. The biologic functions of VLA-integrin are very diverse. Cartilage is the target tissue of various arthritides including rheumatoid arthritis and osteoarthritis and the process of homeostasis in cartilage matrix may be very important in preservation of cartilage. Although VLA integrin may participate in the process of cartilage degeneration and repair mechanism, tissue.distribution and exact role of VLA integtin in cartilage was not yet clearly defined. METHODS:Immunohistochemical analysis of VLA-integrin in cryostat section of articular cartilage was conducted using monoclonal antibody and avidin-biotin complex method. Analysis was performed in 10 rheumatoid arthritis specimens, 7 osteoarthritis specimens and 1 normal control. RESULTS: 1) Normal cartilage showed strong and diffuse stain with CD29, CD51 and moderate stain of VLA-5. Staining pattern of VLA-1 and 3 was inconstant and weak in intensity. 2) The intensity of VLA expression in articular cartilage of osteoarthritis was upregulated chiefly in CD29, CD51 and slightly in VLA-5. The positive rate of VLA-1 and 3 was similar to that of normal cartilage though the intensity was increased especially at cluster of chondrocytes. 3) VLA-integrin expression of rheumatoid arthritis cartilage was similar to that of osteoarthritis cartilage. CONCLUSION: VLA integrins functioning as fibronectin receptor such as VLA-5 and alpha, beta1 were upregulated in osteoarthritis and rheumatoid arthritis. Intensity was increased at clusters of chondrocytes. It was able to presume from above findings that VLA molecule has some role in the maintenance and repair of articular cartilage. The regulation of expression by cytokines and growth factors and exact function of VLA molecule in cartilage have to be elucidated.
Arthritis ; Arthritis, Rheumatoid ; Cartilage ; Cartilage, Articular* ; Chondrocytes ; Collagen ; Cytokines ; Fibronectins ; Homeostasis ; Integrin alpha1beta1 ; Integrin alpha5beta1 ; Integrins ; Intercellular Signaling Peptides and Proteins ; Laminin ; Osteoarthritis

OBJECTIVETo study the role of integrin alpha 6 in cell attachment, spread, survival/proliferation and differentiation of human hepatocellular carcinoma (HCC) BEL-7402 cells on various substrates by monoclonal antibody against the extracellular domain of alpha 6 subunit (IA6ED McAb).

METHODSThe effect of McAb on attachment and spread of BEL-7402 cells on LN or FN substrate was examined. MTT analysis was used to examine the cell survival/proliferation, gelatin zymography to the matrix metalloproteinases (MMPs) secreted by BEL-7402 cells, and microparticle immunoabsorbent kit to AFP secretion while the cells were cultured on LN-, FN- or Matrigel-coated substrates.

RESULTSThe cell attachment, spread and survival/proliferation were inhibited. Moreover importantly, the malignant cell dedifferentiation and abnormal differentiation on LN-coated substrate were also strongly inhibited by IA6ED McAb.

CONCLUSIONLN and integrin alpha 6 regulate human HCC cell phenotypes of survival/proliferation and differentiation. The phenotypes of dedifferentiation and abnormal differentiation can be reversed by blocking the interaction between integrin alpha 6 and LN using IA6ED McAb, which may lower metastatic potency of tumor cells.

Antibodies, Monoclonal ; pharmacology ; Carcinoma, Hepatocellular ; pathology ; Cell Adhesion ; drug effects ; Humans ; Integrin alpha6 ; immunology ; physiology ; Laminin ; physiology ; Liver Neoplasms ; pathology ; Phenotype ; Receptors, Laminin ; physiology ; Tumor Cells, Cultured

To carry out the secretive expression of human 67 kD laminin receptor (67LR), recombinant expression plasmid pPIC9K-67LR was constructed by inserting of 67LR cDNA into yeast expression vector pPIC9K. The 67LR protein was expressed in Pichia pastoris after induced by methanol, and about 12.56 mg electrophoresis purity 67LR could be obtained after the purification of 1L culture using affinity chromatograph column. In vitro competitive binding assay showed that target protein has an excellent biological activity. The successful expression of 67LR has placed a solid foundation for the research on structure and functions of 67LR.
Genetic Vectors ; Humans ; Pichia ; genetics ; metabolism ; Plasmids ; genetics ; Receptors, Laminin ; biosynthesis ; genetics ; Recombinant Proteins ; biosynthesis ; genetics ; metabolism

The validity of (99m)Tc-YIGSR, a novel receptor radio-tracer, in imaging the Ehrlich ascites tumor was evaluated. YIGSR, a pentapeptide of laminin, was labeled with (99m)Tc by using a bifunctional chelator S-Acetly-NH(3)-MAG(3). The MIBI was labeled with (99m)Tc by following the kit instruction. The mice of tumor group were intravenously injected 1-2 mCi of (99m)Tc-YIGSR or (99m)Tc-MIBI via caudal vein, immobilized and imaged under a Gamma camera. The same procedure was performed in mice of blockade group, in which the unlabeled YIGSR was previously injected to block the receptor-recognition sites, and inflammation group serving as control. The reverse-phase Sep-Pak C(18) chromatogram was found to have an essentially complete conjugation between YIGSR and S-Acetly-NH(3)-MAG(3). The conjugated YIGSR could be radio-labeled successfully with (99m)Tc at room temperature and neutral pH, with a radio-labeling yield of 62%. Without the chelator S-Acetly-NH(3)-MAG(3), the YIGSR was labeled with (99m)Tc at an efficiency of 4%. The imagological study revealed obvious tumor accumulation of (99m)Tc-YIGSR 15 min after the injection, and the uptake peaked after 3 h with a tumor-to-muscle ratio (T/M) of 11.36. The radio-tracer was slowly cleared up and resulted in a T/M of 3.01 at the 8th h after the injection. As for blocked group, the tumor uptake of radiotracer was significantly lower, with the highest T/M being 4.61 after 3 h and 0.89 after 8 h. The T/M was 3.72 at the 3rd h and 1.29 at the 8th h after the (99m)Tc-YIGSR injection in the inflammatory group. The T/M was significantly higher in tumor group than in inflammatory group or control group (P<0.001). In the 99mTc-MIBI group, the T/M was 1.40 at the 3rd h and 0.55 at the 8th h after the injection, which showed a significant difference as compared with (99m)Tc-YIGSR (P<0.001). It is concluded that YIGSR can be successfully radiolabelled by using S-Acetly-NH(3)-MAG(3). (99m)Tc-YIGSR has many advantages in tumor imaging, such as quick and clear visualization, high sensitivity and specificity, and satisfactory target/non-target ratio (N/NT). It promises to be tumor radio-tracer.
Animals ; Carcinoma, Ehrlich Tumor ; diagnostic imaging ; Mice ; Radioactive Tracers ; Radionuclide Imaging ; Radiopharmaceuticals ; Receptors, Laminin ; metabolism ; Technetium Tc 99m Mertiatide ; Technetium Tc 99m Sestamibi

The validity of (99m)Tc-YIGSR, a novel receptor radio-tracer, in imaging the Ehrlich ascites tumor was evaluated. YIGSR, a pentapeptide of laminin, was labeled with (99m)Tc by using a bifunctional chelator S-Acetly-NH(3)-MAG(3). The MIBI was labeled with (99m)Tc by following the kit instruction. The mice of tumor group were intravenously injected 1-2 mCi of (99m)Tc-YIGSR or (99m)Tc-MIBI via caudal vein, immobilized and imaged under a Gamma camera. The same procedure was performed in mice of blockade group, in which the unlabeled YIGSR was previously injected to block the receptor-recognition sites, and inflammation group serving as control. The reverse-phase Sep-Pak C(18) chromatogram was found to have an essentially complete conjugation between YIGSR and S-Acetly-NH(3)-MAG(3). The conjugated YIGSR could be radio-labeled successfully with (99m)Tc at room temperature and neutral pH, with a radio-labeling yield of 62%. Without the chelator S-Acetly-NH(3)-MAG(3), the YIGSR was labeled with (99m)Tc at an efficiency of 4%. The imagological study revealed obvious tumor accumulation of (99m)Tc-YIGSR 15 min after the injection, and the uptake peaked after 3 h with a tumor-to-muscle ratio (T/M) of 11.36. The radio-tracer was slowly cleared up and resulted in a T/M of 3.01 at the 8th h after the injection. As for blocked group, the tumor uptake of radiotracer was significantly lower, with the highest T/M being 4.61 after 3 h and 0.89 after 8 h. The T/M was 3.72 at the 3rd h and 1.29 at the 8th h after the (99m)Tc-YIGSR injection in the inflammatory group. The T/M was significantly higher in tumor group than in inflammatory group or control group (P<0.001). In the 99mTc-MIBI group, the T/M was 1.40 at the 3rd h and 0.55 at the 8th h after the injection, which showed a significant difference as compared with (99m)Tc-YIGSR (P<0.001). It is concluded that YIGSR can be successfully radiolabelled by using S-Acetly-NH(3)-MAG(3). (99m)Tc-YIGSR has many advantages in tumor imaging, such as quick and clear visualization, high sensitivity and specificity, and satisfactory target/non-target ratio (N/NT). It promises to be tumor radio-tracer.
Carcinoma, Ehrlich Tumor/*radionuclide imaging ; Radioactive Tracers ; Radiopharmaceuticals/*diagnostic use ; Receptors, Laminin/*metabolism ; Technetium Tc 99m Mertiatide/*diagnostic use ; Technetium Tc 99m Sestamibi/*diagnostic use

Interleukin (IL) 33, a member of the IL-1 superfamily, is an "alarmin" protein and is secreted in its active form from damaged cells undergoing necrotic cell death. Mast cells are one of the main effector cell types in allergic disorders. They secrete a variety of mediators, including T helper 2 cytokines. As mast cells have high-affinity IgE receptors (FcepsilonRI) on their surface, they can capture circulating IgE. IgE-bound mast cells degranulate large amounts of histamine, heparin, and proteases when they encounter antigens. As IL-33 is an important mediator of innate immunity and mast cells play an important role in adaptive immune responses, interactions between the two could link innate and adaptive immunity. IL-33 promotes the adhesion of mast cells to laminin, fibronectin, and vitronectin. IL-33 increases the expression of adhesion molecules, such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, in endothelial cells, thus enhancing mast cell adhesion to blood vessel walls. IL-33 stimulates mast cell proliferation by activating the ST2/Myd88 pathway; increases mast cell survival by the activation of survival proteins such as Bcl-XL; and promotes the growth, development, and maturation of mast cell progenitors. IL-33 is also involved in the activation of mature mast cells and production of different proinflammatory cytokines. The interaction of IL-33 and mast cells could have important clinical implications in the field of clinical urology. Epithelial dysfunction and mast cells could play an important role in the pathogenesis of interstitial cystitis. Urinary levels of IL-33 significantly increase in patients with interstitial cystitis. In addition, the number of mast cells significantly increase in the urinary bladders of patients with interstitial cystitis. Therefore, inhibition of mast cell activation and degranulation in response to increase in IL-33 is a potential therapeutic target in the treatment of interstitial cystitis.
Adaptive Immunity* ; Allergy and Immunology ; Blood Vessels ; Cell Death ; Cystitis, Interstitial ; Cytokines ; Endothelial Cells ; Fibronectins ; Heparin ; Histamine ; Humans ; Immunity, Innate ; Immunoglobulin E ; Interleukin-1 ; Interleukins ; Laminin ; Mast Cells* ; Peptide Hydrolases ; Receptors, IgE ; Urinary Bladder ; Urology ; Vascular Cell Adhesion Molecule-1 ; Vitronectin

Drug-induced gingival overgrowth (DIGO) is characterized by fibrous gingival hyperplasia and increased gingival volume. DIGO is histologically associated with proliferation of cells and deposition of extracellular matrices, particularly collagen. Integrin α2β1 is related to collagen phagocytosis and involved in the occurrence and progression of DIGO. This paper reviews the progress of research on the relationship between integrin α2β1 and DIGO.
Collagen ; Gingiva ; Gingival Overgrowth ; Humans ; Integrin alpha2beta1 ; Phagocytosis

OBJECTIVETo investigate the expression of the integrin alpha6beta4 in experimental allergic neuritis (EAN) and the relationship of the integrin alpha6beta4 with functional states of Schwann cells (Sc) as well as the injury and repair of the myelin during EAN.

METHODSEAN was induced in Lewis rats and sciatic nerves were resected in 18 EAN and 3 normal rats. The expression of tissue integrin alpha6beta4 was analyzed during the course of EAN induction and in controls by in situ hybridization and semi-quantitative RT-PCR.

RESULTSThe detection of integrin alpha6 and beta4 subunit by hybridization in situ demonstrated that expression of alpha6 subunit present no significant changes during the course of EAN, while expression of beta4 declined in the early phase, showing less positive signals than those of the control, and restored its expression in the later or recovery phase. The changes of expression of integrin alpha6 and beta4 in EAN were confirmed by semi-quantitative PT-PCR, using GAPDH as the internal standard.

CONCLUSIONSThe degeneration and injury of Sc caused by inflammation affect the expression of integrin, which shows similar changes in Sc during embryogenesis, indicating alpha6beta4 may be a marker of Sc differentiation and at least an important molecule to mark the course of EAN. The expression of alpha6beta4 correlate with the injury and repair of myelin during EAN.

Animals ; Disease Models, Animal ; In Situ Hybridization ; Integrin alpha6beta4 ; genetics ; physiology ; Neuritis, Autoimmune, Experimental ; metabolism ; pathology ; RNA, Messenger ; analysis ; Rats ; Rats, Inbred Lew ; Reverse Transcriptase Polymerase Chain Reaction