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Clin Orthop. 2000 Oct;(379 Suppl):S242-51.
Complexity of determining cause and effect in vivo after antisense gene therapy.
Hart DA, Nakamura N, Marchuk L, Hiraoka H, Boorman R, Kaneda Y, Shrive NG, Frank CB.
McCaig Centre for Joint Injury and Arthritis Research, Faculty of Medicine, University of Calgary, Alberta, Canada.
Injuries to joint tissues are major clinical problems occurring with significant frequency and resulting in the formation of scar tissue or in some tissues with no healing at all. Such scar tissue has compromised biomechanical integrity, which leads to impaired function, increased risk of reinjury, induction of remodeling in other joint tissues and increases the risk of diseases such as ostheoarthritis. Development of new therapies, such as gene therapy, to enhance repair could have a significant impact on quality of life for patients. The well-characterized rabbit medial collateral ligament injury model was used to transiently modulate the expression of specific molecules during early stages of healing. The small matrix proteoglycan decorin, known to influence matrix assembly and to bind and growth factors, was targeted in vivo using decorin-specific antisense oligodeoxynucleotides and Hemagglutinating Virus of Japan-Liposome method. After 4 weeks of healing, scar tissue was assessed after antisense exposure by reverse transcription polymerase chain reaction, Western Blot analysis, light and transmission electron microscopy, and biomechanically for low and high load behavior. Ligament scar messenger ribonucleic acid and protein levels for decorin decreased and collagen fibril diameter size increased after antisense treatment. Creep and stress at failure improved after antisense treatment indicating a functional improvement in the scar tissue. However, messenger ribonucleic acid levels for multiple genes were affected by the decorin-specific antisense treatment and therefore all of the observed improvements in the scar tissue cannot be directly ascribed to depressing decorin levels.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11039776&dopt=Abstract
Aesthetic Plast Surg. 2002 Sep-Oct;26(5):365-7.
Tranilast as an additional treatment with conservative therapy for concave deformity following traumatic hematoma.
Muraoka M, Ayabe S, Harada T, Motomura H.
muraoka-ed.osaka-cu.ac.jp
Fibrotic scar tissue resulting from a cheek hematoma sometimes seriously contracts to form a concave deformity, despite conservative therapy. We used Tranilast as an additional treatment with conservative therapy for four patients who were resistant to massage and compression therapy. Four months after oral administration of Tranilast, all the deformities were resolved. Tranilast is used for the treatment of allergic diseases and keloids. It inhibits the release of transforming growth factor b-1, interleukin-1 b, and prostaglandin E2. It also suppresses collagen synthesis by fibroblasts.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12432476&dopt=Abstract
Clin Orthop. 2000 Oct;(379):259-69.
The adaptation of perimuscular connective tissue during distraction osteogenesis.
De Deyne PG, Meyer R, Paley D, Herzenberg JE.
Maryland Center for Limb Lengthening & Reconstruction, Division of Orthopaedic Surgery, University of Maryland School of Medicine, Baltimore, USA.
It is not known whether the decreased range of motion observed during distraction osteogenesis results from the lack of adaptation of muscle or from fibrosis in the perimysium. The adaptation of the perimysium in the tibialis anterior muscle in skeletally immature rabbits using two distraction regimens (0.7 and 1.4 mm/day with 15% lengthening) was characterized. The resulting data indicate that during distraction osteogenesis, the muscle adapts by reorganization of its connective tissue. At a lengthening rate of 1.4 mm/day, there is perimysial fibrosis without major cellular pathologic abnormalities in the muscle fibers. The increase in perimysial thickness is characterized by an increase of collagen Type I. In addition, collagen Type I is deposited around the endomysium. The increase in total collagen and its cross-linking are dependent on the lengthening rate. The faster lengthening rate also leads to a significant decreased passive plantar flexion. Supplemental growth of the tibia was not observed, and a lack of adaptation in the muscle (based on resting length) was not seen. Together, the data suggest that decreased range of motion during distraction osteogenesis may be a function of the adaptation of the perimysium rather than of the muscle fibers.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11039815&dopt=Abstract
Oncogene. 2000 Oct 5;19(42):4847-54.
Restoration of positioning control following Disabled-2 expression in ovarian and breast tumor cells.
Sheng Z, Sun W, Smith E, Cohen C, Sheng Z, Xu XX.
Department of Biochemistry and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
The physical interaction of epithelial cells with the basement membrane ensures correct positioning and acts as a survival factor for epithelial cells. Cells that detach from the basement membrane often undergo apoptosis; however, in carcinomas, this positional control is absent, permitting disorganized cell proliferation. In the majority of breast and ovarian carcinomas (85-90%), the expression of a candidate tumor suppressor, Disabled-2 (Dab2), is frequently lost. The Dab2-negative tumor cells are no longer in contact with an intact basement membrane, as indicated by the absence of collagen IV (in about 90% of cases). However, in the subset (10-15%) of ovarian tumors in which Dab2 expression is positive, the presence of a basement membrane-like structure around tumor cells was observed. Recombinant adenovirus-mediated expression of Dab2 was used in Dab2-negative ovarian and breast cancer cells, and re-expression of Dab2 was found to lead to cell death or growth arrest. Dab2 expression suppressed MAPK activation and c-fos expression. Plating the infected cells on a basement membrane matrigel rescued the cells from death and growth arrest. Thus, Dab2 exhibits a negative activity for cell growth and survival, which can be countered by attachment of the cells to basement membrane matrix. We conclude that Dab2 functions in cell positioning control and mediates the exigency for basement membrane attachment of epithelial cells. Loss of Dab2 may contribute to the basement membrane-independent, disorganized proliferation of tumor cells in ovarian and breast carcinomas.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11039902&dopt=Abstract
J Autoimmun. 2000 Nov;15(3):293-300.
Patients with bullous pemphigoid and linear IgA disease show a dual IgA and IgG autoimmune response to BP180.
Kromminga A, Scheckenbach C, Georgi M, Hagel C, Arndt R, Christophers E, Brocker EB, Zillikens D.
Institute for Immunology, Pathology and Molecular Biology (IPM), Hamburg, Germany.
Bullous pemphigoid (BP) and linear IgA disease (LAD) are autoimmune subepidermal blistering skin diseases associated with autoantibodies against the transmembrane hemidesmosomal protein BP180/type XVII collagen. It has been demonstrated previously that BP is characterized predominantly by IgG autoantibodies, while autoantibodies in LAD mainly belong to the IgA isotype. The aim of the present study was to investigate the hypothesis that there is a significant overlap in the autoantibody isotype profiles associated with these two diseases. Several new recombinant forms of BP180 were generated in the baculovirus expression system, including the full-length protein. IgG autoantibodies to BP 180 were detectable in 39 of 40 (98%) of BP sera; interestingly, 88% of BP sera also contained IgA anti-BP180 autoantibodies. Similarly, anti-BP180 reactivity in LAD sera (n=22) was also attributed to both an IgA (68%) and an IgG (76%) autoantibody response. IgA and IgG autoantibodies to the intracellular portion of BP180 were found in 14% and 28% of BP sera, respectively, and in 8% of LAD sera (same percentage for both isotypes). Our findings clearly demonstrate that both BP and LAD patients have a dual IgA and IgG autoimmune response to BP180 which is directed not only to the ectodomain, but also to the intracellular portion of this protein. 2000 Academic Press.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11040070&dopt=Abstract
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