Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of biodegradable scaffolds for articular cartilage repair has been investigated by numerous researchers. The objective of this screening study was to examine how the mechanical and physical properties of four multiphase implants can affect the cartilage healing response. Multiphase implant prototypes were prepared using poly(D,L)lactide-co-glycolide as the base material. PGA fibers (FR), 45S5 Bioglass (BG) and medical grade calcium sulfate (MGCS) were used as additives to vary stiffness and chemical properties. Osteochondral defects (3 mm dia. and 4 mm in depth) were created bilaterally in the medial femoral condyle (high-weight bearing) and the distal medial portion of the patellar groove (low-weight bearing) of 16 Spanish goats. Half of the implants were loaded with autologous costochondral chondrocytes. Defect sites (total n = 64, 4 sites/treatment) were randomly treated and allowed to heal for 16 weeks, fully weight bearing. At euthanasia, gross evaluations and biomechanical testing were conducted. Histological sections of the defect sites were stained with H and E, Safranin O/Fast Green or processed to analyze collagen architecture. Sections were semi-quantitatively scored for repair tissue structure. Qualitative evaluations showed that all groups had a high percentage of hyaline cartilage and good bony restoration, with new tissue integrating well with the native cartilage. Gross and histology scoring indicated a significantly higher score for defect healing in the condyle than in the patellar groove, but no difference in healing for implant types or addition/omission of cells was found. This investigation demonstrates that focal, osteochondral defects in caprine distal femurs treated with various implant constructs were repaired with hyaline-like cartilage and good underlying bone. The multiphase implants show potential for treatment of osteochondral defects and long-term studies need to be undertaken to confirm the longevity of the regenerated tissue.
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PMID:Evaluation of multiphase implants for repair of focal osteochondral defects in goats. 1107 6

We report on the development and characterization of a new composite material consisting of amorphous carbonated apatite, Ca(5)(PO(4), CO(3))(3)(OH), and microstructured poly(hydroxyacetic acid), polyglycolide (PGA). This material is able to keep the pH of a surrounding solution within the physiological range (7.2-7.6). This was achieved by chemical fine-tuning of the counterplay between the acidic degradation of the polyester and the basic dissolution of calcium phosphate. Microporous samples with pore sizes of <1 microm and compact samples were prepared. The biological behavior was assayed in vitro by long-term osteoblast culture. Morphological and biochemical analyses of cell differentiation revealed excellent biocompatibility, leading to cell attachment, collagen and osteocalcin expression, and mineral deposition. This material could be of use as a biodegradable bone substitution material and as a scaffold for tissue engineering.
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PMID:Biologically and chemically optimized composites of carbonated apatite and polyglycolide as bone substitution materials. 1109 75

The sequence of canine COL1A1 cDNA was determined from four overlapping COL1A1 RT-PCR products generated from canine fibroblast RNA. In the translated region, nucleotide identity between canine and human COL1A1 cDNA was 93.2%, although the canine sequence lacked nucleotides 204 to 215 in the region coding for the N-propeptide. Amino acid identity was 97.7%. Total RNA and type I collagen were collected from cultured skin fibroblasts of a 12-week-old male golden retriever with pathologic fractures suggestive of osteogenesis imperfecta (OI) and dentinogenesis imperfecta. Sequential, overlapping approximately 1,000-bp fragments of COL1A1 and COL1A2 cDNA were each amplified by RT-PCR using primers containing 5' T7 polymerase sites. These PCR products were transcribed with T7 RNA polymerase, hybridized into RNA duplexes, and cleaved at mismatch sites with RNase. The proband had an unique cleavage pattern for the fragment of COL1A1 mRNA spanning nucleotides 709 to 1,531. Sequence analysis identified a G to C point mutation for nucleotide 1,276, predicting a codon change from glycine (GGA) to alanine (GCA) for amino acid 208. This change disrupts the normal Gly-X-Y pattern of the collagen triple helix. Restriction enzyme digestion of the RT-PCR product was consistent with a heterozygous COL1A1 mutation. Type I collagen was labeled with 3H-proline, salt precipitated, and analyzed by SDS-PAGE. Pepsin digested alpha chains were over-hydroxylated, and procollagen processing was delayed. Thus, canine and human OI appear homologous in terms of clinical presentation, etiology, and pathogenesis.
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PMID:Sequence of normal canine COL1A1 cDNA and identification of a heterozygous alpha1(I) collagen Gly208Ala mutation in a severe case of canine osteogenesis imperfecta. 1114 34

Tissue generation by autogenous cell transplantation is one of the most promising treatment concepts being developed as it eliminates problems of donor site scarcity, immune rejection and pathogen transfer. Cultured cells are seeded onto a three-dimensional biocompatible scaffold that will slowly degrade and resorb as the soft and hard structures grow and assimilate in vitro and/or in vivo. The 3-D scaffold provides the necessary template for cells to proliferate and maintain their differentiated state. Ultimately, it defines the overall shape of the tissue-engineered transplant. The aim of this review is to describe and discuss the scaffold materials of natural and synthetic origin that are of specific interest to tissue engineers. This review is based on previous publications and our own experience in the use of biomaterials of natural and synthetic origin for tissue engineering applications. Biodegradable polymers which have been used for tissue engineering applications are mainly based on clinically established medical devices and implants. In the group of macromolecules of natural origin collagen, alginate, agarose, hyaluronic acid derivatives, chitosan, and fibrin glue have been used as scaffolds. Man-made polymers such as polyglycolide (PGA), polylactides (PLLA, PDLA), poly(caprolactone) (PCL), and poly(dioxanone) (PDS) have been studied as matrix material to guide the differentiation and proliferation of cells into the targeted functional premature and/or mature tissue. Appropriate selection of scaffold material with respect to the targeted tissue is essential. Today, biomaterials of choice remain to be those approved by the US Food and Drug Administration. In spite of that, novel biomaterials should be developed specifically designed for tissue engineering applications.
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PMID:An introduction to biodegradable materials for tissue engineering applications. 1137 17

Total collagen content in heart decreased significantly till day 8 of dexamethasone (Dex: 2.5 mg/kg week; s.c. for 2 weeks) treatment and increased on withdrawal of Dex. Acid soluble collagen content in heart decreased till day 12 of Dex treatment, reached normal level on day 16 of Dex treatment and exhibited an increase thereafter. Pepsin solubilized fraction in heart also behaved similarly as the acid soluble fraction, but reached normal level on Dex withdrawal. The total collagen content and the acid soluble collagen in kidney decreased significantly throughout treatment as well as on Dex withdrawal whereas, the pepsin solubilized collagen fraction in kidney exhibited a significant increase from day 8 of Dex treatment and the level was maintained throughout the experiment. Incorporation of 14C-proline in both, heart and kidney was found to be reduced. Electrophoretic pattern of pepsin collagen solubilized fraction of heart and kidney revealed alterations in subunit composition and its types on Dex administration and withdrawal. Thus, administration of Dex induced alterations in the metabolism of collagen and on Dex withdrawal, the system slowly tended to attain normalcy.
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PMID:Alterations in collagen metabolism in heart and kidney on dexamethasone administration in rats. 1139 55

Osteoarthritis (OA) is a disorder which results in the destruction of the articular cartilage and the remodeling of the subchondral bone in synovial joints. We have analyzed the cartilage collagen from normal and osteoarthritic free-ranging rhesus monkeys from the Cayo Santiago colony. The cartilage samples were assigned a severity score based on histological staging system and were divided into four groups (normals, mild OA, moderate OA and severe OA). After a 4.0 M guanidinium chloride (GuCl) extraction, the remainder of the cartilage was digested with pepsin and the collagen was salt precipitated at 2.5 M and 4.3 M NaCl. The GuCl solubility of the osteoarthritic cartilage increased compared to normals. Collagen extractability by GuCl also increased with the severity of disease. Pepsin digestion followed by salt precipitation shows that collagen from rhesus osteoarthritis cartilage is more easily extracted than from normal cartilage. With an anti-type I collagen antibody we have detected the presence of type I collagen in the severe OA cartilage samples but not in the milder OA groups or in normal cartilage. Total collagen content decreases with severity of OA, which is not due to changes in propyl hydroxylation because examination of collagen hydroxylation, based on hydroxyproline analysis, shows no difference between OA and normal cartilage.
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PMID:Analysis of collagens solubilized from cartilage of normal and spontaneously osteoarthritic rhesus monkeys. 1155 Jul 7

Arthroscopic thermal modification of collagen in the hip capsular tissue appears to be a treatment option for patients with hip instability. Traumatic hip instability is associated with frank dislocation or a subluxation, and labral tears. Atraumatic hip instability is associated with evidence of generalized ligament laxity. It can be associated with bone-collagen type disorders, including Ehlers-Danlos syndrome, Down syndrome, arthrochalasis multiplex congenita, developmental dysplastic hip, and idiopathic type. As previously discussed by Bellabarba et al, capsular laxity may be the underlying cause of dynamic hip instability. The capsule is a fibrous, thick, and strong structure that encircles the proximal femur and the acetabulum. The capsule is thicker anteriorly than posteriorly, and consists of two sets of fibers, circular and longitudinal. The capsule ligaments play a very important role in hip stability. The hip joint capsule is reinforced by the iliofemoral, pubofemoral, and ischiofemoral ligaments. It remains sensitive to stretch and serves as a mechanism for muscular feedback and pain. The iliofemoral ligament limits hyperextension and lateral rotation of the hip joint and is taut in full extension. Full extension of the hip exposes the capsule and ligaments to a twisting and shortening effect that forces the head onto the acetabulum. We are currently studying the effect of iliofemoral ligament deficiency and its relationship to instability. Many of the properties of synovial lubrication depend on contact with articular surfaces, and incongruency due to instability may have some functional role in distribution of synovial fluid, leading to stresses from weightbearing and eventually to rapid deterioration of the articular surfaces. The high-level athletes in this series include two professional baseball players, three professional golfers (PGA), one professional football player (NFL), one figure skater (Olympic gold medalist), one gymnast (Olympic level, bilateral hips), and one ballet dancer; they returned to their pre-injury level of activity. The other patients returned to their pre-injury functional lifestyle. Hip instability appears to present consistently with stable gait abnormalities and painful sensation of instability. Recognizing the various patterns of hip instability is complicated, and therefore management and outcome of these disorders are quite variable. Bellabarba et al concluded that physical therapy alone had been unsuccessful and that temporary success of a posterior capsular "plication" in one patient showed promise. Arthroscopic thermal modification of collagen in the hip capsular tissue appears to be a treatment option for patients with hip instability. The hip joint capsule is predominantly type 1 collagen, and the mechanism of tissue shrinkage through type 1 collagen alteration is well documented in the literature. Short-term results appear promising, however, more studies are required to determine the long-term efficacy of this procedure in the treatment of this challenging disorder.
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PMID:The role of arthroscopic thermal capsulorrhaphy in the hip. 1167 89

The aim of this study was to determine whether the biomechanical and biochemical properties of tissue-engineered human septal cartilage vary with donor age and in vitro culture time. Chondrocytes were isolated from human septal cartilage of patients from 15 to 60 year old and maintained in primary monolayer culture for 14 days. Cells were seeded onto 0.5% PLA coated PGA disks and kept in stationary three-dimensional culture for either 1 day or 3 weeks. Specimens were then implanted subcutaneously into athymic nude mice and harvested after either 4 or 8 weeks. Upon harvest, the equilibrium confined compression modulus was measured as to quantify mechanical properties, and the glycosaminoglycan, hydroxyproline, and DNA contents were determined as measures of tissue proteoglycans, collagen, and cell density. This study demonstrated that native nasal cartilage showed distinct changes in these parameters with age, but cartilage engineered using the cells of these specimens showed no significant dependence on the age of the donor. There was little difference in quality of cartilage between samples cultured for 3 weeks in vitro and those implanted directly after seeding. Together, the results of this study suggest that the process of extracellular matrix assembly by chondrocytes on three-dimensional scaffolds may be independent of in vivo conditions experienced by the tissue prior to harvest.
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PMID:Age dependence of biochemical and biomechanical properties of tissue-engineered human septal cartilage. 1210 79

Guanidinium chloride treatment of Sepia officinalis cartilage solubilized a component that contained hydroxyproline. Electron-microscopy observation of rotary-shadowed preparations of this component revealed it to consist of rod-like units themselves consisting of filaments. Dialysis of an acetic acid solution against ATP afforded polymeric aggregates consisting of a succession of two or three thick sections showing transverse electron-opaque banding, separated by thinner sections without banding. Electrophoresis produced a main band of about 140 kDa sensitive to bacterial collagenase. After reduction with mercaptoethanol, electrophoresis afforded a 40-kDa band. Pepsin digestion resulted in additional electrophoretic bands. These data suggest the presence of a collagen in Sepia cartilage with characteristics unlike those of any known collagen.
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PMID:A new collagen from the extracellular matrix of Sepia officinalis cartilage. 1239 79

For the regeneration of injured peripheral nerves, we have devised a PGA-tube that is composed of a tube of polyglycolic acid containing collagen sponge. This PGA-tube was applied clinically to reconstruct a peripheral nerve that had been resected during extended surgical resection of for intrapelvic recurrent rectal cancer. Four months after the surgical resection, the function of the left hip joint has improved remarkably, whereas the function had been lost just after the operation. It is suggested that the PGA-tube will be useful for regeneration of peripheral nerves that are resected during operation for intrapelvic malignancy.
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PMID:[Clinical application of PGA-tube for regeneration of intrapelvic nerves during extended surgery for intrapelvic recurrent rectal cancer]. 1248 37


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