Biomedical subjects

T J Gao

Publications and source records attributed to T J Gao.

At least 19 recordsLinked to original sources

PubMed2006

Host-specific response to HCV infection in the chimeric SCID-beige/Alb-uPA mouse model: role of the innate antiviral immune response.

The severe combined immunodeficiency disorder (SCID)-beige/albumin (Alb)-urokinase plasminogen activator (uPA) mouse containing a human-mouse chimeric liver is currently the only small animal model capable of supporting hepatitis C virus (HCV) infection. This model was utilized to characterize the host transcriptional response to HCV infection. The purpose of these studies was to investigate the genetic component of the host response to HCV infection and also to distinguish virus-induced gene expression changes from adaptive HCV-specific immune-mediated effects. Gene expression profiles from HCV-infected mice were also compared to those from HCV-infected patients. Analyses of the gene expression data demonstrate that host factors regulate the response to HCV infection, including the nature of the innate antiviral immune response. They also indicate that HCV mediates gene expression changes, including regulation of lipid metabolism genes, which have the potential to be directly cytopathic, indicating that liver pathology may not be exclusively mediated by HCV-specific adaptive immune responses. This effect appears to be inversely related to the activation of the innate antiviral immune response. In summary, the nature of the initial interferon response to HCV infection may determine the extent of viral-mediated effects on host gene expression.

Albumins↗

PubMed2001

Accelerated up-regulation of L-Sox5, Sox6, and Sox9 by BMP-2 gene transfer during murine fracture healing.

Fracture repair is the best-characterized situation in which activation of chondrogenesis takes place in an adult organism. To better understand the mechanisms that regulate chondrogenic differentiation of mesenchymal progenitor cells during fracture repair, we have investigated the participation of transcription factors L-Sox5, Sox6, and Sox9 in this process. Marked up-regulation of L-Sox5 and Sox9 messenger RNA (mRNA) and smaller changes in Sox6 mRNA levels were observed in RNAse protection assays during early stages of callus formation, followed by up-regulation of type II collagen production. During cartilage expansion, the colocalization of L-Sox5, Sox6, and Sox9 by immunohistochemistry and type II collagen transcripts by in situ hybridization confirmed a close relationship of these transcription factors with the chondrocyte phenotype and cartilage production. On chondrocyte hypertrophy, production of L-Sox5, Sox9 and type II collagen were down-regulated markedly and that of type X collagen was up-regulated. Finally, using adenovirus mediated bone morphogenetic protein 2 (BMP-2) gene transfer into fracture site we showed accelerated up-regulation of the genes for all three Sox proteins and type II collagen in fractures treated with BMP-2 when compared with control fractures. These data suggest that L-Sox5, Sox6, and Sox9 are involved in the activation and maintenance of chondrogenesis during fracture healing and that enhancement of chondrogenesis by BMP-2 is mediated via an L-Sox5/Sox6/Sox9-dependent pathway.

Animals↗

PubMed2001

Composite implant composed of hydroxyapatite and bone morphogenetic protein in the healing of a canine ulnar defect.

BACKGROUND AND AIMS: Hydroxyapatite (HA) has been considered as a carrier material for bone morphogenetic proteins (BMP). The aim of this study was to evaluate the capacity of a composite implant of HA and native bovine BMP to heal a 2 cm segmental defect in the canine ulna. MATERIALS AND METHODS: A composite HA+BMP implant was compared with plain HA implants and cortical autografts. The fixation was accomplished with an intramedullary Kirschner wire. The bone union was evaluated by X-rays taken at operation and after 3, 6, 9, 12, 16, 25, 35 weeks and by histology and mechanical torsion tests. RESULTS: HA implants were not able to produce complete bone union even with BMP. There was some bridging between the implant and the bone in the defects treated with either plain HA or HA+BMP implant, the bridging being slightly more pronounced with HA+BMP. The autografts showed a significantly better capacity to heal the defect. The HA implant did not resorb markedly during the study. There was no significant difference in mechanical strength between the HA and HA+BMP groups. CONCLUSIONS: HA was not an adequate bone substitute material in this study model, and BMP was not able to enhance sufficiently the poor capacity of HA to heal canine ulnar defects.

Animals↗

PubMed1997

Stabilization of an inserted tricalcium phosphate spacer enhances the healing of a segmental tibial defect in sheep.

The effect of inserting a tricalcium phosphate (TCP) spacer stabilized by a rigid or non-rigid fixation technique on the healing of segmental tibial defects of critical size was established. The osteotomized tibiae, 11 with and 8 without TCP spacers, were fixed by an external circular device in 11 mature sheep and by plates in 8 mature sheep, respectively. Healing was evaluated roentgenographically 16 weeks after the operation. Compared with the defects without TCP spacers, enhanced stability and healing were observed in the defects with TCP spacers under an identical external fixation. Furthermore, a significantly higher incidence of healing was obtained with plate fixation than with external device fixation in the TCP-implanted defects (P < 0.04). An abundant bridging callus was roentgenograpically demonstrated in most of the healed defects, but none in the unhealed defects. The TCP spacer with its mechanical integrity enhances the stability of external fixation, and the stable immobilization provided by rigid fixation is essential for osteoconduction of an inserted TCP spacer in the healing of segmental diaphyseal defects in sheep.

Animals↗

PubMed1997

The use of a coral composite implant containing bone morphogenetic protein to repair a segmental tibial defect in sheep.

A composite implant consisting of a coral cylinder, moose bone morphogenetic protein and type IV collagen was used to repair a segmental tibial defect in sheep. Healing, related variance in mechanical strength and immune responses were evaluated. In comparison with a coral control, a larger amount of newly formed external callus was observed in the composite group at 6 weeks. The maximal torque capacity, maximal angular deformation at failure and bone stiffness of a healed osteotomised tibia recovered 113%, 117% and 120% in the coral controls and 67%, 92% and 79% in the composite implants against the corresponding contralateral tibia at 16 weeks respectively. A significantly elevated anti-BMP antibody was detectable in the composite group at 3 and 6 weeks. Augmented bone formation at an early stage and weakened torsional performance at a later stage in the composite implants may indicate the phase-specific osteoinduction and the immune response of xenogenic BMP with time.

Animals↗

PubMed1997

Morphological and biomechanical difference in healing in segmental tibial defects implanted with Biocoral or tricalcium phosphate cylinders.

To evaluate the effects of two bioceramics on bone regeneration during repair of segmental bone defects, Biocoral and tricalcium phosphate cylinders were implanted in osteotomized sheep tibial defects 16 mm in length and followed up for 16 weeks. In comparison with the TCP-implanted defect, a significant increment in area and density of external callus was quantified radiomorphometrically at 3 weeks, and a marked increase in maximal torque capacity, maximal angle of deformation and absorption of energy was demonstrated mechanically in the Biocoral-implanted tibia at 16 weeks after implantation. Better bone integration with the substratum was microscopically observed in Biocoral cylinders. With good osteointegration and biomechanical-performance, Biocoral seems to be superior to TCP in repair of segmental defects in weight-bearing limbs.

Animals↗

PubMed1997

Low dosage of native allogeneic bone morphogenetic protein in repair of sheep calvarial defects.

A sheep skull trephine defect model was used to test the efficacy of allogeneic partially purified sheep bone morphogenetic protein (sBMP), extracted using a low-cost alternative technique based on 60% ammonium sulphate saturation of the guanethidine-HCI extract of pulverized bone matrix. Eight mg of partially purified sBMP was implanted in six 22-mm right-side sheep calvarial critical-size defects trephined in the diploë area using a midline incision; left-side defects implanted with an equal amount of type IV collagen served as controls. After 16 weeks the sheep were killed and the defects removed. Formation of new bone was evaluated using radiomorphometry and histomorphometry. The healing percentage in sBMP-implanted defects was 60.8 +/- 8.1% and in controls 49.8 +/- 6.7% (P < 0.05) as assessed by radiomorphometry. In cross-sectional histomorphometry, newly formed bone regenerated 50.9 +/- 15.1% in the defects with sBMP and 16.1 +/- 10.6% in controls (P < 0.01). The good result, considering the low dosage of sBMP, can be explained by the strong osteoinductivity and low immunogenicity of native allogeneic sBMP.

Ammonium Sulfate↗

PubMed1997

Producing vascularized bone by heterotopic bone induction and guided tissue regeneration: a silicone membrane-isolated latissimus dorsi island flap in a rat model.

Transformation of mesenchymal-type tissue into cartilage and bone can be induced by bone morphogenetic protein, and by its parent substratum, demineralized bone matrix. The authors were interested in transforming muscle island flaps into vascularized bone that could be used as autogeneic skeletal replacement parts. In Wistar rats, tubular latissimus dorsi muscle island flaps were created, using microsurgical techniques. The flaps were inserted by a cylinder of demineralized bone matrix (DBM) and enclosed in silicone rubber membrane tubes. The animals were followed-up for 10, 21, or 35 days. Rats with DBM implanted in muscle pouches served as controls. Quantitative radiomorphometry and qualitative histology were performed. A statistically significant linear time-related increase in radiomorphometrically-measured calcified tissue was found in the flaps with DBM from 10 days to 5 weeks. At 3 and 5 weeks, lamellar and cancellous bone with fully developed marrow was detected microscopically. There was no significant difference in bone quantity in the island flaps after 35 days, compared with the muscle pouches implanted with DBM, although the difference at 21 days was still significantly in favor of the island flaps. Using allogeneic DBM in rat muscle island flaps surrounded with a silicone membrane, it was possible to generate in vivo autogenous new bone with a good vascular supply and good mobility, allowing later transfer to another site. The experiment provided a basic technique that can be used as a standard in testing various osteoinductive substances for the production of vascular-pedicled new bone.

Animals↗

PubMed1996

Enhanced healing of segmental tibial defects in sheep by a composite bone substitute composed of tricalcium phosphate cylinder, bone morphogenetic protein, and type IV collagen.

Diaphyseal segmental defects in the tibia of 18 sheep were used to evaluate the healing potential of a composite bone substitute device (CBS) composed of a tricalcium phosphate cylinder (TCP), naturally occurring sheep bone morphogenetic protein (sBMP), and type IV collagen. A total of 100 mg of sBMP and 20 mg of type IV collagen in the high-dose group (CBSH), and 13 mg of sBMP and 2.5 mg of type IV collagen in the low-dose group (CBSL) were adsorbed to TCP cylinders, respectively. TCP cylinders impregnated with type IV collagen alone (TCPC) were used as control. A significantly larger area and more highly integrated intensity of newly formed external callus between CBSH and CBSL or TCPC group were quantified by computerized image analyzer at both 3 and 6 weeks. A torsion test showed that the maximal torque capacity, maximal angular deformation, and bone stiffness of healed osteotomized tibia with implants recovered 117-125% in CBSH, 72-109% in CBSL, and 63-80% in TCPC, compared with the corresponding contralateral tibia at 16 weeks. A healing superiority of the segmental bone defects replaced by the implants was demonstrated in the CBSH group. Thus, the composite bone substitute device defined in this study was shown to possess osteoinductivity, osteoconductivity, and mechanical strength.

Animals↗

PubMed1996

Time-related deviations of fibronectin and type I, II and III collagen on the interface between a hydroxyapatite disc and the rim of a calvarial trephine defect in rabbits.

To pursue the events around hydroxyapatite (HA) discs (diameter 9 mm), implanted in calvarial defects in rabbits (diameter 11 mm), immunohistochemical changes of fibronectin and type I, II and III collagen were quantitatively determined in the connective tissue-HA (CTHA) and host bone-HA (BHA) interface at 8, 12 and 16 wk postimplantation. A marked enhancement of type I collagen staining in the BHA interface was noted at the 12th and the 16th wk in comparison to the CTHA interface and connective tissue in the untreated control defect. However, one of the characteristics of the staining in the CTHA interface was the finding of exceptionally high fibronectin and type III collagen at the 8th and the 12th wk in contrast to the BHA interface and the untreated control defect. The change in these immunohistochemically determined compositions was probably due to an active proliferation of vascular components in the CTHA interface. Bone regeneration in the CTHA interface was parallel to an increase in type I collagen and a decrease in fibronectin and type III collagen from 8 to 16 wk. This study indicated that variances in composition or characteristics of connective tissue in CTHA interface have taken place ahead of bone morphogenesis. The time-related derivation of connective tissue matrix components in the BHA and CTHA interface was confined to the interaction of implanted HA with host tissues in contact with the implant.

Animals↗

PubMed1996

Xenogeneic moose (Alces alces) bone morphogenetic protein (mBMP)-induced repair of critical-size skull defects in sheep.

A standardized skull defect in adult sheep was used to test the healing capacity of xenogeneic, partially purified, moose-derived bone morphogenetic protein (mBMP) extracted from the fresh long bones of moose (Alces alces) calves. An amount of 52 mg of mBMP mixed with 13 mg of purified type IV collagen (5:1) (mBMP/COL) in gelatin capsules was implanted into six 22-mm-diameter skull defects in adult sheep for comparison with six defects implanted with fresh autogenous bone marrow (BM) and six other controls implanted with a gelatin capsule containing 13 mg of type IV collagen (C). The amount of new bone formed was quantified from radiographs by computerized image analysis and histology. The healing percentage in the mBMP/COL group was significantly higher (93.18 +/- 4.51%) than in the BM (33.17 +/- 20.05%) or C group (31.32 +/- 17.41%) at 16 weeks after implantation. The difference between BM and C was not statistically significant. The level of anti-BMP antibody in the serum showed a significant increase in the group implanted with mBMP, but returned to normal after 6 weeks. The experiment demonstrated that xenogeneic mBMP possesses a strong osteoinductive capacity and weak immunogenicity.

Animals↗

PubMed1996

Partial purification and characterization of bone morphogenetic protein from bone matrix of the premature moose (Alces alces): degradation of bone-inducing activity during storage.

In spite of the advances in recombinant techniques in the production of bone morphogenetic proteins (BMPs), the best clinical results so far have been obtained with human and animal source-extracted BMPs. Also, the poor availability of recombinant products gives rise to continued research with different extracted and purified proteins. In a search for a new source of bone-matrix-derived BMP with high osteoinductive activity, BMP was extracted from fresh bone matrix of the premature moose (Alces alces). Bone-inducing activity was investigated by implanting 0.5-20 mg of BMP into thigh muscle pouches of BALB mice. Radiologically detectable formation of new bone required 2.0 mg of partially purified BMP. Immediately after the extraction, an analytic chromatogram with known molecular weight (MW) markers showed three fractions with different MWs. After 15 months of storage at +1 degree C lyophilized and desiccated, BMP was fractionated by HPLC gel filtration and bioassayed. New bone formation was evaluated qualitatively by histology and quantitatively by radiomorphometry, the quantity of calcified tissue per milligram of implanted agent being determined. Fractions I and III, with high (100-700 kD) and low MW (15-25 kD), respectively, were apparently more effective inducers of new bone than the second-time-tested partially purified BMP complex, the activity of which had significantly (p < 0.05) decreased during 15 months of storage compared to initial results after extraction. However, the bone-inducing activity of fractions I and III corresponded closely to the initial activity of the BMP complex. Fraction II, with medium MW (25-55 kD), caused an apparent inflammatory reaction and no bone formation, and was though to be immunogeneic. Fraction III was considered to include the dominant BMP component with MW 18.5 and fraction I an association of BMP with other non-collagenous bone matrix proteins after one-step gel filtration. The results suggest that BMP from the premature moose has high bone-forming activity. With identification and removal of apparently immunogenic protein fractions, the inflammatory reaction and inhibitory effect on bone induction could be eliminated, and still higher bone-forming activity was attained. Acid protease enzymes were assumed to be responsible for the observed decline in the inductive activity of semi-purified BMP after 15 months of storage, as both osteoinductive fractions proved to be acidic in isoelectric focusing.

Animals↗

PubMed1995

Microscopic evaluation of bone-implant contact between hydroxyapatite, bioactive glass and tricalcium phosphate implanted in sheep diaphyseal defects.

In order to compare morphological discrepancies in bone-implant contact in vertebrates, cylinders of hydroxyapatite, bioactive glass and tricalcium phosphate were implanted in segmental defects of the tibia in sheep. Three types of visible bone-implant contact were observed microscopically at 4 months after implantation. The trabecular web-like bone-implant contact noted in tricalcium phosphate seemed superior to the disseminated patchy bone-implant contact in bioactive glass and the buttressed bone-implant contact in hydroxyapatite with respect to both bone ingrowth and bioresorption of the implant. Differences of physicochemical properties on the surface among the three kinds of bioceramic implants probably give rise to different types of bone-implant contact.

Animals↗

PubMed1994

The role of autogeneic bone marrow in the repair of a skull trephine defect filled with hydroxyapatite granules in the rabbit.

For study of the effect of autogeneic bone marrow on the repair of skull defects filled with hydroxyapatite (HA) granules, 20 trephine defects 11 mm in diameter in 10 New Zealand rabbit skulls were made. Three defects were implanted with HA granules (HAg), and seven defects were implanted with HA granules mixed with autogeneic bone marrow (HAg/BM) from the femoral medullary canal. Autogeneic bone marrow (BM) was implanted in three defects, and seven defects were left unfilled. Histomorphometric quantitation of bone and connective-tissue ingrowth into defects showed that the area of new bone ingrowth in BM (70.3 +/- 8.4%) was significantly larger than that in HAg (34.4 +/- 3.9%) and in HAg/BM (24.0 +/- 5.1%) (P < 0.01 and P < 0.01, respectively). Immunohistologic staining detected fibronectin and collagen type III as the main components in the defects filled with HAg and HAg/BM. The osteoconductive capacity of HA granules was not stimulated by adding fresh autogeneic bone-marrow cells.

Analysis of Variance↗

PubMed1994

[Manufacture and usage of a new rotatometer of spine].

The purposes of this research are to study the changes of some projective points of vertebrae on roentgenogram during consecutive axial rotation and to design and manufacture a new rotatometer of spine for clinical and research work. Using 2 anatomic specimens of normal spines, aged 10 and 17 years. We took anteroposterior roentgenograms for each vertebra during consecutive axial rotation from 0 th 90 degrees. Some projective points on the roentgenograms were selected. Changes of the projective points were measured. The data were analysed with the stepwise regression, linear fitting in a microcomputer. The rotatometer was designed and manufactured upon the linear regressional equation. The results showed that there was an excellent correlation between actual rotation of vertebra and changes of the projective points on anteroposterior roentgenograms. The distances between the center of vertebral pedicle and lateral edge on convex side of vertebra and rotation angle Q were the reliable references which express the actual axial rotation of vertebra. We thought that rotation angle Q was the mark which had advantages of definition, directness, precision and extended measurable range. The 3 sets of graduations were used to measure the segments of T3-6, T7-12 and L1-4 neuromuscular scoliosis, some congenital scoliosis and axial rotation of spine without certain causes in adolescents. Quantitative measurement of scoliotic rotation is very important for determinating and selecting schemes of operations on scoliosis. It is also helpful to predict prognosis of scoliosis and evaluate the results of corrective operations on spinal deformity.

Adolescent↗

PubMed1993

Functional carriers for bone morphogenetic proteins.

This review covers advances in current researches on delivery systems for bone morphogenetic protein. In summary, it notes that the diversity of carriers, inorganic, organic and synthetic composite, have possessed physiochemical and biological properties and efficacy of delivery of bone morphogenetic protein promoting bone induction in experimental animals. It also traces a new trend in research on carrier systems for bone morphogenetic protein. A desirable carrier of BMP will bridge basic research with clinical application of bone morphogenetic protein.

Animals↗

PubMed1993

Bone inductive potential and dose-dependent response of bovine bone morphogenetic protein combined with type IV collagen carrier.

Using type IV collagen as carrier, the expression of bovine bone morphogenetic protein (bBMP) activity and the relation of ectopic bone formation to BMP dosage in the reconstitution were investigated in BALB mice. Visible heterotopic bone was induced by GuHCl-extracted bovine BMP at a minimal dose of 0.5 mg within 21 days after the BMP was covalently bound to type IV collagen of weight 5.6 mg. The dose-dependent osteogenetic response of BMP was retained in the BMP/type IV collagen composite. As the BMP dose increased in the reconstitution, the integrated intensity and area of bone and cartilage formation, as quantified by a computerized scanner, were enhanced. Degradation of the collagenous carrier was improved by BMP, and neovascularization of the implant site initiated by type IV collagen was also observed. The covalent binding of BMP to type IV collagen postponed the time-sequence of ectopic bone development induced by BMP alone. The conclusion was that the exaggerated and extended effects of type IV collagen on BMP are mainly due to chemotaxis to progenitor cells, immunogenetically inert, vascular initiation and biodegradability in type IV collagen.

Animals↗

PubMed1993

Granular hydroxyapatite and allogeneic demineralized bone matrix in rabbit skull defect augmentation.

To study the effect of hydroxyapatite (HA) granules on new bone formation induced by allogeneic demineralized bone matrix (DBM) and to ascertain the specific dose response of bone regeneration in rabbit calvarial defects, implantation with different doses of DBM, HA granules and a mixture of DBM with HA, respectively, was undertaken. The results showed that the largest quantity of cartilage in the fourth week and woven and remodeled bone covering almost the whole area of the defect in the tenth and twelfth week, was visible in the 20-30 mg but not in the 40 mg DBM groups. New bone formation in the defects implanted with DBM and HA was markedly less than in those implanted with DBM alone and a large amount of fibrous tissue was initiated by HA granules. A significant negative correlation between new bone formation and fibrous tissue ingrowth was noted. HA granules, as disturbing the bone regeneration induced by DBM, are thus not a desirable combination, and a dose-block phenomenon according to the amount of DBM must be anticipated in repairing skull defects.

Animals↗