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Biomedical subjects

S L Woo

Publications and source records attributed to S L Woo.

At least 145 records · Page 8Linked to original sources
PubMed1995

Healing of the medial collateral ligament after a combined medial collateral and anterior cruciate ligament injury and reconstruction of the anterior cruciate ligament: comparison of repair and nonrepair of medial collateral ligament tears in rabbits.

The optimal treatment for a combined injury of the medial collateral and anterior cruciate ligaments is controversial, and the question remains as to whether repair of the medial collateral ligament and reconstruction of the anterior cruciate ligament improves healing of the medial collateral ligament. We compared reconstruction of the anterior cruciate ligament with and without repair of the medial collateral ligament in a rabbit model of a combined injury of these two ligaments. The anterior-posterior translation and varus-valgus rotation of the knee, the structural properties of the femur-medial collateral ligament-tibia complex, and the mechanical properties of the midsubstance of the medial collateral ligament were evaluated immediately after surgery and at 6 and 12 weeks postoperatively. Repair of the medial collateral ligament led to significantly less varus-valgus rotation of the knee than did no repair, but the anterior-posterior translation of the knees in the repair and nonrepair groups were not significantly different at any study time. At 12 weeks, the cross-sectional area and ultimate load in the repair group were 60 and 53% greater, respectively, than in the nonrepair group. Among 12 specimens that were repaired (six specimens at 6 weeks and six specimens at 12 weeks), failure occurred within the midsubstance in four (two at each time period); in all of the specimens that were not repaired, failure occurred at the tibial insertion site. There was no significant difference between the modulus of the modulus of the midsubstance in the repaired and the nonrepaired medial collateral ligaments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Gene therapy in heart disease.

As the technology for gene therapy develops in vitro and in vivo in animal models, it is becoming clear that the three principal approaches--recombinant retroviruses, recombinant adenovirus, and direct DNA delivery--will ultimately have applications in specific therapeutic situations that take full advantage of the unique features of the specific delivery system: low level persistent expression after ex vivo recombinant retroviral therapy, high level transient expression after in vivo recombinant adenoviral therapy, or moderate level transient expression after in vivo administration of a synthetic DNA complex, which in principle could be repeated as desired.

Animals↗
PubMed1995

Effect of knee flexion on the in situ force distribution in the human anterior cruciate ligament.

This study was conducted to evaluate the effect of applied load on the magnitude, direction, and point of tibial intersection of the in situ forces of the anteromedial (AM) and posterolateral (PL) bands of the human anterior cruciate ligament (ACL) at 30 degrees and 90 degrees of knee flexion. An Instron was used to apply a 100 N anterior shear force to 11 human cadaver knees, 6 at 30 degrees of knee flexion and 5 at 90 degrees of knee flexion. A Universal Force Sensor (UFS) recorded the resultant 6 degree-of freedom (DOF) forces/moments. Each specimen then underwent serial removal of the AM and PL bands. With the knee limited to 1 DOF (anteroposterior), tests were performed before and after each structure was removed. Because the path was identical in each test, the principle of superposition was applied. Thus, the difference between the resultant forces could be attributed to the force carried by the structure just removed. The magnitudes of force in the ACL at 30 degrees and 90 degrees of knee flexion were 114.1 +/- 7.4 N and 90.8 +/- 8.3 N, respectively (P < 0.05). At 30 degrees, the AM and PL bundles carried 95% and 4% of the total ACL force, respectively. At 90 degrees, the AM and PL bands carried 85% and 13%, respectively (P < 0.05). The direction of the in situ force in the whole ACL as well as its two bands correlated with the anatomic orientation of the ligament.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Dynamic behavior of a biphasic cartilage model under cyclic compressive loading.

It is well known that dynamic mechanical loads can stimulate the biosynthetic activity of articular cartilage. Studying the mechanical environment of chondrocytes under dynamic loading conditions can help to explain this mechano-biological phenomenon in articular cartilage. In this study, the linear biphasic theory was used to examine the dynamic mechanical behavior of articular cartilage under a cyclic compressive force. We first studied the dynamic confined compression of a cartilage disk as a simplified one-dimensional model and then investigated the role of the relatively impermeable subchondral bone structure on the dynamic behavior of the cartilage extracellular matrix (ECM). Under an assumption of articular cartilage as a biphasic composite structure of a porous elastic solid matrix and interstitial fluid, the porous ECM of the articular cartilage was repeatedly compressed and expanded during the loading-unloading phases of the cyclic compressive force. One interesting finding of this study was the oscillating positive (supra-ambient)-negative (sub-ambient) hydrostatic pressure within the cartilage ECM under cyclic compressive loading. The pattern of the dynamic behavior of the cartilage ECM strongly depended on the loading frequency and the primary diffusion characteristic time, tau d. This finding is consistent with those of previous studies (Guilak et al., 1990 Adv Biomech. ASME, 225-228; Mow et al., 1990, Biomechanics of Diarthrodial Joints, pp. 215-260.

Algorithms↗
PubMed1995

A new dynamic testing apparatus to study glenohumeral joint motion.

A dynamic shoulder testing apparatus has been developed to examine unconstrained glenohumeral joint motion in human cadaveric full upper extremities. Six computer-controlled hydraulic cylinders are used to simulate muscle action, while the corresponding tendon excursions and six-degree of freedom joint motion are measured. Trials showed that the testing apparatus creates highly reproducible glenohumeral joint motion in the scapular plane. The apparatus can be used to examine the function of the shoulder musculature and capsuloligamentous structures during normal and pathologic motion at the glenohumeral joint.

Computers↗
PubMed1995

Collagens in an adult bovine medial collateral ligament: immunofluorescence localization by confocal microscopy reveals that type XIV collagen predominates at the ligament-bone junction.

To understand the structure and function of medial collateral ligament, collagens present in an adult bovine ligament were determined. The mid-section of the ligament was powdered and extracted with 4M guanidinium hydrochloride, and the residue was digested with pepsin to solubilize the collagens. Type I collagen was the major fibril collagen recovered in the pepsin solubilized fraction, with types III and V each representing about 5% and 2%, respectively. Type VI collagen was the major collagen present in the guanidinium hydrochloride extract, and it accounted for about 40% of the proteins in the extract or 4% of the tissue dry weight. Type XII and XIV collagens were also detected in the guanadinium hydrochloride extract as minor components. Immunofluorescence localization using confocal microscopy showed that type XII and XIV collagens are associated with the ligament fibrillar network and that type XIV collagen was prominent at the ligament-bone junction. These data reinforce the notion that these collagens are associated with the type I collagen fibrillar network in connective tissues. In view of high mechanical stresses that exist at the ligament-bone interface, presence of type XIV collagen in high concentration at this junction may contribute to the modulation of the biomechanical properties of this tissue.

Animals↗
PubMed1995

Adenovirus-mediated gene therapy in an experimental model of breast cancer metastatic to the brain.

We investigated the therapeutic efficacy of adenovirus-mediated gene therapy to treat malignant mammary tumors in vitro and in vivo in the brain. A mammary adenocarcinoma cell line derived from Fischer rats (13762 MAT B III; MAT-B) was used. In vitro studies demonstrated that the MAT-B cells could be efficiently transduced with a replication-defective adenovirus (ADV) vector that carried the herpes simplex virus gene for thymidine kinase (ADV-tk), and that ADV-tk transduction rendered the MAT-B cells sensitive to killing, in a dose-dependent manner, with ganciclovir (GCV). An animal model of a mammary tumor metastatic to the brain was produced by injecting MAT-B cells into the caudate nucleus of Fischer rats. Seven days after MAT-B cell injection, when the tumors were approximately 5 mm2 in cross-sectional size, the tumors were injected with ADV-tk or a control adenovirus vector containing the beta-galactosidase (beta-Gal) gene (ADV-beta gal). After vector injection the animals were treated with GCV or with saline for 6 days. Sixteen days after tumor cell injection, the brains were examined histologically. The rats that were injected with ADV-beta gal and treated with GCV or saline, and those that were injected with ADV-tk and treated with saline had large tumors, whereas the rats that were injected with ADV-tk and treated with GCV had no visible tumor tissue at the site of tumor cell injection. In survival studies animals treated with ADV-tk+GCV survived a significantly longer time than animals treated with ADV-beta gal+GCV. Our results demonstrate that the recombinant adenoviral vector containing the tk gene confers GCV cytotoxic sensitivity to mammary tumor cells in vitro and in the brain, and suggest that this treatment strategy may be useful in treating somatic tumors that metastasize to the brain.

Adenocarcinoma↗
PubMed1995

Inhibition of melanoma growth by adenoviral-mediated HSV thymidine kinase gene transfer in vivo.

To assess the potential of an in vivo, adenovirus-mediated gene therapy approach for the treatment of malignant melanoma, the efficacy of adenovirus-mediated herpes simplex virus thymidine kinase gene (HSV-Ek) transfer and administration of ganciclovir (GCV) was investigated using a nude mouse model. Initially, B16 murine melanoma cells were efficiently transduced in vitro by a recombinant replication-defective adenovirus containing the HSV-tk gene (ADV/RSVtk), and rendered sensitive to cell killing by 10 micrograms/ml GCV. A significant "bystander effect" was observed at low multiplicity of infection in comparison of cell killing to control B16 transduction by adenovirus containing the beta-galactosidase gene (ADV/RSV-beta-gal). In vivo, melanomas established from subcutaneous injection of 4 x 10(5) B16 cells were injected after 14 d with 1 x 10(10) ADV/RSV-tk viral particles. Subsequent treatment for 6 d with GCV resulted in an inhibition of melanoma growth, with an approximately 40-50% reduction in melanoma volume in comparison to controls in repeated experiments. These data demonstrate that adenovirus-mediated gene transfer can function as an efficient delivery system to reduce established tumor burden in vivo. This result may hold significant promise for the development of effective in situ gene therapy for melanoma in humans.

Adenoviridae↗
PubMed1995

The use of a universal force-moment sensor to determine in-situ forces in ligaments: a new methodology.

Determination of ligament forces is an integral part of understanding their contribution during motion and external loading of an intact joint. While almost all previous investigations have reported only the magnitude of tension, this alone cannot adequately describe the function of a particular ligament. An alternative approach to determine the in-situ forces in ligaments has been developed which utilizes a universal force-moment sensor in conjunction with a force transformation scheme. In addition to providing the magnitude of ligament force, the direction and point of application of this in-situ force can also be determined. Further, the approach does not require mechanical contact with the ligament. Application of this new methodology is demonstrated for the human anterior cruciate ligament in the present study (n = 7) although it may be similarly applied to other ligaments at the knee or in other synovial joints of the human body.

Aged↗
PubMed1995

Complete spectrum of PAH mutations in Tataria: presence of Slavic, Turkic and Scandinavian mutations.

Phenylketonuria (PKU) is an autosomal recessive disorder associated with a deficiency of hepatic phenylalanine hydroxylase (PAH). Although the molecular lesions present in the PAH genes of PKU patients have previously been determined in several Slavic populations, little is known regarding the molecular basis of PKU in the non-Slavic populations of the former Soviet Union. Guthrie card samples from twenty-one classical PKU patients residing in the Tatarian Republic were examined by a combination of denaturing gradient gel electrophoresis and direct sequence analysis. Twelve patients were of Tatarian ancestry, five were of Russian ancestry, and four were of mixed Tatarian and Russian ancestry. Two of the Tatarian patients were related, sharing one mutant allele. The single major allele identified in this study was R408W/RFLP haplotype 2/VNTR 3, which was present on 11/14 or 78.6% of all mutant chromosomes of Slavic origin, but on only 10/27 or 37.0% of mutant chromosomes of Tatarian origin. This result suggests that this allele was introduced into central Asian populations during the eastward expansion of Slavs across the Eurasian landmass. A significant influence of Turkic peoples on Tatars can be inferred from the presence of R261Q. IVS10nt546g --> a, L48S, IVS2nt5g --> c and P281L, all of which are relatively common among Turks or have been observed in Mediterranean populations. Together, these alleles are present on 11/27 or 40.7% of all mutant chromosomes in ethnic Tatars. Surprisingly, the common Scandinavian mutation IVS12ntlg --> a was also present in Tataria, as was the delta agE221D222fs mutation found previously only in Denmark. Thus, some direct or indirect gene flow from Scandinavian into Tataria seems evident. Finally, the complete absence of PAH mutations previously observed in Oriental populations suggests that there was little gene flow into Tataria from Eastern Asia.

Alleles↗
PubMed1995

Efficient gene delivery and expression in mammalian cells using DNA coupled with perfringolysin O.

Current non-viral DNA vectors for gene therapy are limited by low cellular transfection efficiencies and low levels of gene expression due to inefficient endosomal DNA release. We have used perfringolysin O (PFO), a membrane active bacterial protein, to deliver DNA into cells. PFO belongs to the so-called sulphydryl-activated family of membrane active bacterial proteins, which have been used to deliver small molecules and proteins into cells. PFO was incorporated into DNA complexes through a biotin-streptavidin bridge and the DNA-PFO complexes were used to deliver the Escherichia coli beta-galactosidase gene into cells. High levels of gene expression were achieved in murine sol 8 myoblast cells using these DNA-PFO complexes. The level of gene expression correlated well with the content of PFO in the complexes. Under optimal conditions, 15-20% of the cells were stained blue with X-gal. Furthermore, the expression was independent of a receptor ligand. Thus, membrane active bacterial proteins may be an important tool for the future development of non-viral DNA delivery systems for gene therapy.

Animals↗
PubMed1995

Therapeutic serum concentrations of human alpha-1-antitrypsin after adenoviral-mediated gene transfer into mouse hepatocytes.

Alpha-1-antitrypsin is a relatively common genetic deficiency that results in early emphysema. The liver as the natural source of most alpha-1-antitrypsin synthesis was the target organ selected for gene replacement therapy studies. Previous work used recombinant retroviral vectors that encode the human alpha-1-antitrypsin cDNA for ex vivo and direct in vivo transduction of hepatocytes in dogs and rodents. This approach led to low levels of human protein in the serum of recipients. In this study, recombinant adenoviral vectors that express the human alpha-1-antitrypsin cDNA under the transcriptional control of the phosphoglycerate kinase (PGK) or RSV-LTR promoters have been constructed and used for the direct transduction of mouse hepatocytes in vivo. The animals transduced with the recombinant adenoviral vectors had therapeutic serum levels of human alpha-1-antitrypsin of up to 700 micrograms/mL. Thus, adenovirus-mediated gene transfer of the hAAT cDNA into the liver was able to produce therapeutic serum concentrations of protein.

Adenoviridae↗
PubMed1994

Adenovirus-mediated gene therapy of experimental gliomas.

The efficacy of adenovirus (ADV)-mediated gene therapy to treat brain tumors was tested in a syngeneic glioma model. Tumor cells were transduced in situ with a replication-defective ADV carrying the herpes simplex virus thymidine kinase (HSV-tk) gene controlled by the Rous sarcoma virus promoter. Expression of the HSV-tk gene enables the transduced cell to convert the drug ganciclovir to a form that is cytotoxic to dividing cells. Tumors were generated in Fischer 344 rats by stereotaxic implantation of 9L gliosarcoma cells into the caudate nucleus. Eight days later, the tumors were injected either with the ADV carrying the HSV-tk (ADV-tk) gene or a control ADV vector containing the beta-galactosidase (ADV-beta gal) gene and the rats were treated with either ganciclovir or saline. Tumor size was measured 20 days after implantation of 9L cells or at death. Rats treated with ADV-beta gal and ganciclovir or with ADV-tk and saline had large tumors. No tumors were detected in animals treated with ADV-tk and with ganciclovir at doses > or = 80 mg/kg. An infiltrate of macrophages and lymphocytes at the injection site in animals treated with ADV-tk and ganciclovir indicated an active local immune reaction. In survival studies, all animals treated with ADV-tk and ganciclovir have remained alive longer than 80 and up to 120 days after tumor induction whereas all untreated animals died by 22 days. These results demonstrate that ADV-mediated transfer of HSV-tk to glioma cells in vivo confers sensitivity to ganciclovir, and represents a potential method of treatment of brain tumors.

Adenoviridae↗
PubMed1994

Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transfer in vivo.

The therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transduction of rat C6 glioma cells followed by ganciclovir (GCV) administration was studied in tumors generated in the brains of nude mice. C6 glioma cells were efficiently transduced in vitro by a replicative-defective recombinant adenovirus carrying the HSV-tk gene (ADV/RSV-tk) that rendered them sensitive to GCV in a dose-dependent manner. Tumors were generated by stereotaxic intracerebral injection of 1 x 10(4) C6 cells in nude mice. After 8 days of tumor growth, 3 x 10(8) ADV/RSV-tk viral particles were injected into the tumors and the mice subsequently were treated with GCV for 6 days. Tumor size in untreated and treated animals was compared 20 days after tumor implantation. The mean cross-sectional area of the tumors in the treated animals was 23-fold smaller than in control animals and the tumor volume was reduced by > 500-fold. These results demonstrate that the recombinant adenoviral vector can function as an efficient gene delivery vehicle for the treatment of gliomas by in vivo gene therapy.

Adenoviridae↗
PubMed1994

Functional characterization of a unique liver gene promoter.

Human phenylalanine hydroxylase (PAH) is specifically expressed in the liver to convert L-phenylalanine to L-tyrosine. Deficiency of the PAH enzyme causes classic phenylketonuria, a common genetic disorder. The human PAH gene has a TATA-less promoter with multiple transcriptional initiation sites. A 9-kilobase DNA fragment 5'-flanking to the human PAH gene is sufficient to confer tissue- and developmental stage-specific expression of a reporter gene in transgenic mice. Deletion studies showed that the -121-base pair proximal promoter still retained a significant level of activity in hepatic cells. At least two protein binding sites, PAH-A and PAH-B, were identified in the proximal region of the human PAH promoter using rat liver nuclear extract. The PAH-A site covers a unique palindromic sequence, and the PAH-B site contains CCCTCCC repeats. Both elements are ubiquitous and essential regulatory elements for transcriptional activity. Nuclear protein factors that bind to the PAH-A and -B sites are detected in different cell types and are distinct from previously characterized transcription factors. No tissue-specific transcription factor binding sites have been detected within the proximal promoter region of the human PAH gene. These results suggest that the PAH gene promoter has a unique organization of regulatory elements for its tissue-specific expression in comparison with other liver gene promoters.

Base Sequence↗
PubMed1994

Healing of the rabbit medial collateral ligament following an O'Donoghue triad injury: effects of anterior cruciate ligament reconstruction.

The effects of healing time and anterior cruciate ligament reconstruction on healing of the medial collateral ligament and stability of the knee joint were evaluated in a rabbit model of an O'Donoghue triad injury (rupture of the medial collateral ligament with removal of the anterior cruciate ligament and part of the medial meniscus). At time 0 and at 6 and 12 weeks postoperatively, the anterior-posterior translation and varus-valgus rotation of the knee, the structural properties of the femur-medial collateral ligament-tibia complex, and the mechanical properties of the substance of the medial collateral ligament were evaluated. Although anterior-posterior translation increased significantly with time, we could not demonstrate a significant temporal effect on varus-valgus rotation. The ultimate load, elongation at failure, and energy absorbed to failure improved with time. In addition, with time, failure of the complex occurred more often in the ligament substance than at the osseous insertion. Because healing time did not affect the cross-sectional area or modulus of the medial collateral ligament, the improved structural properties of the complex resulted not from improvements in the mechanical properties of the tissue but rather from healing of the tibial insertion site. By 12 weeks, the reconstructed knees had only minor signs of osteoarthrosis on the tibiofemoral surfaces; this is in contrast to the findings in anterior cruciate ligament-deficient knees in our earlier study. Additionally, at 12 weeks, the stiffness of the complexes from the reconstructed group was 1.3 times that of the anterior cruciate ligament-deficient group (p < 0.05), and te ultimate load had increased by a factor of 1.6 (p < 0.05). Our findings demonstrate that reconstruction of the anterior cruciate ligament in the rabbit helps to stabilize the joint, improves healing of the medial collateral ligament, and may decrease the incidence of early-onset osteoarthrosis after an O'Donoghue triad injury.

Animals↗