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Biomedical subjects

S L Woo

Publications and source records attributed to S L Woo.

At least 163 records · Page 9Linked to original sources
PubMed1994

Tensile and viscoelastic properties of human patellar tendon.

The tensile and viscoelastic properties of fresh-frozen, nonirradiated human patellar tendon were investigated in two groups of 15 specimens: one group was from individuals 29-50 years old and the other group was from individuals 64-93 years old. The central portion of each patella-patellar tendon-tibia complex was subjected to cyclic preconditioning, stress-relaxation, cyclic stress-relaxation, and load to failure tests. For each age group, stress-relaxation and stress-strain curves were obtained, from which percentage relaxation, ultimate tensile strength, strain at failure, modulus, and strain energy density were determined. Viscoelastic behavior was described with use of quasilinear viscoelasticity. The younger group showed a 46 +/- 9% (mean +/- SD) decrease in stress after 15 minutes, whereas the older group exhibited a 50 +/- 6% decrease. The values for ultimate tensile strength and strain at failure, respectively, were 64.7 +/- 15.0 MPa and 14 +/- 6% for the younger group and 53.6 +/- 10.0 MPa and 15 +/- 5% for the older group. Modulus values were 660 +/- 266 MPa for the younger group and 504 +/- 222 MPa for the older group. Except for ultimate tensile strength, which was 17% less for the older group than for the younger one, no statistically significant differences were found in tensile or viscoelastic properties. This study indicated that there were minimal differences in biomechanical properties of the substance of the patellar tendon between younger and older age groups.

Adult↗
PubMed1994

A simple, rapid, and highly informative PCR-based procedure for prenatal diagnosis and carrier screening of phenylketonuria.

The polymorphic information content (PIC) and the degree of heterozygosity of several polymorphic systems within the phenylalanine hydroxylase (PAH) gene were determined in 85 European Caucasian and 19 Chinese phenylketonuria (PKU) kindreds. The first system examined, a short tandem repeat (STR), had a PIC of 80 and 73 per cent in these Caucasian and Chinese samples, respectively. The degree of heterozygosity actually observed for this system was 81 and 64 per cent in the Caucasian and Chinese PKU families, respectively. Through the addition of a second polymorphism based on a variable number of tandem repeats (VNTR), the PIC was increased to 90 per cent in Caucasians, but only to 75 per cent in Chinese. The degree of heterozygosity observed for this combination was 94 per cent in European PKU families and 67 per cent in Chinese PKU families. The further addition of an Xmnl RFLP increased both the PIC and the level of heterozygosity in Caucasians to 95 per cent, but did not change either of these measures in Chinese. The combined use of these three polymorphisms significantly increases the informativity of prenatal diagnostic and carrier screening procedures in both Caucasian and Chinese PKU kindreds. Furthermore, since each of these polymorphisms can be studied by PCR-based methods, these new tests can be performed more quickly and easily than previous Southern-based procedures.

Alleles↗
PubMed1994

Potential of genes and gene products from Trichoderma sp. and Gliocladium sp. for the development of biological pesticides.

Fungal cell wall degrading enzymes produced by the biocontrol fungi Trichoderma harzianum and Gliocladium virens are strong inhibitors of spore germination and hyphal elongation of a number of phytopathogenic fungi. The purified enzymes include chitinolytic enzymes with different modes of action or different substrate specificity and glucanolytic enzymes with exo-activity. A variety of synergistic interactions were found when different enzymes were combined or associated with biotic or abiotic antifungal agents. The levels of inhibition obtained by using enzyme combinations were, in some cases, comparable with commercial fungicides. Moreover, the antifungal interaction between enzymes and common fungicides allowed the reduction of the chemical doses up to 200-fold. Chitinolytic and glucanolytic enzymes from T. harzianum were able to improve substantially the antifungal ability of a biocontrol strain of Enterobacter cloacae. DNA fragments containing genes encoding for different chitinolytic enzymes were isolated from a cDNA library of T. harzianum and cloned for mechanistic studies and biocontrol purposes. Our results provide additional information on the role of lytic enzymes in processes of biocontrol and strongly suggest the use of lytic enzymes and their genes for biological control of plant diseases.

Acetylglucosaminidase↗
PubMed1994

Gene therapy for metabolic disorders.

Most diseases caused by genetic deficiencies could, in theory, be treated by the introduction and expression of a normal gene into an appropriate target tissue. It seems likely that gene therapy strategies for most metabolic disorders will not require strict gene regulation, as a fraction of the normal levels of gene activity could result in amelioration or significant improvement in the clinical outcome. Gene therapy is making rapid progress towards the goal of treating various disorders: here, we summarize the state of gene therapy for metabolic disorders.

Animals↗
PubMed1994

Biomechanical function of the human anterior cruciate ligament.

Knowledge about the biomechanical function of the anterior cruciate ligament (ACL) is very important in the treatment of the ACL deficient knee. This article presents an overview of the biomechanical function of the ACL, including its structural and mechanical properties as well as its role in knee stabilization and normal kinematics. Tensile properties of the prospective biological grafts and future directions in ACL research are also discussed.

Anterior Cruciate Ligament↗
PubMed1994

Population genetics of phenylketonuria.

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a large number of mutations at the phenylalanine hydroxylase (PAH) locus, most of which are strongly associated with specific RFLP or VNTR haplotypes. One of the major questions remaining in PKU research is why this apparently maladaptive disorder has been maintained at a frequency of approximately 1 in 10,000 among Caucasians. A growing number of studies have provided evidence that both the relatively high frequency of PKU and the strong mutation/haplotype associations might reflect the existence of multiple founding populations for PKU. Examples of putative founding populations for PKU in both Europe and Asia will be presented. Some PAH mutations are associated with multiple haplotypes, suggesting recurrence. Evidence for and against recurrence as the mechanism responsible for the association of the R408W mutation with RFLP haplotypes 1 and 2 will be discussed.

Asia↗
PubMed1994

Molecular analysis of PKU in Ireland.

Classical phenylketonuria (PKU: McKusick No. 261600) is caused by mutations occurring at the phenylalanine hydroxylase (PAH) locus on chromosome 12 and has a prevalence in Ireland of 1 in 4500. We examined 304 independent alleles from 350 patients for the presence of six mutations and have characterized VNTR alleles within the minisatellite region 3' to the PAH gene in patients carrying the most prevalent mutation. R408W was the most common mutation found, with a relative frequency of 42%. All other mutations had relative frequencies of < 10%. VNTR analysis showed that the R408W mutation is associated with the VNTR-8 allele in the Irish population, indicating that R408W is associated with RFLP haplotype 1. This differs from that reported from eastern Europe where R408W is associated with RFLP haplotype 2/VNTR-3; an observation which has led several groups to propose a Balto-Slavic origin for this mutation. These results support the hypothesis of a second, independent founding event for the R408W mutation on an RFLP haplotype 1 VNTR-8 chromosome background in the Irish/Celtic population.

Gene Frequency↗
PubMed1994

Gene therapy for phenylketonuria.

Classical phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). Three different vector systems have been developed to examine the potential of somatic gene therapy for the treatment of PKU. Recombinant retroviral vectors and DNA/protein complexes can efficiently transduce PAH-deficient hepatocytes in vitro, but their present application is limited by their low transduction efficiency in vivo. In contrast, infusion of a recombinant adenoviral vector expressing the human PAH cDNA into the portal circulation of PAH-deficient mice restores 10-80% of normal hepatic PAH activity and completely normalizes serum phenylalanine levels. At present, this effect is transient and re-administration has no further effect. However, this result suggests that PKU can be completely corrected by somatic gene therapy as more persistent vectors are developed.

Animals↗
PubMed1994

Origins of hyperphenylalaninemia in Israel.

Mutations and polymorphisms at the phenylalanine hydroxylase (PAH) gene were used to study the genetic diversity of the Jewish and Palestinian Arab populations in Israel. PAH mutations are responsible for a large variety of hyperphenylalaninemias (HPAs), ranging from the autosomal recessive disease phenylketonuria to various degrees of nonclinical HPA. Seventy-two Jewish and 36 Palestinian Arab families with various HPAs, containing 115 affected genotypes, were studied by haplotype analysis, screening for previously known PAH lesions and a search for novel mutations. Forty-one PAH haplotypes were observed in this sample. Four mutations previously identified in Europe (IVS10nt546, R261Q, R408W and R158Q) were found, and were associated with the same haplotypes as in Europe, indicating possible gene flow from European populations into the Jewish and Palestinian gene pools. Of particular interest is a PAH allele with the IVS10nt546 mutation and haplotype 6, that might have originated in Italy more than 3,000 years ago and spread during the expansion of the Roman Empire. These results, together with previous identification of three PAH mutations unique to Palestinian Arabs [IVSnt2, Edel(197-205) and R270S], indicate that the relatively high genetic diversity of the Jewish and Palestinian populations reflects, in addition to genetic events unique to these communities, some gene flow from neighboring and conquering populations.

Amino Acid Metabolism, Inborn Errors↗
PubMed1994

Folate receptor mediated DNA delivery into tumor cells: potosomal disruption results in enhanced gene expression.

We have used a particular folate receptor, which is overexpressed in tumor cells, for targeted DNA delivery into these cell types. This folate receptor internalizes folate through caveolae by a process named potocytosis, which is distinct from endocytosis, through clathrin-coated pits. When folate conjugated to poly-L-lysine was used to deliver the E. coli beta-galactosidase gene into tumor cells overexpressing the folate receptor, only low levels of beta-galactosidase activity were detectable. When a replication-defective adenovirus was coincubated with the DNA/folate complexes, 20 to 30% of the cells stained blue with X-gal and a 1000-fold increase of beta-galactosidase activity was observed. Thus, for high efficient DNA delivery and gene expression via the caveolae system, a potosomal disruption agent is needed. Furthermore, folate-mediated DNA delivery is restricted to tumor cells that highly overexpress the folate receptor, which will permit future development of tumor cell-specific delivery of toxic genes for cancer gene therapy.

Adenoviridae↗
PubMed1994

Gene therapy for phenylketonuria: phenotypic correction in a genetically deficient mouse model by adenovirus-mediated hepatic gene transfer.

Classical phenylketonuria (PKU), which predisposes affected individuals to severe mental retardation, is caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). A recombinant adenoviral vector containing the human PAH cDNA was constructed and administered to PAH-deficient mice (strain PAHenu2). The hyperphenylalaninemic phenotype of these animals was completely normalized within 1 week of treatment. Although this therapeutic effect did not persist, analysis of the relationship between hepatic PAH activity and serum phenylalanine levels indicated that only 10-20% of normal enzymatic activity in the mouse liver is sufficient to restore normal serum phenylalanine levels. These results demonstrate that PKU and other metabolic disorders secondary to hepatic deficiencies can be completely corrected by gene therapy when more persistent vector systems are developed.

Adenoviridae↗
PubMed1993

Hepatic gene therapy: efficient gene delivery and expression in primary hepatocytes utilizing a conjugated adenovirus-DNA complex.

Receptor-mediated endocytosis is an effective method for gene delivery into target cells. We have previously shown that DNA molecules complexed with asialoglycoprotein can be efficiently endocytosed by primary hepatocytes and the internalized DNA can be released from endosomes by the use of a replication-defective adenovirus. Because the DNA and virus enter target cells independently, activity enhancement requires high concentrations of adenoviral particles. In this study, adenoviral particles were chemically conjugated to poly(L-lysine) and bound ionically to DNA molecules. Quantitative delivery to primary hepatocytes was achieved with significantly reduced viral titer when the asialoorosomucoid-poly(L-lysine) conjugate was included in the complex. The conjugated adenovirus was used to deliver a DNA vector containing canine factor IX to mouse hepatocytes, resulting in the expression of significant concentrations of canine factor IX in the culture medium. The results suggest that receptor-mediated endocytosis coupled with an efficient endosomal lysis vector should permit the application of targeted and efficient gene delivery into the liver for gene therapy of hepatic deficiencies.

Adenoviridae↗
PubMed1993

Hepatic gene therapy: adenovirus enhancement of receptor-mediated gene delivery and expression in primary hepatocytes.

We have combined a receptor-mediated DNA delivery system with the endosomal lysis ability of adenovirus and shown that DNA can be delivered into primary hepatocytes, resulting in a high level of gene expression. When asialoorosomucoid conjugated with poly(L-lysine) was used to deliver the Escherichia coli beta-galactosidase gene into primary hepatocytes through binding with the hepatic asialoglycoprotein receptor, only a low level of beta-galactosidase was detectable, with less than 0.1% of the hepatocytes being transfected. This level of activity can be greatly enhanced by the cointernalization of the DNA.protein complex with a replication-defective adenovirus, resulting in 100% of the hepatocytes staining blue with 5-bromo-4-chloro-3-indolyl beta-D-galactoside. Quantitative analysis of beta-galactosidase expression also showed a 1000-fold enhancement of activity. To test the applicability of this DNA delivery system for the correction of phenylketonuria, a metabolic disorder that causes severe mental retardation in children, we have delivered the human phenylalanine hydroxylase (PAH) gene to hepatocytes derived from a PAH-deficient mouse strain and demonstrated complete reconstitution of enzymatic activity. This method shows great promise for efficient gene delivery to the liver for correction of hepatic disorders.

3T3 Cells↗
PubMed1993

Methods for electrophoretic karyotyping of filamentous fungi in the genus Trichoderma.

Methods for electrophoretic karyotyping of filamentous fungi in the genus Trichoderma were developed. These techniques permitted the separation and visualization of intact chromosomes from viable protoplasts. Three strains were analyzed: Trichoderma harzianum strains T12 his-2 and T95 lys-1, and a prototrophic strain (1295-22) produced by protoplast fusion of T12 his-2 with T95 lys-1. Four chromosome bands ranging in size from 2.2 Mb (megabase pairs) to 5.4 Mb were visualized with strain T95 lys-1, whereas two chromosome bands were visualized for strains T12 his-2 and 1295-22. The largest chromosome of all three strains seems to be similar in size and has been estimated to be approximately 5.4 Mb. All remaining chromosomes observed were dissimilar in size. Methods for protoplast isolation, protoplast embedding, and electrophoretic conditions useful for separation of intact chromosomes ranging in size from 50 kb (kilobase pairs) up to approximately 6.0 Mb utilizing transverse alternating field electrophoresis (TAFE) will be discussed. The techniques provided should be applicable to a variety of lower eukaryotic organisms when using the TAFE system.

Chromosome Banding↗