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Biomedical subjects

T K Taylor

Publications and source records attributed to T K Taylor.

At least 19 recordsLinked to original sources
PubMed2001

Regulation of gelatinase-A (MMP-2) production by ovine intervertebral disc nucleus pulposus cells grown in alginate bead culture by Transforming Growth Factor-beta(1)and insulin like growth factor-I.

The aim of this study was to gain information relevant to disc repair processes. Limited degradation of the collagen matrix by matrix metalloproteases (MMPs) may facilitate the loosening of cell-cell and cell-matrix interactions within the injured intervertebral disc (IVD) to favour the penetration of blood vessels and migration of fibroblasts into the defect to promote repair processes. Gelatinase A (MMP-2) has a particularly important role to play in angiogenesis, in the present study we investigated the in vitro regulation of MMP-2 by Transforming Growth Factor-beta 1 (TGF-beta 1) and Insulin-like Growth Factor-1 (beta IGF-I) in cells from the nucleus pulposus (NP) of the ovine IVD. Ovine NP cells were grown in alginate bead cultures in complete medium (10% foetal calf serum) for 7 days, established in serum-free conditions for 24 h, then stimulated with TGF-beta 1 (0.1 or 10 ng/ml) or IGF-I (2 or 50 ng/ml) +/-Concanavalin A (20 microg/ml) for an additional 48 h. Conditioned medium was examined for matrix metalloproteases using gelatin zymography, Tissue Inhibitor of Metalloproteinase 2 (TIMP-2) and Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) were immunolocalised in beads. Pro (72 kDa) and active (59 kDa) MMP-2 were the major gelatinolytic MMPs detected in control cultures, the TGF-beta 1 and IGF-I treatments significantly decreased levels of the active MMP-2, inclusion of Concanavalin A resulted in a complete reversal of this trend with IGF-I, and to a lesser extent with TGF-beta 1. Cell surface levels of TIMP-2 and MT1-MMP were decreased by the TGF-beta 1 treatment while IGF-I only appeared to decrease TIMP-2 expression. The findings of this study provide some insight as to why dense avascular connective tissues such as the intervertebral disc have such a poor healing potential.

Alginates↗
PubMed2001

A comparative analysis of the differential spatial and temporal distributions of the large (aggrecan, versican) and small (decorin, biglycan, fibromodulin) proteoglycans of the intervertebral disc.

This study provides a comparative analysis of the temporal and spatial distribution of 5 intervertebral disc (IVD) proteoglycans (PGs) in sheep. The main PGs in the 2 and 10 y old sheep groups were polydisperse chondroitin sulphate and keratan sulphate substituted species. Their proportions did not differ markedly either with spinal level or disc zone. In contrast, the fetal discs contained 2 slow migrating (by composite agarose polyacrylamide gel electrophoresis, CAPAGE), relatively monodisperse chondroitin sulphate-rich aggrecan species which were also identified by monoclonal antibody 7-D-4 to an atypical chondroitin sulphate isomer presentation previously found in chick limb bud, and shark cartilage. The main small PG detectable in the fetal discs was biglycan, whereas decorin predominated in the 2 and 10 y old IVD samples; its levels were highest in the outer annulus fibrosus (AF). Versican was most abundant in the AF of the fetal sheep group; it was significantly less abundant in the 2 and 10 y old groups. Furthermore, versican was immunolocalised between adjacent layers of annular lamellae suggesting that it may have some role in the provision of the viscoelastic properties to this tissue. Versican was also diffusely distributed throughout the nucleus pulposus of fetal IVDs, and its levels were significantly lower in adult IVD specimens. This is the first study to identify versican in ovine IVD tissue sections and confirmed an earlier study which demonstrated that ovine IVD cells synthesised versican in culture (Melrose et al. 2000). The variable distribution of the PGs identified in this study provides further evidence of differences in phenotypic expression of IVD cell populations during growth and development and further demonstrates the complexity of the PGs in this heterogeneous but intricately organised connective tissue.

Aggrecans↗
PubMed2001

Differential expression of proteoglycan epitopes and growth characteristics of intervertebral disc cells grown in alginate bead culture.

This study assessed the growth characteristics and proteoglycan (PG) production in vitro of cells isolated from various zones; annulus fibrosus (AF), the transitional zone (TZ, an opalescent region situated between the AF and nucleus pulposus, NP) and the NP of the ovine intervertebral disc. The isolated cells were subsequently cultured in calcium alginate microspheres. Cellular metabolic activity was assessed over the 10 days of culture by the bioreduction of a tetrazolium dye substrate to a coloured formazan chromophore which could be measured colorimetrically at 490 nm. These data were correlated with the DNA content of beads measured using the fluorescent dye Hoechst 33258. Viable and non-viable cells in alginate beads were also assessed histochemically using the fluorescent dyes 5-chloromethylfluorescein diacetate and ethidium homodimer-1. PGs synthesised in culture were examined immunohistologically using monoclonal antibodies to defined glycosaminoglycan side chain PG epitopes. The results obtained clearly showed that AF and TZ cells differed from NP cells in the measured indices of cellular metabolism and in the extent of matrix deposition. In contrast to cells from the NP the cells from the AF and TZ were more metabolically active and programmed more to cellular proliferation than to matrix production.

Alginates↗
PubMed2000

Spinal biomechanics and aging are major determinants of the proteoglycan metabolism of intervertebral disc cells.

STUDY DESIGN: The proteoglycan metabolism of ovine disc nucleus pulposus and anulus fibrosus cells was investigated in relation to age, spinal level, and intrinsic spinal biomechanical properties. OBJECTIVE: To evaluate the hypothesis that with aging loss of proteoglycans from the lumbosacral disc exceeds that from upper lumbar discs because of its proximity to a rigid segment, the sacrum. SUMMARY OF BACKGROUND DATA: The proteoglycan and associated water of the disc decreases with aging. METHODS: Proteoglycans were extracted directly from the disc tissues using 4 M GuHCl and examined by composite agarose polyacrylamide gel electrophoresis. Disc cells were cultured in alginate beads, and their metabolic activity was assessed by 3H-thymidine incorporation into DNA and by bioreduction of a cell proliferation dye. Newly synthesized proteoglycans were radiolabeled with 35S, and their molecular weight distributions and ability to aggregate with hyaluronan were determined by Sephacryl S1000 gel chromatography. Resident proteoglycans extracted from disc tissues with 4 M GuHCl were similarly evaluated. A group of adult animals also were studied biomechanically to evaluate the range of spinal motion (L4/L5 to L7/S1). RESULTS: In contrast to the neonatal proteoglycan samples, the biosynthesis of proteoglycans by nucleus pulposus cells of adult discs increased progressively toward the sacrum. This correlated with increased metabolic activity. Analysis of the resident proteoglycans by composite agarose polyacrylamide gel electrophoresis indicated that although the aggrecan-1 population was present almost exclusively in the neonatal group, it was the aggrecan-2 population that predominated in the adult discs, and it became progressively more heterogeneous with aging and proximity of the disc to the sacrum. CONCLUSIONS: The proteoglycans of the lumbosacral disc of adult animals turned over faster than proteoglycans of adjacent lumbar discs. The reduced proteoglycan content and ability to aggregate, particularly in the nucleus pulposus of lumbosacral discs, indicated that proteoglycan catabolism exceeded the rate of biosynthesis. These events in the lumbosacral disc are thought to be determined mechanically by its proximity to the sacrum.

Aging↗
PubMed2000

Why have we been more successful in reducing tobacco use than violent crime?

Tobacco control efforts have been associated with a significant reduction in the prevalence of tobacco use in the United States. Efforts to reduce the incidence of violent crime have been much less successful. This paper argues that progress on tobacco control stems from the existence of a clear, empirically based, and widely understood analysis of the tobacco problem that articulates (a) the harms associated with its use, (b) the causes of tobacco use, and (c) the programs and policies that could reduce tobacco use. This analysis has guided the development of a network of social organizations that have been advocating for policies and programs that are reducing tobacco use. In contrast, there is not a widely shared, cogent, and empirically based analysis of the problem of violent crime. As a result, efforts to combat violent crime are fragmented and it has proven difficult to generate support for preventive programs and policies. Substantial empirical progress has been made, however, on how violent crime could be prevented. That evidence is reviewed. It is argued that the articulation of this evidence is a critical first step for achieving widespread reduction in the incidence of violent crime. Communication of that evidence to audiences that matter will require that behavioral scientists become better organized to advocate for the adoption of empirically supported practices.

Antisocial Personality Disorder↗
PubMed1999

How best to fix a broken hip. Fractured Neck of Femur Health Outcomes Project Team.

OBJECTIVES: To develop evidence-based guidelines for the treatment of proximal femoral fractures to optimise functional outcome while minimising length of stay in hospital. DATA SOURCES: Systematic literature search of MEDLINE and CINAHL computer databases, bibliographies, and current contents of key journals for 1966-1995. STUDY SELECTION: English-language randomised controlled trials of all aspects of acute-care hospital treatment of proximal femoral fracture among subjects aged 50 years and over with proximal femoral fractures not due to metastatic disease. DATA EXTRACTION: Two independent reviewers, blinded to authors, institution and study results, followed a standard Cochrane Collaboration protocol and assessed study quality and treatment conclusions. When necessary, a third review was performed to reach consensus. RESULTS: Of the 120 articles published between 1966 and December 1995, 97 met the inclusion criteria. Fifteen clinical interventions were reviewed. Five were supported by National Health and Medical Research Council (NHMRC) level I evidence (prophylactic anticoagulants, prophylactic antibiotics, regional anaesthesia, pressure-relieving mattresses, and internal surgical fixation), two had no supporting randomised controlled trial evidence (time to surgery, time to mobilisation after surgery) and the remainder were classified as having Level II evidence. A review of current practice (1993-94) identified wide variability in these interventions across five acute-care hospitals in the Northern Sydney Area Health Service. CONCLUSIONS: Randomised controlled trial evidence (NHMRC Levels I and II) exists for many, but not all, aspects of hip fracture treatment. There is a need for changes to be made to some aspects of practice in accordance with evidence-based guidelines.

Anesthesia, Conduction↗
PubMed1999

Interpersonal skills training to reduce aggressive and delinquent behavior: limited evidence and the need for an evidence-based system of care.

The prevention of aggressive and delinquent behavior during childhood and adolescence is one of the highest priorities for public health and crime prevention. The most common approach to preventing or treating these conduct problems has been to provide interpersonal skills training to the affected youth. This paper reviews all randomized controlled trials evaluating interpersonal skills training programs as an intervention to reduce conduct problems. Research shows that such programs have weak empirical support as isolated interventions. An alternative evidence-based system of care is described. Such a system would include behavioral parent training and behavioral classroom-based interventions for young children at risk of developing problems, as well as multisystemic family therapy or multidimensional treatment foster care for chronic delinquents. Within such a network of services, interpersonal skills training could play an important supportive role. Such a system holds the greatest promise for reducing the prevalence of aggressive and delinquent behavior in communities.

Adolescent↗
PubMed1998

Behavioral family interventions for improving child-rearing: a review of the literature for clinicians and policy makers.

This paper reviews evidence that behavioral family interventions are effective at improving child-rearing in distressed families and families with children exhibiting disruptive behavior. Essential therapeutic strategies offered within a collaborative therapeutic process are identified. Exemplary materials for parents and clinicians are identified. Differences between behavioral family interventions and two popular press parenting approaches are highlighted, including the lack of empirical support for these widely used programs and the advice they offer which runs counter to behavioral approaches. Recommendations are offered for combining behavioral family interventions with other empirically supported approaches, promoting more widespread use of empirically supported treatments, such as behavioral family interventions, and the need for a public health perspective on family functioning, involving collaboration among clinicians, policy makers, and researchers.

Attention Deficit and Disruptive Behavior Disorder↗
PubMed1997

Traction-induced rupture of an extracranial vertebral artery aneurysm associated with neurofibromatosis. A case report.

STUDY DESIGN: This report describes presumed traction-induced rupture of a vertebral artery aneurysm in a patient with neurofibromatosis Type I. OBJECTIVE: To draw attention to the need for preoperative arteriography in the surgical management of severe cervical kyphosis in neurofibromatosis. SUMMARY OF BACKGROUND DATA: Aneurysmal dilatation is a rare but well-documented manifestation of neurofibromatosis. The complication of rupture of a vertebral artery lesion has not been described previously. METHODS: The clinical features of the reported complication in a 56-year-old woman are detailed. RESULTS: A successful outcome was achieved by embolization and later anterior and posterior spinal fusions. CONCLUSIONS: Vertebral arteriography should be part of the preoperative assessment of neurofibromatotic cervical kyphosis. Skull traction may produce aneurysmal rupture.

Aneurysm, Ruptured↗
PubMed1997

The serine proteinase inhibitory proteins of the chondrodystrophoid (beagle) and non-chondrodystrophoid (greyhound) canine intervertebral disc.

Trypsin inhibitory proteins of low buoyant density (p < or = 1.35 g/mL) fractions were prepared by CsCl density gradient ultracentrifugation of 4 M guanidinium hydrochloride extracts of lumbar beagle and greyhound annulus fibrosus and nucleus pulposus from animals aged 1 to 6 years. Affinity blotting with biotinylated trypsin was used to identify active trypsin inhibitory protein species; these species were also identified immunologically by Western blotting using antibodies against bovine pancreatic trypsin inhibitor (BPTI), and human inter-alpha-trypsin inhibitor (ITI). None of the trypsin inhibitory species evident in Western blots were reactive with anti-human alpha1-proteinase inhibitor (alpha-1-PI), alpha2-macroglobulin or secretory leucocyte proteinase inhibitor. The greyhound intervertebral disc samples generally had higher levels of active trypsin inhibitor species per unit weight of tissue extracted, and a more extensive range of inhibitor species. Inhibitor species of 30, 32, 34 kDa were identified in both beagle and greyhound intervertebral disc samples; these species were generally most prominent in the annulus fibrosus samples. In contrast, the nucleus pulposus samples contained relatively large trypsin inhibitor species; the anti-BPTI detected an inhibitor species of approximately 85-90 kDa; anti-ITI detected species of 120-250 kDa; biotinylated trypsin detected species of 60-110 kDa. A small molecular mass trypsin inhibitor species of 6 kDa, which was of similar mobility to BPTI, was also detected in annulus fibrosus samples; however, this species did not react with anti-BPTI.

Age of Onset↗
PubMed1997

Elevated synthesis of biglycan and decorin in an ovine annular lesion model of experimental disc degeneration.

The aim of this study was to extend our earlier observations on the changes that occur in the proteoglycans (PGs) of discs subjected to experimental injury to the annulus fibrosus (AF). We employed the alginate bead culture method to examine the metabolism of the dermatan sulphate (DS) containing PGs by cells derived from different regions of ovine discs that had been subjected to experimental annular injury. This was compared with the metabolism of the DS-PGs by cells isolated from equivalent regions of normal sham-operated discs. Six months after induction of the annular lesion, AF cells isolated from the lesion produced significantly higher levels of decorin and biglycan in alginate bead culture than did cells from equivalent zones of the controls. Decorin and biglycan were identified in culture media samples by immunoblotting, using specific antibodies (6-B-6, LF-96), and also by positive identification of their de-glycosylated core proteins. The core protein of the DS-PGs has been shown to inhibit type I/II collagen fibrillogenesis, to negatively regulate the action of transforming growth factor-beta (TGF-beta) and to diminish cellular proliferation in vitro; events which may be detrimental to tissue repair. The findings are therefore consistent with our previous observation the annular lesions in the avascular inner annulus have no capacity to heal.

Animals↗
PubMed1997

Topographical variation in the catabolism of aggrecan in an ovine annular lesion model of experimental disc degeneration.

An established model of experimental disc degeneration (Osti et al., Spine 15:762, 1990; Melrose et al., J Orthop Res 10:655, 1992) was used in this study. Four 2-year-old sheep received anterolateral incisions (4 x 10 mm) in the outer one-third of the annulus fibrosus of their L2-L3 and L4-L5 discs (lesion group). The annulus was not incised in another four sham-operated animals. After 6 months the sheep were killed, lumbar discs were dissected into lateral halves of the annulus fibrosus and the nucleus pulposus. Cells were isolated from disc tissues enzymatically and were grown in alginate bead culture to examine the proteoglycan metabolism of cells from lesion and control zones. The media of lesion zone cultures contained relatively high levels (compared with sham cultures) of catabolic fragments of the large, high-buoyant-density proteoglycans as demonstrated by Western blotting using monoclonal antibodies (5-D-4, 3-B-3, 1-C-6) and biotinylated hyaluronan and also by gel chromatography. Furthermore, cells from the vicinity of the lesion site also synthesized significantly lower levels (compared with sham cultures) of aggrecan that was retained within the alginate beads. Collectively, these data indicated that focal depletion of large, high-buoyant-density proteoglycans was evident within lesion sites in this model of experimental disc degeneration. The introduction of an annular lesion therefore significantly affected the proteoglycan metabolism of endogenous disc cell populations. The unique hydrodynamic and viscoelastic properties of the intervertebral disc are dependent to a large degree on the tissue levels of aggrecan. The focal depletion of aggrecan by annular lesions therefore may represent an important predisposing factor to the subsequent degeneration of these intervertebral discs.

Aggrecans↗
PubMed1996

Screening of children with Down syndrome for atlantoaxial (C1-2) instability: another contentious health question.

Screening for atlantoaxial (C1-2) instability in children with Down syndrome before their participation in sport is called into serious question. Despite the lack of clear supporting data to justify screening, it has been widely recommended and enforced by some sporting organisations for several decades. Experience in New South Wales during the past 25 years strongly suggests that routine screening should be discontinued, and the existing literature supports this move.

Adolescent↗
PubMed1996

Intervertebral disc reconstitution after chemonucleolysis with chymopapain is dependent on dosage.

STUDY DESIGN: The current report describes a study in beagles in which the effects of intradiscal injection of three doses of chymopapain were evaluated with respect to the reduction of disc width and reconstitution of the nucleus pulposus. OBJECTIVES: To establish an intradiscal dose of chymopapain that would achieve optimal reduction in disc height followed by maximum reconstitution of the nucleus pulposus. SUMMARY OF BACKGROUND DATA: Earlier reports of the efficacy of high and low doses of chymopapain for chemonucleolysis have provided conflicting data, and a scientific basis for an appropriate dose is lacking. METHODS: Four mature, female beagles were subjected to chemonucleolysis using three doses of chymopapain as Chymodiactin (31, 63 and 125 picokatals/disc) injected into the L2-L3, L1-L2, and L3-L4 discs. Disc widths were monitored radiographically over 32 weeks. Proteoglycans were radiolabeled by intravenous injection with Na2 35SO4 (1 mCi/kg) 24 hours before sacrifice, and their specific activities (disintegrations per minute/mg proteoglycan), hydrodynamic size, and ability to aggregate determined. RESULTS: Sixty-three picokatals of Chymodiactin produced optimal disc reconstitution after chemonucleolysis. A reduction in disc height of approximately 35% was evident within 1 month and this slowly returned to approximately 90% of the preinjection value after 32 weeks. The nucleus pulposus contained approximately 75% of the proteoglycan content of control tissues, and most of these formed aggregates with hyaluronan. Disc collagen levels remained relatively unaffected by treatment. CONCLUSIONS: This study demonstrates that an effective reduction in disc width compatible with later reconstitution of the nucleus pulposus can be achieved experimentally with an appropriate dose of chymopapain. These data clearly indicate that an optimal dose of chymopapain for chemonucleolysis in humans needs to be established.

Animals↗
PubMed1996

Variation in intervertebral disc serine proteinase inhibitory proteins with ageing in a chondrodystrophoid (beagle) and a non-chondrodystrophoid (greyhound) canine breed.

Intervertebral disc (IVD) proteoglycans (PGs) and trypsin inhibitory protein levels were assessed for groups of beagles and greyhounds aged between 4 and 80 months. A significant age-dependent decline in PGs and in trypsin inhibitory protein levels was evident in extracts of the beagle nucleus pulposus (NP). This was confirmed for the semi-purified trypsin inhibitor, using Western blotting. These age changes, however, were not evident in the greyhound NP. Furthermore, no significant ageing trends in PG or trypsin inhibitory protein levels were evident in extracts of the annulus fibrosus of either animal. The early onset of IVD degeneration in the beagle, a canine breed of the chondrodystrophoid (achondroplastic) classification, may be related to this decline in the anti-catabolic effects of the endogenous serine proteinase inhibitory proteins.

Aging↗