Biomedical subjects

S Byers

Publications and source records attributed to S Byers.

At least 37 records · Page 2Linked to original sources

PubMed1997

Enzyme replacement therapy from birth in a feline model of mucopolysaccharidosis type VI.

We report evidence of a dose responsive effect of enzyme replacement therapy in mucopolysaccharidosis type VI cats from birth, at the clinical, biochemical, and histopathological level. Cats treated with weekly, intravenous recombinant human N-acetylgalactosamine-4-sulfatase at 1 and 5 mg/kg, were heavier, more flexible, had greatly reduced or no spinal cord compression, and had almost normal urinary glycosaminoglycan levels. There was near normalization or complete reversal of lysosomal storage in heart valve, aorta, skin, dura, liver, and brain perivascular cells. No reduction in lysosomal vacuolation was observed in cartilage or cornea; however, articular cartilage was thinner and external ear pinnae were larger in some treated cats. Degenerative joint changes were not obviously delayed in treated cats. Skeletal pathology was reduced, with more normalized bone dimensions and with more uniform bone density and trabecular pattern clearly visible on radiographs by 5 to 6 mo; however, differences between 1 and 5 mg/kg dose rates were not clearly distinguishable. At a dose of 0.2 mg/kg, disease was not significantly altered in the majority of parameters examined. Lysosomal storage was present in all tissues examined in the midterm mucopolysaccharidosis type VI fetus and increased rapidly in extent and severity from birth.

Animals↗

PubMed1997

Quantitative analysis of trabecular morphogenesis in the human costochondral junction during the postnatal period in normal subjects.

BACKGROUND: Quantitative histomorphometric features of the bone growth plate in the human rib have been investigated in infants, ranging in age from 3-36 weeks (mean 18.6 weeks) to provide data currently not available. METHODS: Measurements were taken in each histological zone of the growth plate. Data from 20 cases were pooled and parameters describing the characteristic features of trabecular bone calculated using morphometric formulae. The measurements were made from the resting zone of the cartilage to the secondary spongiosa, 3.78 mm from the starting point. RESULTS: Cartilage volume fraction decreased from 78% in the resting zone to a bone volume fraction of between 20% and 30% in the secondary cancellous bone. Cartilage matrix surface increased rapidly in the cartilage and bone mineral surface declined in correspondence with the development of primary bone. The distance between chondrocyte lacunae was observed to decrease throughout the cartilage to a transverse septa thickness of 18 microns in the hypertrophic zone. A rapid increase in trabecular thickness to 128 microns was observed in the primary spongiosa, the secondary spongiosa ranging between 137 microns and 168 microns. Spacing, chondrocyte profile transverse diameter, increased to 30 microns in the hypertrophic zone, following which an increase in trabecular separation to 347 microns was observed in the primary spongiosa. The number of transverse intervals between individual chondrocyte lacunae was observed to increase in the cartilage to a maximum of 21.3 cartilaginous or mineralised septa per mm of growth plate length in the hypertrophic zone. Trabeculae in the metaphysis then decreased in number to approximately 1.5 trabeculae per mm in the secondary spongiosa. CONCLUSIONS: These data thus provide new insight into the development of trabecular structure during growth and normal values for the comparison of tissue from skeletal dysplasias and growth disorders.

Achondroplasia↗

PubMed1997

Structural changes in the large proteoglycan, aggrecan, in different zones of the ovine growth plate.

The large cartilage proteoglycan, aggrecan, was found to vary throughout the ovine physis corresponding to the maturational state of the resident chondrocytes. Two populations of proteoglycan monomer were observed in articular, epiphyseal, and in the resting zone of growth plate cartilage. These proteoglycans contained chondroitin sulfate glycosaminoglycan chains sulfated predominantly in the 4 position along with lesser amounts of chondroitin-6-sulfate and keratan sulfate. In the proliferative zone of the growth plate, chondrocytes synthesize one population of proteoglycan monomer which was significantly larger than monomer populations in articular, epiphyseal, or resting zone and this size increase could be attributed to an increase in its constituent chondroitin sulfate side chains. As these chondrocytes progress through their life cycle they continue to modify the structural characteristics of the aggrecan molecule they synthesize. Thus, in the hypertrophic region of the growth plate, the proteoglycan monomer is larger again than in the proliferative region. Variation in sulfation pattern on aggrecan chondroitin sulfate side chains is also observed in the hypertrophic region with an increasing proportion of unsulfated residues present, which may play a role in the initiation of mineralization. In addition, increasing amounts of the carbohydrate sequence recognized by monoclonal antibody 7-D-4 are observed in the hypertrophic zone.

Aggrecans↗

PubMed1997

Effect of enzyme replacement therapy on bone formation in a feline model of mucopolysaccharidosis type VI.

A range of skeletal abnormalities are evident in mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome) including short stature and dysostosis multiplex, resulting from a deficiency in the lysosomal hydrolase N-acetylgalactosamine-4-sulphatase (4S). In this article, bone pathology was assessed in a feline model of MPS VI to evaluate the efficacy of enzyme replacement therapy (ERT) as a treatment modality for this genetic disorder. Osteopenia is clearly evident in MPS VI animals, with bone mineral volume (BV/TV) falling well below that of normal animals (4.39% vs. 20.11%, respectively). Trabecular bone architecture was also affected in MPS VI with fewer, thinner, and more widely spaced trabeculae apparent. Bone formation rate (BFR/BS) was also lower in MPS VI animals than controls (0.0011 mm3/mm2 per day vs. 0.008 mm3/mm2 per day, respectively). Vertebral and tibial bone length in MPS VI animals progressively fell behind normal values with increasing age, as did cortical bone thickness. Vertebral body shape was also altered. ERT with recombinant human 4S (rh4S) resulted in a vertebral BV/TV of 8.23% in animals treated with an intravenous enzyme dose of 1 mg/kg and a BV/TV of 14.33% in animals treated with a dose of 5 mg/kg. BFR/BS also increased to 0.0034 mm3/mm2 per day in animals treated with enzyme doses of either 1.0 or 5.0 mg/kg rh4S. All other affected histomorphometric parameters also improved with ERT to a level intermediate between MPS VI untreated animals and normals. However, individual animals treated with 0.2 mg/kg rh4S intravenously or 1.0 mg/kg rh4S administered subcutaneously did not exhibit an improvement over untreated MPS VI animals. Vertebral and tibial bone lengths, tibial cortical bone thickness, and vertebral body shape also responded to ERT, with a trend away from the untreated group. Thus, ERT had a positive effect on bone development in MPS VI animals that was dependent upon the dose of enzyme administered and the route of administration.

Animals↗

PubMed1996

Enzyme replacement therapy in a feline model of Maroteaux-Lamy syndrome.

We report studies that suggest enzyme replacement therapy will result in a significant reduction in disease progression and tissue pathology in patients with Maroteaux-Lamy syndrome (Mucopolysaccharidosis type VI, MPS VI). A feline model for MPS VI was used to evaluate tissue distribution and clinical efficacy of three forms of recombinant human N-acetylgalactosamine-4-sulfatase (rh4S, EC 3.1.6.1). Intravenously administered rh4S was rapidly cleared from circulation. The majority of rh4S was distributed to liver, but was also detected in most other tissues. Tissue half-life was approximately 2-4 d. Three MPS VI cats given regular intravenous infusions of rh4S for up to 20 mo showed variable reduction of storage vacuoles in Kupffer cells and connective tissues, however cartilage chondrocytes remained vacuolated. Vertebral bone mineral volume was improved in two MPS VI cats in which therapy was initiated before skeletal maturity, and increased bone volume appeared to correlate with earlier age of onset of therapy. One cat showed greater mobility in response to therapy.

Animals↗

PubMed1996

Periprocedural Doppler coronary blood flow predictors of myocardial perfusion abnormalities and cardiac events after successful coronary interventions.

Thirty-four consecutive patients had coronary flow velocity assessed under basal and hyperemic conditions in the proximal and distal coronary artery, followed by rest-stress technetium 99m sestamibi myocardial tomography within 3 months of successful coronary angioplasty. In spite of significant angiographic improvement, 29% of patients had a persistent reversible myocardial perfusion defect associated with a residual abnormality of the proximal-to-distal coronary average peak velocity ratio (p/d APV = 2.2 +/- 1.5 vs 1.1 +/- 0.6; p = 0.02). Patients with an abnormal p/d APV ratio (>1.7) had more numerous angioplasty-zone perfusion defects (4.2 +/- 3.3 vs 0.8 +/- 2.0; p = 0.005). Multivariable analysis of clinical, angiographic, coronary flow, and scintigraphic data demonstrated that the relative risk of cardiac events (n = 11) was greatest in patients with a reversible angioplasty-zone perfusion defect (relative risk, 5.5), poststenotic coronary flow reserve <2.0 (relative risk, 8.3) and p/d APV ratio >1.7 (relative risk, 6.2). Residual basal coronary flow-velocity abnormalities are significant physiologic correlates of stress-induced myocardial perfusion defects and are a prognostic covariable associated with future ischemic cardiac events.

Adult↗

PubMed1996

Retinoids increase cell-cell adhesion strength, beta-catenin protein stability, and localization to the cell membrane in a breast cancer cell line: a role for serine kinase activity.

In this study we show that a breast cancer cell line (SKBR3) that expresses no E-cadherin and very low levels of beta-catenin protein and exhibits a poorly adhesive phenotype in Matrigel responds to retinoic acid (RA) by a marked increase in epithelial differentiation. Specifically, treatment of cells with all-trans-RA, 9-cis-RA, or a RA receptor alpha-specific ligand resulted in a large increase in cell-cell adhesive strength and stimulated the formation of fused cell aggregates in Matrigel. A retinoid X receptor-specific ligand was ineffective. Exposure of cells to 9-cis-RA for as little as 4 h was sufficient to maintain the adhesive phenotype for at least 4 days. The effects of 9-cis-RA required protein and RNA synthesis, but were not mediated by factors secreted by stimulated cells or by direct cell contact and did not require serum. These 9-cis-RA-induced morphological effects were completely reversed by growing cells in 50 microM Ca2+, suggesting a mechanism involving a 9-cis-RA-induced increase in Ca(2+)-dependent adhesion. Consistent with this, beta-catenin protein levels were markedly elevated in the 9-cis-RA-treated cells, and beta-catenin became localized to a Triton-insoluble pool at regions of cell-cell contact. No change could be detected in beta-catenin steady state messenger RNA levels, but 9-cis-RA did increase beta-catenin protein stability. Treatment of cells with low calcium medium did not prevent the 9-cis-RA-induced increase in total beta-catenin protein, but did prevent its movement to a Triton-insoluble pool at the cell membrane. Among several kinase inhibitors, only the broad spectrum kinase inhibitor staurosporine and the protein kinase C inhibitor bisindoylmaleimide reversed the morphological changes induced by 9-cis-RA. Like treatment with low calcium medium, these inhibitors did not prevent the 9-cis-RA-induced increase in total beta-catenin protein levels, but completely prevented the movement of beta-catenin to the cell membrane. These results point to a role for beta-catenin and serine kinase activity in mediating the action of 9-cis-RA in epithelial differentiation.

Breast Neoplasms↗

PubMed1995

The effect of extracellular calcium on colonocytes: evidence for differential responsiveness based upon degree of cell differentiation.

Calcium supplementation decreases the incidence of colon cancer in animal models and may prevent colon cancer in man. Potential mechanisms include binding of mitogens and direct effects of calcium on colonic epithelial cells. In this study, the effects of extracellular calcium on epithelial cell growth and differentiation were studied in three colon carcinoma and two colonic adenoma cell lines. The characteristics studied included morphology, cell cycle kinetics, [Ca2+]IC (intracellular calcium concentration), proliferation, and expression of differentiation markers such as carcinoembryonic antigen (CEA) and alkaline phosphatase (AP). Sodium butyrate (NaB) and 1,25-dihydroxyvitamin D3 were used as controls in the latter three assays as these two agents are known differentiating agents. Alteration of [Ca+2]EC (extracellular calcium concentration) did not affect carcinoembryonic antigen (CEA) or alkaline phosphatase (AP) expression. NaB enhanced the expression of AP three-fold and CEA five-fold. This effect was augmented by increasing [Ca2+]EC. The exposure of cells to 1,25-(OH)2-Vitamin D3 increased CEA but not AP. [Ca2+]IC increased in response to 1,25-(OH)2-vitamin D3 and NaB but not with variation in [Ca2+]EC. Increased [Ca2+]EC inhibited proliferation of well-differentiated cells, but had no effect on poorly-differentiated cells. Morphological studies showed that extracellular calcium was necessary for normal cell-cell interactions. These studies have demonstrated direct effects of calcium on colonic epithelial cells which may contribute to the protective effects of dietary calcium against colon cancer. Loss of responsiveness to the antiproliferative effects of [Ca2+]EC with de-differentiation suggests that calcium supplementation may be most beneficial prior to the development of neoplastic changes in colonic epithelium.

Alkaline Phosphatase↗

PubMed1995

Tumor-stroma interactions and stromal cell density regulate hepatocyte growth factor protein levels: a role for transforming growth factor-beta activation.

Hepatocyte growth factor/scatter factor (HGF/SF), a fibroblast-derived mediator of epithelial and endothelial growth and motility, is regulated by factors present in media conditioned by breast tumor cell lines. Both inhibitory and stimulatory effects were observed dependent on culture conditions. The present work shows that breast tumor cell conditioned medium contains a latent HGF/SF inhibitory activity, which can be activated by a variety of treatments known to activate latent transforming growth factor-beta. Using blocking antibodies and other criteria, we show that transforming growth factor-beta present in epithelial cell conditioned medium is primarily responsible for mediating the down-regulation of fibroblast HGF/SF. Epithelial cell conditioned medium also contains a trypsin-sensitive and heat-stable stimulatory activity. Stromal cell density but not proliferation rate markedly alters HGF/SF expression. These results indicate that the expression of at least one epithelial morphogen, HGF/SF, is interdependently regulated by mesenchymal condensation and by factors released by neighboring epithelial and carcinoma cells.

Antibodies↗

PubMed1994

Preoperative clinical assessment and dipyridamole thallium-201 scintigraphy for prediction and prevention of cardiac events in patients having major noncardiovascular surgery and known or suspected coronary artery disease.

The aim of this study was to assess the relative prognostic use of clinical risk stratification and intravenous dipyridamole thallium-201 scintigraphy in patients with an intermediate to high prevalence of coronary artery disease (CAD) who have undergone major noncardiovascular surgery, and to assess the effects of medical therapy or coronary revascularization based on the result of this clinical scintigraphic screening on perioperative cardiac morbidity and mortality. Patients (n = 161) with an intermediate to high likelihood of CAD had clinical assessment and intravenous dipyridamole planar thallium-201 testing which was analyzed semiquantitatively. Cardiac events were cardiac death (n = 9), nonfatal myocardial infarction (n = 6), acute pulmonary edema (n = 6), and unstable angina (n = 4). Multiple (> or = 2) clinical risk variables predicted any cardiac event (p = 0.04). Presence of multiple (> or = 2) abnormal thallium-201 segments was the only independent predictor of cardiac death or nonfatal myocardial infarction (p < 0.001), and was the most powerful multivariate predictor of any cardiac event (p < 0.002). Patients with an abnormal dipyridamole thallium-201 scan had a higher risk of perioperative cardiac death, myocardial infarction (18% vs 2%; p < 0.001), or any perioperative cardiac event (27% vs 6%; p < 0.001) when compared with those with a normal scan. Preoperative changes in anti-ischemic therapy or coronary revascularization in 36 of 72 patients with abnormal dipyridamole thallium-201 studies reduced perioperative death or myocardial infarction from 31% to 6% (p < 0.01), and all cardiac events from 47% to 8% (p < 0.001) compared with those in patients without intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Chi-Square Distribution↗

PubMed1994

The implantation of cartilaginous and periosteal tissue into growth plate defects.

This experimental study reports the results of implantation of cartilaginous and periosteal tissues into growth plate defects in the tibiae of sheep. When no material was used, the defect rapidly filled with marrow-like tissue. When cartilage from the margin of the secondary centre of ossification was implanted, endochondral ossification continued and no shortening or deformity resulted. Implantation of periosteum with or without reconstructed peripheral tissues resulted in the formation of a bony bridge which led to a 32% inhibition of longitudinal growth and a 12 degrees varus deformity in the absence of peripheral connective tissues. After reconstruction with these tissues, the inhibition of longitudinal growth was 47% with a 28 degrees varus deformity. The chondroprogenitor cells in the implanted tissues cannot change phenotypic expression. Periosteum has a strong potential for bone formation after it has been implanted.

Animals↗

PubMed1994

Modulation of breast cancer progression and differentiation by the gp30/heregulin [correction of neregulin].

In the last decade we have come to understand that the growth of cancer cells in general and of breast cancer in particular depends, in many cases, upon growth factors that will bind to and activate their receptors. One of these growth factor receptors is the erbB-2 protein which plays an important role in the prognosis of breast cancer and is overexpressed in nearly 30% of human breast cancer patients. While evidence accumulates to support the relationship between erbB-2 overexpression and poor overall survival in breast cancer, understanding of the biological consequence(s) of erbB-2 overexpression remains elusive. Our recent discovery of the gp30 has allowed us to identify a number of related but distinct biological endpoints which appear responsive to signal transduction through the erbB-2 receptor. These endpoints of growth, invasiveness, and differententiation te have clear implications for the emergence, maintenance and/or control of malignancy, and represent established endpoints in the assessment of malignant progression in breast cancer. We have shown that gp30 induces a biphasic growth effect on cells with erbB-2 over-expression. We have recently determined the protein sequence of gp30 and cloned its full length cDNA sequence. We have also cloned two additional forms to the ligand, that are believed to be different isoforms. We are currently expressing the different forms in order to determine their biological effects. To elucidate the cellular mechanisms underlying cell growth inhibition by gp30, we tested the effect of this ligand on cell growth and differentiation of the human breast cancer cells which overexpress erbB-2 and cells which express low levels of this protooncogene.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1994

Breast carcinoma: a collective disorder.

The development and differentiation of the epithelial component of glandular tissues such as the breast is regulated by two apparently unrelated processes. One of these is presumed to be epithelial cell collective autonomous, that is, it is mediated by gene products which act directly on the epithelial cells. An important component of autonomous regulation is the functional expression of homotypic cell-cell adhesion molecules such as cadherins. The second process is non-autonomous and involves an inductive effect of the neighboring mesenchymal cell collective. An important component of non-autonomous regulation is the aggregation/condensation of mesenchyme closely associated with the epithelium. We propose that molecular alterations in autonomous and non-autonomous pathways are important causes and indicators respectively of breast cancer progression and that these two fundamental regulators of epithelial collective organization are in fact inter-dependent. For example, we show that the expression of hepatocyte growth factor (HGF), an epithelially targeted mesenchymally derived morphogenic factor is regulated by mesenchymal cell density (condensation) and by factors released from epithelial cells. Breast epithelial cells produce factors which inhibit and stimulate HGF expression. The inhibitory factor is transforming growth factor beta (TGF-beta) and the activation state of TGF-beta is a crucial element in HGF homeostasis. The balance of negative and positive HGF regulators is markedly affected by the growth conditions and differentiation state of the epithelial cells. The expression of the HGF receptor, met, is high in normal breast epithelial cells and in dedifferentiated (ER negative) tumor cells but is reduced or lost in ER positive well differentiated epithelial cells. Our results indicate that the expression of at least one epithelial morphogen, HGF, is inter-dependently regulated by mesenchymal condensation and by factors released by neighboring epithelial cells.

Breast Neoplasms↗

PubMed1994

Oncogene-induced basement membrane invasiveness in human mammary epithelial cells.

Expression of the intermediate filament protein vimentin, and loss of the cellular adhesion protein uvomorulin (E-cadherin) have been associated with increased invasiveness of established human breast cancer cell lines in vitro and in vivo. In the current study, we have further examined these relationships in oncogenically transformed human mammary epithelial cells. A normal human mammary epithelial strain, termed 184, was previously immortalized with benzo[a]pyrene, and two distinct sublines were derived (A1N4 and 184B5). These sublines were infected with retroviral vectors containing a single or two oncogenes of the nuclear, cytoplasmic, and plasma membrane-associated type (v-rasH, v-rasKi, v-mos, SV40T and c-myc). All infectants have been previously shown to exhibit some aspects of phenotypic transformation. In the current study, cellular invasiveness was determined in vitro using Matrigel, a reconstituted basement membrane extract. Lineage-specific differences were observed with respect to low constitutive invasiveness and invasive changes after infection with ras, despite similar ras-induced transformation of each line. Major effects on cellular invasiveness were observed after infection of the cells with two different oncogenes (v-rasH + SV40T and v-rasH + v-mos). In contrast, the effects of single oncogenes were only modest or negligible. All oncogenic infectants demonstrated increased attachment to laminin, but altered secretion of the 72 kDa and 92 kDa gelatinases was not associated with any aspect of malignant progression. Each of the two highly invasive double oncogene transformants were vimentin-positive and uvomorulin-negative, a phenotype indicative of the epithelial-mesenchymal transition (EMT) previously associated with invasiveness of established human breast cancer cell lines. Weakly invasive untransformed mammary epithelial cells in this study were positive for both vimentin and uvomorulin, suggesting that uvomorulin may over-ride the otherwise vimentin-associated invasiveness.

Animals↗

PubMed1993

Comparison of the Asymptomatic Cardiac Ischemia Pilot and modified Asymptomatic Cardiac Ischemia Pilot versus Bruce and Cornell exercise protocols.

The Asymptomatic Cardiac Ischemia Pilot (ACIP) and modified ACIP treadmill exercise protocols were developed to test patients with coronary artery disease and to linearly increase work load between stages. The physiologic changes that occurred with ACIP and modified ACIP were compared to those with the Bruce and Cornell protocols in 28 normal subjects and 16 men with coronary artery disease. The exercise protocols were randomly assigned over 2 days, and gas exchange data were obtained continuously with each test. In normal subjects, the peak heart rate, systolic blood pressure, peak oxygen consumption rate (VO2) and minute ventilation were similar for the 4 protocols tested, with exercise time shortest for the Bruce protocol in comparison with the ACIP, modified ACIP and Cornell protocols (10.2 +/- 3.1 vs 13.4 +/- 4.9, 13.9 +/- 4.5, and 15.0 +/- 4.2 minutes, respectively; p < 0.001). The difference between predicted and observed VO2 was smallest for the ACIP protocol (37.0 +/- 11.0 vs 35.8 +/- 13.5 ml/kg/min) and greatest for the Bruce protocol (41.1 +/- 11.8 vs 36.7 +/- 15.0 ml/kg/min) in normal subjects, as well as in patients with coronary artery disease (ACIP protocol 26.9 +/- 7.1 vs 22.5 +/- 6.7, and Bruce protocol 29.1 +/- 7 vs 22.6 +/- 5.7 ml/kg/min, respectively). The ratio of VO2 to work rate, expressed as a slope, was similar in normal subjects for the 4 protocols tested. However, in patients with coronary artery disease, the slope was 0.84 and 0.83 for the ACIP and modified ACIP protocols, respectively, versus 0.61 and 0.71 for the Bruce and Cornell protocols, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Immunohistochemical characterisation of the costochondral junction in SIDS.

AIM: To characterise the distribution of major growth plate proteoglycans in a group of infants who died of SIDS. METHODS: Nine such infants and eight age matched controls were selected from the necropsy files at the Adelaide Children's Hospital. Sections of rib and adjacent costal cartilage were stained for chondroitin-4-sulphate, chondroitin-6-sulphate, and keratan sulphate with antibodies 2-B-6, 3-B-3, and 5-D-4, respectively, using standard techniques. RESULTS: The distribution of proteoglycans within the extracellular matrix of the costochondral junction in the group of SIDS infants was identical with that found in control infants. CONCLUSION: Any changes present in the growth plate in cases of SIDS are most likely caused by secondary phenomena.

Cartilage↗

PubMed1992

Fibroblast growth factor receptors contain a conserved HAV region common to cadherins and influenza strain A hemagglutinins: a role in protein-protein interactions?

The first extracellular domain of the cadherins has been shown to exhibit extensive sequence homology with the amino termini of the HA1 chains of influenza strain A hemagglutinins. These regions of homology are known to be functionally important in both the cadherins and the hemagglutinins. The homologous regions harbor the tripeptide HAV, which has been identified as being the cadherin cell adhesion recognition sequence. Here we report that members of the rapidly expanding family of fibroblast growth factor receptors also possess HAV-containing regions. These regions are homologous to the HAV-containing regions present within both the hemagglutinins and the cadherins and appear to be involved in regulating the function of the fibroblast growth factor receptors. We speculate that the HAV motif may represent an evolutionarily conserved amino acid sequence that will prove to be functionally important in a wide variety of proteins.

Amino Acid Sequence↗

PubMed1992

Immunolocation analysis of glycosaminoglycans in the human growth plate.

Monoclonal antibodies were used in this study to immunolocate glycosaminoglycans throughout the human growth plate. Chondroitin-4-sulfate, chondroitin-6-sulfate, and keratan sulfate were observed in the extracellular matrix of all zones of the growth plate and persisted into the cartilage trabeculae of newly formed metaphyseal bone. Also present in the extracellular matrix was an oversulfated chondroitin/dermatan sulfate glycosaminoglycan which appeared to be specific to the proliferative and hypertrophic zones of the growth plate. As with the other extracellular matrix molecules, this epitope persisted into the cartilage trabeculae of the metaphyseal bone. Zonal differences between the extracellular and pericellular or lacunae matrix were also observed. The hypertrophic chondrocytes appeared to synthesize chondroitin sulfate chains containing a non-reducing terminal 6-sulfated disaccharide, which were located in areas immediately adjacent to the cells. This epitope was not found to any significant extent in the other zones. The pericellular region around hypertrophic chondrocytes also contained a keratan sulfate epitope which was also observed in the resting zone but not in the proliferative zone. These cell-associated glycosaminoglycans were not found in the cartilage trabeculae of metaphyseal bone, indicating their removal as the terminal hypertrophic chondrocytes and their lacunae are removed by invading blood vessels. These changes in matrix glycosaminoglycan content, both in the different zones and within zones, indicate constant subtle alterations in chondrocyte metabolic products as they proceed through their life cycle of proliferation, maturation, and hypertrophy.

Aging↗