Biomedical subjects

W T Butler

Publications and source records attributed to W T Butler.

At least 37 records · Page 2Linked to original sources

PubMed1995

Bone matrix proteins in osteogenesis and remodelling in the neonatal rat mandible as studied by immunolocalization of osteopontin, bone sialoprotein, alpha 2HS-glycoprotein and alkaline phosphatase.

The neonatal rat mandible was used as a model to study bone formation, mineralization, quiescence, and resorption, using immunolocalization and a variety of tissue-processing techniques. Monospecific antibodies for osteopontin (OPN), bone sialoprotein (BSP), alkaline phosphatase (AP) and alpha 2HS-glycoprotein (alpha 2HS-GP) were used on fixed paraffin-embedded tissue, fixed frozen tissue and unfixed frozen tissue. Immunostaining was correlated with mineral content by two procedures, the von Kossa and the morin techniques. Morin fluorescence was used with secondary immunostaining to provide a way of closely correlating bone matrix proteins and matrix mineralization. Co-immunolocalization procedures were used to compare the sites of bone proteins in the matrix. AP was found earliest during osteogenic cell differentiation, appearing in the preosteoblasts, followed by OPN and BSP, which first appeared in osteoblasts. alpha 2HS-GP expression was not observed in cells. The results provide clear evidence for the presence of OPN in osteoid, while BSP and alpha 2HS-GP were confined to the mineralized matrix. Immunostaining of bone proteins is highly technique-dependent: immunolocalization investigations required several methods of approach to ensure adequate demonstration of these proteins in cells and matrix. The results support the contention that osteopontin is multifunctional in bone metabolism, and that alpha 2HS-GP, though produced in the liver, is abundant in bone matrix and may also have a function in bone metabolism.

Alkaline Phosphatase↗

PubMed1995

Characterization of cellular responses involved in reparative dentinogenesis in rat molars.

During primary dentin formation, differentiating primary odontoblasts secrete an organic matrix, consisting principally of type I collagen and non-collagenous proteins, that is capable of mineralizing at its distal front. In contrast to ameloblasts that form enamel and undergo programmed cell death, primary odontoblasts remain metabolically active in a functional tooth. When dentin is exposed to caries or by operative procedures, and when exposed dentinal tubules are treated with therapeutic dental materials, the original population of odontoblasts is often injured and destroyed. The characteristics of the replacement pool of cells that form reparative dentin and the biologic mechanisms that modulate the formation of this matrix are poorly understood. Based on the hypothesis that events governing primary dentinogenesis are reiterated during dentin repair, the present study was designed to test whether cells that form reparative dentin are odontoblast-like. Cervical cavities were prepared in rat first molars to generate reparative dentin, and animals were killed at various time intervals. In situ hybridization with gene-specific riboprobes for collagen types I and III was used to study de novo synthesis by cells at the injured dentin-pulp interface. Polyclonal antibodies raised against dentin sialoprotein (DSP), a dentin-specific protein that marks the odontoblast phenotype, were used in immunohistochemical experiments. Data from our temporal and spatial analyses indicated that cells forming reparative dentin synthesize type I but not type III collagen and are immunopositive for DSP. Our results suggest that cells that form reparative dentin are odontoblast-like.

Animals↗

PubMed1995

Dentin matrix proteins and dentinogenesis.

The precise mechanisms involved in dentinogenesis are not understood; however, the information to date suggests that a number of highly controlled extracellular events are involved. Mature odontoblasts secrete collagen at the cell border into predentin. They synthesize and secrete other non-collagenous proteins (NCPs) at the mineralization front, possibly through odontoblastic processes. A collagen-NCP complex is formed at the predentin-dentin border and apatite crystal initiation and growth takes place. One of the research needs is to uncover the nature of this dentin collagen-NCP complex and to understand how it controls mineralization. At least three dentin specific NCPs are known: phosphophoryn(s), dentin sialoprotein (DSP) and AG1 (Dmp1). Other macromolecules are commonly made by osteoblasts and odontoblasts and participate in bone and dentin formation. Some progress in understanding dentin mineralization has been gained by focusing upon the role of phosphophoryns. These highly phosphorylated proteins are secreted at the mineralization front, where a small portion binds in the gap region of type I collagen fibrils. This portion of phosphoproteins probably initiates formation of plate-like apatite crystals. Additional phosphoryns in higher concentrations bind to the growing apatite crystals and slow their growth, possibly influencing their size and shape. Other areas which need careful investigations are those involving the mechanisms involved in odontoblast differentiation, how the synthesis of the dentin specific NCPs is controlled and the precise roles of these macromolecules in dentinogenesis. Future experimentation will focus on the gene structures for these NCPs and the mechanisms of tissue specific gene regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Apatites↗

PubMed1995

Molecular analysis of rat dentin sialoprotein.

Dentin sialoprotein (DSP) is a noncollagenous protein originally isolated from rat dentin. Because it is made by odontoblasts that are actively synthesizing dentin. DSP may play an important role in dentinogenesis. We have isolated a full length DSP cDNA from a rat odontoblast/dental pulp cDNA library (Ritchie et al. [1994] J. Biol. Chem. 269:3698-3702) which codes for a 17 residue signal peptide and a 366 residue, 53 kDa mature protein. In situ hybridization revealed DSP mRNA expression by odontoblasts, but no other cells, in jaws from newborn rat. Northern analysis of various rat tissues demonstrated the presence of DSP transcripts in newborn tooth germs and 21 day old rat incisors. Moreover, multiple transcripts of 4.6 kb and 1.5 kb were found in these two tissues. To better understand the origin of these DSP mRNA multiple transcripts, we have isolated two rat genomic clones. Digestion of each clone with EcoRI followed by Southern analysis revealed that DSP cDNA hybridized to a 4 kb fragment in a lambda dash clone and to a 6 kb fragment in a cosmid clone. Since DSP cDNA hybridized to a 6 kb EcoRI fragment and a 4 kb EcoRI fragment obtained from a rat liver genomic cDNA digested with EcoRI, the multiple DSP mRNA transcripts are most likely derived from two related DSP genes which coexist in the rat genome.

Animals↗

PubMed1995

The nature and functional significance of dentin extracellular matrix proteins.

Odontoblasts are responsible for formation of predentin, which is transformed to dentin when apatite crystals are formed and the fibrillar matrix becomes mineralized. Odontoblasts are specialized cells that synthesize and secrete a unique set of non-collagenous proteins (NCPs), as well as the collagenous matrix largely comprised of type I collagen. The NCPs consist of dentin specific and mineralized tissue specific proteins, as well as other proteins that are found in a variety of tissues. Three dentin specific proteins have been recognized to date: dentin phosphoprotein (DPP), also called phosphophoryn, AG1 (dentin matrix protein 1, Dmp1) and dentin sialoprotein (DSP). DPP appears to be made by odontoblasts and appears at the mineralization front within a short time. It may be secreted via odontoblastic processes. DPP binds to collagen and potentially initiates formation of apatite crystals. A second DPP function appears to be to bind to the 100 face of growing apatite crystals and to inhibit or slow their growth; thus, DPP may play a dual role by initiating mineralization and then affecting the crystal growth and perhaps the habit of the crystals. Although no function has been ascribed to AG1 or DSP, they should prove to be important markers for the odontoblast phenotype. A recent unique finding is that two separate genes appear to code for more than one DSP mRNA; other transcripts may result from differential splicing. Examples of mineralized tissue specific proteins expressed by osteoblasts as well as odontoblasts are bone sialoprotein (BSP) and osteocalcin. Some NCPs expressed by osteoblasts, odontoblasts and several other tissues include osteopontin (OPN) and the chondroitin sulfate containing proteoglycans, decorin and biglycan. We propose that characterization of odontoblasts in tissues and cultures should rely upon utilization of sets of markers for the above NCPs and their mRNAs. Similar approaches are commonly used in investigations on osteoblasts. Finally, dentin (like bone) contains other molecules such as growth factors, and serum derived proteins, found within the matrix; no functional significance has yet been placed upon this finding. Future experiments should focus upon the elucidation of the three dimensional structures of the collagenous fibrillar network and of the NCPs to determine the relationships to mineralization. The role played by odontoblasts in controlling extracellular events, such as by selective secretory routes, will require careful exploration.

Amino Acid Sequence↗

PubMed1994

Cloning and sequence determination of rat dentin sialoprotein, a novel dentin protein.

Dentin sialoprotein (DSP) is a 53-kDa protein isolated from rat dentin. It contains 29.6% carbohydrate (including 9% sialic acid) and has an overall composition similar to that of the bone sialoproteins osteopontin and bone sialoprotein (i.e. rich in Asp, Ser, Glu, and Gly). Using a monospecific anti-DSP polyclonal antibody to screen a rat incisor odontoblast cDNA library, a cDNA clone was isolated and sequenced. This approximately 750-base pair clone contained a DNA sequence corresponding to the NH2-terminal 9 amino acids of DSP. A second cDNA clone was isolated by using the first cDNA as a probe to rescreen the library. This second clone had the full-length DSP coding region. From the sequence, we deduced that the DSP cDNA coded for 366 amino acids, predominantly Asp, Ser, Glu, and Gly. The amino acid composition calculated for this sequence was very similar to that for purified DSP reported earlier; likewise the deduced molecular weight (53,045) was essentially identical to that determined by sedimentation equilibrium. Six potential N-linked glycosylation sites were present in the predicted DSP sequence. No Arg-Gly-Asp sequence was found, and the sequence for DSP was dissimilar to those of osteopontin and bone sialoprotein. Multiple transcripts near 4.6 and 1.5 kilobases were detected by Northern blot analysis in the incisor of 21-day-old rat and the tooth germ of the newborn rat. Consistent with previous immunohistochemical findings, no transcripts were detected in brain, salivary gland, heart, muscle, spleen, kidney, intestine, lung, liver, pancreas, tibia, calvaria, or osteoblast-like osteosarcoma (ROS 17/2.8) cells, indicating that DSP is specifically expressed by odontoblasts and related cells.

Amino Acid Sequence↗

PubMed1994

Immunolocalization of osteopontin, osteocalcin, and dentin sialoprotein during dental root formation and early cementogenesis in the rat.

Using immunohistochemical methods we studied the tissue localization of the extracellular matrix proteins osteopontin (OPN), osteocalcin (OC), and dentin sialoprotein (DSP) during the formation of acellular and cellular cementum in newly born rats. In the layer of acellular cementum of developing incisor and molar teeth we found a very strong staining for OPN but not for DSP or OC. Many cells immediately adjacent to acellular cementum and PDL cells were also positive for OPN but not for DSP or for OC. In contrast, cellular cementum in molar teeth stained strongly for OPN and OC but not for DSP. Consistent with these observations, the cells engaged in the formation of cellular cementum (cementoblasts and cementocytes) reacted strongly for OPN and OC but not for DSP. In advanced stages of dentinogenesis, both crown and root odontoblasts and dentin stained for OPN, OC, and DSP. Cells and matrices of surrounding alveolar bone stained for OPN and OC but not for DSP. We conclude that cementoblasts and cementocytes of cellular cementum produce OPN and OC but not DSP and thus express an osteoblast-like, not an odontoblast-like, phenotype. The cells responsible for the production of acellular cementum are likely cells of the PDL in close contact with the dental root surface. These fibroblast-like cells express OPN but not OC or DSP and accordingly express only a partial osteoblastic phenotype.

Animals↗

PubMed1994

Osteopontin-stimulated vascular smooth muscle cell migration is mediated by beta 3 integrin.

Osteopontin (OPN), a 41-kDa phosphorylated glycoprotein, has been detected in rat aorta and carotid arteries, and expression of its mRNA in blood vessels is strongly increased in response to vascular injury. To investigate the potential role of OPN in vascular pathophysiology, we studied the effect of rat OPN on aortic smooth muscle cell migration and proliferation in vitro. OPN enhanced the migration of rat smooth muscle cells in a time- and concentration-dependent manner with an EC50 value of 46 +/- 11 nmol/liter (n = 5). The maximal increase in cell migration by OPN was 29-fold over basal levels. OPN-induced smooth muscle cell migration was inhibited in a concentration-dependent manner by the monoclonal antibody F11, which recognizes the rat integrin subunit beta 3. In contrast, polyclonal antiserum recognizing the rat integrin beta 1 subunit did not inhibit smooth muscle cell migration in response to OPN, but did block fibronectin-promoted migration. Moreover, OPN-induced smooth muscle cell migration was dependent on the presence of extracellular divalent cations and was significantly inhibited by anti-OPN antibodies. OPN did not stimulate [3H]thymidine incorporation into cultured smooth muscle cells, indicating that it selectively enhanced migration. In view of the pathological significance of arterial smooth muscle cell migration in the formation of intimal thickening, our results suggest that smooth muscle cell recognition of OPN, probably through the vitronectin receptor, alpha v beta 3, could play a role in the cells' response to vascular injury and especially neointima formation.

Animals↗

PubMed1993

Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption.

We have investigated the mechanism by which osteoclasts adhere to and resorb bone. We show that these cells express beta 1 and beta 3 integrins which are involved in attachment to purified bone matrix proteins. Binding to osteopontin and bone sialoprotein is mediated by alpha v beta 3, while a beta 1 integrin is responsible for attachment to fibronectin. Both the rapid attachment by osteoclasts to intact bone particles and their subsequent resorption are blocked by a monoclonal antibody directed to the alpha v beta 3 complex but not by an antibody against beta 1 integrins. Attachment of osteoclasts to bone is also inhibited with soluble osteopontin, Arg-Gly-Asp-containing peptides derived from both osteopontin and bone sialoprotein, or a monospecific polyclonal antibody against osteopontin. We conclude that both osteoclast adherence to bone and subsequent resorption of its matrix are dependent on interactions between the bone matrix proteins osteopontin and/or bone sialoprotein and the integrin alpha v beta 3. Moreover, collagen, which constitutes 90% of its organic matrix, is minimally involved in binding of chicken osteoclasts to bone.

Amino Acid Sequence↗

PubMed1993

Ultrastructural immunolocalization of noncollagenous (osteopontin and osteocalcin) and plasma (albumin and alpha 2HS-glycoprotein) proteins in rat bone.

The high-resolution, postembedding protein A-gold immunocytochemical technique was used to visualize the distribution of two noncollagenous bone proteins, osteopontin (OPN) and osteocalcin (OC), and two plasma proteins, alpha 2HS-glycoprotein (alpha 2HS-GP) and albumin (ALB), in sections of Lowicryl K4M-embedded rat tibial and alveolar bone. In the primary spongiosa of the metaphysis, a seam of organic material (lamina limitans) that labeled intensely with OPN and OC antibodies was observed at the bone/calcified cartilage interface just below the zone of vascular invasion of the growth plate. With deposition of bone matrix proper by osteoblasts in this region and its subsequent mineralization, extensive areas of bone were heavily labeled with anti-OPN, anti-OC, and anti-alpha 2HS-GP antibodies, where the majority of gold particles were associated with amorphous, electron-dense patches of organic material throughout the mineralized bone. In the unmineralized osteoid, substantially less labeling was observed, and where occasional mineralization loci were dispersed throughout the osteoid layer, these sometimes showed a concentration of gold particles. ALB labeling, on the other hand, was moderate and generally diffuse throughout the mineralized bone matrix and the osteoid. In alveolar bone, labeling patterns were generally similar to those found in tibial bone. Particularly striking in alveolar bone, however, was an intense anti-OPN labeling of (1) the lamina limitans at cell-lined bone surfaces, including that surrounding cell processes and osteocytes, (2) cement (reversal, resting) lines, and (3) the perilacumar matrix of some osteocytes. In summary, these data suggest that certain plasma proteins, such as alpha 2HS-GP, interact with bone matrix proteins, such as OPN and OC, at sites of tissue mineralization and that the presence of OPN in mineralized bone and at bone surfaces (lamina limitans) and cement lines has a multifunctional role, including regulation of mineralization and mediation of cell dynamics during endochondral and intramembranous bone modeling and remodeling.

Animals↗

PubMed1993

Evidence that a non-RGD domain in rat osteopontin is involved in cell attachment.

The bone sialoprotein osteopontin (OPN) promotes cell attachment and spreading through its RGD (Arg-Gly-Asp) sequence. To study additional regions of OPN involved in cell attachment, peptides of rat OPN were evaluated for their capacity to mediate cell binding to wells in vitro. Human gingival fibroblasts were incubated on microtiter plates coated with either OPN or OPN peptides. A peptide of M(r) 28 kD, obtained after digestion with endoproteinase Arg-C and isolated by reversed-phase HPLC, enhanced cell attachment to a similar degree as OPN. Sequence analysis showed that the amino terminus of the 28 kD peptide starts at Ser142 and therefore does not contain the RGD cell attachment sequence (residues 128-130). Cell attachment mediated through both OPN and the 28 kD peptide was blocked by the addition of GRGDSPA peptides or LM-609, a monoclonal antibody to the integrin alpha V beta 3, a receptor for vitronectin. A variant peptide, GRG-ESPA, did not alter cell attachment. Based on these observations, we conclude that (1) binding of OPN and the 28 kD peptide to fibroblasts involves binding to alpha V beta 3, (2) a site other than the RGD sequence on OPN is also involved in binding to integrins, and (3) the binding of this second site to alpha V beta 3 is inhibited by RGD-containing peptides.

Amino Acid Sequence↗

PubMed1993

Dentin sialoprotein: biosynthesis and developmental appearance in rat tooth germs in comparison with amelogenins, osteocalcin and collagen type-I.

A non-collagenous protein, extracted from rat incisor dentin, is a dentin sialoprotein (DSP). We examined immunohistochemically the developmental appearance and tissue distribution of DSP in 1 to 3-day-old rat molar and incisor tooth germs. The earliest staining for DSP was observed in newly differentiated odontoblasts. In more advanced stages, immunostaining for DSP gradually increased in pre-dentin, odontoblasts and dentin, and appeared in many cells of the dental papilla. In early stages of development before the breakdown of the dental basement membrane, pre-ameloblasts were also positive for DSP. This staining disappeared from the ameloblast cell body soon after deposition of the first layer of mineralized dentin. Radiolabelling of tooth matrix proteins with 14C-serine in vitro followed by immunoprecipitation and fluorography confirmed that DSP was synthesized by tooth-forming cells. The immunolocalization for DSP was different from that of either collagen type-I, osteocalcin or the amelogenins. Whereas collagen type-I and osteocalcin were restricted to the mesenchymal dental tissues, the amelogenins were detectable in both epithelial and mesenchymal dental cells and tissues at the epithelio-mesenchymal interface at early stages of development, prior to the onset of dentin mineralization. We conclude that DSP is expressed in and secreted by odontoblasts and some dental papilla cells from early stages of dentinogenesis onwards, i.e. later than type-I collagen, but before deposition of the first layer of mineralized dentin. In pre-mineralizing stages, some of the matrix proteins may be endocytosed from the pre-dentin by both cell types involved in the epithelio-mesenchymal interaction.

Amelogenin↗

PubMed1993

Osteopontin-hydroxyapatite interactions in vitro: inhibition of hydroxyapatite formation and growth in a gelatin-gel.

Osteopontin is a phosphorylated bone matrix sialoprotein, postulated to play a regulatory role in biomineralization. The effects of a crude preparation of rat bone osteopontin and a more highly purified bovine bone osteopontin were evaluated using a gel diffusion system to measure effects of 0.1-100 micrograms/ml of this matrix protein on hydroxyapatite formation and crystal proliferation. Bovine osteopontin at concentrations greater than 25 micrograms/ml inhibited both hydroxyapatite formation and growth in a dose-dependent manner. Osteopontin at concentrations lower than 25 micrograms/ml had no detectable effect on the amount of mineral accumulated in experiments with and without pre-formed hydroxyapatite seed crystals either when initial mineral deposition was assessed at 3.5 days, or when mineral formation and growth were assessed at 5 days. There was a statistically significant dose-dependent decrease in crystal length at all concentrations tested. The rat osteopontin preparation had similar inhibitory abilities. Partial dephosphorylation of bovine osteopontin with alkaline phosphatase removed its inhibitory ability, and reduced its ability to bind calcium. The affinity of bovine osteopontin for hydroxyapatite was determined based on a Langmuir adsorption isotherm, with values of K (binding affinity) and N (number of binding sites) being 0.026 ml/microgram and 1084 micrograms/m2, respectively. The data suggest that, in this system, osteopontin is an effective inhibitor of hydroxyapatite formation and growth due to its affinity for the hydroxyapatite crystals. In this system, osteopontin, distinct from other phosphoproteins which both promote and inhibit hydroxyapatite deposition, did not enhance mineral formation at any concentration tested.

Animals↗

PubMed1993

Differences in composition of cell-attachment sialoproteins between dentin and bone.

Matrices of dentin and bone were compared with respect to the content of cell-attachment sialoproteins. The levels of two sialoproteins, osteopontin (OPN) and bone sialoprotein (BSP), were determined in dentin and bone by immunochemical procedures. Polyclonal antibodies against bovine BSP and an antibody against the amino-terminal decapeptide of rat OPN were used. The relative levels of OPN and BSP in dentin were less than one-tenth of the levels in bone. The differences between dentin and bone levels of OPN and BSP were thus larger than those for osteonectin or bone Gla protein in the two tissues. The scarcity of the cell-attachment proteins in dentin may reflect the metabolic inactivity of dentin.

Animals↗

PubMed1992

Evidence for the formation of a complex between osteopontin and osteocalcin.

We hypothesize that the mechanisms governing bone formation and remodeling involve the assembly of some of the components of the extracellular matrix into supramolecular complexes. We have examined the associations of osteopontin (OPN) with other proteins isolated from demineralized rat long bones. Three ligand binding techniques were used to demonstrate the formation of complexes between osteopontin and osteocalcin (OCN). Using gel overlay assays, the binding between soluble 125I-OPN and OCN immobilized in acrylamide gels was visualized. Competition for 125I-OPN-OCN complexes was demonstrated when unlabeled OCN-enriched bone extract was included in gel overlay solutions. Also, gel overlay assays showed 125I-OCN binding to OPN. Saturable binding was shown in solid-phase filter binding assays, which yielded an equilibrium binding constant of moderately high affinity (approximately 10(-8) M). Specificity of OPN-OCN complex formation was confirmed by measuring binding in the presence of unlabeled OPN and OCN versus a bone-localized serum protein, alpha 2HS-glycoprotein. Finally, the formation of soluble complexes were demonstrated in a modified Hummel-Dreyer gel filtration assay. These results indicate that OPN and OCN form complexes in vitro. The possible functions of OPN-OCN complexes in osteoclast recruitment and attachment are discussed.

Animals↗

PubMed1992

Improved binding of acidic bone matrix proteins to cationized filters during solid phase assays.

A number of commercially available matrix filter supports have been designed for the immobilization of proteins following either electrotransfer from sodium dodecyl sulfate (SDS) polyacrylamide gels or direct application during dot blotting assays. These matrices differ with respect to chemical composition, charge, pore size, and degree of hydrophobicity. It follows that the properties of the protein(s) of interest will greatly influence the degree to which they interact with and ultimately bind to various filters. Acidic bone proteins contain diverse post-translational modifications that influence their interactions with solid phase matrices such as those used in immunoblotting (Western or dot blotting) or ion binding (overlay) procedures. This communication describes the results of a study comparing binding of various mixtures of non-collagenous acidic bone matrix phosphoproteins as well as purified osteopontin and osteocalcin to various filters including nitrocellulose and cationized paper or nylon. Based on our findings, we recommend the use of cationized filters for solid phase assays requiring the binding of these acidic macromolecules to background supports.

Animals↗

PubMed1992

Isolation, characterization and immunolocalization of a 53-kDal dentin sialoprotein (DSP).

We isolated a sialic-rich protein from rat dentin extracts and have named it dentin sialoprotein, DSP (formerly called 95K glycoprotein). DSP is rich in aspartic acid, glutamic acid, glycine and serine, but contains no cysteine or phosphate. The 30% carbohydrate content includes about 9% sialic acid and indicates that several N-glycosides and O-glycosides are present. Sedimentation equilibrium analysis gave a M(r) of 52,570. Based on this molecular weight we calculated that DSP contains about 350-amino acids and 75 monosaccharides. With automated Edman degradation the sequence of the first 8-amino acids was shown to be: Ile-Pro-Val-Pro-Gln-Leu-Val-Pro. The initial 3 residues of this sequence are identical to the first 3 in human osteopontin (OPN) and are closely similar to the Leu-Pro-Val sequences of OPN from other species, as well as at the beginning of bone acidic glycoprotein-75 (BAG-75). On Western immunoblots, purified polyclonal antibodies reacted only with DSP in dentin extracts and with none of the proteins from bone. Similarly, immunolocalization experiments showed the presence of DSP in dentin but not in enamel or alveolar bone. Along with immunohistochemical localization data reported elsewhere, these observations suggest that DSP may be an important marker for cells in the odontoblast lineage.

Amino Acid Sequence↗

PubMed1992

Academic medicine's season of accountability and social responsibility.

The author declares that academic medicine has entered a new and stormy "season" of accountability and social responsibility, due to public concerns about the overall health care system. He reviews earlier seasons, identifying paramount issues or activities that dominated the specific eras the Association of American Medical Colleges (AAMC) has responded to since the twentieth century began. He recommends how the AAMC can achieve several near-term solutions to pressing demands of the current season, such as the needs to manage academic medical centers more efficiently and to restore public confidence in the integrity of biomedical research. Next, he focuses on proposals for academic medicine to provide leadership, through the AAMC, in two major areas: preparing more generalist physicians, and assuring greater access to health care for those who live in underserved urban and rural areas. He describes models of existing, successful programs. The author concludes by proposing to create a "National System of Regional Medical Care." He urges the AAMC to continue its leadership by designating a task force to examine how such a regional system could be established within this decade.

Education, Medical↗