Biomedical subjects

A Cavender

Publications and source records attributed to A Cavender.

12 recordsLinked to original sources

PubMed2006

Folk medical uses of plant foods in southern Appalachia, United States.

An analysis of information obtained from interviews with 660 older native inhabitants of the southern Appalachian region in the United States indicates that plant foods, especially cultivars and materials processed from them, and some wildcrafted plant foods as well, constituted the bulk of the folk materia medica in the 1920s and 1930s. Aside from their use for the treatment of common ailments, many plant foods were, and still are to a lesser extent, valued in the region for cleaning and building blood, cleaning the bowel, and as a source of vitamins and minerals. The dependence on plant foods and wildcrafted medicinal plants, however, appears to have diminished considerably in recent years.

Appalachian Region↗

PubMed2002

A novel mutation in human PAX9 causes molar oligodontia.

Experimental and animal studies, as well as genetic mutations in man, have indicated that the development of dentition is under the control of several genes. So far, mutations in MSX1 and PAX9 have been associated with dominantly inherited forms of human tooth agenesis that mainly involve posterior teeth. We identified a large kindred with several individuals affected with molar oligodontia that was transmitted as an isolated autosomal-dominant trait. Two-point linkage analysis using DNA from the family and polymorphic marker D14S288 in chromosome 14q12 produced a maximum lod score of 2.29 at theta = 0.1. Direct sequencing of exons 2 to 4 of PAX9 revealed a cytosine insertion mutation at nucleotide 793, leading to a premature termination of translation at aa 315. Our results support the conclusion that molar oligodontia is due to allelic heterogeneity in PAX9, and these data further corroborate the role of PAX9 as an important regulator of molar development.

Adult↗

PubMed2001

Identification of tooth-specific downstream targets of Runx2.

Odontogenesis or tooth development is a highly regulated process that involves complex epithelial-mesenchymal signaling interactions that lead to cuspal morphogenesis, cell differentiation and the subsequent formation of the specialized matrices of enamel, dentin, cementum and bone. Although studies on tooth epithelial-mesenchymal signaling interactions have greatly increased our understanding of molecules that regulate tooth initiation and early morphogenesis (review: Jernvall and Thesleff, Mech. Dev. 92 (2000) 19), the precise nature of the molecular events controlling late morphogenesis and terminal cytodifferentiation is not known. We have recently reported a unique phenotype involving dentition in mice lacking a functional Runx2 gene (D'Souza et al., Development 126 (1999) 2911). The markedly hypoplastic tooth organs as well as defects in the maturation of ameloblasts and odontoblasts point to an important and non-redundant role for Runx2 in tooth morphogenesis and cytodifferentiation. In order to identify genes that are affected by the absence of Runx2, a cDNA library was generated from Runx2(-/-) and Runx2(+/+) first molar organs. Thus far, our analysis has revealed several tooth-specific downstream target genes of Runx2 that include extracellular matrix proteins, kinases, receptors, growth factors, mitochondrial proteins and transcription molecules. Sequence analysis of 61 differentially expressed genes revealed that 96.03% of the clones matched previously described genes in the GenBank/EBML database and 3.96% did not match any entries in the database. Our preliminary expression analysis of one of the differentially expressed clones which encodes for a zinc finger transcription factor termed Zfp reveals that the gene is temporally regulated during tooth development. In conclusion, we have successfully generated a library enriched in genes expressed in Runx2(+/+) molar tooth organs and performed preliminary studies to assess the role of Zfp in tooth development.

Animals↗

PubMed2001

Cell-specific patterns of Cbfa1 mRNA and protein expression in postnatal murine dental tissues.

Cbfa1 (core binding factor alpha 1) is a transcription factor that is a key determinant of the osteoblastic lineage. Recent data showed that Cbfa1 is also highly expressed in early stages of tooth development and is involved in crown morphogenesis and cytodifferentiation of odontoblasts. Here we report the mRNA expression and protein localization of Cbfa1 in the mouse dentition in (later) stages of crown and root development. In addition to osteoblasts, osteocytes, chondrocytes, odontoblasts, dental follicle cells, cementoblasts and periodontal ligament cells, we report also Cbfa1 expression in dental epithelial cells (secretory and maturation ameloblasts) and several non-mineralizing cell types (hair follicles, ducts of salivary glands, and junctional epithelium of the gingiva).

Age Factors↗

PubMed2001

Gene expression in a pure population of odontoblasts isolated by laser-capture microdissection.

Studies of odontoblast differentiation and function have been limited due to difficulties in obtaining sufficient numbers of intact cells. We describe a novel approach of laser-capture microdissection to obtain homogenous populations of pre-odontoblasts and odontoblasts from tissue sections of mouse molar cusp tips. Fixation, processing, and staining conditions were assessed for the optimal retrieval of total RNA from microdissected odontoblasts. Fluorometric assays and RT-PCR analysis of alpha1(I) collagen, dentin sialophosphoprotein (Dspp), and osteocalcin (OC) confirmed that the total RNA from three-day-old captured odontoblasts was sufficient in quantity and quality. Odontoblast-specific gene expression was studied by RT-PCR analysis performed in a single streptavidin-coated tube. At E15.5, Days 0 and 3, gene expression in laser-captured odontoblasts resembled that seen in vivo by in situ hybridization. The use of LCM is thus a valuable means of retrieving quality RNA from discrete populations of odontoblasts at different stages of dentinogenesis.

Animals↗

PubMed2001

Molecular insights into the lineage-specific determination of odontoblasts: the role of Cbfa1.

The role of stable transcription complexes in initiating and consolidating programs of gene expression during lineage specification has been extensively studied. Despite the progress made in the identification of key molecules of tooth initiation and patterning, the mechanisms leading to cell differentiation during odontogenesis are unknown. Odontoblasts are exclusive dentin-producing cells that are phenotypically and functionally distinct from osteoblasts. However, not much is known about the precise determinants of odontoblast terminal differentiation--in particular, how the fate of these cells becomes delineated from that of osteogenic mesenchyme. Cbfa1(-/-) mice completely lack osteoblasts and bone, while tooth development arrests at the time of odontoblast differentiation. The purpose of this paper is to overview our studies on the role of Cbfa1 in odontoblast determination and differentiation using the Cbfa1(-/-) mouse model and various experimental approaches. Our expression analyses confirm the down-regulation of Cbfa1 expression in newly differentiated and functional odontoblasts. Second, we demonstrate that Cbfa1(-/-) incisor organs arrest at a later stage than molars, and that alpha 1 (I) collagen, a marker of odontoblast differentiation shared in common with osteoblasts, is not significantly affected by the absence of the transcription factor. Interestingly, Dspp expression in Cbfa1(-/-) appeared markedly down-regulated in putative odontoblasts. The overexpression of Cbfa1 in an odontoblast cell line (MDPC-23) results in the selective down-regulation of Dspp and not type I collagen. It is likely that, in addition to its influence on tooth epithelial morphogenesis, Cbfa1 plays a non-redundant and stage-specific role in the lineage determination and terminal differentiation of odontoblasts from dental papilla mesenchyme.

Animals↗

PubMed1999

Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice.

Osteoblasts and odontoblasts, cells that are responsible for the formation of bone and dentin matrices respectively, share several molecular characteristics. Recently, Cbfa1 was shown to be a critical transcriptional regulator of osteoblast differentiation. Mutations in this gene cause cleidocranial dysplasia (CCD), an autosomal dominant disorder in humans and mice characterized by defective bone formation. CCD also results in dental defects that include supernumerary teeth and delayed eruption of permanent dentition. The dental abnormalities in CCD suggest an important role for this molecule in the formation of dentition. Here we describe results of studies aimed at understanding the functions of Cbfa1 in tooth formation. RT-PCR and in situ hybridization analyses show that Cbfa1 has a unique expression pattern in dental mesenchyme from the bud to early bell stages during active epithelial morphogenesis. Unlike that observed in osteoblast differentiation, Cbfa1 is downregulated in fully differentiated odontoblasts and is surprisingly expressed in ectodermally derived ameloblasts during the maturation phase of enamel formation. The role of Cbfa1 in tooth morphogenesis is further illustrated by the misshapen and severely hypoplastic tooth organs in Cbfa1-/- mice. These tooth organs lacked overt odontoblast and ameloblast differentiation and normal dentin and enamel matrices. Epithelial-mesenchymal recombinants demonstrate that dental epithelium regulates mesenchymal Cbfa1 expression during the bud and cap stages and that these effects are mimicked by the FGFs but not by the BMPs as shown by our bead implantation assays. We propose that Cbfa1 regulates the expression of molecules in mesenchyme that act reciprocally on dental epithelium to control its growth and differentiation. Taken together, our data indicate a non-redundant role for Cbfa1 in tooth development that may be distinct from that in bone formation. In odontogenesis, Cbfa1 is not involved in the early signaling networks regulating tooth initiation and early morphogenesis but regulates key epithelial-mesenchymal interactions that control advancing morphogenesis and histodifferentiation of the epithelial enamel organ.

Animals↗

PubMed1998

Compulsory medical service in Ecuador: the physician's perspective.

Compulsory medical service programs for physicians and other health care professionals have been installed in developing countries around the world. The underlying assumption for the creation of these programs is that the increased presence of physicians will improve the health status of rural populations which exhibit higher rates of morbidity and mortality compared to urban populations. This assumption, however, has been challenged by recent evaluative studies of compulsory service programs in Latin America. This paper reports on the physician's perspective of Ecuador's compulsory service program, known as medicatura rural. Based on responses to a self-administered questionnaire completed by 127 physicians who had fulfilled or were currently fulfilling their medicatura rural requirement, in-depth interviews with physicians and other officials, and visits to several rural placement sites, the paper examines some of the fundamental programmatic and logistical problems that have impeded the successful implementation of the program since its inception in 1970. While the majority of the physicians reported that the medicatura rural experience was both professionally and personally rewarding, many view the program as conceptually flawed with respect to its goal of improving the health status of rural communities. The physicians' suggestions for improving the medicatura rural, which elucidate some of the program's basic conceptual flaws and reflect the criticisms of compulsory medical programs in other Latin American countries, are discussed. Finally, Ugalde's (1988) recommendation for replacing compulsory medical service programs with a "rural health corps" is considered.

Adaptation, Psychological↗

PubMed1998

TGF-beta1 is essential for the homeostasis of the dentin-pulp complex.

Among the complex network of cytokines that influence odontoblast function during development and repair, TGF-beta1 is unique in its dual abilities to function as a potent immunosuppressant and as an inducer of extracellular matrix production. These properties underscore the importance of this molecule in maintaining the homeostasis of the dentin-pulp complex after injury. The purpose of this paper is to describe new findings of our phenotypic analysis of dentition in mice in which the TGF-beta1 gene has been disrupted. The major phenotype of TGF-beta1(-/-) offspring is one of diffuse immune system activation with progressive inflammation, wasting and death. Our studies of adult TGF-beta1(-/-) dentition show widespread pulpal and periapical inflammation and necroses. In addition, the coronal surfaces of occluding molars show marked attrition. To determine whether the phenotypic changes in TGF-beta1(-/-) dentition are directly linked to the loss of TGF-beta1 rather than the inflammatory process itself, we studied adult dentition in TGF-beta1(-/-) mice backcrossed into immunodeficient backgrounds. Results of our histopathologic and radiographic analyses show that teeth of TGF-beta1(-/-) immunodeficient mice retain vitality in pulpal and periapical regions but show excessive wear of occlusal surfaces.

Animals↗

PubMed1998

Developmental regulation of dentin sialophosphoprotein during ameloblast differentiation: a potential enamel matrix nucleator.

The two major dentin matrix proteins, dentin sialoprotein and dentin phosphoprotein have been shown to be expressed as a single large transcript termed dentin sialophosphoprotein (DSPP). These non-collagenous matrix proteins, identified biochemically by their unique physical-chemical properties, are specific cleavage products of a large parent acidic phosphorylated protein (pI 4.0). Previous studies have shown expression of dentin sialoprotein at the protein level by ameloblasts. The purpose of this study was to determine the temporal-spatial pattern of DSPP expression during amelogenesis. In situ hybridization and immunohistochemistry were performed on sections of developing mouse molars. These data were correlated with RT-PCR analysis of in vitro enamel organ epithelium monolayer cell cultures enriched for ameloblasts. Our data indicates initial expression of the DSPP transcripts and protein during early ameloblast differentiation prior to the secretory phase when the majority of the enamel matrix is formed. Ameloblasts appear to tightly down-regulate DSPP transcription as enamel matrix formation is up-regulated. These data demonstrate DSPP expression during amelogenesis is under highly controlled developmental regulation. Therefore, DSPP may have a primary role in the initial mineralization events of both enamel and dentin, acting as a potential nucleator of hydroxyapatite crystal formation.

Ameloblasts↗

PubMed1997

Gene expression patterns of murine dentin matrix protein 1 (Dmp1) and dentin sialophosphoprotein (DSPP) suggest distinct developmental functions in vivo.

Although the precise mechanisms of the conversion of predentin to dentin are not well understood, several lines of evidence implicate the noncollagenous proteins (NCPs) as important regulators of dentin biomineralization. Here we compared the in vivo temporospatial expression patterns of two dentin NCP genes, dentin matrix protein 1 (Dmp1), and dentin sialophosphoprotein (DSPP) in developing molars. Reverse transcription-polymerase chain reaction was performed on embryonic day 13 to 1-day-old first molars using Dmp1- and DSPP-specific primer sets. Dmp1 transcripts appeared at the late bud stage, while DSPP mRNA was seen at the cap stage. Expression of both genes was sustained throughout odontogenesis. In situ hybridization analysis revealed interesting differences in the expression patterns of these genes. While Dmp1 and DSPP showed coexpression in young odontoblasts before the start of mineralization, the expression of these genes was notably distinct at later stages. Dmp1 expression decreased in secretory odontoblasts after the appearance of mineral, while high levels of DSPP were sustained in odontoblasts. In early secretory ameloblasts, DSPP expression was transient and down-regulated with the appearance ofdentin matrix. Interestingly, Dmp1 expression became evident in ameloblasts during the maturative phase of amelogenesis. In contrast to Dspp expression that was tooth-specific, Dmp1 was expressed by osteoblasts throughout ossification in the skeleton. Probes directed to the "DSP" and "DPP" regions of the DSPP gene showed identical patterns of mRNA expression. These data show that the developmental expression patterns of Dmp1 and DSPP are distinct, implying that these molecules serve different biological functions in vivo.

Animals↗

PubMed1996

Local unorthodox healers of cancer in the Appalachian south.

This paper examines the local popular tradition of unorthodox cancer healers and treatments in the Appalachian South. An indepth case study of an unorthodox cancer healer is presented which focuses on his recruitment to the role of healer, the origin and method of his cancer treatment, and a profile of his client population. The case study is followed by a discussion of other unorthodox healers of cancer in the region for the purpose of elucidating the distinction between the local and mass popular traditions of unorthodox cancer medicine. There is an historically deep and enduring tradition of unorthodox cancer treatments in the Appalachian South, and no doubt other regions of the U.S. as well, which should be considered for a better understanding of the health care alternatives available and the health seeking behavior of individuals who use them.

Appalachian Region↗