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Biomedical subjects

K M Lyons

Publications and source records attributed to K M Lyons.

At least 19 recordsLinked to original sources
PubMed1999

Notch signaling imposes two distinct blocks in the differentiation of C2C12 myoblasts.

Notch signal transduction regulates expression of downstream genes through the activation of the DNA-binding protein Su(H)/CBF1. In Drosophila most of Notch signaling requires Su(H); however, some Notch-dependent processes occur in the absence of Su(H) suggesting that Notch signaling does not always involve activation of this factor. Using constitutively active forms of Notch lacking CBF1-interacting sequences we identified a Notch signaling pathway that inhibits myogenic differentiation of C2C12 myoblasts in the absence of CBF1 activation. Here we show that ligand-induced Notch signaling suppresses myogenesis in C2C12 myoblasts that express a dominant negative form of CBF1, providing additional evidence for CBF1-independent Notch signal transduction. Surprisingly mutant forms of Notch deficient in CBF1 activation are unable to antagonize MyoD activity, despite the fact that they inhibit myogenesis. Moreover, Notch-induced antagonism of MyoD requires CBF1 suggesting that the CBF1-dependent pathway mediates a cell-type-specific block in the myogenic program. However, Notch signaling in the absence of CBF1 activation blocks both myogenesis and osteogenesis, indicative of a general block in cellular differentiation. Taken together our data provide evidence for two distinct Notch signaling pathways that function to block differentiation at separate steps during the process of myogenesis in C2C12 myoblasts.

3T3 Cells↗
PubMed1999

Barodontalgia: a review, and the influence of simulated diving on microleakage and on the retention of full cast crowns.

This paper reviews the causes of barodontalgia and reports on a study that indicates a possible cause of barodontalgia in the diver. In the study, extracted teeth had full cast crowns cemented with either a zinc phosphate, a glass ionomer, or a resin cement, and simulated diving to 30 m (3.0 atmospheres) was performed. During simulated diving, the teeth were pressure cycled 15 times to 3 atmospheres and microleakage was monitored. The force required to dislodge the crown was then tested; a significant difference was found between the zinc phosphate and the glass ionomer cement groups (p < 0.01). No difference was found between the resin cement groups. Microleakage was also detected in the zinc phosphate and glass ionomer cement groups and was found to occur sooner, and to a greater extent with zinc phosphate. No microleakage was detected in the resin cement experimental group. This study showed that the retention of full cast crowns to extracted teeth is reduced after pressure cycling and that microleakage does occur if the crowns are cemented with either zinc phosphate cement or glass ionomer cement.

Barotrauma↗
PubMed1998

Mice lacking Bmp6 function.

Bmp6, a member of the 60A subgroup of bone morphogenetic proteins (BMPs), is expressed in diverse sites in the developing mouse embryo from preimplantation stages onwards. To evaluate roles for Bmp6 signaling in vivo, gene targeting was used to generate a null mutation at the Bmp6 locus. The resulting Bmp6 mutant mice are viable and fertile, and show no overt defects in tissues known to express Bmp6 mRNA. The skeletal elements of newborn and adult mutants are indistinguishable from wild-type. However, careful examination of skeletogenesis in late gestation embryos reveals a consistent delay in ossification strictly confined to the developing sternum. In situ hybridization studies in the developing long bones and sternum show that other BMP family members are expressed in overlapping domains. In particular we find that Bmp2 and Bmp6 are coexpressed in hypertrophic cartilage, suggesting that Bmp2 may functionally compensate in Bmp6 null mice. The defects in sternum development in Bmp6 null mice are likely to be associated with a transient early expression of Bmp6 in the sternal bands, prior to ossification. These sternal defects are slightly exacerbated in Bmp5/6 double mutant animals.

Animals↗
PubMed1998

The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes.

We have taken advantage of the sequence relationships among the bone morphogenetic proteins (BMPs) to identify the mouse Bmp15 and human BMP15 genes. The 392-amino acid prepropeptides encoded by these BMP genes exhibit significant homology to each other, although the 70% identity observed between the 125-amino acid mature peptides is considerably lower than that seen in comparisons of other mouse and human orthologs. Both genes share a common structural organization and encode mature peptides that lack the cysteine residue normally involved in the formation of a covalent dimer. In addition, mouse Bmp15 and human BMP15 map to conserved syntenic regions on the X chromosome. We demonstrate, through a combination of Northern blot and in situ hybridization analyses, that mouse Bmp15 is expressed specifically in the oocyte beginning at the one-layer primary follicle stage and continuing through ovulation. Interestingly, BMP-15 is most closely related to and shares a coincident expression pattern with the mouse growth/differentiation factor 9 (GDF-9) gene that is essential for female fertility. Our findings will be important for defining the role of BMP-15 in follicular development.

Amino Acid Sequence↗
PubMed1997

The effect of environmental pressure changes during diving on the retentive strength of different luting agents for full cast crowns.

STATEMENT OF PROBLEM: The effect of pressure cycling on the bond strength of cement luting agents is largely unknown. PURPOSE: This study investigated the effect of pressure cycling on the retention of full cast crowns to extracted teeth. MATERIAL AND METHODS: Sixty extracted single-rooted premolar teeth had full cast crowns cemented, 20 with a zinc phosphate cement, 20 with a glass ionomer, and 20 with a resin cement. After 7 days of storage, each of the teeth in the experimental groups was pressure cycled 15 times from 0 to 3 atmospheres (304 KPa), after which the force required to dislodge the crowns was tested in an Instron testing machine. RESULTS: A significant difference was found (Students t test; p > 0.01) between the force required to remove the crowns in the zinc phosphate control (142.10 +/- 36.42 N) and experimental (15.93 +/- 11.13 N) groups and the glass ionomer cemented control (186.33 +/- 24.33 N) and experimental (91.50 +/- 33.07 N) groups; no difference was found between the resin cemented control (291.15 +/- 78.48 N) and experimental (281.32 +/- 85.43 N) groups. CONCLUSION: This study showed that the retention of full cast crowns to extracted teeth is reduced after pressure cycling if the crowns are cemented with either zinc phosphate cement or glass ionomer cement. Dentists should consider using a resin cement when cementing crowns and fixed partial dentures for patients, such as divers, who are likely to be exposed to pressure cycling.

Air Pressure↗
PubMed1996

Bone morphogenetic protein-2: biology and applications.

Bone morphogenetic protein-2 is a low molecular weight glycoprotein, classified as a morphogen. The sine qua non of bone morphogenetic protein is consistently reproducible induction of bone development in heterotopic sites. Bone morphogenetic proteins belong to the expanding transforming growth factor-beta superfamily. Bone morphogenetic protein-2 has pleiotropic functions that range from extraskeletal and skeletal organogenesis to bone generation and regeneration. Bone morphogenetic protein induced bone formation in postfetal life recapitulates the process of embryonic and endochondral ossification. Through recombinant gene technology, human bone morphogenetic protein-2 is available in almost unlimited amounts for basic research and clinical trials. Human bone morphogenetic protein-2 induces structurally sound orthotopic bone in a variety of experimental systems, including femoral defects in rats, tibial and ulnar defects in rabbits, femoral defects in sheep, mandibular defects in dogs, spinal fusion in dogs, and porous ingrowth in rats. Human bone morphogenetic protein-2 research extends to the fields of developmental biology, genetics, and evolution. Bone morphogenetic protein has been used successfully at the authors' institution to heal clinical nonunions and to achieve spinal fusion. This report reviews the current understanding of bone morphogenetic proteins in general and BMP-2 in particular and summarizes their potential applications.

Animals↗
PubMed1995

A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye.

BMP-7/OP-1, a member of the transforming growth factor-beta (TGF-beta) family of secreted growth factors, is expressed during mouse embryogenesis in a pattern suggesting potential roles in a variety of inductive tissue interactions. The present study demonstrates that mice lacking BMP-7 display severe defects confined to the developing kidney and eye. Surprisingly, the early inductive tissue interactions responsible for establishing both organs appear largely unaffected. However, the absence of BMP-7 disrupts the subsequent cellular interactions required for their continued growth and development. Consequently, homozygous mutant animals exhibit renal dysplasia and anophthalmia at birth. Overall, these findings identify BMP-7 as an essential signaling molecule during mammalian kidney and eye development.

Animals↗
PubMed1995

Colocalization of BMP 7 and BMP 2 RNAs suggests that these factors cooperatively mediate tissue interactions during murine development.

Members of the bone morphogenetic protein (BMP) class of transforming growth factor beta (TGF beta)-related molecules have been implicated in a variety of inductive processes throughout vertebrate development. The 60A subclass of BMPs contains at least four vertebrate members, BMPs 5-8. We have shown by library screening and in situ hybridization that of these four genes, BMP 7 is expressed earliest, in gastrulating embryos. Furthermore, BMP 7 transcripts are present at diverse sites throughout development, in a pattern consistent with a role in a variety of inductive interactions. Recent studies have shown that BMP 2/7 heterodimers have unique activities compared to the corresponding homodimers. For this reason, we compared the patterns of expression of BMP 2 and BMP 7 using in situ hybridization. Our results demonstrate that these BMPs are coexpressed in a number of tissues that are known to be the source of inductive signals, including the zone of polarizing activity and apical ectodermal ridge of the developing limb and the notochord, raising the possibility that BMP 2/7 heterodimers may mediate aspects of these tissue interactions. We also show that BMP 2 transcripts are restricted within the developing gut to dorsal endoderm, whereas sonic hedgehog has been localized to ventral and medial regions of the developing gut endoderm. These markers provide the first molecular evidence for dorsal/ventral polarity in the developing gut.

Animals↗
PubMed1994

A mammalian serine/threonine kinase receptor specifically binds BMP-2 and BMP-4.

Bone morphogenetic proteins (BMPs) are a class of related growth and differentiation factors within the TGF-beta superfamily of proteins which are known to induce cartilage and bone formation in adult animals and to be involved in many inductive events throughout embryonic development. Here we describe the molecular cloning and characterization of a mammalian receptor, CFK-43a, which specifically binds BMP-2 and BMP-4. This molecule is a member of the serine/threonine kinase receptor family which includes receptors for other TGF-beta superfamily members. CFK-43a binds other BMP family members with lower affinity, but does not bind TGF-beta. During embryogenesis, in situ hybridization analysis indicates that CFK-43a mRNA is localized in developing skeletal tissues in a complementary fashion to the transcripts for its ligands.

Amino Acid Sequence↗
PubMed1994

A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse.

The 413.d insertional mutation arrests mouse development shortly after gastrulation. nodal, a novel TGF beta-related gene, is closely associated with the locus. The present study provides direct evidence that the proviral insertion causes a loss of function mutation. nodal RNA is initially detected at day 5.5 in the primitive ectoderm. Concomitant with gastrulation, expression becomes restricted to the proximal posterior regions of the embryonic ectoderm. nodal RNA is also expressed in the primitive endoderm overlying the primitive streak. A few hours later, expression is strictly confined to the periphery of the mature node. Interestingly 413.d mutant embryos show no morphological evidence for the formation of a primitive streak. Nonetheless, about 25% of mutant embryos do form randomly positioned patches of cells of a posterior mesodermal character. Data presented in this report demonstrate the involvement of a TGF beta-related molecule in axis formation in mammals.

Animals↗
PubMed1993

The structure and evolution of the human salivary proline-rich protein gene family.

We present the nucleotide sequences of four members of the six-member human salivary proline-rich protein (PRP) gene family. The four genes are PRB1 and PRB2, which encode basic PRPs, and PRB3 and PRB4, which encode glycosylated PRPs. Each PRB gene is approximately 4.0 kb in length and contains four exons, the third of which is entirely composed of 63-bp tandem repeats and encodes the proline-rich portion of the protein products. Exon 3 contains different numbers of tandem repeats in the different PRB genes. Variation in the numbers of these repeats is also responsible for length variations in different alleles of the PRB genes. We have determined a probable evolutionary history of the human PRP gene family by comparing the nucleotide sequences of the six PRP genes. The present-day six PRP loci probably evolved from a single ancestral gene by four sequential gene duplications, leading to six genes that fall into three subsets, each consisting of two genes. During this evolutionary process, multiple rearrangements and gene conversion occurred mainly in the region from the 3' end of IVS2 and the 3' end of exon 3.

Alleles↗
PubMed1992

The TGF-beta-related DVR gene family in mammalian development.

The genes that encode the bone morphogenetic proteins and the Vg-related proteins are mammalian members of a group of TGF-beta-related genes, designated the DVR family, that includes the decapentaplegic gene of Drosophila and the Vg1 gene of Xenopus. Members of the DVR (decapentaplegic-Vg-related) family have been implicated in diverse processes during development, particularly in epithelial-mesenchymal interactions. The results of our in situ hybridization studies with postimplantation mouse embryos provide evidence for the involvement of DVR family members, particularly DVR-2, DVR-4 and DVR-6, in specific inductive interactions during the development of many organs, including the limb, the whisker follicle and the heart.

Animals↗