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Biomedical subjects

K Ryder

Publications and source records attributed to K Ryder.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pitfalls and outcomes from accelerated wear testing of mechanical heart valves.

In 1990 Sorin Biomedica introduced a new bileaflet heart valve called the Bicarbon valve. This design was reported to eliminate wear in the hinge mechanism. Clinical quality Sorin Bicarbon, CarboMedics, St. Jude Medical, Duromedics and Jyros valves were obtained to test this claim and to compare the wear in the pivot of this new valve to other available heart valves. The valves were visually inspected then subjected to 4,000 cycles at a physiological beat rate in vitro. The valves were re-inspected then subjected to 400 million cycles in a Reul type accelerated wear tester. Scanning electron microscope photographs were taken of all contact areas at 40, 80, 120, 160, 200, 240, 280 and 400 million cycles. Wear marks on the inflow side of the Sorin, CarboMedics and St. Jude leaflets were measured and compared. Orifice wear was not quantified because of difficulty with measuring inside complex depressions. After 4,000 cycles of testing at a physiological beat rate the CarboFilmTM coating on the Sorin orifice showed signs of erosion. The other valve components only exhibited minor burnishing after 4,000 cycles. Following completion of 400 million cycles in an accelerated wear tester, approximately ten years in vivo, all valves showed significant wear. The inflow face of the pivot on the Sorin Bicarbon leaflets exhibited the deepest wear marks. The CarboFilm coating on the Sorin Bicarbon orifices was removed from most areas of leaflet contact. The transition between the remaining coating and the eroded areas created a rough edge. The tips of the Sorin leaflets contacted the bottom of the orifice pivot, in contrast to the St. Jude Medical and CarboMedics designs, which had minimal contact between the leaflet and the orifice.

Biocompatible Materials↗
PubMed1995

Complex genetic organization of junB: multiple blocks of flanking evolutionarily conserved sequence at the murine and human junB loci.

A comparison of the murine and human junB loci reveals nine regions of distal 5'- and 3'-flanking DNA that exhibit greater than 72% sequence identity. A large fraction (over 50%) of the junB locus is contained in these flanking evolutionarily conserved sequences (FECS), which may be required for effecting the proper transcriptional regulation of this gene. Comparative sequence analyses involving kilobases of distal flanking DNAs have been performed for only a small number of vertebrate genes. The available data and the results presented here suggest that FECS may emerge as common yet important functional components of genes, a hypothesis with significant implications for characterizing genes involved in human disease.

Animals↗
PubMed1995

Analysis of the hormone-dependent regulation of a JunD-estrogen receptor chimera.

The modular ligand-binding domains of steroid receptors have been widely used to generate protein chimeras that are ligand dependent for activity. In a similar manner, we generated a series of conditionally active JunD and c-Fos proteins by fusing their carboxyl (COOH)-terminal ends with a COOH-terminal fragment of the human estrogen receptor (ER) that contains the ligand-binding domain. JunD-ER (DER) and Fos-ER (FER) chimeras with an intact leucine zipper and basic region exhibit hormone-dependent activation of activator protein-1-directed transcription in transient expression assays. One of these fusions, DER, has been examined in detail to determine its mechanism of action. Results from immunoprecipitation experiments with extracts from DER and Fos transfected cells demonstrate that Fos and DER readily form heterodimer complexes. Surprisingly, the formation of Fos:DER heterodimers, and possibly DER homodimers, is estrogen-independent. However, gel shift assays clearly demonstrate that DNA binding to AP1 sites by Fos:DER heterodimers or DER homodimers is estrogen-dependent. Moreover, in the absence of estrogen, the DER protein is an effective inhibitor of Fos-mediated transactivation, and this effect is reversed by the presence of estrogen. Our results indicate that the DER protein is a direct, hormone-reversible inhibitor of Fos and that estrogen controls the conditional positive or dominant negative activities of DER at the level of DNA binding to AP1 sites. Accordingly, clonally derived fibroblast cell lines that stably express the DER protein exhibit reduced entry into the S phase of the cell cycle when quiescent cells are serum stimulated in the absence of estrogen. This is in contrast to the estrogen-treated controls. These results support the hypothesis that AP1 is important for cell cycle progression and provide a unique approach for examining the role of AP1 in this process.

Animals↗
PubMed1994

Quantitative analysis of the contribution made by 5'-flanking and 3'-flanking sequences to the transcriptional regulation of junB by growth factors.

We have identified four DNAase I-hypersensitive regions (DHRs) at the junB locus. DHR1 is located between sequences -100 and +250, DHR2 is centered at -1000, DHR3 at -1650, and DHR4 at +2040 relative to the junB transcriptional start site. Sequence analysis of these DHRs revealed two serum response elements at -1452 and +2091, two cyclic AMP response elements at +2071 and +2116, and a 12-O-tetradecanoylphorbol-13-acetate (TPA) response element at -949. To study the contribution made by these cis-elements to junB transcriptional regulation, we stably transfected a recombinant mouse junB gene (JBSV4) containing the intact junB coding sequences, 6.3 kb of 5'-flanking DNA, and 2.0 kb of 3'-flanking DNA into Rat1A cells. The pattern of DHRs identified at the mouse junB locus was re-established at the JBSV4 locus. By directly comparing JBSV4 and rat junB mRNA levels, we found that these genes were induced to equivalent levels by serum, TPA, cyclic AMP, platelet-derived growth factor, epidermal growth factor, and basic fibroblastic growth factor. These results established that JBSV4 resides in a physical environment within chromatin that closely mimics that of the junB locus, and contains the necessary sequence information to recapitulate the transcriptional regulation of junB. By analysing a series of recombinant mouse junB genes containing deletion mutations in 5'-flanking and 3'-flanking sequences, we provide a quantitative assessment of the contribution these sequences make to junB induction by different regulatory agents.

3T3 Cells↗
PubMed1992

Fetomaternal hemorrhage in threatened abortion.

In this study, we compared the incidence of fetomaternal hemorrhage between patients with threatened abortion and a control population of similar gestational age. The study population comprised pregnant patients at less than 20 weeks' gestation who presented to our emergency room with a history of vaginal bleeding without cervical dilatation or passage of tissue. The control population consisted of women presenting for elective pregnancy termination; they were excluded from the study if they gave a history of any antepartum bleeding. The amount of fetomaternal hemorrhage was evaluated using the Kleihauer-Betke acid elution assay. A positive result in our laboratory, as determined by a nonpregnant control group, was a value of 0.07% or more fetal cells. Using this criterion, 11% of the study population had a positive Kleihauer-Betke test, compared with 4% in the pregnant control group. Rho(D) immunoglobulin may be indicated in Rho(D)-negative patients who present with threatened abortion.

Abortion, Threatened↗
PubMed1990

A growth factor-inducible nuclear protein with a novel cysteine/histidine repetitive sequence.

Growth factors rapidly induce transcription of a set of genes that encode regulatory proteins, many of which have been identified by cDNA cloning. Here we report the analysis of a cDNA corresponding to a gene induced in mouse 3T3 cells by growth factors and a variety of other extracellular signaling agents. The cDNA encodes a proline-, serine-, and glycine-rich nuclear protein designated Nup475 of 319 amino acids that contains two tandemly repeated cysteine- and histidine-containing sequences (CX8CX5CX3H) suggestive of a novel heavy metal-binding domain. Nup475 produced in Escherichia coli binds zinc. Its mRNA is present in a number of mouse tissues and cell lines, being especially abundant in intestine, thymus, and regenerating liver and in a macrophage cell line stimulated by gamma-interferon. We hypothesize that Nup475 is a regulatory protein with a novel zinc finger structure.

Amino Acid Sequence↗
PubMed1989

jun-D: a third member of the jun gene family.

The protooncogene c-jun encodes a component of the transcription factor AP-1. Both murine c-jun and a related gene (jun-B) are rapidly activated in BALB/c3T3 cells by serum growth factors. We report here the cloning and analysis of a cDNA encoding a third member of the murine jun family, jun-D. The amino acid sequence encoded by jun-D has two extensive regions of homology with the other Jun proteins. One homology region includes the DNA-binding domain and sequences required for dimer formation and interaction with the Fos oncoprotein; the other includes the acidic sequence thought to be involved in gene activation. All three jun mRNAs are present in a variety of murine tissues and cell lines. In resting 3T3 cells, jun-D is expressed at a higher level compared to c-jun and jun-B, and its transcription is stimulated only slightly by serum growth factors. Thus, jun-D appears to be regulated differently than c-jun and jun-B.

Amino Acid Sequence↗
PubMed1989

A growth factor-responsive gene of murine BALB/c 3T3 cells encodes a protein homologous to human tissue factor.

Polypeptide growth factors rapidly induce the transcription of a set of genes that appear to mediate cell growth. We report that one of the genes induced in BALB/c mouse 3T3 cells encodes a transmembrane protein (mTF) homologous to human tissue factor, which is involved in the proteolytic activation of blood clotting. mTF mRNA is present in many murine tissues and cell lines. Our results raise the possibility that mTF may also play a role in cell growth.

Amino Acid Sequence↗
PubMed1988

DNA binding activities of three murine Jun proteins: stimulation by Fos.

Three members of the Jun/AP-1 family have been identified in mouse cDNA libraries: c-Jun, Jun-B, and Jun-D. We have compared the DNA binding properties of the Jun proteins by using in vitro translation products in gel retardation assays. Each protein was able to bind to the consensus AP-1 site (TGACTCA) and, with lower affinity, to related sequences, including the cyclic AMP response element TGACGTCA. The relative binding to the oligonucleotides tested was similar for the different proteins. The Jun proteins formed homodimers and heterodimers with other members of the family, and they were bound to the AP-1 site as dimers. When Fos translation product was present, DNA binding by Jun increased markedly, and the DNA complex contained Fos. The C-terminal homology region of Jun was sufficient for DNA binding, dimer formation, and interaction with Fos. Our general conclusion is that c-Jun, Jun-B, and Jun-D are similar in their DNA binding properties and in their interaction with Fos. If there are functional differences between them, they are likely to involve other activities of the Jun proteins.

Animals↗
PubMed1988

The role of operator position in SV40 T-antigen-mediated repression.

We have manipulated positional relationships between the SV40 early operator and promoter to study the repression of transcription by T antigen. Single or multiple insertions of T-antigen-binding region I resulted in only weak repression even when the operator was placed immediately adjacent to known promoter elements. The low levels of repression appear to reflect the intrinsic strength of the T-antigen-operator interaction.

Antigens, Polyomavirus Transforming↗
PubMed1988

Convulsant-induced increase in transcription factor messenger RNAs in rat brain.

Administration of the convulsants pentylenetetrazole (Metrazole) or picrotoxin to rats caused a dramatic increase in mRNAs of four putative transcription factor genes, zif/268, c-jun, jun-B, and c-fos, in neurons of the hippocampus and dentate gyrus, as well as other areas of the cerebral cortex, including pyriform cortex and cingulate cortex. The increase in these mRNAs was rapid and transient: amounts peaked within 1 hr and returned to baseline within 2 hr. These results extend the observation made by Morgan et al. [Morgan, J. I., Cohen, D. R., Hempstead, J. L. & Curran, T. (1987) Science 237, 192-197] that c-fos mRNA and protein are induced in rat brain after seizures. We hypothesize that the increase of these putative transcription factor mRNAs in the brain is part of a programmed genomic response of neurons to intense stimulation, which is analogous to the genomic response of nonneuronal cells to growth factors.

Animals↗
PubMed1988

Induction of protooncogene c-jun by serum growth factors.

We have previously reported that one of the genes that is rapidly induced in mouse 3T3 cells by serum growth factors (jun-B) encodes a protein related to the onco-protein v-jun. By using jun-B as a probe, we have isolated a cDNA encoding a second member of the jun family (jun-A) that is the murine version of the protooncogene c-jun, which encodes the mammalian transcription factor AP-1. jun-B and jun-A (c-jun) have two highly conserved regions and two regions with little sequence similarity. Like jun-B, jun-A (c-jun) is rapidly activated by serum, platelet-derived growth factor, or fibroblast growth factor and is superinduced by serum in the presence of an inhibitor of protein synthesis. Both jun proteins are likely to play a role in regulating the genetic program induced by growth factors.

Amino Acid Sequence↗
PubMed1988

A gene activated by growth factors is related to the oncogene v-jun.

We have recently identified by cDNA cloning a set of genes that are rapidly activated in cultured mouse cells by protein growth factors. Here we report that the nucleotide sequence of a cDNA (clone 465) derived from one of these immediate early genes (hereafter called jun-B) encodes a protein homologous to that encoded by the avian sarcoma virus 17 oncogene v-jun. Homology between the jun-B and v-jun proteins is in two regions: one near the N terminus and the other at the C terminus. The latter sequence was shown by Vogt et al. [Vogt, P. K., Bos, T. J. & Doolittle, R. F. (1987) Proc. Natl. Acad. Sci. USA 84, 3316-3319] to have regions of sequence similarity to the DNA-binding domain of the yeast transcriptional regulatory protein GCN4 and to the oncogenic protein fos. Southern blots of human, mouse, and chicken DNA demonstrate that jun-B and c-jun are different genes and that there may be other vertebrate genes related to jun-B and c-jun. These findings suggest that there is a jun family of genes encoding related transcriptional regulatory proteins. The jun-B protein, and perhaps other members of the jun family, may play a role in regulating the genomic response to growth factors.

Amino Acid Sequence↗
PubMed1986

An altered DNA conformation in origin region I is a determinant for the binding of SV40 large T antigen.

Seventeen base pairs of DNA from SV40 origin region I encode a tripartite binding site for a dimeric mass of SV40 large T antigen. Two binding components are the directly repeated pentanucleotide sequences 5'-GAGGC-3'/5'-GCCTC-3'. The third component is the asymmetric sequence 5'-TTTTTTG-3'/5'-CAAAAAA-3' that separates the pentanucleotides. Nucleotide-specific features of this spacer element stabilize binding to the adjacent pentanucleotides. We report here that the spacer sequence determines a DNA conformation that correlates with high affinity binding of T antigen. The nature of the spacer sequence suggests that the DNA is bent. We propose that binding of T antigen to region I proceeds through monomer-pentanucleotide interactions and either protein-protein or protein-spacer interactions directed by the spacer-encoded structure.

Antigens, Viral, Tumor↗