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Biomedical subjects

J M Murray

Publications and source records attributed to J M Murray.

At least 109 records · Page 6Linked to original sources
PubMed1990

Echistatin is a potent inhibitor of bone resorption in culture.

The venom protein, s-echistatin, originally derived from the saw-scaled viper Echis carinatus, was found to be a potent inhibitor of bone resorption by isolated osteoclasts. This Arg24-Gly25-Asp26-(RGD)-containing protein inhibited the excavation of bone slices by rat osteoclasts (IC50 = 0.1 nM). It also inhibited the release of [3H]proline from labeled bone particles by chicken osteoclasts (IC50 = 100 nM). By comparison, the tetrapeptide Arg-Gly-Asp-Ser (RGDS) inhibited resorption by rat or chicken osteoclasts with an IC50 of 0.1 mM while ala24-echistatin was inactive. Video microscopy showed that rat osteoclast attachment to substrate was more sensitive to s-echistatin than was the attachment of mononuclear cells or chicken osteoclasts. The difference in sensitivity of rat and chicken osteoclasts to s-echistatin may be due to differences between receptors on rat and chicken osteoclasts for s-echistatin. Antibody localization of echistatin on these cells showed much greater echistatin binding to rat osteoclasts than to chicken osteoclasts. Laser scanning confocal microscopy after immunohistochemical staining showed that s-echistatin binds to osteoclasts, that s-echistatin receptors are most abundant at the osteoclast/glass interface, and that s-echistatin colocalizes with vinculin. Confocal interference reflection microscopy of osteoclasts incubated with s-echistatin, demonstrated colocalization of s-echistatin with the outer edges of clusters of grey contacts at the tips of some lamellipodia. Identification of the echistatin receptor as an integrin was confirmed by colocalization of echistatin fluorescence with staining for an alpha-like subunit. Attachment of bone particles labeled with [3H]proline to chicken osteoclasts confirmed that the mechanism of action of echistatin was to inhibit osteoclast binding to bone presumably by disrupting adhesion structures. These data demonstrate that osteoclasts bind to bone via an RGD-sequence as an obligatory step in bone resorption, that this RGD-binding integrin is at adhesion structures, and that it colocalizes with vinculin and has an alpha-like subunit.

Amino Acid Sequence↗
PubMed1990

Differentiation of F9 cells is independent of c-myc expression.

The level of c-myc expression rapidly decreases during in vitro induced differentiation of mouse F9 embryonic teratocarcinoma to endoderm cells, raising the question of whether down regulation of c-myc expression is a part of the mechanism regulating differentiation. We have investigated the effect of enforced increases or decreases in c-myc RNA expression in F9 cells on growth and differentiation. The enforced expression of c-myc RNA in clones transfected with sense c-myc did not inhibit their terminal differentiation. Dramatically decreased c-myc RNA expression in antisense c-myc transfected clones also did not substantially alter the differentiation pathway, although the transformed cells withdraw from the cell cycle slightly earlier than control cells during the differentiation induction. These results suggest that the mechanism controlling differentiation operates independently of the level of c-myc RNA expression in F9 teratocarcinoma cells.

Animals↗
PubMed1989

Drug errors and incidents in a neonatal intensive care unit. A quality assurance activity.

We prospectively examined the causes of medication errors and incidents in a level 3 neonatal intensive care unit for a 2-year period. There were 313 incidents in 23,307 patient days (13.4 incidents per 1000 patient days). The relative risk of incidents was greater in more intensive levels of care. The two most common causes of incidents were neglecting to give a medication on schedule (n = 52) and nonregulation of an intravenous infusion (n = 32). Twenty percent of orders made by physicians that were in error resulted in serious incidents compared with only 6% of all other causes.

Drug Administration Schedule↗
PubMed1988

Genetic control and fine specificity of the immune response to a synthetic peptide of influenza virus hemagglutinin.

The immune response to a synthetic peptide, H3 HA1(305-328), representing the C'-terminal 24 amino acid residues of the HA1 chain of the hemagglutinin of the H3 subtype of influenza virus is controlled by genes in the I region of the major histocompatibility complex. Mice of the H-2d haplotype are high responders and produce antibody for several months after a single injection of peptide without carrier. Mice of the H-2b, H-2k, and H-2q haplotypes are low antibody responders. Investigation of recombinant and congenic mouse strains revealed that high responsiveness requires the genes that encode the I-Ed molecule. Immunoassays, involving direct binding to analogs of this peptide and inhibition by both these analogs and synthetic epitopes, were used to analyze the specificity of the polyclonal response. In BALB/c mice, the primary antibody response is directed principally against the antigenic site 314-LKLAT-318, whereas the secondary response after a boost is predominantly directed to a distinct site, 320-MRNVPEKQT-328. The T-cell response to the peptide H3 HA1(305-328), as measured by antigen-induced proliferation of primed T cells in vitro, is also I-Ed restricted in high-responder H-2d mice and is directed against an antigenic site that does not require the four C-terminal residues unique to the H3 influenza subtype. A different epitope appears to be recognized by T cells from CBA (H-2k) mice, which proliferate to a moderate extent on exposure to the peptide but, nevertheless, do not provide help for an antibody response.

Animals↗
PubMed1988

The mechanism of inactivation of the normal c-myc gene locus in human Burkitt lymphoma cells.

In human Burkitt lymphoma, the expression of the c-myc allele that has been translocated to the immunoglobulin gene locus is constitutively elevated, whereas transcription from the normal untranslocated allele on chromosome 8 is usually undetectable. Our experiments were carried out to check several plausible mechanisms proposed to explain this selective inactivation. By examining the c-myc transcripts in the presence of cycloheximide and/or actinomycin D and using differential S1 mapping, which distinguishes the c-myc transcripts of the translocated from the untranslocated allele, we found that the selective inactivation of the normal c-myc gene locus is not by a post-transcriptional regulatory mechanism, by autorepression from the constitutive expression of c-myc protein derived from the translocated locus, nor by suppression due to the previously proposed labile protein repressor. Our results are accommodated most easily by an inactivation mechanism that stably modifies the structure of the untranslocated c-myc gene.

Burkitt Lymphoma↗
PubMed1987

Effect of target size on anomalous sensory responses in the Bagolini striated lens test.

Different results obtained by different methods of retinal correspondence testing are generally accepted to be a sign of the depth of the anomalous sensory adaptation. The Bagolini striated lens test is considered a standard "natural" test to which others are compared. In this study, the Bagolini striated lens test was performed on 25 strabismic subjects using three target sizes in order to determine if target size might be a factor in response variability. Kappa Measure of Agreement, used to analyze the results statistically, showed a moderately high to high level of agreement among the three targets. This indicates that practitioners can feel confident of consistent test results on the striated lens test using any of the three readily available target sizes selected. A brief literature review has been provided as a guide to the theories of strabismus and correspondence and to emphasize the purpose of this research.

Child↗
PubMed1987

Local tissue oxygenation following radial artery cannulation.

The effect of radial artery cannulation on local tissue oxygenation and acid-base balance was studied in 20 patients. Using capillary samples drawn from each thumb, a significant difference was observed between capillary PO2 on each side (p less than 0.001), with the higher PO2 on the cannulated side. There were no significant differences between sides in terms of [H+] or PCO2. It is considered that the differences in capillary PO2 were due to local tissue vasodilatation. The presence of chlorbutol in the sodium heparin flushing solution is implicated as the causative factor. Further study of 20 patients using preservative-free heparin demonstrated no significant differences between cannulated and non-cannulated sides in terms of capillary PO2, PCO2 or [H+]. Sodium heparin with chlorbutol appears to improve local tissue oxygenation and is recommended for use in flushing solutions for invasive arterial monitoring.

Adolescent↗
PubMed1987

Intercostal catheterisation. An alternative approach to the paravertebral space.

Twenty-one patients scheduled to undergo thoracotomy or median sternotomy had intercostal catheters inserted pre-operatively. During thoracotomy, under direct vision, the spread of 20 ml of a solution containing bupivacaine and methylene blue was followed. In most cases the spread involved one or two intercostal spaces. However, in all but one patient, dye spread medially to the paravertebral space where it then spread in both caudad and cephalad directions to reach between two and five vertebrae. In three cases, dye was seen crossing the anterior surface of the vertebrae to reach the contralateral aspect. It is concluded that a major component of dermatomal block during intercostal catheterisations may be secondary to paravertebral spread.

Adolescent↗
PubMed1987

Antisense RNA of proto-oncogene c-fos blocks renewed growth of quiescent 3T3 cells.

Mouse 3T3 cells were transformed with an antisense c-fos gene fused to a mouse mammary tumor virus promoter. In transformants that integrated a large number of antisense c-fos sequences, the usual large increase in c-fos mRNA and protein following stimulation of quiescent cells by platelet-derived growth factor was blocked in the presence of dexamethasone. These cells subsequently also failed to show the stimulation of DNA synthesis normally induced by platelet-derived growth factor. Appropriate expression of c-fos appears to be a prerequisite for reentry of quiescent cells into the cell cycle.

Animals↗
PubMed1986

Effects of colcemid and taxol on microtubules and intermediate filaments in chick embryo fibroblasts.

Reports on how changes in microtubule (MT) distribution or polymerization affect the distribution of intermediate filaments (IFs) differ. Therefore, we have used cytoimmunofluorescence techniques and electron microscopy to systematically examine and compare the arrangements of MTs and IFs in cultures of chick embryo fibroblasts under the following conditions: at different times during the cell cycle, in the presence of Colcemid or of taxol, in the presence of both drugs in succession or simultaneously in varying ratios, and during recovery from treatment with Colcemid or taxol. We have found that depolymerization of MTs by 1 microM Colcemid resulted in the rapid formation of massive IF-cables, structures distinct from "collapsed IFs" or "juxtanuclear coils." Neither the rapid formation of IF-cables nor their dispersion during recovery required protein synthesis. Cells treated with 10 microM taxol rapidly formed MT-bundles, as well as aggregates of intertwining IFs, termed "IF-skeins." MT-bundles and IF-skeins displayed strikingly complementary distributions. This reciprocal distribution of packed MTs and IFs was also obvious in untreated anaphase and telophase cells. When 10 microM taxol and 1 microM Colcemid were applied simultaneously, the complementary distributions of MT-bundles and IF-skeins mimicked those in taxol alone. This ability of taxol to block Colcemid's effects was concentration dependent. Decreasing the taxol: Colcemid ratio allowed the depolymerization of MTs, which correlated with the formation of IF-cables.

Alkaloids↗
PubMed1986

Antigenic determinants of influenza virus hemagglutinin. XII. the epitopes of a synthetic peptide representing the C-terminus of HA1.

A synthetic peptide comprising the C-terminal 24 amino acids of the heavy chain (HA1) of influenza virus hemagglutinin was constructed and examined for antigenic and immunogenic activity. Monoclonal antibodies as well as polyclonal antisera raised against the synthetic peptide were able to bind to intact virus. This binding was greatly enhanced if the virus was first subjected to pH 5, suggesting that this treatment exposes the C-terminus of HA1. Using synthetic analogs of the native sequence it was shown that the epitope recognized by one of the monoclonal antibodies encompasses one or more of the C-terminal four amino acids of HA1 (residues 325-328), which are conserved within subtypes but differ between subtypes, while the other monoclonal antibody recognizes a different epitope which involves at least one of the five variable residues at positions 311-315.

Amino Acid Sequence↗
PubMed1985

Antibodies elicited by influenza virus hemagglutinin fail to bind to synthetic peptides representing putative antigenic sites.

A number of peptides of the hemagglutinin (HA) of X-31 influenza virus have been synthesised. The amino acid sequences of some of these peptides represent regions of HA which have been postulated [Wiley et al., Nature, Lond. 289, 373-378 (1981)] to form the antigenic sites of this molecule. Animals were immunized with free peptide or peptide conjugated to a carrier and the resulting antisera examined for their capacities to bind to homologous peptide, whole HA, reduced and alkylated HA, and intact virus. Not all peptides examined in this way were immunogenic. Only antibodies raised against the C-terminus of HA1 peptide displayed binding to virus. This antiserum bound to the intact HA but not to the reduced and alkylated form of the molecule. These results raise questions as to the feasibility of using synthetic peptides of the influenza HA in short linear sequences to elicit neutralising antibody.

Amino Acid Sequence↗
PubMed1984

Three-dimensional structure of a membrane-microtubule complex.

The unicellular algae Distigma proteus contain a group of aligned microtubules associated with their cell membrane. The association is maintained in isolated membrane fragments. The membrane-microtubule complex also includes a crystalline array of membrane particles. The major peptide component of this array was identified by labeling whole cells with radioiodine. The entire complex of membrane, particles, and microtubules is sufficiently well ordered to permit reconstruction from electron micrographs by Fourier techniques. A three-dimensional model of the membrane array at a nominal resolution of 2.5 nm has been calculated. Some similarities were apparent between lattice spacings in the membrane array and in microtubules. Analysis of these lattice correlations suggests a way in which the array of membrane particles may serve as scaffolding for microtubule attachment.

Cell Membrane↗
PubMed1984

Disassembly and reconstitution of a membrane-microtubule complex.

The cell membrane of the unicellular algae Distigma proteus is associated with arrays of parallel microtubules. Fragments of the membrane-microtubule complex have been isolated and partially purified. The microtubules were stable in vitro at room temperature as well as at 0 degree C, but were specifically and rapidly disassembled by Ca2+. After removal of all endogenous microtubules, the membrane-microtubule complex could be reassembled from brain microtubule protein and denuded Distigma membrane fragments. The readded microtubules bound in a fixed orientation, and only to those regions of membrane that are normally associated with microtubules in vivo.

Calcium↗
PubMed1983

Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome.

The inheritance of two restriction fragment length polymorphisms (RFLPs) on the short arm of the human X chromosome has been studied relative to Duchenne muscular dystrophy. This provides a partial genetic map of the short arm of the human X chromosome between Xp110 and Xp223. The data were derived from the segregation between a RFLP located at Xp21-Xp223, the DMD locus, and a RFLP located at Xp110-Xp113. The genetic distance from Xp110 to Xp223 was found to be approximately 40 centimorgans (cM). This provides experimental confirmation that 1cM corresponds to approximately 1,000 kilobase pairs of DNA for this region of the human X chromosome. Our data confirm that the DMD mutation lies between Xp223 and Xp110. The availability of flanking probes surrounding the DMD locus will assist in the ordering of further DNA sequences relative to the mutation.

Alleles↗