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Biomedical subjects

D G Ferguson

Publications and source records attributed to D G Ferguson.

At least 19 recordsLinked to original sources
PubMed1992

Whiplash and its effect on the visual system.

Whiplash or indirect injuries to the neck as a consequence of motor vehicle collisions are a common occurrence in which the frequency of ocular complications is largely unknown. Ophthalmic and oculomotor function was investigated in a longitudinal study of 39 cases who had their initial ophthalmological assessment within one week of the whiplash injury. Ten of 39 cases had ocular symptoms and signs which developed shortly after the accident. The principal abnormality in 6 of these was decreased convergence and accommodation, superior oblique muscle paresis in 2, decreased stereoacuity in 1 and bilateral vitreous detachments in 1 patient. All but 2 had complete resolution of their symptoms within 9 months. Four other patients were asymptomatic but had ophthalmic signs which resolved within 3 months. Oculomotor abnormalities following whiplash injuries are generally mild, have a good prognosis, and would appear from this study to be commoner than hitherto expected.

Accidents, Traffic↗
PubMed1992

Mouse phospholamban gene expression during development in vivo and in vitro.

To establish a murine model that may allow for definition of the precise role of phospholamban in myocardial contractility through selective perturbations in the phospholamban gene, we initiated studies on the role of phospholamban in the murine heart. Intact beating hearts were perfused in the absence or presence of isoproterenol, and quantitative measurements of cardiac performance were obtained. Isoproterenol stimulation was associated with increases in the affinity of the sarcoplasmic reticulum Ca2+ pump for Ca2+ that were due to phospholamban phosphorylation. To assess the regulation of phospholamban gene expression during murine development, Northern blot and polymerase chain reaction analyses were used. Phospholamban mRNA was first detected in murine embryos on the ninth day of development (the time when the cardiac tube begins to contract). In murine embryoid bodies, which have been shown to recapitulate several aspects of cardiogenesis, phospholamban mRNA was detected on the seventh day (the time when spontaneous contractions are first observed). Only those embryoid bodies that exhibited contractions expressed phospholamban transcripts, and these were accompanied by expression of the protein, as revealed by immunofluorescence microscopy. Sequence analysis of the cDNA encoding phospholamban in embryoid bodies indicated complete homology to that in adult hearts. The deduced amino acid sequence of murine phospholamban was identical to rabbit cardiac phospholamban but different from dog cardiac and human cardiac phospholamban by one amino acid. These data suggest that phospholamban, the regulator of the Ca(2+)-ATPase in cardiac sarcoplasmic reticulum, is present very early in murine cardiogenesis in utero and in vitro, and this may constitute an important determinant for proper development of myocardial contractility.

Amino Acid Sequence↗
PubMed1991

Regulation of rat cardiac nuclei-associated Mg(2+)-NTPase by phosphorylation.

A nucleoside triphosphatase (NTPase) activity appeared to be associated with a highly purified nuclear preparation from rat cardiac ventricles. Different nucleoside triphosphates (UTP greater than GTP greater than ITP greater than CTP) supported this enzymic activity, which was stimulated by Mg2+ but not by Ca2+. The nuclear NTPase activity could be down regulated by endogenous phosphorylation of a 55,000 Mr protein. Maximal phosphorylation of the 55,000 Mr protein occurred in the presence of Mg(2+)-ATP. Addition of cAMP, cGMP, Ca2+, Ca2+/phospholipid, Ca2+/calmodulin, and catalytic subunit of cAMP-dependent protein kinase was not associated with any further phosphorylation of the 55,000 Mr protein. However, in the presence of Ca2+/calmodulin or the catalytic subunit of the cAMP-dependent protein kinase additional proteins became phosphorylated, but these had no effect on the Mg(2+)-NTPase activity. These results indicate that a protein with Mr 55,000 may be involved in the regulation the Mg(2+)-NTPase activity associated with rat cardiac nuclei.

Animals↗
PubMed1990

A 70-kDa apolipoprotein designated ApoJ is a marker for subclasses of human plasma high density lipoproteins.

A new apolipoprotein, termed apolipoprotein J (apoJ), was purified from human plasma by immunoaffinity chromatography. ApoJ is a glycoprotein consisting of disulfide-linked subunits of 34-36 and 36-39 kDa. Each subunit is glycosylated and has a pI range of 4.9-5.4. ApoJ exists in the plasma associated with high density lipoproteins (HDL) and specifically with subclasses of HDL which also contain apoAI and cholesteryl ester transfer protein activity. Immunoaffinity purified apoJ-HDL subclasses have apparent molecular masses of 80, 160, 240, 340, and 520 kDa, as determined by gradient gel electrophoresis. By negative staining electron microscopy, apoJ-HDL range in diameter from 5 to 16 nm. Fractionation of plasma by vertical gradient density centrifugation revealed apoJ-HDL in HDL2 (d 1.063-1.125 g/ml) with the majority overlapping HDL3 (d 1.125-1.21 g/ml) and very high density lipoprotein (d 1.21-1.25 g/ml). The bimodal density distribution of apoJ-HDL suggests that these subclasses have a unique metabolic relationship and may play a role in the transport of cholesterol from peripheral tissues to the liver.

Antibodies, Monoclonal↗
PubMed1990

Functional reconstitution of the cardiac sarcoplasmic reticulum Ca2(+)-ATPase with phospholamban in phospholipid vesicles.

The Ca2(+)-ATPase in cardiac sarcoplasmic reticulum (SR) is under regulation by phospholamban, an oligomeric proteolipid. To determine the molecular mechanism by which phospholamban regulates the Ca2(+)-ATPase, a reconstitution system was developed, using a freeze-thaw sonication procedure. The best rates of Ca2+ uptake (700 nmol/min/mg reconstituted vesicles compared with 800 nmol/min/mg SR vesicles) were observed when cholate and phosphatidylcholine were used at a ratio of cholate/phosphatidylcholine/Ca2(+)-ATPase of 2:80:1. The EC50 values for Ca2+ were 0.05 microM for both Ca2+ uptake and Ca2(+)-ATPase activity in the reconstituted vesicles compared with 0.63 microM Ca2+ in native SR vesicles. Inclusion of phospholamban in the reconstituted vesicles was associated with a significant inhibition of the initial rates of Ca2+ uptake at pCa 6.0. However, phosphorylation of phospholamban by the catalytic subunit of the cAMP-dependent protein kinase reversed the inhibitory effect on the Ca2+ pump. Similar findings were observed when a peptide, corresponding to amino acids 1-25 of phospholamban, was used. These findings indicate that phospholamban is an inhibitor of the Ca2(+)-ATPase in cardiac SR and phosphorylation of phospholamban relieves this inhibition. The mechanism by which phospholamban inhibits the Ca2+ pump is unknown, but our findings with the synthetic peptide suggest that a direct interaction between the Ca2(+)-ATPase and the hydrophilic portion of phospholamban may be one of the mechanisms for regulation.

Animals↗
PubMed1989

Structural characterization of phospholamban in cardiac sarcoplasmic reticulum membranes by cross-linking.

The native form of phospholamban in cardiac sarcoplasmic reticulum membranes was investigated using photosensitive heterobifunctional cross-linkers, both cleavable and noncleavable, and common protein modifiers. The photosensitive heterobifunctional cleavable cross-linker ethyl 4-azidophenyl-1, 4-dithiobutyrimidate was used in native SR vesicles and it cross-linked phospholamban into an apparent phospholamban-phospholamban dimer and into an approximately 110,000-Da species. The phospholamban dimer migrated at approximately 12,000 Da on sodium dodecyl sulfate-polyacrylamide gels, and upon cleavage of the cross-linker before electrophoresis the dimer disappeared. The approximately 110,000-Da cross-linked species was not affected by boiling in sodium dodecyl sulfate prior to electrophoresis. This cross-linked form of phospholamban migrated approximately 5500 Da above the Ca2(+)-ATPase, which was visualized using fluorescein 5'-isothiocynate, a fluorescent marker that binds specifically to the Ca2(+)-ATPase. p-Azidophenacyl bromide, iodoacetic acid, and N-ethylmaleimide, all of which react with sulfhydryl groups, were also employed to further characterize phospholamban in native sarcoplasmic reticulum membranes. Cross-linking with p-azidophenacyl bromide resulted in only monomeric and dimeric forms of phospholamban as observed on sodium dodecyl sulfate-polyacrylamide gels. Iodoacetic acid and N-ethylmalemide were found to be effective in disrupting the pentameric form of phospholamban only when reacted with sodium dodecyl sulfate solubilized sarcoplasmic reticulum. In view of these findings, the amino acid sequence of phospholamban was examined for possible protein-protein interaction sites. Analysis by hydropathic profiling and secondary structure prediction suggests that the region of amino acids 1-14 may form an amphipathic alpha helix and the hydrophobic surface on one of its sites could interact with the reciprocal hydrophobic surface of another protein, such as the Ca2(+)-ATPase.

Amino Acid Sequence↗
PubMed1988

The Ca2+ ATPase content of slow and fast twitch fibers of guinea pig.

The Ca ATPase content in the sarcoplasmic reticulum (SR) of fast and slow twitch skeletal fibers was estimated using two well-characterized muscles of the guinea pig: the white bundle of the vastus lateralis and the soleus. Ca ATPase surface density was determined by counting the projections of individual molecules revealed on the cytoplasmic surface of freeze-dried, rotary-shadowed microsomal vesicles isolated from the two muscles. The Ca ATPase densities were 32,000/micron 2 and 25,000/micron 2 for the vastus lateralis and soleus muscles, respectively. The percentage of membrane area occupied by Ca ATPase-free lipid patches was estimated using freeze-fractured, rotary-shadowed in situ SR. In soleus muscle the free SR of terminal cisternae and the longitudinal SR have 34.5 and 19.7% of their surface free of ATPase, respectively. In the white vastus less than 1% of the surface was not occupied by Ca ATPase. These values were combined with stereological data from the literature to give a ratio of total Ca ATPase content per unit fiber volume of 1:2, slow versus fast. This is considerably less than the approximately sixfold difference in the overall relaxation time and the half times to relaxation between the two fiber types. This suggests that other factor such as differences in enzyme kinetics or cytoplasmic Ca buffering proteins must also play a role in determining rate of relaxation.

Animals↗
PubMed1988

Discrimination between fast- and slow-twitch fibres of guinea pig skeletal muscle using the relative surface density of junctional transverse tubule membrane.

The black reaction of Golgi was used to infiltrate transverse (T) tubules in fast-twitch glycolytic (FW), fast-twitch oxidative-glycolytic (FR) and slow-twitch (S) type fibres in muscles of guinea pigs. Non-junctional (fT) and junctional (jT) segments of the T-tubule network are clearly demarcated by this technique. Digitized planimetry and direct measurements were used to determine the proportion of T-tubule network forming junctions with the sarcoplasmic reticulum (%LjT) and to estimate the surface density (surface area per fibre volume) of total and junctional T membrane. From these data, the volume density (number per fibre volume) of junctional feet was calculated. All three types of fibres have approximately equal surface density of T tubules, but the FW and FR fibres have a much higher proportion of jT. The calculated volume density of feet is twice as high in fast-twitch as in slow-twitch fibres.

Animals↗
PubMed1988

Mallet finger: a trial of two splints.

Over a period of twelve months, 116 cases of mallet finger were allocated randomly to treatment with either a Stack or Abouna splint. The two splints were equally effective, producing a cure or a significant improvement in approximately 50% of cases. However, the Stack splint was much preferred by the patients, who found it more comfortable, more robust and easier to keep clean.

Adult↗
PubMed1988

Mallet finger: comparison between operative and conservative management in those cases failing to be cured by splintage.

Sixty-nine patients with mallet finger who failed to be cured by a period of splintage were offered either tenodermodesis or Kirschner wire fixation of the DIP joint. Eleven (16%) accepted the offer and eight of these were significantly improved. Of those patients declining surgery, 30 were available for review after a minimum period of six months; of these 13 (43%) had undergone a significant spontaneous improvement.

Bone Wires↗
PubMed1988

Localization of phospholamban in smooth muscle using immunogold electron microscopy.

Phospholamban, the putative regulator of the Ca2+-ATPase in cardiac sarcoplasmic reticulum, was immunolocalized in canine visceral and vascular smooth muscle. Gently disrupted tissues were labeled with an affinity-purified phospholamban polyclonal antibody and indirect immunogold, using preembedding techniques. The sarcoplasmic reticulum of smooth muscle cells was specifically labeled with patches of immunogold distributed in a nonuniform fashion, while the sarcolemma did not appear to contain any phospholamban. The outer nuclear envelopes were also observed to be heavily labeled with the affinity-purified phospholamban polyclonal antibody. These findings suggest that phospholamban may play a role in the regulation of cytoplasmic and intranuclear calcium levels in smooth muscle cells.

Animals↗
PubMed1987

Acute management of the self-cutter.

'Self-cutting' is a specific type of emergency presenting to accident and emergency departments. All cases presenting in Sheffield in a 6-month period were studied. The self-cutter is most often a young, unemployed man: this is the group most likely to cut repeatedly. At least 45% of all cutters had a past psychiatric history, and a quarter of them were judged a high suicidal risk. The seriousness of the physical injury and the suicidal risk cannot be simply correlated. The crucial part of acute management is the decision about psychiatric referral. As with a complex physical injury, formal assessment must be performed and specialist referral made on that basis.

Adult↗