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Biomedical subjects

D R Phillips

Publications and source records attributed to D R Phillips.

At least 235 records · Page 13Linked to original sources
PubMed1980

Biochemical studies of two patients with the gray platelet syndrome. Selective deficiency of platelet alpha granules.

The biochemistry of platelets from two unrelated patients with the gray platelet syndrome, a deficiency of platelet alpha-granules, has been evaluated. Ultrastructural studies of their platelets revealed the number of alpha-granules to be less than 15% of normal, whereas the number of dense bodies was within normal limits. Platelets from both patients had severe deficiencies of platelet factor 4 and beta-thromboglobulin (less than 10% of normal). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a marked deficiency of thrombin-sensitive protein in both patients. Analysis of the platelet-derived growth factor in one patient showed it was also markedly reduced. Levels of lysosomal enzymes, adenine nucleotides, serotonin, and catalase, and conversion of arachidonic acid by the lipoxygenase and cyclo-oxygenase enzymes, were within normal limits. The results provide important evidence to define the contents of alpha-granules and to differentiate these contents from the contents of lysosomal granules, dense bodies, and peroxisomes. Functional studies of these platelets showed deficiencies in ADP, thrombin, and collagen aggregation. The results suggest that alpha-granules or their contents make a contribution to normal platelet aggregation.

Acid Phosphatase↗
PubMed1980

Spatial patterns of surgery attendance: some implications for the provision of primary health care.

The results from a survey of the use of general practitioner services are discussed to illustrate variations in patterns of surgery attendance. These patterns were partly influenced by factors such as social status and personal mobility of respondents. Age of respondents did not cause much differentiation of patterns but respondents were often found to be maintaining contact with practices in areas in which they previously lived, even where this involved travelling considerable distances. The implications of these findings are considered, given current tendencies to centralize primary care services, particularly into neighbourhood health centres.

Attitude to Health↗
PubMed1979

alpha-Actinin deficiency in thrombasthenia: possible identity of alpha-actinin and glycoprotein III.

Blood platelets contain a variety of contractile protein species, including the glycoprotein alpha-actinin, which is found at the Z disc in skeletal muscle cells. In the present study, we have considered the possibility that alpha-actinin might be one of several previously described platelet surface glycoproteins. Purified anti-alpha-actinin antibody was found to react strongly with partially purified platelet glycoprotein III, weakly with platelet glycoprotein IIb, and not at all with platelet glycoproteins Ib and IV. Platelets from three siblings with thrombasthenia, a disorder characterized by severe deficiency of platelet glycoproteins IIb and III, were found also to be equally deficient in alpha-actinin. These findings indicate that alpha-actinin and glycoprotein III are identical and suggest that this protein may be an anchor point for actin on the inside of the membrane. Combined with ultrastructural studies of normal and thrombasthenic platelets, the new findings provide a clearer understanding of contraction in single cells and small aggregates.

Actinin↗
PubMed1978

A defined molecular-weight distribution of deoxyribonucleic acid after extensive sonication.

Concentrated solutions of low-molecular-weight DNA (Mw=35000) with a known molecular-weight distribution can be prepared in several hours, and require no additional fractionation procedures. This is achieved by sonication of the DNA in 1.0 M-NaCl at high power at 0--2 degrees C. No denaturation of the DNA is detectable, even after 8h of continuous sonication. After 2h, the molecular-weight distribution of the total DNA sample is that of the most probably Schulz distribution, described by-Mn:-Mw:-Mz ...=1:2:3 ...etc. Such a molecular-weight distribution is expected for a random break-up of indefinitely long macromolecules and indicates that the sonication process is essentially by random double-strand scission. DNA was also sonicated in the presence of ligands capable of modifying the DNA tertiary structure. The results support the idea that inflexibility of the DNA is required for efficient sonic degradation.

Chromatography, Gel↗
PubMed1978

Thrombin-induced platelet aggregation is mediated by a platelet plasma membrane-bound lectin.

Throbin-activated human platelets cause agglutination of trypsinized, formalinized bovine erythrocytes. This lectin activity of stimulated platelets was blocked by galactosamine, glucosamine, mannosamine, lysine, and arginine, but not by N-acetylated sugars, other neutral sugars, or other amino acids. Inhibitors of the thrombin-induced lectin activity also blocked thrombin-induced platelet aggregation. It appears that a membrane surface component that has lectin activity mediates platelet aggregation.

Agglutinins↗
PubMed1978

The interaction of daunomycin with polydeoxynucleotides.

The ability of daunomycin to bind to various DNA polymers has been sutided by thermal denaturation, spectrophotometric analysis and inhibition of the polymerisation reactions catalysed by Escherichia coli DNA polymerase I and rat liver DNA polymerase alpha. The quantitative binding measurements revealed that the antibiotic binds tightly to all synthetic polydeoxynucleotides studied. The results demonstrated that daunomycin can bind with equal affinity to dG . dC or dA . dT basepaired sequences. However, the number of binding sites per nucleotide for poly(dA) . poly(dT) is significantly lower than that found for poly(dA-dT) . poly(dA-dT), thus indicating an appreciable preference of the drug for the alternating copolymer. The inactivation of the template properties of the synthetic DNA polymers in the DNA polymerase system is consistent with their daunomycin binding ability. However, a lack of correlation was observed between the drug binding ability of different DNA polymers and the binding-induced stabilisation of the double helix to heat denaturation.

Animals↗
PubMed1977

Ca2+-dependent protease in human platelets. Specific cleavage of platelet polypeptides in the presence of added Ca2+.

A pronounced Ca2+-dependent protease in lysed platelets was detected by the hydrolysis of an added substrate, azocasein. This protease also catalyzed the cleavage of endogenous platelet polypeptides which was demonstrated by the disappearance of four high molecular weight polypeptides (greater than 200,000) either by adding Ca2+ to lysed platelets or by increasing the cytoplasmic Ca2+ within intact platelets with the ionophore A 23187. In both cases, lower molecular weight cleavage products were clearly identified. The caseinolytic activity as well as the cleavage of the high molecular weight polypeptides was inhibited by sulfhydryl reagents, but not by reagents reacting with trypsin-like proteases. Because of the similarity between this Ca2+-dependent protease and myofibrillar Ca2+-dependent protease (CAF), we have termed the former "platelet CAF".

Blood Platelets↗
PubMed1977

Thermodynamics of the interaction of daunomycin with DNA.

The association constant for the interaction of daunomycin with DNA was determined as a function of temperature (using [3H] daunomycin in conventional equilibrium dialysis cells) and ionic strength (using a spectrophotometric titration method). The association constant varied between 3.1 X 10(-6) M(-1) (4 degrees C) and 3.9 X 10(5) M(-1) (65 degrees C). The free energy change was -8.2 to -8.8 kcal/mol, the enthalpy change -5.3 kcal/mol and the entropy change +10 to +11 eu, all values being consistent with that expected of an intercalation process. The apparent number of intercalation sites detected (0.15 to 0.16 per nucleotide) was independent of temperature. The large positive entropy change accompanying the interaction appears to be due to extensive release of water from the DNA and daunomycin. The apparent number of binding sites increased dramatically with decrease of ionic strength, although the apparent association constant remained largely unaffected by ionic strength.

Animals↗