Biomedical subjects
A J Jones
Publications and source records attributed to A J Jones.
Effect of microheterogeneity on the structure and function of the myelin basic protein.
The basic protein is a major component of central nerve myelin containing species with varying amounts of phosphorylation and deamidation in situ. Components of basic protein were separated on the basis of net charge. Differences in ionic interactions of components of basic protein in a two-phase partition system with beef brain phosphatidyl serine were small, but there was a tendency for less charged components to require less lipid to achieve the same degree of solubilization into the chloroform phase. Spectroscopic properties of the components were identical using the following techniques: far ultraviolet circular dichroism, difference ultraviolet spectroscopy, fluorescent determination of tyrosine pK values and fluorescence energy transfer. At alkaline pH transfer from Trp to Tyr O- was 25% efficient which indicates that the closest accepting tyrosine is approx. 10 A away (the closest fluorescent tyrosine is over 20 A away). In 6 M guanidinium chloride this transfer was abolished while difference spectra indicated that the aromatic amino acids became more exposed in this solvent. These results show that the basic protein has definite secondary structure but that is not affected by the post-translation modifications.
AFP-screening for all?
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Measurement of choline concentration and transport in human erythrocytes by 1H NMR: comparison of normal blood and that from lithium-treated psychiatric patients.
Choline is known to accumulate in the erythrocytes of manic depressive psychotics who are treated with high doses of lithium. High field 1H spin-echo nuclear magnetic resonance was used to study human erythrocytes and measure the intracellular concentration of choline. Only 0.5 ml of cells are required and sample handing is minimal. The rate of uptake of choline was measured using a paramagnetic ferric ion complex to depress the resonance of the extracellular choline while observing the growth of the intracellular peak. The general applicability of these new observations and methods to the study and treatment regimes in manic depressive psychosis and schizo-affective disorders is discussed.
Effects of oxygen on pulmonary macrophages and alveolar epithelial type II cells in culture.
Cultures of Chinese hamster lung fibroblasts and explants of 20-day-old rat lungs were exposed to 95% oxygen with 5% CO2 in vitro. The Chinese hamster cells had stopped dividing after 17 hours exposure and cell death occurred at a mean time of 67 hours (s.d. 15 hours). The rat lung explants showed macrophages moving over a monolayer of alveolar type II epithelial cells. Both cell types appeared to function normally for 24 hours but cell division in the type II cells was about 50% of control between 12 and 24 hours of exposure and virtually ceased after 26 hours. Cell death commenced after 4 days and was complete in 9 days. Macrophages divided freely in the control cultures but only one division was seen during exposure to oxygen and that occurred during the first 24 hours. Motility was reduced by 50% during the second day of exposure and stopped during the 3rd day. No live macrophages were seen after 4 days exposure. These culture systems appear very suitable for screening drugs for their protective effect against oxygen toxicity.
Halothane does not inhibit human neutrophil function in vitro.
Various indices of function of neutrophils from normal healthy volunteers have been examined after in vitro exposure to halothane. Random free movement on glass was unaffected, but random migration through millipore filters was slightly increased. There was no significant change in migration in response to casein chemotaxis. Phagocytosis, degranulation and the enhanced non-mitochondrial respiration associated with phagocytosis were unaffected. Electron-microscopic appearance at 30 s after exposure to latex particles was normal in all respects.
Size and shape of the model lipoprotein complex formed between glucagon and dimyristoylglycerophosphocholine.
Glucagon forms water-soluble lipoprotein particles with dimyristoylglycerophosphocholine at temperatures below the phase-transition temperature of the lipid. The shape and size of this lipoprotein particle were studied by viscometry, sedimentation velocity, sedimentation equilibrium, quasielastic light scattering, and electron microscopy using both negative-staining and freeze-fracture techniques. The lipoprotein particle has an oblate ellipsoid shape with dimensions of 250 X 70 A and an approximate molecular weight of 1.4 X 106. This molecular weight is similar to that found for small unilamellar phospholipid vesicles but is achieved in the presence of glucagon without sonication. The shape of the glucagon lipoprotein particle is similar to that found for the complex formed between some serum apolipoproteins and dimyristoylglycerophosphocholine. From these data, a model for the glucagon-dimyristoylglycerophosphocholine is proposed consisting of a single bilayer of phospholipid with the glucagon incorporated into the bilayer structure in such a manner as not greatly to disturb the average area occupied per phospholipid molecule.
Interaction of the myelin basic protein with the anionic detergent sodium dodecyl sulphate.
The interaction of the myelin basic protein and two peptides derived from it with the anionic detergent SDS (sodium dodecyl sulphate) was studied. At molar ratios of detergent/protein of up to approx. 20:1 the transient increase in turbidity (as measured by increases in A230) is proportional to the ratio. Between ratios of 30:1 and 100:1 the effect of the detergent is constant and maximal. At molar ratios exceeding 100:1 the transient increase in turbidity decreases with increasing amounts of detergent. With increasing ionic strength the rapid development of turbidity is inhibited, whereas the slow decay of turbidity is not affected. Neither of the peptide fragments produced by cleavage of the myelin basic protein at the single tryptophan residue, nor both when mixed, produce measurable turbidity when mixed with SDS. Under similar conditions poly-L-lysine of similar molecular size to the basic protein shows the increase in turbidity but not the decay. The interaction between the protein and SDS is interpreted in molecular terms, which involve the initial ionic interaction of the detergent with protein resulting in aggregation and turbidity in the solution. Within the aggregated complexes molecules rearrange to maximize hydrophobic interactions.
Pressure enhancement of the depressant effect of halothane on cilial beat.
In order to test the applicability of the critical volume hypothesis of anaesthetic action to the side effects of anaesthesia, we have studied the pressure-anaesthetic interactions on cilial beat. The swimming speed of Tetrahymena pyriformis was determined at one and 137 atmospheres with 0 to 4 per cent halothane. The pressure and anaesthetic effects were synergistic with the halothane dose-response curve being shifted to the left and increased in slope at the high pressure, although high pressure alone had no significant effect. These results are contrary to the predictions of the critical volume hypothesis and appear to demarcate the narcotic effect of anaesthetics from the type of molecular interaction which is concerned in the effect on cilial beat.
Localization of sites for ionic interaction with lipid in the C-terminal third of the bovine myelin basic protein.
The myelin basic protein from bovine brain tissue was purified and the two peptides obtained by cleavage of the polypeptide chain at the single tryptophan residue were isolated. The interaction of these peptides and the intact basic protein with complex lipids was investigated by following the solubilization of lipid-protein complexes into chloroform in a biphasic solvent system. The C-terminal peptide fragment (residues 117-170) and the intact basic protein both formed chloroform-soluble complexes with acidic lipids, but not with neutral complex lipids. The N-terminal fragment (residues 1-115) did not form chloroform-soluble complexes with either acidic or neutral complex lipids. The molar ratio of lipid to protein that caused a 50% loss of protein from the upper phase to the lower chloroform phase was the same for the intact basic protein as for the smaller C-terminal peptide fragment. Phosphatidylserine and phosphatidylinositol were approximately twice as efficient as sulphatide at causing protein redistribution to the chloroform phase. The results are interpreted as indicating that the sites for ionic interactions between lipid and charged groups on the basic protein of myelin are located in the C-terminal region of the protein molecule.
Molecular interactions in the model lipoprotein complex formed between glucagon and dimyristoylglycerophosphocholine.
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Interaction of glucagon with dimyristoyl glycerophosphocholine.
Glucagon can form amphipathic helices and can interact with dimyristoyl glycerophosphocholine at temperatures below the phase transition leading to a shift in the fluorescence emission maximum of tryptophan from 350 to 338 nm and a 3-fold enhancement of fluorescence intensity as well as a change in the polarization of fluorescence. The circular dichroism properties of the lipid-associated glucagon indicates that it has an increased content of alpha-helix. The phase transition temperature of the lipid as monitored by pyrene excimer fluorescence is not altered by interaction with glucagon although at higher glucagon/lipid ratios a decrease in excimer formation is noted at low temperature. Above the phase transition temperature, the addition of lipid has no effect on the fluorescence emission or circular dichroism of glucagon. Thus this hormone can interact with dimyristoyl glycerophosphocholine and this interaction is stronger below the phase transition temperature than above it.
Lipoprotein complexes between glucagon and dimyristoylglycerophosphocholine (dimyristoyl phosphatidylcholine) [proceedings].
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Gastroenteritis causing failure of oral contraception.
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Trisomy 21 and trisomy 18 in half-siblings.
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The intrinsic fluorescence characteristics of the myelin basic protein.
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The early development of substrate-brooding cichlids (Teleostei: Cichlidae) with a discussion of a new system of staging.
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Interaction of divalent manganese ion with adenosine triphosphate and related compounds.
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