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Biomedical subjects

M J Dawson

Publications and source records attributed to M J Dawson.

At least 55 records · Page 3Linked to original sources
PubMed1992

A novel gene constitutively expressed in human lymphoid cells is inducible with interferon-gamma in myeloid cells.

A cluster of at least six interferon-gamma (IFN gamma)-inducible genes designated Ifi201-204 and located on mouse chromosome 1 has recently been described. Here, we report a human IFN-gamma-inducible gene, IFI 16, which has nucleotide sequence similarity with portions of two of the mouse genes, Ifi202 and Ifi204. A full-length cDNA clone derived from IFI 16 [2.709 kilobases (kb)] contained a single open reading frame of 2.187 kb which encoded a putative polypeptide of 729 amino acids and a predicted non-glycosylated M(r) of 80020. IFI 16 mRNA was found to be constitutively expressed in lymphoid cells and in cell lines of both the T and B lineages. By contrast, the mRNA was not expressed by the cell lines HL-60, U937, and K562, which represent early stages of myeloid development, but was strongly inducible in HL-60 and U937 with IFN-gamma. The IFI 16 protein demonstrated a putative domain structure with patchy similarity to the proteins expressed from genes Ifi202 and Ifi204. The mouse and human proteins each contain two analogous approximately 200 amino acid domains which are imperfect copies, but IFI 16 demonstrated additional unique regions, including a Lys-rich N-terminal portion and a "spacer" region between the reiterated domains, analogous to spacer regions in the CD5 and CD8 alpha molecules. Using a panel of inter-species somatic cell hybrid cell lines, IFI 16 was localized to the chromosomal region 1q12----1qter, a region syntenic between mouse and man. DNA blotting indicated that, in contrast to the mouse, IFI 16 is present as a single copy gene in the human genome.

Amino Acid Sequence↗
PubMed1992

Resolution of 4-amino-cyclopentanecarboxylic acid methyl esters using hydrolytic enzymes.

A number of esterases (EC 3.1.1.1) and lipases (EC 3.1.1.3) of microbial and mammalian origin were screened for the ability to resolve racemic 4-amino-cyclopentanecarboxylic acid methyl ester derivatives as potential intermediates in the production of carbocyclic nucleosides. Surprisingly, functionalization of the remote amino group had a profound effect on both the rate and enantioselectivity of hydrolysis of the methyl ester. 4-(Benzoylamino)-2-cyclopentenecarboxylic acid, methyl ester (V) with pig liver esterase gave the highest enantioselectivity. The residual ester, which was of the correct absolute stereochemistry [(+) 1S, 4R] for carbocyclic nucleoside synthesis, could be obtained in high optical purity. Optimization of pH, solvent type, and concentration improved the enantioselectivity of the process by a further twofold.

Animals↗
PubMed1992

The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity.

During the screening of fungi for inhibitors of squalene synthase, Phoma sp. C2932 was found to produce three structurally related novel inhibitors. These compounds, designated the squalestatins, exhibited potent activity against both mammalian (rat liver) and fungal (Candida albicans) squalene synthase. Furthermore, they also had broad spectrum in vitro antifungal activity.

Animals↗
PubMed1990

Biochemical evaluation of endometrial biopsies by magnetic resonance spectroscopy--preliminary data.

Biochemical study of tissue biopsy samples by magnetic resonance spectroscopy involves relatively small capital and running costs and could become a routine diagnostic or screening procedure if its utility were to be adequately demonstrated. We have demonstrated feasibility of evaluation of endometrial biopsy samples by magnetic resonance previous to histopathologic examination. Preliminary comparisons of magnetic resonance spectra with histopathologic evaluation indicates that in at least some instances, magnetic resonance may be the more sensitive indicator of disease.

Biopsy↗
PubMed1989

Phosphorus 31 nuclear magnetic resonance examination of female reproductive tissues.

Nuclear magnetic resonance spectroscopy is a powerful method of investigating the relationship between metabolism and function in living tissues. We present evidence that the phosphorus 31 spectra of myometrium and placenta are functions of physiologic state and gestational age. Specific spectroscopic abnormalities are observed in association with disorders of pregnancy and gynecologic diseases. Our results suggest that noninvasive nuclear magnetic resonance spectroscopy examinations may sometimes be a useful addition to magnetic resonance imaging examinations, and that nuclear magnetic resonance spectroscopy of biopsy specimens could become a cost-effective method of evaluating certain biochemical abnormalities.

Biopsy↗
PubMed1989

Phosphorus-31 nuclear magnetic resonance spectroscopy of toad retina.

Phosphorus-31 nuclear magnetic resonance (31P-NMR) spectra were obtained from living toad retinae and toad retinal extracts at 4 degrees C. Several phosphorus metabolites--nucleoside di- and triphosphates (NTP), phosphocreatine, phosphodiesters, inorganic phosphate, and phosphomonoesters--were identified from the spectra of whole retinae. The intracellular pH was determined to be 7.27 +/- 0.06 at 4 degrees C and the intracellular MgNTP/NTP ratio was at least 0.77. These results are consistent with those reported by other techniques, and they show that 31P-NMR spectroscopy can be used for noninvasively and quantitatively studying the metabolism of living toad retinae, and for monitoring its changes over time.

Animals↗
PubMed1988

The relation between muscle contraction and metabolism: studies by 31P nuclear magnetic resonance spectroscopy.

We have used 31P nuclear magnetic resonance spectroscopy (31PNMRS) to study the relation between metabolism and contraction in frog skeletal muscle. Our results show a close association between [H2PO4(1-)] and both contractile and metabolic characteristics of muscle. We suggest that this metabolite links energy requiring to energy yielding function by participating in intermediate reactions which help to determine the rates of both processes. The observed relation between [H2PO4(1-)] and force production is consistent with the suggestion of Hibberd and colleagues, that Pi is reversibly released during the transition to the major force-producing actomyosin ATPase state. Our results also suggest that force fatigue is due to the buildup of the [H2PO4(1-)] product of ATP hydrolysis and that the effect of pH on force production is largely the result of altering H2PO4(1-)/HPO4(2-). We have found that it is the extent of glycogenolysis rather than the maximum activities of glycogenolytic enzymes that determines how much glycogen is broken down following anaerobic contraction. The most likely explanation for our results is that the ATP-forming reactions of glycolysis come to equilibrium during metabolic recovery from contraction under anaerobic conditions.

Animals↗
PubMed1985

The effects of pregnancy and parturition on phosphorus metabolites in rat uterus studied by 31P nuclear magnetic resonance.

Concentrations of phosphorus metabolites and intracellular pH have been measured in non-pregnant, late-pregnant and post-partum rat uterus using 31P nuclear magnetic resonance (31P n.m.r.). Intact uterine tissue was superfused with oxygenated de-Jalon solution at 4, 20 or 37 degrees C while inside the n.m.r. spectrometer. The phosphocreatine concentration [PCr], was higher and the inorganic phosphate concentration [Pi], lower than values determined by chemical analysis of extracts from both pregnant and non-pregnant rat uterus. [PCr] was 1.4-fold greater in late-pregnant than in non-pregnant rat uterus. Following parturition, large changes were observed in [PCr], [Pi] and in an unidentified metabolite in the phosphomonoester (PME) region of the n.m.r. spectrum. The time course of the recovery of these metabolites to prepregnant values was determined. The [PCr] remained below the non-pregnant value for at least 1 week post-partum and the [Pi] was elevated, compared to the non-pregnant value, during this period. More rapid changes were seen in the [PME], which doubled on day 0 post-partum but almost returned to its non-pregnant value on day 1 post-partum. No significant difference was observed between intracellular pH values in late-pregnant and non-pregnant rat uterus; however, there was a large acid shift following parturition. Intracellular pH depended upon the temperature at which the tissue was maintained. The effect of muscular work during parturition was investigated by comparing Caesarian-sectioned uteri with uteri which had undergone normal parturition. Uteri examined 1 day after Caesarian operation showed no differences in metabolite levels from normal, 1 day post-partum uteri. We conclude that concentrations of phosphorus metabolites depend upon the physiological state of the uterus. We suggest that the changes following parturition are not a consequence of the mechanical work performed by the uterus, but must be caused by some other event associated with parturition such as hormonal changes.

Animals↗
PubMed1984

31P NMR studies of resting muscle in normal human subjects.

Study of human tissues using 31P topical Magnetic Resonance is completely atraumatic; it allows simultaneous measurement of the concentrations of many important metabolites and of intracellular pH. In some critical situations, TMR yields more accurate results than those obtained by chemical analysis of tissue biopsies. We have shown that TMR can be calibrated to obtain quantitative measurements in human subjects. We have also shown that theories of control of glycolysis based on regulation by key metabolites of rate-limiting enzymes are inconsistent with the observed changes in intact muscle.

Adenosine Triphosphate↗
PubMed1984

Effects of facial screening and blindfold on self-injurious behavior.

Previous research has demonstrated that a variety of maladaptive behaviors in children can be suppressed by facial screening. The effectiveness of various screening procedures for reducing self-injurious behaviors were compared in three experiments using alternating treatments designs. In Experiments 1 and 2, an immediate substantial response reduction occurred with facial screening in which visual blocking was present but not when visual blocking was absent. In Experiment 3, both facial screening with visual blocking and a blindfold procedure proved equally effective in reducing self-injury but for practical reasons, therapists preferred to use facial screening.

Adult↗
PubMed1983

Non-invasive investigation of cerebral metabolism in newborn infants by phosphorus nuclear magnetic resonance spectroscopy.

Intracellular metabolism in the brains of seven infants, born at 33-40 weeks' gestation and aged 44 h to 17 days, was studied on fourteen occasions by phosphorus nuclear magnetic resonance spectroscopy (31P NMRS). The characteristic spectral peaks of ATP, phosphocreatine (PCr), phosphodiesters, and inorganic orthophosphate (Pi) were always detected, together with a large peak attributed mainly to ribose-5-phosphate. The ratio of PCr to Pi NMRS signals (which are related to concentration) in one infant thought to have a normal brain was 1.7. In three infants who had severe birth asphyxia the PCr/Pi ratio ranged from 0.2 to 1.0 but increased as their clinical condition improved: infusions of mannitol solution caused a rapid increase in the ratio on four occasions in two of these infants. The PCr/Pi ratio was 1.4 in an infant with congenital cerebral atrophy and 0.7 in an infant with meningitis. Grossly abnormal 31P spectra antedated the detection by ultrasound of large porencephalic cysts in two infants. No systematic changes in intracellular pH (calculated from the chemical shift of the Pi resonance) were observed: the mean value for all observations was 7.2 +/- SD 0.1 (n = 14).

Adenosine Triphosphate↗
PubMed1981

Respiration-linked proton translocation in the obligate methylotroph Methylophilus methylotrophus.

The stoicheiometries of respiration-linked proton translocation in Methylophilus methylotrophus were determined by using both the oxygen-pulse and initial-rate methods. The latter has also been used to determine leads to charge/O quotients (measured as yield K+/O quotients) in order to ascertain whether the leads to H+/O quotients might be underestimated by H+/anion symport. The results suggest that 6H+/O are translocated during NADH oxidation, and that 2H+/O are translocated during the oxidation of methanol to formaldehyde. There was no evidence for underestimation of the leads to H+/O quotients due to H+/anion symport, except by the movement of formic acid during formate oxidation. By comparing these results with the known growth efficiencies of this organism, an leads to H+/ATP quotient of close to 2 g-ions of H+/mol of ATP can be calculated. It is proposed that the respiratory chain in Methylophilus methylotrophus is arranged such that there are three sites of energy conservation for NADH oxidation, each translocating 2H+ and each linked to the synthesis of one molecule of ATP. Only the third site of energy conservation is involved in methanol oxidation.

Electron Transport↗
PubMed1981

The activity of creatine kinase in frog skeletal muscle studied by saturation-transfer nuclear magnetic resonance.

1. The activity of creatine kinase in intact anaerobic frog muscle at 4 degrees C at rest and during contraction was investigated by using saturation-transfer 31P n.m.r. 2. At rest, the measured forward (phosphocreatine to ATP) reaction flux was 1.7 X 10(-3) M . s-1 and the backward flux was 1.2 X 10(-3) M . s-1. The large magnitude of both fluxes shows that creatine kinase is active in resting muscle, so the observed constancy of [phosphocreatine] demonstrates that the enzyme and its substrates are at equilibrium. 3. The apparent discrepancy between the fluxes must arise largely from an underestimation of the backward flux resulting from interaction of ATP with other systems, e.g. via adenylate kinase. For purposes of further calculation we have therefore adopted 1.6 X 10(-3) M . s-1 as an estimate of both fluxes. 4. During contraction, when the creatine kinase reaction is no longer at equilibrium, the net rate of phosphocreatine breakdown, estimated directly from the change in area of the inorganic phosphate peak, was 0.75 X 10(-3) M . s-1. Saturation transfer indicates that the forward reaction flux remains at approx. 1.6 X 10(-3) M . s-1 and the backward flux decreases to about 0.85 X 10(-3) M . s-1. 5. The activity of creatine kinase during contraction is large enough to account for the well-established observation that, during contraction, the concentration of ATP falls by less than 2-3%. The reaction catalysed by creatine kinase is driven forward during contraction by the large relative increase in the concentration of free ADP, which is more than doubled. 6. The observation that the forward flux does not increase during contraction and that the backward flux decreases can most simply be explained on the basis of competition of reactants for a limited amount of enzyme.

Adenosine Triphosphate↗
PubMed1981

The effects of physical restraint on self-injurious behaviour.

Two experiments investigated the effects of two durations (one and three minutes) of physical restraint on the rate of self-injurious behaviour of a profoundly retarded girl. In the first experiment, a reversal design was used in which three-minute and one-minute restraint conditions were used sequentially. In the second experiment, an alternating treatments design was used in which the two conditions were alternated within the same experimental phase. Physical restraint was made contingent on each instance of SIB during experimental sessions. In the first experiment, with the introduction of three-minute restraint phase SIB increased to a rate high than baseline. However, it was reduced to near-zero levels during the one-minute restraint phase when it followed the three-minute phase. Although three-minute restraint did reduce the rate of SIB in the second experiments, it was found that one-minute restraint was more effective. In both experiments one-minute restraint was found to be more effective than three-minute restraint in reducing the rate of SIB.

Adolescent↗