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Biomedical subjects

M J Dawson

Publications and source records attributed to M J Dawson.

At least 19 recordsLinked 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↗
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↗
PubMed1980

Studies of the biochemistry of contracting and relaxing muscle by the use of 31P n.m.r. in conjunction with other techniques.

When n.m.r. is applied to suitable chosen biological problems it yields a wealth of fundamental information unmatched by any other technique. By means of 31P n.m.r. we have studied intact living muscle at rest, during contraction and during recovery from contraction. Phosphocreatine, ATP, inorganic phosphate, phosphorylated intermediaries of glycolysis, pH and the binding of Mg2+ to ATP are observed directly in the spectra. From the spectra can be calculated the concentration of free ADP, the free energy change of ATP hydrolysis, the production of lactic acid and the total ATP turnover. Changes in these quantities can thus be followed continuously in vivo and we have shown how they are related to the decline in force development and to the slowing of relaxation that occur during fatigue. Similar methods have been applied to study the control of glycolysis.

Adenine Nucleotides↗
PubMed1978

Muscular fatigue investigated by phosphorus nuclear magnetic resonance.

Muscular fatigue has been studied using 31PNMR to measure the levels and rates of utilisation of several key metabolites and the free-energy change for ATP hydrolysis. Force development is closely correlated with metabolite levels and is proportional to the rate at which ATP is hydrolysed.

Adenosine Triphosphate↗
PubMed1977

Contraction and recovery of living muscles studies by 31P nuclear magnetic resonance.

1. Phosphorus nuclear magnetic resonance ((31)P NMR) can be used to measure the concentrations of phosphorus-containing metabolites within living tissue. We have developed methods for maintaining muscles in physiological condition, stimulating them and recording tension while at the same time accumulating their (31)P NMR spectra. Experiments were performed on frog sartorii and frog and toad gastrocnemii at 4 degrees C.2. The NMR signals from (31)P (the naturally occurring phosphorus) is weak, and signal averaging is required. In order to follow the time course of reactions it is necessary to maintain the muscles in a steady state for many hours while they are undergoing repeated contractions. Signals were accumulated in separate computer bins according to time after initiation of contraction. By these means spectra were obtained which corresponded to the different intervals during the contraction and recovery cycle.3. In the absence of stimulation, the spectra of frog sartorius muscles and of their extracts indicated concentrations of adenosine triphosphate (ATP), phosphoryl creatine (PCr), inorganic orthophosphate (P(i)) and sugar phosphates (sugar P) which are in reasonable agreement with the values obtained by chemical analysis.4. We have confirmed that unidentified resonances representing unknown compounds appear in the spectra of both frog and toad muscle; one of these is much larger in spectra from toad than from frog. We have found an additional small, unidentified resonance which appears to be specific to toad muscle.5. Spectra accumulated during actual contractions (1 s tetani every 2 min) did not differ dramatically from those accumulated throughout the 2 min cycle of contraction and partial recovery.6. Following 25 s tetanii, approximately 20% of the PCr had been hydrolysed; it was then rebuilt exponentially with a half-time of about 10 min. The increase in [P(i)] immediately after contraction and the time course of its disappearance corresponded to the changes in [PCr]. During the later half of the recovery period the concentration of P(i) was reduced to below that in resting muscle. The [sugar P] remained very high ( approximately 4 mmol kg(-1)) throughout the 56 min interval between contractions.7. When frog sartorii were tetanized for 1 s every 2 min, the changes in [PCr] and [P(i)] between contractions could not be observed because too little signal was obtained from these small muscles. However, when toad gastrocnemii were similarly stimulated, the changes in these compounds could be readily detected and were even greater than expected.8. The position of the P(i) resonance can be used to monitor intracellular pH and changes in pH. Under the conditions of our experiments the average intracellular pH in unstimulated frog sartorius muscles was 7.5. After a 25 s tetanus this was observed to move in the acid direction by a few tenths of a pH unit and to return to its pre-stimulation value before the end of the recovery period. After a 1 s contraction of toad gastrocnemius the environment of P(i) became slightly more alkaline for the first few seconds.

Adenosine Triphosphate↗
PubMed1975

Restoration of potassium-stimulated respiration of glycerol-treated muscle.

Agent that produced contracture in skeletal muscle, such as caffeine or K-depolarization, also caused an increased rate of oxygen consumption. Both of these functions are calcium dependent. In this study the respiratory response to K-depolarization and to caffeine was monitored in glycerol-treated and normal frog sartorius muscles. Although glycerol-treated muscle does not contract in response to K-depolarization, it does develop normal caffeine contractures. The respiratory response to both potassium and caffeine is greatly inhibited in glycerol-treated muscles. Pretreatment with dibutyryl cyclic AMP restored the respiratory response to normal levels in glycerol-treated muscle. Pretreatment with low levels of caffeine that had no effect on oxygen uptake markedly enhanced oxygen uptake with higher concentrations of caffeine and resulted in a normal respiratory response to K-depolarization even though there was no tension development. Caffeine had no effect on adenyl cyclase activity even at concentrations that markedly stimulated oxygen uptake. The data suggest that potassium stimulation of oxygen uptake in glycerol treated muscle is uncoupled by a defect in the formation of a cyclic nucleotide cofactor, rather than a defect in calcium influx.

Animals↗
PubMed1971

Cholinergic sensitivity: normal variability as a function of stimulus background.

The sensitivity of the normally innervated iris sphincter to its neuro-transmitter, acetylchloline, and to relatd agents varies inversely with the preexisting physiological stimulus background, that is, the environmental light intnsity. This normal variability suggests the existence of a negative feedback mechahnism whereby sensitivity of the effector cell is modutlated by a product of neuronal activity.

Acetylcholine↗