Radiological case of the month. Wilson's disease.
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Adult↗
Biomedical subjects
M T King
Publications and source records attributed to M T King.
Satisfaction with postnatal care--the choice of home or hospital.
This paper reports the findings of a study of client satisfaction with postnatal midwifery care. Women could choose one of two forms of care; either domiciliary care following early discharge, or hospital care until discharge. Consumers' perceptions of their postnatal care were examined at the end of the period of care. Women assessed the midwives' interest and caring, education and information provided, their own progress with feeding and baby care, and their own physical and emotional health. They were also asked about their expectations of and gains from postnatal care. The findings indicated that women choosing domiciliary care and women choosing hospital care had different expectations of their postnatal care, but were largely satisfied with the quality of the care they chose. The women who chose domiciliary care rated their postnatal care more highly than the women who stayed in hospital. The findings reinforce the importance of providing women with choices for the maternity care which best suits their needs.
Adult↗
The Newcastle study of snoring and sleep disordered breathing.
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Body Mass Index↗
A comparison of clinical assessment and home oximetry in the diagnosis of obstructive sleep apnea.
In order to determine whether measurement of arterial oxygen saturation (SaO2) could identify patients with obstructive sleep apnea (OSA), 98 consecutive patients referred for assessment of snoring and/or daytime somnolence were assessed clinically and then underwent both unsupervised oximetry in their homes and formal polysomnography. Clinical assessment identified patients with an apnea+hypopnea index (AHI) > or = 15 events per hour with a sensitivity of 79% and a specificity of 50%. Home oximetry analyzed by counting the number of arterial oxygen desaturations recorded was inferior to clinical assessment. For desaturations of 2% or more from baseline, desaturation index (DI) > or = 15 per hour identified patients with AHI > or = 15 with sensitivity 65% and specificity 74%; for 3% desaturations, sensitivity was 51% and specificity 90%; and for 4% desaturations, sensitivity was 40% and specificity 98%. From the oximetry data, the percentage of time spent at SaO2 below 90% (CT90) was also calculated. CT90 > or = 1% identified patients with AHI > or = 15 with sensitivity 93% and specificity 51%; for patients with AHI > or = 15 ultimately given nasal continuous positive airway pressure (CPAP), the sensitivity of a CT90 > or = 1% was 100%. We concluded that home oximetry with CT90 < 1% practically excludes clinically significant OSA. Conversely, home oximetry with DI > or = 15 for 4% desaturations makes OSA likely: the positive predictive value for OSA is 83% if the pretest probability of OSA is 30% and over 90% if the pretest probability is at least 50%.
Adult↗
Regulation of the purine salvage pathway in rat liver.
The regulation of purine metabolism in rat liver has been examined under conditions that alter the flux through the pathway. Rats were given intraperitoneal injections of ethanol, sodium acetate, or sodium phosphate to attain body water concentrations of approximately 70, 20, and 10 mM, respectively. The livers were freeze-clamped after 30 min, and extracts were made for the analysis of metabolites, cofactors, purine bases, and nucleosides; homogenates were made for the measurement of the activities and kinetic parameters of seven enzymes that participate in purine salvage. The values of the equilibrium constants of nine reactions were determined in vitro and compared with the ratios of the reactants measured in liver. The changes in phosphoribosylpyrophosphate (PRPP), a key intermediate in both the de novo and salvage pathways of purine metabolism, were directly correlated with the changes in ribose 5-phosphate (ribose-5-P); ([PRPP] = 1.7[ribose-5-P] - 7.4 mumol/kg). Ribose-5-P concentrations in turn could be predicted from the liver content of fructose 6-phosphate and glyceraldehyde 3-phosphate by calculation from the known equilibria. The maximum velocities in the tissue of the seven enzymes measured were calculated from the measured substrate values in the liver and with consideration of other effectors of enzyme activity. PRPP synthetase was the least active of the enzymes measured, indicating a possible rate-limiting step. The delta G of the enzyme steps differed from equilibrium values by factors ranging from 4 (nucleoside phosphorylase) to 10(5) (PRPP synthetase and purine transferase reactions). The regulation of purine salvage appeared to depend on the levels of PRPP and ribose-5-P.
Acetates↗
Radiometric measurement of phosphoribosylpyrophosphate and ribose 5-phosphate by enzymatic procedures.
Methods for the measurement of phosphoribosylpyrophosphate (PRPP) and ribose 5-phosphate (R-5-P) in tissues have been developed. The lability of these compounds during tissue extraction and the recovery of standards from tissue preparations have been examined. Enzymatic conversion of phosphoribosylpyrophosphate to [14C]AMP in the presence of labeled adenine or formation of [14C]GMP ([14C]IMP) in the presence of labeled guanine or hypoxanthine was accomplished in the first step. In the second step, the labeled product was separated from the substrate. For the measurement of R-5-P, the first step included phosphoribosylpyrophosphate synthetase, as well as the appropriate substrate and effector (ATP and Pi), in combination with adenine phosphoribosyl transferase. The product [14C]AMP was measured in three ways: (1) HPLC separation with an on-line radioisotope detector; (2) butanol extraction of the labeled base, and measurement of an aliquot of the aqueous phase in a scintillation counter; (3) filtration of the incubation mixture with chromatographic filter paper disks, which were then counted in a scintillation counter. When [14C]guanine was the substrate, HPLC separation was used because the butanol or paper separation was not adequate. Measurement of 5-125 pmol of PRPP or R-5-P gave a linear response.
Adenine Phosphoribosyltransferase↗
Determination of short-chain coenzyme A compounds by reversed-phase high-performance liquid chromatography.
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Acyl Coenzyme A↗
Early metabolic effects of platelet-derived growth factor and transforming growth factor-beta in rat liver in vivo.
The short term metabolic effects of the in vivo administration of platelet-derived growth factor have been examined in the liver of the rat. Meal-fed male Wistar rats weighing between 150-180 g received an intraperitoneal injection of platelet-derived growth factor (17 units/100 g weight), transforming growth factor-beta (185 ng/100 g weight), or saline. At 5 min after injection, the livers were freeze-clamped. Samples of the tissue were subsequently assayed for metabolite content and enzyme activities. Platelet-derived growth factor injection caused an elevation in the liver content of pyruvate from 0.14 +/- 0.012 to 0.19 +/- 0.009 mumol/g wet weight liver (p less than or equal to 0.01) and an increase in the cytosolic phosphorylation potential [sigma ATP]/[sigma ADP][sigma Pi] from 6670 +/- 540 to 8970 +/- 750 (p less than or equal to 0.01). In addition an increase in the hepatic content of the hexose monophosphate pathway metabolites, 6-phosphogluconate (0.027 +/- 0.004 to 0.037 +/- 0.005 mumol/g wet weight) (p less than or equal to 0.05), ribulose 5-phosphate (0.013 +/- 0.001 to 0.017 +/- 0.001 mumol/g wet weight) (p less than or equal to 0.05) and combined sedoheptulose 7-phosphate and ribose 5-phosphate (0.052 +/- 0.007 to 0.062 +/- 0.004 mumol/g wet weight) (p less than or equal to 0.05) was observed. The elevation in the hexose monophosphate pathway metabolites resulted from a 1.3-fold elevation in the activity of glucose-6-phosphate dehydrogenase [EC 1.1.1.49] when measured in a crude homogenate. Kinetic analysis performed on partially purified glucose-6-phosphate dehydrogenase demonstrated no significant change in the Km of the enzyme for either NADP+ or glucose 6-phosphate, while a 2.4-fold increase in the Vmax was observed. In view of the rapidity of the change in total measured enzyme activity and increase in the Vmax of glucose-6-phosphate dehydrogenase, it is postulated that platelet-derived growth factor causes a covalent modification of the existing enzyme. Transforming growth factor-beta caused no change in the hepatic metabolite content in the treated animals when compared to saline treated controls.
Adenosine Diphosphate↗
The effect of short chain fatty acid administration on hepatic glucose, phosphate, magnesium and calcium metabolism.
Intra peritoneal administration of the short chain fatty acids, acetate, propionate and butyrate, in amounts calculated to reach 20 mM in total body water were given to fed and 48 hour starved male Wistar rats. One half hour after administration, the livers were freeze-clamped and the hepatic contents of various intermediary metabolites were measured. The liver content of total glycolytic intermediates was elevated by short chain fatty acids. In fed animals, the portion of glycolysis from fructose 1,6-bisphosphate (FBP) to PEP was elevated 2 to 4 fold. In 48 hour starved animals, where gluconeogenesis is active, the portion of the gluconeogenetic pathway from FBP to glucose was elevated 1.5 to 3.5 fold with the exception of the butyrate treated animals where blood glucose was not elevated. The metabolites of the hexose-monophosphate pathway that were measured, namely 6-phosphogluconate, ribulose 5-phosphate and xylose 5-phosphate were increased in both fed and starved animals. The free cytoplasmic [NAD+]/[NADH], [NADP+]/[NADPH], and [epsilon ATP]/[epsilon ADP] X [epsilon Pi] ratios were all decreased in both fed and starved animals after short chain fatty acid administration. The liver content of calcium increased 1.2 to 2 fold in fed animals and 2 to 3 fold in starved animals while total liver magnesium was either unchanged or increased only 1.2 times. The liver pyrophosphate (PPi) content increased a minimum of 10 fold in fed animals and over 100 fold in starved animals. In all cases no PPi could be detected in vivo by 31P NMR even though in the starved rats the PPi levels approached those of ATP. The liver content of inorganic Pi increased 1.3 to 1.5 fold in fed animals and 1.5 to 2 fold in starved animals. The total "rapidly metabolizing" Pi pool, that includes adenine and guanine nucleotides, glycolytic and shunt intermediates, Pi and PPi increased 1.3 times in fed animals (from 13.8 mumole/g fresh weight) and 1.5 to 1.7 fold in starved animals (from 15.7 mumol/g fresh weight). The total phosphate taken up from blood and entering the rapidly turning over pool of liver phosphate ranged between 4 and 12 mumols/g of liver.(ABSTRACT TRUNCATED AT 400 WORDS)
Adenine Nucleotides↗
Chemical structure and mutagenic activity of aminoimidazoquinolines and aminonaphthimidazoles related to 2-amino-3-methylimidazo[4,5-f]quinoline.
We have synthesized 11 heterocyclic aromatic amines with chemical structures related to that of 2-amino-3-methylimidazo [4,5-f] quinoline (IQ), a potent mutagen occurring in broiled sardines, fried beef and beef extract. The mutagenic activity of these IQ analogs was studied and compared with that of IQ using the Ames test with strain TA98 of Salmonella typhimurium in presence of a metabolic activation system (S9 mix) derived from rat liver. The mutagenic activities of the IQ analogs vary over a million-fold; structure-activity comparisons indicate major contributions of the methyl substitution in the imidazole ring and of the quinoline-N, and significant contributions of methylation of the exocyclic amino group and of the geometry of the entire ring system.
Animals↗
Genotoxic activity of IQ (2-amino-3-methylimidazo [4,5-f]quinoline) and structural analogs.
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Animals↗
Separation and measurement of short-chain coenzyme-A compounds in rat liver by reversed-phase high-performance liquid chromatography.
A high-performance liquid chromatographic method has been developed to measure short-chain CoA compounds in freeze-clamped liver. Seventeen CoA compounds can be quantitated in 37 min using a 3-micron octadecylsilica column (4.6 mm X 7.5 cm). The chromatographic separation of CoA compounds is conducted with a gradient system of sodium phosphate and acetonitrile. The large amount of uv-absorbing, non-CoA material present in liver extracts is eluted earlier than the CoA compounds when the phosphate concentration is 0.2 M. The CoA compounds that can be resolved by this method include acetoacetyl-CoA, acetyl-CoA, butyryl-CoA, CoASH, crotonyl-CoA, dephospho-CoA, glutathione-CoA, 3-hydroxy-3-methylglutaryl-CoA, isobutyryl-CoA, isovaleryl-CoA, malonyl-CoA, 3-methylcrotonyl-CoA, methylmalonyl-CoA, oxidized-CoA, propionyl CoA, succinyl-CoA, and valeryl-CoA. Comparisons at pH 3 and 6 showed that the stability of the CoA compounds is much greater when perchloric acid extracts of rat liver are adjusted to pH 3. Recovery of CoA standards added in tissue extracts ranged from 83 to 107%. The method is linear over the range of 12 to 700 pmol, and this sensitivity allows acetyl-CoA content to be determined in extracts of as little as 0.1 mg of liver. The values for CoA compounds obtained for freeze-clamped liver from starved rats include (units are nmol/g wet weight +/- SE) malonyl-CoA, 1.50 +/- 0.14; glutathione-CoA, 6.57 +/- 1.72; CoASH, 56.06 +/- 2.90; methylmalonyl-CoA, 4.60 +/- 1.27; succinyl-CoA, 13.52 +/- 0.76; 3-hydroxy-3-methylglutaryl-CoA, 7.06 +/- 0.89; and acetyl-CoA, 100.5 +/- 6.4.(ABSTRACT TRUNCATED AT 250 WORDS)
Acyl Coenzyme A↗
Maternal-foetal distribution studies in late pregnancy. II. Distribution of [1-14C]acrylamide in tissues of beagle dogs and miniature pigs.
[carbonyl-14C]Acrylamide was administered iv as a single dose (5 mg/kg) to pregnant beagle dogs and miniature pigs late in gestation. After a 2-hr equilibration period, the animals were killed and foetuses were removed for determination of the amount of radioactivity in maternal and foetal tissues. In total, six dog litters (33 foetuses) and seven pig litters (45 foetuses) were examined. In dogs, acrylamide was distributed readily to both maternal and foetal tissues with a placental distribution factor of 17.7%. The blood/brain distribution factor was insignificant (5.9%) in maternal dogs and 0% in the foetuses. Maternal liver was the largest depot of the administered acrylamide in the dog, followed by the maternal kidney. In pigs, the placental distribution factor was 31%, and the blood/brain distribution factor was insignificant in both maternal and foetal pigs. Liver and kidney of maternal pigs also contained the greatest amount of radioactivity. Although there appears to be some placental protection of the foetuses from the xenobiotic in the maternal circulation, foetal brain would be exposed to the effect of any acrylamide present in the foetal circulation, since the foetuses of both species had blood/brain distribution factors that were either small or zero, reflecting the absence of a blood-brain barrier.
Acrylamide↗
Criteria for the standardization of Salmonella mutagenicity tests: results of a collaborative study. II. Studies to investigate the effect of bacterial liquid culture preparation conditions on Salmonella mutagenicity test results.
The influence of various parameters and growth conditions in the "overnight culture" of Salmonella typhimurium strains on mutagenicity test results was investigated. A number of factors were first suspected to be of some importance for the quantitative outcome of the mutagenicity test. None of them, however, was found to influence the results to such a marked extent as to be a major source of variability. Only the brand of nutrient broth used for the propagation of the bacteria proved finally to have a certain effect on the number of (spontaneous and induced) revertant colonies, although no precise and quantitative statements can be made with regard to a possible standardization of this experimental segment in the Salmonella mutagenicity test. The occurrence of such unpredictable but noticeable influences is, however, evidence for the importance of an intralaboratory optimization and standardization of all parts of the test procedure.
Animals↗
Genotoxicity study of CS (ortho-chlorobenzylidenemalononitrile) in Salmonella, Drosophila, and mice. Failure to detect mutagenic effects.
The lacrimatory agent CS was examined for genotoxic properties. In vitro, Salmonella typhimurium was exposed to CS at concentrations up to 1.5 mg per plate and reverse mutations were assayed. In vivo: male Drosophilae were fed with CS and sex-linked recessive lethal mutations in sperm cells were assayed using the Basc test. Further, mice were exposed to CS by oral or intraperitoneal administration; bone marrow erythrocytes were analysed for chromosomal mutations by means of the micronucleus test. All experiments failed to show a mutagenic activity of CS.
Animals↗
The mutagenic potential of hyperthermia and fever in mice.
The cytogenetic effects of hyperthermia resulting from climatic influences as well as from infections were studied. Whole-body exposure of NMRI mice to an elevated environmental temperature induced a high frequency of micronucleated polychromatic erythrocytes in bone marrow. Hyperthermia at high relative humidity was more effective in increasing body temperature and cytogenetic damage than at low RH. A sex-related difference in response to heat stress was observed. Hyperthermia on pregnant mice induced a significant increase in the incidence of micronucleated PEs in fetal blood cells. Parenteral administration of bacterial endotoxin, lipopolysaccharides, induced either hypothermia or hyperthermia. However, LPS-induced hypothermia as well as fever does not so far appear to produce cytogenetic damage.
Animals↗
Autoradiographic detection of 6-thioguanine-resistant lymphocytes of mice. A novel system in somatic mutagenesis testing.
After treatment of mice with ethylnitrosourea in vivo, induction of 6-thioguanine-resistant splenic lymphocytes was measured in vitro. The lymphocytes were mitogen-stimulated in presence of thioguanine. After a culture period of 30 h, TG resistance was determined by the ability of cells to incorporate [3H]thymidine. The results suggest that at this selection condition the majority of resistant cells stem from somatic mutations. Thus, the system is potentially useful as a screening assay for somatic mutagenesis testing. The problem of misleading results due to the presence of phenocopies was investigated by treatment in vitro with UV radiation or ethylnitrosourea.
Animals↗
Mutagenicity studies with the mouse spot test.
The mammalian spot test, which detects somatic gene mutations in mouse embryos, was investigated with selected chemicals to (a) further validate this test system (ENU, EMS, 2AAF, colchicine) and (b) evaluate the mutagenic potential, in a whole-mammal system, of environmental compounds that had been previously recognized as mutagens in other mammalian or submammalian test systems (1,2-dichloroethane, hydroquinone, nitrofurantoin, o-phenylenediamine, fried sausage extract). Of these substances, ENU, EMS and 2AAF were significantly mutagenic, 1,2-dichloroethane was probably weakly mutagenic. The ENU data were used to estimate the number of pigment precursor cells present at the time of treatment (day 9.25). We also describe in this report the use of a fluorescence microscope for classification of hairs from spots on the coat of C57BL/6JHan X T hybrids.
2-Acetylaminofluorene↗