Selection and evaluation of laboratory instrumentation in clinical chemistry: I. Survey of major analysers in the United Kingdom.
Explore the source record for details and available documents.
Chemistry, Clinical↗
Biomedical subjects
J L Robinson
Publications and source records attributed to J L Robinson.
Evaluation of the mass detector for quantitative detection of triglycerides and fatty acid methyl esters.
The mass detector, a light scattering detector for use with high-performance liquid chromatography systems, was studied in order to determine which factors might affect sensitivity and quantification in the determination of triglycerides and other lipid materials. The detector response was found to be non-linear for triglycerides. The sensitivity was not only affected by evaporation temperatures and atomiser inlet air pressures within the detector, but also by the mobile phase flow-rate, and its composition. Detection limits of less than 1 microgram were achieved for non-volatile, saturated triglycerides, by direct injection, and the reproducibility of responses was about +/- 6% with isocratic elution (excluding tributyrin which was too volatile to be quantified accurately), but somewhat greater (+/- 16%) with gradient elution.
Butter↗
Metabolic investigations of fibroblasts from horses, Equus caballus, with hereditary severe combined immunodeficiency.
In an attempt to determine the metabolic defect causing severe combined immunodeficiency (SCID) in horses in which altered purine metabolism has been observed, various parameters of purine and pyrimidine metabolism were evaluated. The activities of nine purine enzymes (adenosine kinase, purine nucleoside phosphorylase, deoxyadenosine kinase, deoxycytidine kinase, 5'-nucleotidase, AMP deaminase, hypoxanthine-guanine phosphoribosyl transferase, and adenine phosphoribosyl transferase were measured in fibroblasts. All activities determined for SCID horses were normal. Uptake of 10 microM adenosine or 2'-deoxyadenosine (a growth inhibitory concentration for SCID fibroblasts) by SCID fibroblasts was identical to that found for normal fibroblasts in the presence of both 1 and 50 microM phosphate. The Km determined for the transport of both adenosine and 2'-deoxyadenosine was 35 microM. In the presence of p-nitrobenzylthioguanosine (a nucleoside transport inhibitor), 2'-deoxyadenosine uptake was inhibited to the same extent in all fibroblast lines tested. To determine if the last step in pyrimidine biosynthesis might be altered in SCID fibroblasts, UMP synthase activities were evaluated but found to be normal (0.5 nmol UMP formed/min/mg protein).
5'-Nucleotidase↗
Assessment in humans of hypolipidemia induced by orotic acid.
The hypolipidemia induced by oral orotic acid in rats but not in other experimental species was investigated in human adults. Twelve outpatients in a medically-supervised weight reduction program participated in the study. After adaptation to their restricted dietary regime for at least 8 weeks, all subjects were given placebos (1 g lactose/day) for 2 weeks, then orotic acid (1 g/day) for 4 weeks, followed by placebos for 2 more weeks. Pertinent dietary, urinary, and serum parameters were monitored biweekly and intake of calories, carbohydrate, protein and fat was similar throughout. The ingestion of orotic acid did not lower serum triglycerides or cholesterol in these subjects. Since the daily dose tested corresponds to the orotic acid in 12 liters of cow's milk, milk orotic acid at levels normally consumed should not be considered a hypolipidemic or hypocholesteremic agent for humans.
Adult↗
Erythrocyte ribosyluric acid of dairy cattle normal and deficient for uridine monophosphate synthase.
An inherited deficiency of uridine-5'-monophosphate synthase has recently been discovered in dairy cattle. The possibility was explored that this deficiency might be detected by low amounts of erythrocyte 3-N-ribosyluric acid, since it is synthesized by uridine monophosphate synthase. Ribosyluric acid was lower in six dairy cows with the deficiency compared to six controls, paired on the basis of age, stage of lactation, and diet (.66 vs. 1.38 mumol/ml). However, ribosyluric acid concentration measured in 50 normal cows showed a wide range (.28 to 2.35 mumol/ml), with nine lower than the mean for the deficient animals. This extensive variability may limit the usefulness of ribosyluric acid in diagnosing the inherited deficiency of uridine monophosphate synthase.
Animals↗
Characterization of 5-hydroxytryptamine receptors in rat stomach fundus.
1-Arylpiperazines (MK-212, quipazine, m-chlorophenylpiperazine and m-trifluoromethylphenylpiperazine) caused a serotonin (5-HT) receptor-mediated contraction of rat fundic strips. m-chlorophenylpiperazine and m-trifluoromethylphenylpiperazine had high affinity for the receptor but little efficacy, whereas quipazine and MK-212 had lesser affinity and much greater efficacy. 5-HT itself was the most potent (EC50 = 6-9 nM) agonist and possessed the greatest affinity (KA = 9.7 nM). Assessment of receptor occupancy vs. functional response (as well as receptor alkylation studies) demonstrated a very small, if any, receptor reserve in this tissue. Several arylquinolizines were found to be competitive antagonists of 5-HT-induced contraction, the most potent being L-653,267 and rauwolscine (KB values = 1.9 and 3.8 nM). Clozapine, trazodone and propranolol were identified as less potent, competitive antagonists, whereas various ergolines (including LY 53857), L-646,462 (cyproheptadine analog) and mianserin were noncompetitive. Potent 5-HT2 receptor antagonists (pirenpirone and ketanserin) antagonized only weakly or were without effect against 5-HT, indicating that the fundic 5-HT receptor is not of the 5-HT2 subtype. Because the fundic receptor has high affinity for 5-HT (as does the 5-HT1 binding site in brain tissue), the possible correspondence of the fundic 5-HT receptor with the 5-HT1 recognition site in rat brain cortex was considered. 5-HT, the nonindole agonists (1-arylpiperazines) and the competitive antagonists all competed with [3H]-5-HT for the 5-HT1 site. However, all compounds except 5-HT had Hill slopes significantly less than 1.0, precluding a valid comparison with dissociation constants derived pharmacologically in the fundus. With respect to having a high affinity for 5-HT, the 5-HT receptor mediating contraction of fundic smooth muscle resembles the 5-HT1 recognition site (as defined in brain tissue by radioligand binding), but identity remains unproven.
Animals↗
Nicotinic receptors in mammalian brain.
Nicotine has marked effects on CNS function increasing brain excitability and spontaneous activity and also has antinociceptive actions. Agonist radioligands for the nicotinic cholinergic receptor bind with high affinity in a saturable manner. Binding is however, insensitive to the ganglionic blockers, hexamethonium and mecamylamine. This suggests that agonists and antagonists bind to different sites on the receptor or that the nicotinic receptor in brain is different from that found in peripheral tissues. The nicotinic antagonist, dihydro-beta-erythroidine binds with high affinity (Kd = 4 nM) to rat brain membranes in a stereospecific, saturable, manner with a regional distribution similar to that seen with radiolabeled acetylcholine. Binding is insensitive to hexamethonium and mecamylamine. It is concluded that the nicotinic recognition sites to which dihydro-beta-erythroidine binds are neuromuscular rather than ganglionic in nature.
Animals↗
Hypocholesteremia induced by orotic acid: dietary effects and species specificity.
Effects of 1% dietary orotic acid on lipid metabolism were examined in rats, mice, hamsters and guinea pigs. The influences of diet composition, age and sex on alterations induced by orotic acid were also studied. Hypocholesteremia and hepatic steatosis developed in rats fed orotic acid. These responses were little affected by dietary changes in lipid (0, 2 or 5% corn oil) or carbohydrate (high sucrose, high starch or high fiber). When included in diets containing cholesterol and cholic acid, orotic acid prevented a rise in serum cholesterol but did not maintain a normal ratio of HDL to total cholesterol. The responses of mice to orotic acid were opposite to those of rats; liver lipid was decreased, and serum cholesterol was increased. Hamsters and guinea pigs were unaffected by the compound. Thus, orotic acid is hypocholesteremic in rats, hypercholesteremic in mice and normocholesteremic in hamsters and guinea pigs. Age did not alter responses of rats to 1% dietary orotic acid. In rats and mice, sex influenced changes in hepatic lipid, with females more responsive than males.
Aging↗
Orotate in milk and urine of dairy cows with a partial deficiency of uridine monophosphate synthase.
Cows with a partial deficiency of uridine monophosphate synthase have elevated orotate in their milk and urine. Variability of orotate was assessed in two such cows monitored biweekly for two complete lactations. Concentrations of milk and urinary orotate showed extensive variation during lactation, but coefficients of variation were similar for deficient and normal cows. Orotate averaged 500 micrograms/ml milk for deficient cows (versus a normal of 80 micrograms/ml), and a threshold of 200 micrograms/ml distinguished normal from deficient cows. Deficient cows had low milk orotate upon initiation of lactation and exhibited a latency of 1 to 7 wk to attain that threshold. The deficiency also resulted in a lactation-induced orotic aciduria. Orotate averaged 32.2 micrograms/ml urine for deficient cows (versus a normal of 7.3 micrograms/ml), and a threshold of 15 micrograms/ml urine differentiated the animals. Latency was 3 to 18 wk for deficient cows to exceed that threshold. Total orotate output and orotate concentration were elevated in milk and urine of lactating cows deficient for uridine monophosphate synthase. The output of orotate was predominantly in milk rather than urine for both deficient and normal cows. Additionally, orotate was elevated in blood of deficient cows when they were lactating.
Animals↗
Binding of the nicotinic cholinergic antagonist, dihydro-beta-erythroidine, to rat brain tissue.
The nicotinic cholinergic antagonist, dihydro-beta-erythroidine, binds to two sites in rat cortical membranes with dissociation constants of 4 and 22 nM and respective apparent Bmax values of 52 and 164 fmol/mg of protein. Binding to the higher affinity site, defined by the use of 2 nM [3H]dihydro-beta-erythroidine, was saturable, reversible, and susceptible to protein denaturation. Binding was highest in the thalamus and lowest in the spinal cord and showed preferential enrichment in a synaptosomal subfraction of rat brain. Nicotine displaced [3H]dihydro-beta-erythroidine in a stereospecific manner, the (-)-isomer being approximately 6 times more potent than the (+)-isomer. The alkaloid nicotinic agonists, cytisine and lobeline, were potent inhibitors of binding, while acetylcholine in the presence of the cholinesterase inhibitor di-isopropylfluorophosphate was equipotent with (+)-nicotine. Binding was also inhibited by the muscarinic ligands, arecoline, atropine, and oxotremorine. The nicotinic antagonists mecamylamine, hexamethonium, and pempidine were essentially inactive in displacing [3H]dihydro-beta-erythroidine. These findings indicate that dihydro-beta-erythroidine binds to a nicotinic recognition site in rat brain which is neuromuscular, rather than ganglionic, in nature and that such binding is similar in several respects to that seen with nicotinic agonists. Whether such binding is to a nicotinic, as opposed to nicotinic cholinergic, recognition site or to a "common" nicotinic/muscarinic site is an issue that requires further study.
Alkaloids↗
L-646,462, a cyproheptadine-related antagonist of dopamine and serotonin with selectivity for peripheral systems.
The selectivity, peripheral vs. central actions, of the antidopaminergic agent L-646,462 was assessed in two ways. First, elevation of prolactin in serum (peripheral) and homovanillic acid in the striatum were measured in rats. L-646,462 was found to have a central/peripheral activity ratio of 143, whereas comparable values derived for haloperidol, metoclopramide and domperidone were 1.4, 9.4 and 1305, respectively. Second, the ID50 values required to block apomorphine-induced emesis in beagles (peripheral receptor-mediated response) were compared with those required to block apomorphine-induced stereotypy (central receptor-mediated response) in rats. Central/peripheral ID50 ratios of 234, 9.2, 129 and 7040 were obtained, respectively, for L-646,462, haloperidol, metoclopramide and domperidone. The selectivity of L-646,462 for peripheral serotonin (5-HT) receptors in rats was determined by measuring its effectiveness in blocking 5-HT-induced paw edema (peripheral response) and 5-hydroxytryptophan-induced head twitch (central response); a ratio of 114 was obtained. This value agrees nicely with the ratio of 143 derived in the rat ( vide supra) for peripheral selectivity for dopamine receptors. L-646,462 is, therefore, selective in vivo, preferentially blocking dopamine and 5-HT receptors located outside the blood-brain barrier. With regard to dopamine-receptors, L-646,462 was about equipotent and more selective than metoclopramide, while being less potent and less selective than domperidone. Unlike metoclopramide or domperidone, L-646,462 also possessed a reasonably potent 5-HT receptor antagonist effect in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Assessment of the chloroethyl analog of 3-PPP (N-n-propyl-3-(3-hydroxyphenyl)-piperidine), 3-PPP-C1 as an irreversible ligand for central dopaminergic recognition sites.
NCA, the chloro analog of the potent dopamine agonist NPA is an irreversible ligand at dopamine receptors in mammalian brain. The chloroethyl analog of the recently described putative dopamine autoreceptor agonist 3-PPP, 3-PPP-C1, was evaluated for its potential use as an irreversible autoreceptor ligand. N-Chloroethylation of 3-PPP reduced the intrinsic affinity of the agonist seven-fold and, consequently, in contrast to NCA, it was found that 3-PPP-C1 was not a good irreversible ligand at dopamine receptors.
Animals↗
Chronic in vivo treatment with desmethylimipramine and mianserin does not alter adenosine A-1 radioligand binding in rat cortex.
Antidepressants and electroconvulsive shock therapy (ECS) have been reported to alter adenosine-sensitive adenylate cyclase responses in rat brain, suggesting an involvement of the purine in the mechanisms by which antidepressants and antidepressant therapy produce their clinical effects. Chronic (14-21 days, 10 mg/kg/day by Alzet minipump) treatment with desmethylimipramine (DMI) and mianserin, while producing changes in beta-adrenoceptor (DMI) and serotonin-2 (DMI and mianserin) radioligand binding similar to those reported in the literature, has no effect on adenosine A-1 radioligand binding.
Adenosine↗
Synthesis and receptor binding studies relevant to the neuroleptic activities of some 1-methyl-4-piperidylidene-9-substituted-pyrrolo[2,1-b][3]benzazepine derivatives.
The synthesis of a series of 1-methyl-4-(9-substituted-11H-pyrrolo[2,1-b]benzazepin-11-ylidene)piperidines (4a-f) and 1-methyl-4-(9-substituted-6,11-dihydro-5H-pyrrolo[2,1-b][3]benzazepin-11-ylidene)piperidines (4g-l) is described. As with th e 3-substituted cyproheptadine compounds 1b-e, atropisomerism exists in 4b-f, but unlike the enantiomers of 1b-e, the pyrrolobenzazepine enantiomers racemize at room temperature. Thus, the bromo compound (+)-4b has a half-life of 128 +/- 1 min at 25 degrees C, while the chloro compound (-)-4c has a half-life of 114 +/- 9 min at 25 degrees C. Compounds 4a-l have been examined for receptor binding affinities in assays that have been recognized as predictive for antipsychotic activity. The displacement of specifically bound tritiated ligands, comprising the dopamine antagonist [3H]spiperone, the dopamine agonist [3H]apomorphine, the muscarinic cholinergic antagonist [3H]quinuclidinyl benzilate (QNB), the alpha-adrenergic antagonist [3H]prazosin, the alpha-adrenergic agonist [3H]clonidine, the serotonin-1 binding agent [3H]serotonin, and the mixed serotonin agonist-antagonist [3H]lysergic acid diethylamide (LSD), by 4a-l has been measured utilizing membrane preparations of mammalian brain. Certain of the features of the receptor binding of these compounds have been shown to be common to several of the receptor sites. Data from these binding studies have been compared to corresponding data previously obtained for a series of chiral 3-substituted cyproheptadine analogues, and the receptor binding data of the two classes of compounds are discussed with respect to their molecular geometries.
Animals↗
The effect of phenylephrine upon arterial pressure, carotid sinus radius and baroreflex sensitivity in the conscious greyhound.
1. A method for recording carotid sinus diameter in conscious dogs has been developed, using an ultrasound transit time technique. We have used this method to measure the distensibility of the carotid sinus in resting animals, and we have investigated the effect of injecting the vasoactive drug phenylephrine on the mechanical behaviour of the sinus wall. 2. Baroreflex sensitivity was measured in the dogs by the usual method of relating the slowing of the heart to the transient pressure rise induced by the injections of phenylephrine. 3. We have shown that phenylephrine directly reduces the radius of the carotid sinus during the measurements of baroreflex sensitivity. At a dose of 2-4 micrograms/kg, phenylephrine has an enhancing effect on the baroreflex response, possibly resulting from a modification of baroreceptor output.
Animals↗
Consequences of UMP synthase deficiency in cattle.
Several dairy cows have been identified as partially deficient in UMP synthase. Although erythrocytes of normal cows contained 2.54 units of enzyme per ml, four cows were discovered with only 1.08 units per ml. Cows deficient in UMP synthase secreted milk with abnormally high levels of orotate, 300-1,000 micrograms of orotate per ml compared to 80 micrograms/ml for normal cows. The deficiency also was accompanied by a lactation-induced orotic aciduria. Although bovine urinary orotate was generally less than 10 micrograms/ml, the urine of the deficient cows, when lactating, contained 20-200 micrograms/ml. Their plasma orotate also was elevated. Genetic transmission of the condition was suggested by a common bull in the pedigrees of all deficient animals. Indeed, these cows, with half the normal level of UMP synthase, are probably heterozygotes with a 50% chance of passing the deficient allele to their progeny. For these putative heterozygotes, the condition is apparently benign because longevity and production were unaffected. However, the existence of a gene for UMP synthase deficiency in the dairy cow population poses a hazard with respect to the conception of homozygotic, deficient animals. These, in analogy with a comparable human condition, would be expected to exhibit high perinatal morbidity and mortality.
Aging↗
The selective utilization of prenatal genetic diagnosis. Experiences of a regional program in upstate New York during the 1970s.
The regional prenatal diagnosis program of the Finger Lakes Health Systems Area in upstate New York has been monitored since its start in 1971. By the end of 1980, more than 1,250 diagnostic procedures had been successfully completed. Based on analyses of regional vital statistics, genetic services data, repeated surveys of obstetricians, and an ongoing survey of recent mothers older than 34 years of age, the authors concluded that: 1) in the study region, most women with an indication for prenatal diagnosis because of age are aware of the possibility of prenatal diagnosis; 2) the majority of obstetricians discuss amniocentesis with their patients; 3) after a period of rapid growth the utilization rate in the study region reached about 40% in 1981; 4) nonuse of prenatal diagnosis is based mostly on a patient's decision rather than system deficiencies; and 5) a community approach to increase utilization will have to focus on how to provide a supportive social climate for these services rather than on increasing awareness among potential patients or more referrals by providers.
Abortion, Induced↗
Hemodynamic effects of vasodilator therapy in severe left heart failure combined with large atrial septal defects.
Two patients presented with severe left heart failure and large secundum atrial septal defects without severe pulmonary hypertension. The acute hemodynamic effects of two commonly used vasodilator agents, isosorbide dinitrate and hydralazine, are described. Although isosorbide dinitrate improved systemic forward cardiac output, it also increased left-to-right intracardiac shunting in both patients. On the other hand, hydralazine dramatically improved systemic toward output and concomitantly diminished left-to-right shunt flow in each patient (43 and 21 percent). The complexities of combined severe left ventricular failure and a large atrial septal defect with left-to-right shunting, and the importance of extensive hemodynamic monitoring at the time of pharmacologic intervention, are discussed.
Blood Pressure↗