Showing papers by "Medical Research Council published in 1970"
Book•
01 Jan 1970626 citations
TL;DR: Calcium absorption was measured by plasma radioactivity after oral calcium isotopes in seventy-five men and one hundred and fifteen women aged 20-95 years and everyone over 80 had significant malabsorption.
394 citations
352 citations
TL;DR: The results showed that in brain tissue incubated under the conditions used, the organization underlying metabolic compartmentation was preserved and the observed concentration ratios of amino acids between tissue and medium were also similar to those obtaining in vivo.
Abstract: 1. Cerebral-cortex slices prelabelled with gamma-amino[1-(14)C]butyrate (GABA) were incubated in a glucose-saline medium. After the initial rapid uptake there was no appreciable re-entry of (14)C into the GABA pool, either from the medium or from labelled metabolites formed in the tissue. The kinetic constants of GABA metabolism were determined by computer simulation of the experimental results by using mathematical procedures. The GABA flux was estimated to be 0.03mumol per min/g, or about 8% of the total flux through the tricarboxylic acid cycle. It was found that the assumption of compartmentation did not greatly affect the estimates of the GABA flux. 2. The time-course of incorporation of (14)C into amino acids associated with the tricarboxylic acid cycle was followed with [1-(14)C]GABA and [U-(14)C]-glucose as labelled substrates. The results were consistent with the utilization of GABA via succinate. This was confirmed by determining the position of (14)C in the carbon skeletons of aspartate and glutamate formed after the oxidation of [1-(14)C]GABA. These results also indicated that under the experimental conditions the reversal of reactions catalysed by alpha-oxoglutarate dehydrogenase and glutamate decarboxylase respectively was negligible. The conversion of [(14)C]GABA into gamma-hydroxybutyrate was probably also of minor importance, but decarboxylation of oxaloacetate did occur at a relatively slow rate. 3. When [1-(14)C]GABA was the labelled substrate there was evidence of a metabolic compartmentation of glutamate since, even before the peak of the incorporation of (14)C into glutamate had been reached, the glutamine/glutamate specific-radioactivity ratio was greater than unity. When [U-(14)C]glucose was oxidized this ratio was less than unity. The heterogeneity of the glutamate pool was indicated also by the relatively high specific radioactivity of GABA, which was comparable with that of aspartate during the whole incubation time (40min). The rates of equilibration of labelled amino acids between slice and medium gave evidence that the permeability properties of the glutamate compartments labelled as a result of oxidation of [1-(14)C]GABA were different from those labelled by the metabolism of [(14)C]glucose. The results showed therefore that in brain tissue incubated under the conditions used, the organization underlying metabolic compartmentation was preserved. The observed concentration ratios of amino acids between tissue and medium were also similar to those obtaining in vivo. These ratios decreased in the order: GABA>acidic acids>neutral amino acids>glutamine. 4. The approximate pool sizes of the amino acids in the different metabolic compartments were calculated. The glutamate content of the pool responsible for most of the labelling of glutamine during oxidation of [1-(14)C]GABA was estimated to be not more than 30% of the total tissue glutamate. The GABA content of the ;transmitter pool' was estimated to be 25-30% of the total GABA in the tissue. The structural correlates of metabolic compartmentation were considered.
303 citations
TL;DR: The effects of loud noise are examined by observing its influence upon a combined tracking and multi-source monitoring task, which improves in noise, as does the detection of centrally located signals in the monitoring task.
Abstract: The effects of loud noise are examined by observing its influence upon a combined tracking and multi-source monitoring task. Tracking (the primary task) improves in noise, as does the detection of centrally located signals in the monitoring task. Peripheral signals are detected less often in noise. The data are interpreted in terms of increased selectivity of attention with arousal.
295 citations
01 Jun 1970
TL;DR: The metabolic fate of intravenous and oral propranolol has been studied after single doses in man using 14C labelled proPRanolol and the major metabolite so far identified in the urine is naphthoxylactic acid.
Abstract: 1. The metabolic fate of intravenous and oral propranolol has been studied after single doses in man using 14C labelled propranolol. — 2. After oral administration there is virtually complete absorption and peak blood levels of propranolol and 4-hydroxy propranolol (a beta blocking metabolite) are seen at about 1 1/4 h after administration. Studies in normal subjects confirm that the maximum degree of beta blockade occurs at this time. — 3. Following intravenous administration, no 4-hydroxy propranolol is seen and the possible reasons for this are discussed. — 4. Excretion of the administered radio-active dose is mainly in the urine, with only 1%–4% of the administered radio-activity appearing in the faeces after both intravenous and oral dosing. — 5. The major metabolite so far identified in the urine is naphthoxylactic acid, which accounts for approximately 20% and 40% of oral and i.v. doses respectively. — 6. The greater proportion of radio-activity excreted in the urine (30–60% of the administered dose) is as yet unidentified although it may be a conjugate of propranolol. The level of total blood radio-activity following both intravenous and oral propranolol is very much higher than that of either propranolol or 4-hydroxy propranolol. The major portion of this blood radio-activity appears to be the same as the unidentified urinary metabolite. — 7. Following intravenous doses the decline of pharmacological response roughly parallels that of propranolol concentration in the plasma, and does not correlate with the plasma concentration of the unidentified metabolite.
254 citations
TL;DR: Temperature-sensitive mutants of vesicular stomatitis virus induced by 5-fluorouracil (FU), 5-azacytidine (ACR), and ethyl methane sulfonate (EMS) have been assigned to four complementation groups by a qualitative test.
Abstract: One hundred and seventy-five temperature-sensitive ( ts ) mutants of vesicular stomatitis virus (type Indiana-C) induced by 5-fluorouracil (FU), 5-azacytidine (ACR), and ethyl methane sulfonate (EMS) have been assigned to four complementation groups by a qualitative test. Group I contains 151 mutants; group II, 2 mutants; group III, 1 mutant; and group IV, 15 mutants; 6 are unclassified. FU was much more effective as a mutagen than either ACR or EMS. The proportion of the mutants belonging to groups I and IV, however, was similar in the case of all three mutagens. Fifteen mutants from groups I and IV have been used to obtain quantitative complementation data. Both groups appear to be homogeneous. Complementation yields increase with increasing multiplicity, but the number of particles per cell required to elicit maximal complementation is small. The pattern of genetic recombination parallels that of complementation. No recombination could be detected in crosses within group I (
222 citations
TL;DR: Blood-lymphocytes of patients with a malignant neoplasm (even in its earliest stages) are sensitised to basic proteins derived from both the central and peripheral nervous system, independent of clinical signs of (non-metastatic) involvement of the nervous system.
177 citations
TL;DR: It is suggested that antagonism to 5‐HT and glutamate excitation of brain stem neurones may be the basis of the psychotomimetic action of LSD 25 and there may be similarities in the mechanisms by which 5‐ HT and glutamate produce excitation where they act on the same neurone.
Abstract: 1. 5-Hydroxytryptamine (5-HT), acetylcholine (ACh), noradrenaline (NA), glutamate, D,L-homocysteic acid (DLH), glycine and gamma-aminobutyric acid (GABA) were applied to single neurones in the brain stem of decerebrate cats by microiontophoresis. The abilities of D-lysergic acid diethylamide tartrate (LSD 25), methysergide maleate (UML 491) and 2-bromo-lysergic acid diethylamide (BOL 148) to antagonize the actions of these compounds were studied.2. LSD 25 antagonized 5-HT excitation of single neurones when applied iontophoretically or administered intravenously. LSD 25 also antagonized glutamate excitation of neurones which could be excited by 5-HT. Inhibitory effects of 5-HT, the action of glutamate on neurones which could be inhibited by 5-HT and the actions of all the other compounds tested were unaffected by LSD 25.3. Iontophoretically applied UML 491 was also a specific antagonist to 5-HT and glutamate excitation but was less potent than LSD 25, and BOL 148 rarely exhibited antagonism.4. It is suggested that antagonism to 5-HT and glutamate excitation of brain stem neurones may be the basis of the psychotomimetic action of LSD 25. It is also suggested that there may be similarities in the mechanisms by which 5-HT and glutamate produce excitation where they act on the same neurone.
163 citations
TL;DR: Although positive Kveim tests were found in a proportion of mice given homogenates from Crohn's disease tissues and were all associated with granulomas in the footpads, all KveIM tests were negative in mice given non-Crohn's homogenate.
160 citations
TL;DR: It is concluded that the nature of the group substituted at the enzyme active site determines the toxic response and the delayed neurotoxic effects of some organophosphorus compounds.
Abstract: 1. The delayed neurotoxic effects of some organophosphorus compounds are associated with phosphorylation of the active site of a nervous-tissue enzyme capable of hydrolysing phenyl phenylacetate. 2. Neurotoxic organophosphorus compounds and some carbamates and sulphonyl fluorides progressively inhibit the enzyme, attaching a substituent covalently at the active site. 3. Prolonged inhibition of the enzyme by phenyl N-benzyl-N-methylcarbamate or phenylmethane-sulphonyl fluoride does not lead to neurotoxic effects. 4. Prior inhibition of the enzyme by carbamates or sulphonyl fluorides in vivo prevents the neurotoxic effects of several organophosphorus compounds. 5. After dosage of hens with protective compounds, protection lasts until about 70% of the enzyme site again becomes available for phosphorylation. 6. Reaction of all the inhibitors at the active site of the enzyme leads to the same inhibitory effect with respect to hydrolysis of phenyl phenylacetate but does not in all cases lead to delayed neurotoxicity. It is concluded that the nature of the group substituted at the enzyme active site determines the toxic response.
TL;DR: The results indicate that the classification should be satisfactory for many epidemiologic purposes, but it is clear that further improvement in definitions and in the standard films might be expected to improve the agreement between readers.
TL;DR: It is suggested that severe necrosis of liver cells causes increased intravascular coagulation and the accelerated utilisation of clotting factors, at a time when their synthesis is reduced by liver damage, would contribute to the high incidence of bleeding in this condition.
TL;DR: The rate of protein synthesis was low in the newborn; it reached a peak at about 15 days and slowed down moderately later and incorporation into brain lipids was relatively low under the experimental conditions.
Abstract: —(1) The fate of [U-14C]leucine was studied in rat brain in vivo from birth to five weeks of age. The major route of leucine metabolism at all ages was conversion into protein. The rate of protein synthesis was low in the newborn; it reached a peak at about 15 days and slowed down moderately later. Incorporation into brain lipids was relatively low under the experimental conditions (less than 2 per cent of the total tissue 14C).
(2) The conversion of leucine-carbon into amino acids associated with the tricarboxylic acid cycle was low in the first 9 days after birth (less than 4 per cent of the acid-soluble 14C at 10 min after injection) and increased rapidly until 15 days when the level characteristic of the adult was approached (about 20 per cent of the acid-soluble 14C). The results indicated that the oxidation of acetyl-CoA derived from leucine reached the adult level at an earlier age than that derived from glucose.
(3) The glutamine/glutamate specific radioactivity ratio was 0·3 in the brain of newborn animals and increased progressively; it was 1·3 and 2·4 at 15 and 35 days of age respectively. The specific radioactivity of aspartate and of GABA relative to that of glutamate was less than 1 throughout the experimental period.
(4) The factors involved in the development of metabolic compartmentation in brain were analysed. It is proposed that although the experimental results show that a 'small’compartment becomes functionally manifested with maturation the primary cause is the development of the‘large’metabolic compartment.
(5) Morphological correlates of the metabolic compartments in brain tissue are suggested and it is concluded that the manifestation of metabolic compartmentation is related to maturational changes in glia-neuronal relations rather than to developmental processes affecting the individual components only.
TL;DR: The present experiment examines the effect of changing the distribution of signals across the monitoring display and points to the selectivity effect in noise being a function of task priorities and not of physical location.
Abstract: It was previously found that noise increased both performance on a primary tracking task and the detection of centrally located signals in a secondary multi-source monitoring task. The present experiment examines the effect of changing the distribution of signals across the monitoring display. When equal numbers are seen at all locations there is no differential effect of noise for central and peripheral locations. Such an effect only occurs when central signals are seen to have greater probability. This result points to the selectivity effect in noise being a function of task priorities and not of physical location.
TL;DR: Anoxic-ischaemic neuronal damage was studied by a combined light and electron microscope study of the brains of 4 rats exposed to nitrogen intermittently during a period of 40 min after interruption of blood flow in the right common carotid artery.
TL;DR: Procedures are described for estimating pyrrole and N-oxide metabolites formed in animal tissues from pyrrolizidine alkaloids in vivo or in vitro.
TL;DR: Detailed error analysis suggested a dichotomous classification of subjects into those primarily relying on artioulatory coding (A group) and those relying on some other mediating code which could depend on shape (non-A group), which correlated significantly with teachers' ratings of speech quality.
Abstract: Two experiments are reported. In the first, profoundly deaf schoolboys read consonant sequences for immediate written recall, reading, according to instruction, either silently or aloud. Detailed error analysis suggested a dichotomous classification of subjects into those primarily relying on artioulatory coding (A group) and those relying on some other mediating code which could depend on shape (non-A group). This classification correlated significantly with teachers' ratings of speech quality.
The A group showed no effect of reading mode on total number of errors. But the non-A group were significantly worse when reading aloud. Errors were distributed across serial positions effectively identically, regardless both of coding behaviour and reading mode. A recency effect was found of an order somewhere between that for hearing subjects reading this kind of material silently and reading it aloud.
A test of the reliability of the classification into A group and non-A group was made in the second experiment. In this the same subjects silently read word lists for immediate written recall. Lists were drawn from one of two vocabularies: one consisting of five pairs of common homophones, the other of five pairs of common words assumed to look similar. The A group recalled significantly more words of the latter lists, while the non-A group recalled both lists equally well.
The results are discussed in relation to current models for short-term memory and to their implications for the education of the deaf. In the former connexion, the presence of recency with subjects who have no auditory feedback would be an embarrassment to ‘echo-box’-type accounts of recall. With respect to the latter, two main points are made: (1) Deaf school children do not all memorize in the same code, and for some it may be different from that used by teachers. (2) If memorizing names of things is impaired by reciting them aloud, a hitherto concealed weakness of a common instructional procedure is exposed.
TL;DR: Tryptophan content of several pure intact proteins when treated with the above method gave values in good agreement with those reported by others.
Abstract: 1. A method is given for the quantitative determination of free tryptophan or tryptophan in the intact protein by treating with ninhydrin in a mixture of formic acid and hydrochloric acid (reagent b), for 10min at 100°C. Glycyltryptophan was used as a standard for the determination of tryptophan in the intact protein. The extinction at 390nm was linear in the range 0.05–0.5μmol for free tryptophan (∈7120) and 0.05–0.30μmol for glycyltryptophan (∈15400). 2. Free tryptophan in the presence of protein may be determined by treating with ninhydrin in a mixture of acetic acid and 0.6m-phosphoric acid (reagent a) for 10min at 100°C, the extinction being linear for tryptophan in the range 0.05–0.9μmol. N-Terminal tryptophan peptides also give the typical yellow product on treatment with reagent a. 3. Tryptophan content of several pure intact proteins when treated with the above method gave values in good agreement with those reported by others. A mean tryptophan content of 11.25 (s.e.m. ±0.08) μmol/100mg of protein was found in rat brain during development from 1 to 82 days after birth.
TL;DR: It seems that serum is necessary for the initiation of the cycle but may not be necessary continuously in the medium for completion of the cycles, which can lead to growth in a medium which does not promote growth.
TL;DR: Two different subcellular fractionation techniques were applied to guinea-pig intestinal mucosa and the composition of the brush borders prepared by the two methods were compared and the possible role of peptidases in protein digestion is discussed.
Abstract: 1. Two different subcellular fractionation techniques were applied to guinea-pig intestinal mucosa and the composition of the brush borders prepared by the two methods were compared. 2. By using a kinetic assay system the subcellular distribution of activity against ten dipeptides and five tripeptides was studied. 3. Only small amounts (5–10%) of activity against dipeptides were found in the brush-border region, the enzymes being concentrated in the cytosol. 4. Significant amounts (10–60%) of activity against tripeptides were found in the brush border with the remainder largely present in the soluble fraction. 5. The relevance of these studies to the localization in vivo and the possible role of peptidases in protein digestion is discussed.
TL;DR: It is suggested that the gene for the α‐chain of the South East Asian haemoglobin is linked with one for α thalassaemia.
Abstract: Summary Six samples of Haemoglobin Q were examined, three from Iran, two from Thailand, and one from California (Chinese). They all yielded identical fingerprints. The substitution was found to be α74 or 75 aspartic acidhistidine in five of the samples. In one from Thailand ‘sequencing’ established the mutation to be at position α74 (EF3), and in one from Iran it was at position α75 (EF4). It is suggested that the gene for the α-chain of the South East Asian haemoglobin is linked with one for α thalassaemia.
TL;DR: There is reason to suspect a common or related cause for diseases which are both associated with one another in their geographical distribution and tend to occur together in the same patients.
TL;DR: Levodopa (L-dopa) produced in three patients a striking though temporary improvement in the level of consciousness together with striking improved in the previously abnormal electroencephalographic (E.G.) recordings, suggesting that a defect of dopaminergic neurotransmission is present in hepatic coma.
TL;DR: In this paper, the properties of oxalic acid are reviewed, together with the use that may be made of these in various methods for oxalate analysis, which are critically compared.
Abstract: The properties of oxalic acid are reviewed, together with the use that may be made of these in various methods of oxalate analysis, which are critically compared. Information is given on the oxalate content of biological fluids, urinary calculi, tissues, and foods.
TL;DR: A technique for the study of local metabolic changes in coronary venous blood draining from a small area of ischemic myocardium, characterized by acute S-T segment elevation in the epicardial electrocardiogram, is described.
Abstract: A technique for the study of local metabolic changes in coronary venous blood draining from a small area of ischemic myocardium is described. Overt left ventricular failure, ventricular arrhythmias and possible secondary effects on local metabolic changes were avoided. Metabolic changes in local coronary venous blood and in coronary sinus blood were compared. Gross changes detected by local coronary venous sampling were not observed in coronary sinus blood samples. The possible relevance of this observation to clinical studies was noted. The small ischemic lesion usually involved less than 10 percent of the heart volume and was characterized by acute S-T segment elevation in the epicardial electrocardiogram and by positive changes in values for local coronary venous blood lactate, pyruvate, lactate/ pyruvate ratio, glucose, potassium and phosphate. Free fatty acids and beta hydroxybutyrate and acetoacetate levels were also studied. The technique and its results are compared with other methods of study of the metabolism of ischemic heart tissue.
TL;DR: A longitudinal study of the effects of ageing on bone mass, height, and body weight was made in random samples of a defined population of elderly men and women, and the women tended to lose more bone than the men.
Abstract: Summary A longitudinal study of the effects of ageing on bone mass, height, and body weight was made in random samples of a defined population of elderly men and women. The observations were made twice with an interval of 11 years between them. At initial survey ages ranged from 55 to 64 years. Bone mass was assessed from measurements of the second metacarpal cortex made directly from radiographs. Loss of bone occurred in both sexes but this was not a universal phenomenon; some men and women lost little or no bone over the period of study. In those persons in whom bone loss did take place this happened at different rates; and the women tended to lose more bone than the men.Change in bone mass in the metacarpal was not related to loss of heigh, change in body weight, the occurence of fracture, or the presence of back pains. A separate population of persons with the clinical syndrome of senile osteoporosis was not identified.
TL;DR: In three patients with the carcinoid syndrome the necrosis was reflected biochemically by an immediate and striking rise in urinary 5-hydroxyindoleacetic-acid excretion followed by a return towards normal levels, and in these patients it is preferable to precede hepatic-artery ligation by a period of hepatotoxic infusion with cytotoxic drugs to ensure more controlled release of metabolites.