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Showing papers by "Medical Research Council published in 1973"


Journal ArticleDOI
TL;DR: With some antisera the immunoreactivity of the antigen was diminished by the introduction of a single I atom into the tyrosyl groups, whereas antigen containing a single (125)I-labelled 3-(4-hydroxyphenyl)propionamide group showed the same immunore activity as the unmodified antigen.
Abstract: 1. A new method is described for labelling proteins to high specific radioactivities with (125)I. The protein is treated with a (125)I-labelled acylating agent, iodinated 3-(4-hydroxyphenyl)propionic acid N-hydroxysuccinimide ester, which reacts with free amino groups in the protein molecule to attach the (125)I-labelled groups by amide bonds. 2. Three protein hormones have been labelled by this method, human growth hormone, human thyroid-stimulating hormone and human luteinizing hormone. Specific radioactivities of up to 170, 120 and 55muCi/mug respectively have been obtained for these hormones. 3. The immunoreactivity of these labelled hormones has been investigated by using a radioimmunoassay system specific for each hormone. These preparations have also been compared with and found to be equal or superior to labelled hormones prepared by chemical substitution of (125)I into tyrosine residues of the proteins by using the chloramine-t-oxidation procedure. 4. With some antisera the immunoreactivity of the antigen was diminished by the introduction of a single I atom into the tyrosyl groups, whereas antigen containing a single (125)I-labelled 3-(4-hydroxyphenyl)propionamide group showed the same immunoreactivity as the unmodified antigen.

3,120 citations


Journal ArticleDOI
TL;DR: In the procedure presented here, hydrogen peroxide is measured by reaction with quadrivalent titanium and xylenol orange, which constitutes a one-enzyme assay with stable reagents, which does not require protein precipitation and is not subject to interference from hemoglobin or bilirubin.
Abstract: I describe the characterization, extraction, and purification of a cholesterol:oxygen oxidoreductase (EC 1.1.3.6) from Nocardia sp. This enzyme catalyzes oxidation of cholesterol to Δ4-choIestenone, with production of hydrogen peroxide. It is very stable, active over a wide pH range, and has a Km of 1.4 x 10-5 mol/ liter. It is highly specific for Δ4- or Δ5-3β-hydroxycholestanes, and may be applied to the assay of serum total cholesterol. In the procedure presented here, hydrogen peroxide is measured by reaction with quadrivalent titanium and xylenol orange. This constitutes a one-enzyme assay with stable reagents, which does not require protein precipitation and is not subject to interference from hemoglobin or bilirubin.

1,476 citations


Journal ArticleDOI
TL;DR: The C-protein molecule contains a single polypeptide chain of molecular weight 140,000 and the intrinsic viscosity of 13.6 ml/g suggests that the molecule is neither completely globular nor as elongated as molecules like paramyosin or tropomyosin.

582 citations


Journal ArticleDOI
TL;DR: The 10-year results of a controlled trial of a policy of surgery and a strategy of radical radiotherapy in the treatment of patients with small-cell or oat-celled carcinoma of the bronchus diagnosed preoperatively on bronchial biopsy and thought likely to be operable were given in this paper.

474 citations


Journal ArticleDOI
TL;DR: The work reported here was undertaken to remedy what were seen as three important deficiencies that reduced the usefulness of the S.R.E.M.R .E.

349 citations


Journal ArticleDOI

260 citations


Journal ArticleDOI
TL;DR: This paper examined the relationships to be expected between different aspects of climate and various dimensions of organizational structure and context and examined the suggested relationships using data from 387 respondents working at all levels in 14 different work organizations.
Abstract: The authors would like to thank John Fairhead for his help with the fieldwork, Mrs. P. Clark and Mrs. R. Goodkin for their help in data handling, and Diana Pheysey for her many contributions to all aspects of the study. This paper considers the concept of organizational climate and examines the relationships to be expected between different aspects of climate and various dimensions of organizational structure and context. The suggested relationships are examined using data from 387 respondents working at all levels in 14 different work organizations. Examination of the effect of hierarchical level on perceptions of organizational climate showed significant variations by level.1

245 citations


Journal ArticleDOI
TL;DR: All patients with anorexia nervosa were extracted from three psychiatric case registers and in all three areas the number of cases reported per year was increasing, and in Camberwell, but not in Monroe County or North-East Scotland, there was a significant excess of patients from middle-class backgrounds.
Abstract: All patients with anorexia nervosa were extracted from three psychiatric case registers— North-East Scotland, Camberwell, and Monroe County. The average incidence varied from 0·37 per 100,000 population per year in Monroe County to 1·6 per 100,000 in North-East Scotland, in all three areas the number of cases reported per year was increasing, and in Camberwell, but not in Monroe County or North-East Scotland, there was a significant excess of patients from middle-class backgrounds.

235 citations



Journal ArticleDOI
TL;DR: Patients with residual symptoms on entry to the trial derived more benefit from continuation therapy than patients who had made a complete recovery, and any possible advantage of continuation therapy over a longer period remains uncertain.
Abstract: A double-blind clinical trial has been carried out to ascertain whether patients making a good recovery from depressive illness with tricyclic antidepressant medication derive any benefit from continuation of therapy with the same drug at a lower dose level. Of the 92 patients who entered the trial significantly fewer on active treatment relapsed during the six-month trial period: 22% as compared with 50% of patients receiving placebo. Patients with residual symptoms on entry to the trial derived more benefit from continuation therapy than patients who had made a complete recovery. The findings relate to a six-month trial period only, and any possible advantage of continuation therapy over a longer period remains uncertain.

216 citations



Journal ArticleDOI
TL;DR: The semi-defined medium contains an acid hydrolysate of casein : in the empirically devised defined medium the casein requirement has been circumvented by inclusion of additional vitamins and amino acids, which are very hypertonic.
Abstract: Semi-defined and defined media for the growth of culture forms of Trypanosoma brucei sspp. have been developed by enrichment of tissue culture medium 199 with additional vitamins, amino acids, salts and other compounds. The semi-defined medium contains an acid hydrolysate of casein: in the empirically devised defined medium the casein requirement has been circumvented by inclusion of additional vitamins and amino acids. Both media are very hypertonic. Control of pH was found to be particularly critical for growth. The optimum temperature for growth in the semidefined medium was between 25°C and 28°C, but cells would undergo one or two division cycles at 37°C.

Journal ArticleDOI
TL;DR: The authors found that the presence of words interferes with the task of naming colours and suggested a modification of the usual account such that stress is laid on the correspondence between the nature of the response (verbal) and that feature of a stimulus which will dominate.
Abstract: In the Stroop test it is found that the presence of words interferes with the task of naming colours. The usual account of this phenomenon is that the names of words are more readily obtained than are the names of colours and that the production of the latter is interfered with by the spontaneous occurrence of the former. Treisman and Fearnley (1969) have suggested a modification of the usual account such that stress is laid on the correspondence between the nature of the response (“verbal”) and that feature of a stimulus which will dominate. The present experiments seem to demonstrate that the data which Treisman and Fearnley use in support of their claim can be attributed to the strategy which their subjects adopted in their task. Some further observations are made concerning the different levels at which comparisons can be made between two stimuli.

Journal ArticleDOI
TL;DR: Analysis of the fate of d‐[U‐14C] glucose given subcutaneously 5 min before death showed that glucose uptake was reduced, however brain glucose concentration rose three to five‐fold 20–30 min after 2‐deoxy‐d‐glucose, and the majority of glucose entering the brain after 10 min of 2‐ deoxy‐ d‐glUCose treatment was recovered as glucose.
Abstract: —The time course of effects of 2-deoxy-d-glucose on cerebral glucose metabolism has been studied in vivo and the inhibitory actions of 2-deoxy-d-glucose and 2-deoxy-d-glucose-6-phosphate on cerebral glycolytic enzymes in vitro. Mice were given 2-deoxy-d-glucose 3 g/kg intraperitoneally. Blood 2-deoxy-d-glucose/glucose ratio was 2–3 from 5 to 30 min after injection, the hyperglycaemic response to 2-deoxy-d-glucose having been suppressed with propranolol. Maximal cerebral 2-deoxy-d-glucose uptake observed was 1μ11 μmol/g/min between 5 and 10 min after injection. At 10 min brain concentrations of 2-deoxy-d-glucose and 2-deoxy-d-glucose-6-phosphate were 5·82 and 3·12 μmol/g. Analysis of the fate of d-[U-14C] glucose given subcutaneously 5 min before death showed that glucose uptake was reduced to 40–60 per cent of control from 5 to 30 min after 2-deoxy-d-glucose. However brain glucose concentration rose three to five-fold 20–30 min after 2-deoxy-d-glucose. The majority of glucose entering the brain after 10 min of 2-deoxy-d-glucose treatment was recovered as glucose. Conversion of brain glucose to other acid soluble components was reduced to 1/3 at 10 min and 1/5 at 20–30 min. Glucose-6-phosphate concentration rose from 5 min onwards and was maintained at twice control concentration from 10–30 min. However, because of the rapid entry of 2-deoxy-d-glucose and its conversion to 2-deoxy-d-glucose-6-phosphate, the 2-deoxy-d-glucose 6-P/glucose 6-P ratio was between 19 and 32. Brain adenosine triphosphate concentration did not change, creatine phosphate concentration fell after 25 min. Measurement of enzyme activities in cerebral homogenates (using 1 mivs substrate concentration) showed that hexokinase (EC 2.7.1.1) was 40 per cent inhibited by 5 mm-deoxy-d-glucose (but not by 2-deoxy-d-glucose 6-P). Glucose 6-P dehydrogenase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 1.1.1.43) and phosphoglucomutase (EC 2.7.5.1) were not affected by either 2-deoxy-d-glucose (5 mm) or 2-deoxy-d-glucose 6-P (5 or 20 mm). Hexose-phosphate isomerase (EC 5.3.1.9) was 70 per cent inhibited by 20 mm-d-deoxy-d-glucose 6-P. Phosphofructokinase (EC 2.7.1.11) was inhibited by 17 per cent by 2-deoxy-d-glucose 6-P (20 mm). During the initial impairment of cerebral function by 2-deoxy-d-glucose there is competitive inhibition of glucose transport into the brain; later, glycolysis is more powerfully depressed by the inhibition of isomerase produced by the high intracerebral concentration of 2-deoxyglucose-6-phosphate.

Journal ArticleDOI
TL;DR: Activity of glutamic-acid decarboxylase was found to be reduced by 80-90% in the basal ganglia of the choreic group when compared with the controls, suggesting that there may be a selective reduction in the activity of G.A.B.A.-containing neurons in basal Ganglia in patients with Huntington's chorea.

Journal ArticleDOI
TL;DR: It is suggested that maternal serum-A.F.P. levels may be useful in the screening of large numbers of pregnancies for possible central-nervous-system malformations.


Journal ArticleDOI
TL;DR: Inhibition of GAD activity was evident 30–60 min before seizure onset following allylglycine or 4‐deoxypyridoxine administration, and was maximal just before or during seizure activity.
Abstract: 1. DL-C-Allyglycine, 4-deoxypyridoxine hydrochloride and 3-mercaptopropionic acid have been studied with reference to their convulsant effects in mice and in baboons (Papio papio) with photosensitive epilepsy, and their action on the cerebral enzyme synthesizing γ-aminobutyric acid (L-glutamate-1-carboxy-lyase). 2. In mice, the ED50 values for seizures following intraperitoneal injection were allylglycine 1·0 mmol/kg body weight, 4-deoxypyridoxine 1·1 mmol/kg and 3-mercaptopropionic acid 0·27 mmol/kg. Latency to seizure onset was longest after allylglycine (44-240 min), intermediate after 4-deoxypyridoxine (9-114 min) and shortest after 3-mercaptopropionic acid (2·5-8 min). 3. In Papio papio intravenous administration of subconvulsant doses of allylglycine (0·87-3·1 mmol/kg), or of 4-deoxypyridoxine (0·21-0·53 mmol/kg) enhanced the occurrence and persistence of myoclonic responses to intermittent photic stimulation, and augmented the associated electroencephalographic abnormalities, without modifying their character or distribution. Higher doses produced brief seizures recurring at regular intervals, between 2-14 h after allylglycine (4·0-4·3 mmol/kg) or 1-4 h after 4-deoxypyridoxine (0·53-0·87 mmol/kg). Electroencephalographically these seizures originated unilaterally in the occipital or posterior parietal cortex. 4. In Papio papio photically-induced epileptic responses were enhanced 5-10 min after the intravenous injection of 3-mercaptopropionic acid (0·09-0·28 mmol/kg). A sequence of brief generalized seizures followed by complete recovery occurred 4-17 min after the injection of 3-mercaptopropionic acid (0·28-0·38 mmol/kg). Fatal status epilepticus followed the injection of 3-mercaptopropionic acid (0·57-0·75 mmol/kg). E.E.G. records showed generalized cortical involvement at the onset of the seizures. 5. L-Glutamate 1-carboxy-lyase (GAD) activity was determined in whole brain homogenates from mice killed at various intervals after receiving i.p. a convulsant dose of one of the compounds. Inhibition of GAD activity was evident 30-60 min before seizure onset following allylglycine or 4-deoxypyridoxine administration, and was maximal (40-60%) just before or during seizure activity. Addition of pyridoxal phosphate to the brain homogenate relieved inhibition produced by 4-deoxypyridoxine but not that produced by allylglycine. Inhibition of GAD activity in brain homogenates from animals killed 2 or 4 min after injection of a convulsant dose of 3-mercaptopropionic acid varied from 0-49% depending on the dose of 3-mercaptopropionic acid and the concentration of substrate in the assay system. 6. Kinetic analysis of the inhibition of GAD activity following direct addition of the compounds to mouse brain homogenates indicated that 3-mercaptopropionic acid (0.01-0.5 mM) was competitive with respect to the substrate. A comparable percentage inhibition of GAD activity was obtained only with much higher concentrations of 4-deoxypyridoxne, i.e. 10-50 mM. Allylglycine in vitro was a very weak inhibitor of GAD activity. 7. Three biochemically different mechanisms underlie the inhibition of cerebral GAD activity that precedes seizures induced by ailylglycine, 4-deoxypyridoxine and 3-mercaptopropionic acid. The data are consistent with a critical reduction in the rate of synthesis of γ-aminobutyric acid being responsible for the onset of seizures.

Journal ArticleDOI
TL;DR: The combination of normal unbound-plasma- œstradiol and reduced unbound androgen levels of hypo- gonadism in chronic liver disease and increased hepatic S.B.H.G. production is suggested.

Journal ArticleDOI
TL;DR: Ileal resection may increase the load delivered to the colon, resulting in diarrhœa when the absorptive capacity of the colon is reduced by disease or resection, and it is important to preserve as much colon as possible at operation to contribute significantly to the future wellbeing of the patient.


Journal ArticleDOI
TL;DR: The results imply that the accumulation of fluid in oedematous grey matter is confined to the astrocytic compartment, which implies that the reversibility or otherwise of all the neuronal alterations is discussed.
Abstract: A combined light and electron microscope study was made of the alterations occurring in the neurones and astrocytes of the neocortex and hippocampus of rats killed immediately after intermittent exposures to nitrogen of 5 and 15 min. Blood flow in the right common carotid artery had previously been interrupted by application of an artery clasp which was removed after the exposure to nitrogen and the animals killed by perfusion-fixation with glutaraldehyde. Microvacuolation (MV), the earliest stage of anoxic-ischaemic neuronal damage, was observed in the ipsilateral neocortex and hippocampus of both groups and ischaemic cell change (ICC) bilaterally in the neocortex of animals exposed for 15 min. Ultrastructural examination showed the microvacuoles to be swollen mitochondria. Slightly dense, mildly distorted, non-vacuolated neurones were also seen in the neocortex and hippocampus. They did not exhibit the ultrastructural changes seen in MV and ICC. Swollen astrocytic processes were sometimes seen around the damaged neurones, more frequently after 15 min exposure. Slight swelling of perivascular astrocytic processes was occasionally observed while the extracullular spaces in the neuropil remained unaltered. This implies that the accumulation of fluid in oedematous grey matter is confined to the astrocytic compartment. The reversibility or otherwise of all the neuronal alterations is discussed.

Journal ArticleDOI
TL;DR: One of the compensatory mechanisms for the severe depression of mitotic activity in the brain of undernourished animals Seems to involve a reduction in the normal rate of cell loss.
Abstract: — Rats were undernourished by approximately halving the normal food given from the 6th day of gestation throughout lactation. Growth of the foetuses was nearly normal, in marked contrast to the severe retardation caused by undernutrition during the suckling period. In comparison with controls the size and the DNA content of the brain were permanently reduced by undernutrition during the suckling period: this effect was relatively small, approx. 15 per cent decrease at 21 and 35 days. The rate of 14C incorporation into brain DNA at 30 min after administration of [2-14C] thymidine was taken as an index of mitotic activity; compared with controls there was severe reduction in mitotic activity (maximal decrease by about 80 per cent at 6 days in the cerebrum and by 70 per cent at 10 days in the cerebellum). The rate of acquisition of cells was calculated from the slopes of the logistic curves fitted to the estimated DNA contents. In normal animals the maximal slope was attained at 2·7 days and at 12·8 days after birth in cerebrum and cerebellum respectively; the daily acquisition of cells at these times was 4·8 × 106 and 18 × 106 cells respectively. The fractional increase in cell number at the maximum was 5·4 percent per day in the cerebrum and 15·2 per cent per day in the cerebellum. The rate of acquisition of cells relative to the rate of mitotic activity was higher in the brains of undernourished animals than in controls. One of the compensatory mechanisms for the severe depression of mitotic activity in the brain of undernourished animals Seems to involve a reduction in the normal rate of cell loss.

Journal ArticleDOI
TL;DR: In this article, Billewicz et al. showed that subtle and progressive changes in the shape of the glucose response curve were observed in healthy pregnant women with no family history of diabetes.

Journal ArticleDOI
19 Oct 1973-Nature
TL;DR: The question arises of why one administration of a carcinogenic methyl-nitroso compound, or of most other liver carcino gens, rarely induces liver cancer in the intact adult rat, and a high incidence of liver cell cancer could be induced by one treatment with a nitrosamine if given after partial hepatectomy.
Abstract: AN outstanding problem in understanding the mechanism of carcinogenesis by nitroso compounds is the apparent immunity of the liver to a single treatment with the carcinogen. While dimethylnitrosamine (DMN) in the diet induces tumours in liver and kidney of rats, a single injection given to adult animals usually induces only kidney tumours1. One treatment with nitrosomethylurea (NMU) induces tumours in many tissues, but not in liver2,3. In each case, liver cells have been transformed by treatment in vitro with the carcinogen4. There fore the question arises of why one administration of a carcinogenic methyl-nitroso compound, or of most other liver carcino gens, rarely induces liver cancer in the intact adult rat. One answer is suggested by experiments in which a high incidence of liver cell cancer could be induced by one treatment with a nitrosamine if given after partial hepatectomy.

Journal ArticleDOI
TL;DR: The possible role of environmental stress in precipitating the onset or relapse of acute schizophrenia was investigated by Brown and Birley (1968), Birley and Brown (1970), and two small sub-groups found that 4 of 13 patients who relapsed after reducing or discontinuing phenothiazine therapy had experienced a life event in the three weeks before relapse.
Abstract: The possible role of environmental stress in precipitating the onset or relapse of acute schizophrenia was investigated by Brown and Birley (1968), Birley and Brown (1970). They enquired about events which could be dated to a definite point in time and which usually involved either actual or threatened danger or important fulfilments or disappointments. They distinguished between independent events, which were outside the control of the subject, and possibly independent events, which were not so clearly out of his control but which seemed unlikely to be produced by unusual behaviour of the subject himself. In their main group of patients a significant concentration of independent events (about 60 per cent) was found in the three weeks preceding onset or relapse of schizophrenia. In examining two small sub-groups they found that 4 of 13 patients (31 per cent) who relapsed after reducing or discontinuing phenothiazine therapy had experienced a life event in the three weeks before relapse, compared with 3 of 5 patients (60 per cent) who had been taking phenothiazines regularly at the time of relapse. Although these proportions are very different, the numbers in the groups are too small for the difference to reach significance. Furthermore the groups were not matched in any way, and there may be important differences between patients who discontinue medication themselves and those who carry on taking it regularly.


Journal ArticleDOI
TL;DR: The results are consistent with the view that thyroid deficiency may lead not only to quantitative but also to qualitative changes in synaptic organization: the ‘wiring’ pattern in the cerebellum persists for a long time in an immature form which could favour the dominance of the climbing fibre-Purkinje cell circuit over the mossy fibre- granule cell- Purkinje circuit.

Journal ArticleDOI
TL;DR: In many instances it was possible to identify the enzyme forms characterizing clones of parasite in individual blood samples, but rarely to estimate the actual number of clones present in a given sample.
Abstract: A study has been made of electrophoretic forms of enzymes of P. falcaparum in samples of blood from Gambian women and children. Variation was found in each of the 3 enzymes examined. 2 forms of parasite GPI, labelled GPI-1 and GPI-2, 2 forms of parasite LDH, labelled LDH-1 and LDH-2 and 3 forms of parasite 6PGD, labelled 6PGD-1, 6PGD-2 and 6PGD-3 were identified. Different combinations of enzyme forms occurred among different samples demonstrating genetic diversity of the parasite within and between blood samples. The distribution of enzyme forms among the samples suggested that the parasites belong to a single mendelian population. From statistical considerations of the distribution of enzyme forms among the samples it was estimated that the samples contained an average of about 2 parasite clones each. It was also possible to estimate the frequencies of variant forms of GPI among parasite clones as 0·62 and 0·38 for GPI-1 and GPI-2 respectively and LDH as 0·76 and 0·24 for LDH-1 and LDH-2 respectively. 6PGD-1 occurred in about 95% of blood samples showing activity of this enzyme, the remaining variants of 6PGD occurred in only 2 samples each. In many instances it was possible to identify the enzyme forms characterizing clones of parasite in individual blood samples, but rarely to estimate the actual number of clones present in a given sample. In a few samples, however, in which a single form of each enzyme occurred it could be estimated that probably only 1 parasite clone was present.

Journal ArticleDOI
TL;DR: The toxic compound dioxin (dioxin) was shown to cause pericardial oedema and death in chickens after a single oral dose of 25-50 μg/kg and the extreme toxicity to the guinea-pig was confirmed.