Showing papers by "Medical Research Council published in 1975"
TL;DR: The body cholesterol pool increases with decreasing plasma-high-density-lipoprotein (H.D.L.) but is unrelated to the plasma concentrations of total cholesterol and other lipoproteins, and it is proposed that a reduction of plasma-H.H.L.D., is reduced in several conditions associated with an increased risk of future ischaemic heart-disease, by impairing the clearance of cholesterol from the arterial wall.
2,626 citations
TL;DR: This article explored the hypothesis that immediate memory span is not constant, but varies with the length of the words to be recalled, finding that words of short temporal duration are better recalled than words of long duration.
1,892 citations
TL;DR: Proteolytic activity was demonstrated in semi-purified trypanosome extracts, providing one reason for the heterogeneity sometimes observed in surface glycoprotein antigen preparations.
Abstract: Soluble glycoproteins have been purified from a series of clones of Trypanosoma brucei 427. Each clone yielded a characteristic predominant glycoprotein which induced clone-specific immunity to trypanosome infection in mice. These glycoproteins were shown by specific labelling and enzyme digestion of cells to be the major components of the trypanosome surface coat. Each glycoprotein consisted of a single polypeptide chain having an apparent molecular weight of 65 000 (as measured by SDS-polyacrylamide gel electrophoresis) and containing around 600 amino acid and 20 monosaccharide residues. Preliminary structural studies indicated large changes in amino acid sequence dispersed over a considerable length of the polypeptide chain. Proteolytic activity was demonstrated in semi-purified trypanosome extracts, providing one reason for the heterogeneity sometimes observed in surface glycoprotein antigen preparations.
845 citations
TL;DR: Attention should be focused on fruit and vegetable gels rather than wheat fibre in the search of natural hypocholesterolaemic agents, according to this small study of healthy volunteers taking normal diet.
291 citations
TL;DR: It is discussed that evaluation of the UCS by the subject, shown to be a sufficient condition for learning, may also be the only necessary condition, which would imply a model of conditioning based on affective evaluation rather than on response production.
252 citations
01 Jun 1975
TL;DR: The aim of the Toxicology Unit is to establish the basic concepts necessary for explaining at a molecular level the mechanisms of toxicity and of chemical and physical injury.
Abstract: “The aim of the (Toxicology) Unit is to establish the basic concepts necessary for explaining at a molecular level the mechanisms of toxicity and of chemical and physical injury.”
241 citations
TL;DR: In this article, the mechanism by which some phosphinates protect hens against neurotoxic compounds is explained, and the effects of compounds on NE activity of hen brain in vitro and in vivo are assessed.
Abstract: Evidence is reviewed that the initial biochemical event leading to delayed neurotoxicity is phosphorylation of the active site of a specific enzyme called Neurotoxic Esterase. This is followed by a bondcleavage (? hydrolytic) leading to formation of a mono-substituted phosphoric acid residue on the protein. The mechanism by which some phosphinates protect hens against neurotoxic compounds is explained. Assay of effects of compounds on Neurotoxic Esterase activity of hen brain in vitro and in vivo provides a quick biochemical screen to supplement the 3-week clinical test. This test provides an estimate of safety margin for compounds which give negative results in the clinical test and are currently used as pesticides, plasticisers, etc. Simplified assay procedures are being developed. Data is now available for the biochemical and neurotoxic activity of many compounds. This provides a basis for structure/activity predictions; neurotoxicity data published since 1930 has been assessed in this light.
240 citations
TL;DR: Evidence is presented confirming that, for cytogenetic dosimetry, in vitro dose-response curves of unstable chromosome aberrations in human lymphocytes should be prepared by irradiating whole blood maintained at 37 degrees C and prior to PHA stimulation.
Abstract: In vitro dose-response curves of unstable chromosome aberrations in human lymphocytes have been obtained for 250 kV X-rays and cobalt-60gamma-radiation. The aberration yields have been fitted to the quadratic function Y = alphaD +betaD2, which is consistent with the single-track and two-track model for aberration formation. The values of the coefficients alpha and beta support the hypothesis that the dose-rate effect is limited to the D2 term. The main difference between the coefficients for X- and gamma-radiation is in the alpha values, indicating that X-rays are slightly more efficient, at lower doses, in producing two lesions with a single ionizing track. The lower limits of dose estimate, with 500 cells analysed, are 4 rad for X-rays and 10 rad gamma-radiation. Further evidence is presented confirming that, for cytogenetic dosimetry, in vitro dose-response curves should be prepared by irradiating whole blood maintained at 37 degrees C and prior to PHA stimulation. Curves were plotted showing the variation of the number of cells without aberrations with radiation dose and the shape of these curves were compared with those from human cell survival experiments.
231 citations
TL;DR: The x-ray analysis of the monoclinic form of yeast tRNAPhe has been taken to a resolution of 2.5 A by the method of isomorphous replacement and an extensive hydrogen bonding network is described involving specific interactions between bases and the ribose-phosphate backbone.
Abstract: The x-ray analysis of the monoclinic form of yeast tRNAPhe has been taken to a resolution of 2.5 A by the method of isomorphous replacement. The model proposed at 3 A has been confirmed and extended to reveal additional features of the tertiary structure and of the stereochemistry. An extensive hydrogen bonding network is described involving specific interactions between bases and the ribose-phosphate backbone. The structure of a G-U base pair has been solved.
228 citations
TL;DR: The C-protein in native thick filaments is probably bound to the shaft of the filament with a periodicity determined by the underlying myosin assembly, and binding measurements at low ionic strength reveal a strong affinity for myosIn and also for rod and light meromyosin.
TL;DR: End-expiratory sampling of breath H2 would seem to be a simple, non-invasive, and accurate method of diagnosing hypolactasia, which is also very acceptable to patients, which should make it a valuable tool both in diagnostic gastroenterology and in epidemiological surveys.
TL;DR: TMV RNA, like many animal cellular and viral mRNAs recently examined, has a 5' terminus blocked by a methylated nucleotide inverted with respect to the rest of the chain, yielding products which imply the structure m7G5'ppp5'Gp.
Abstract: RNA extracted from CsC1-purified virions of tobacco mosaic virus is shown to give rise to an unusual nucleotide on digestion which RNAase T2, in addition to the four major nucleotides. This minor component has the electrophoretic characteristics of a phosphorylated end group, but is partially resistant to bacterial alkaline phosphatase. It is, however, a substrate for venom phosphodiesterase or nucleotide pyrophosphatase, yielding products which imply the structure m7G5'ppp5'Gp. TMV RNA, like many animal cellular and viral mRNAs recently examined, therefore has a 5' terminus blocked by a methylated nucleotide inverted with respect to the rest of the chain.
TL;DR: In preliminary performance trials, the four-choice test appeared to reflect fatigue due to continuous repetitive responding in a way similar to classical, nonportable, multiple-choice serial reaction tests, but over a shorter time scale and with greater internal consistency.
Abstract: A small (20 × 11 × 6 cm), battery-powered, fully portable device is described for administering a four-choice serial reaction time test and recording the results on a standard magnetic tape cassette. The mains-powered decoder through which the tape is subsequently replayed is also described. The main application is the self-administration of the test by the subject in the field, particularly in studies of environmental stress, the data-bearing cassettes being passed to the experimenter for laboratory-based analysis. In preliminary performance trials, the four-choice test appeared to reflect fatigue due to continuous repetitive responding in a way similar to classical, nonportable, multiple-choice serial reaction tests, but over a shorter time scale and with greater internal consistency.
TL;DR: The similarity of the mortality relationship to that for burns suggests that both the I.S.S.'s and surface area of burn are comparable measures of the lethality of injury and the Probit fits suggest that at given ages there are normal distributions of susceptibility.
TL;DR: Knowing the positions at which the five restriction enzymes cleave the genomes of the parental serotypes, it was possible to decide which regions of each recombinant DNA are composed of Ad5 and which of Ad2+ND1 sequences.
TL;DR: Two infants investigated for allergy to cow's milk proteins exhibited a local reaginic reaction in the small intestine after ingestingCow's milk, as shown by increased mucosal IgE plasma-cells and degranulation of mast cells, indicating several simultaneous immune reactions in the intestinal mucosa.
TL;DR: The structure-activity relationships presented give some guidance for design of non-neurotoxic pesticides and more stable and less toxic alternatives to Mipafox as a selective inhibitor of neurotoxic esterase have been found.
TL;DR: Findings support the hypothesis that immunoglobulins and complement are present in vessels of some patients prior to chemotaxis of polymorphonuclear leukocytes and the resulting inflammatory purpuric lesions so characteristic of necrotizing vasculitis.
TL;DR: Results indicate that the measurement of plasma beta-thromboglobulin concentrations may be of use in the diagnosis of deep venous thrombosis.
TL;DR: The amino acid compositions of several culture media have been analysed and compared: glutamine was consumed more rapidly than glutamic acid, which was itself used at about the same rate as proline, and threonine was cleaved to form glycine and acetate, which accumulated in the medium.
Abstract: The amino acid compositions of several culture media have been analysed and compared. The utilization and excretion of amino acids and other metabolites have been followed during growth of Trypanosoma brucei S42 in a defined medium. All of the added L-threonine was metabolized by the cells, even when it was present at elevated concentrations. Glucose was consumed throughout the growth cycle: glutamine was consumed more rapidly than glutamic acid, which was itself used at about the same rate as proline. Threonine was cleaved to form glycine and acetate, both of which accumulated in the medium. Alanine and succinate were excreted together with a small amount of pyruvate, but these three products accounted for less than half of the glucose used. CO2 production from glucose was not measured, but insignificant amounts of CO2 were produced from threonine. Tetraethylthiuram disulphide blocked the cleavage of threonine and was a potent inhibitor of trypanosome growth.
TL;DR: The early components of the auditory evoked responses (waves I-V) have been studied in 30 patients with multiple sclerosis and all patients with an internuclear ophthalmoplegia and half those with no detectable brainstem abnormality had abnormal responses, although none was clinically deaf.
TL;DR: A rapid 5 h radioimmunoassay method for the determination of progesterone and oestradiol in the plasma of non‐pregnant women is described, due to the high specificity of the antisera used, without employing chromatographic purification of the steroids.
Abstract: SUMMARY
A rapid 5 h radioimmunoassay method for the determination of progesterone and oestradiol in the plasma of non-pregnant women is described. Due to the high specificity of the antisera used, it is possible to perform the radioimmunoassay directly on the ether extracts of plasma, without employing chromatographic purification of the steroids.
Evidence is presented indicating that the rapid assay is almost as reliable as the previously described radioimmunoassay method which involves chromatography. The within-assay and between-assay coefficients of variation in the progesterone assay were 7.74 and 14.9 and in the oestradiol assay 7.36 and 18.1 respectively. Comparisons between increasing doses of authentic hormone and endogenous hormone extracted from plasma indicated no deviation from parallelism. Progesterone and oestradiol were assayed in 300 plasma samples by the rapid method and by the method involving chromatography. The slopes obtained by a regression analysis were close to unity for both progesterone and oestradiol (1.04 and 1.06, respectively), the y-intercepts were −0.21 and −0.16 and the correlation coefficients 0.98 and 0.88, respectively. When the data obtained by both techniques in fourteen menstrual cycles were compared, the results were practically identical.
In ten repeated studies conducted by four investigators it was shown that two workers can complete the assay of both progesterone and oestradiol in twentyfive plasma samples in duplicates within 5 h. The same time is required for the assay of either progesterone or oestradiol in twenty-five duplicates by one worker.
TL;DR: A radioimmunoassay method developed previously for the measurement of unconjugated pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone and oestradiol in peripheral plasma was applied to the assay of these steroids in seminal plasma of normal, oligospermic and azoOSpermic males.
Abstract: A radioimmunoassay method developed previously for the measurement of unconjugated pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone and oestradiol in peripheral plasma was applied to the assay of these steroids in seminal plasma of normal, oligospermic and azoospermic males. It was not possible to use the plasma assay method for the determination of progesterone and oestrone in seminal plasma, because some of the reliability criteria were not fulfilled. A detailed analysis of these steroids in the peripheral plasma of the same subjects has been described previously. The levels of all steroids in seminal plasma were significantly lower than the corresponding blood levels. The ratios of blood plasma/seminal plasma levels of the various steroids varied from 37 (testosterone) to 1.7 (dihydrotestosterone). There was a positive correlation between the testosterone and dihydrotestosterone levels of the seminal plasma of normal and azoospermic subjects. The concentrations of dihydrotestosterone, pregnenolone and oestradiol were significantly lower in azoospermic subjects than in normals. The only pathological finding in the seminal plasma of oligospermic subjects was a diminished level of dihydrotestosterone. Enzymic hydrolysis of a seminal plasma pool resulted in a 3- to 8-fold increase in the concentration of pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone and oestradiol, indicating that human seminal plasma contains large amounts of steroid conjugates. It is suggested that the analysis of steroids in the seminal plasma in combination with determinations in peripheral plasma may be a valuable aid to the assessment of testicular function.
TL;DR: In undernourished rats aged up to 21 days, the DNA synthesis period in dividing cells of the subependymal and external granular layers is consistently and markedly prolonged, while rates of cell production from these layers are only slightly altered.
TL;DR: Analysis of the causes of death by day of occurrence during two heat waves in New York City in 1972 and 1973 established that there was a great increase in the numbers of deaths in each heat wave after several days of excessively warm weather and on the day which followed the hottest day.
TL;DR: Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects.
Abstract: Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects. At a daily dose of 6 mg, the average plasma levels of both substances were about 50ng/ml, and individual values ranged from 30 to about 80ng/ml. There was a linear correlation between changes in dose and the resulting plasma levels, which indicates first order elimination kinetics. Side-effects were frequent, but neither their severity nor their occurrence could be related to plasma levels or to the rate of increase in plasma concentration of the drug. Three out of five patients who developed serious dysphoria had significantly high CNP levels. The concentration of ACNP was considerably increased in four patients who subsequently suffered from withdrawal symptoms. Drug interaction with diphenylhydantoin, i.e. decreased CNP level, was observed in all five patients who received both compounds. In general it is not yet possible to define an upper limit for the plasma levels of CNP and ACNP at which toxicity occurs. In patients treated with conventional doses of CNP, measurement of plasma concentration is not required, except in special circumstances, because of the lack of correlation between plasma level and side-effects.
TL;DR: A single injection of dimethylnitrosamine (DMN) induced hepatocellular carcinoma in rats and no tumors developed when another alkylating carcinogen, methyl methanesulphonate (MMS), was administered after partial hepatectomy; the significance of these results in relation to the mechanism of initiation of carcinogenesis is discussed.