Showing papers by "Medical Research Council published in 1974"
TL;DR: The structure of a tRNA has been determined by isomorphous replacement but the interactions which maintain the tertiary structure are of a novel type and this model differs significantly from one which has recently been proposed.
Abstract: The structure of a tRNA has been determined by isomorphous replacement. Some of the interactions which maintain the tertiary structure are of a novel type. Our model differs significantly from one which has recently been proposed.
901 citations
TL;DR: It is suggested that osteomalacia in the elderly makes an important contribution to the steep rise in femoral-neck fractures with advancing age in the U.K. and that this is attributable to an absolute or relative deficiency of vitamin D.
316 citations
TL;DR: The first clue to the identity of the structural modification was the isolation of the tryptic peptides Gly-Phe-Leu-Glx- Glx-Val-Arg-Lys from positions 410 and 411 in normal prothrombin, which carried two negative charges more at neutral pH than could be attributed to normal glutamic acid residues.
258 citations
248 citations
Journal Article•
Abstract: Neuroleptic drugs of various types were more potent inhibitors of dopamine-sensitive production of adenosine cyclic 39,59-monophosphate in homogenates of rat brain striatum than non-neuroleptic drugs of similar structures. The most potent drugs were phenothiazines and thioxanthenes with a -CF3 group in position 2 of the tricyclic system and a piperazino side chain. There were also large differences in the effects of cis and trans isomers of thioxanthenes in which the 2-substituent and the side chain are on the same or opposite side of the double bond connecting the side chain to the ring system. Thus α-flupenthixol, α-clopenthixol, and α-chlorprothixene, which are the cis isomers, were considerably more potent than the corresponding β-isomers of the same drugs. α-Flupenthixol was also considerably more potent than the β-isomer in antagonizing the effect of dopamine on cyclic AMP production in the olfactory tubercle and nucleus accumbens, and in antagonizing the potent dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene in the striatum. These results are discussed in relation to the hypothesis that neuroleptic activity may be related to the blockade of dopamine receptors in the central nervous system.
248 citations
TL;DR: In 1967, knowing that cheese is a common dietary trigger to migraine, Hanington fed tyramine, which it is known to contain, to affected subjects and by this action was able to initiate headache episodes.
Abstract: FOR some two hundred years, certain foodstuffs have been known to trigger migraine attacks1. In 1967, knowing that cheese is a common dietary trigger to migraine, Hanington2 fed tyramine, which it is known to contain, to affected subjects and by this action was able to initiate headache episodes.
234 citations
TL;DR: This chapter reviews gene or point mutations and discusses the fine structure of mutation-induced point mutations in mice and finds that with postnatal irradiation at any age, the progeny will be derived from irradiated dictyate oocytes, unless fertilization of the eggs takes place within 12 hours of the irradiation.
Abstract: Publisher Summary This chapter reviews gene or point mutations. It also discusses the fine structure of mutation-induced point mutations in mice. The work on mutation induction in mice has lead to an accurate assessment of human genetic hazards from radiation. Induced point mutations are detected and studied mainly by genetic methods, although biochemical techniques have also been used. Male germ cells take up a more central or medullary position whereas female germ cells take up a more peripheral or cortical one. It has been found that on the development and radiation response of germ cells in female mice that with postnatal irradiation at any age, the progeny will be derived from irradiated dictyate oocytes, unless fertilization of the eggs takes place within 12 hours of the irradiation. With neonatal and late fetal irradiation, exposed germ cells are normally in predictyate stages of meiotic prophase. Irradiations of younger embryos expose oogonia and their precursors. The specific locus method is the most efficient way of studying point mutations in mice. It is designed to detect mutations affecting a particular set of loci in the mouse that are chosen because their known mutant alleles have a clear-cut and easily visible effect.
233 citations
TL;DR: In this article, position effect variegation has been studied in female mice heterozygous for the flecked X-autosome translocation, T(7; X)Ct, and found that early occurring events do not lay down fixed programs of gene suppression, as proposed for Drosophila, but that, like the lateroccurring events, they represent the reactivation of previously inactivated loci.
Abstract: Position effect variegation has been studied in female mice heterozygous for the flecked X-autosome translocation, T(7; X)Ct Some of these carried the spotting gene (s) which clarifies the variegated patterns Others carried a second X-autosome translocation, T(X; 16)16H, which suppresses the randomness of X-chromosome activityIt was found the position effect variegation stems primarily from early occurring events which lead to the formation of clones of cells with different phenotypes In this respect the phenomenon appears to parallel that found in Drosophila However, in the mouse, late-occurring events are also found which can only be readily accounted for by the reactivation of previously inactive loci They occur, not only during foetal development, but throughout the life-time of the animals and in a manner which suggests they derive from a progressive retreat of the inactivating influence of the heterochromatic X chromosome back along the attached autosome towards the breakpoint It is proposed that the early occurring events do not lay down fixed programmes of gene suppression, as proposed for Drosophila, but that, like the later-occurring events, they represent the reactivation of previously inactivated loci The possibility that this might also be true for Drosophila is discussedThe study also provided evidence favouring the view that the X-chromosome controlling element, Xce, modifies the heterozygous phenotypes of X-linked genes by biasing the randomness of the X-inactivation process, rather than by operating through cell selection mechanisms The data also support and extend Mintz's (1967) concept of pigment pattern differentiation
188 citations
TL;DR: It is hypothesised that Down's syndrome is associated with specific difficulties in using long term motor programmes and that mongol children may therefore be dependent on simple feedback processes to perform motor tasks.
Abstract: SUMMARY
Children with Down's syndrome (Mongolism) were compared with severely subnormal autistic children and with normal children on two simple motor tasks: pursuit rotor tracking and finger tapping. Although the groups were matched on initial tracking performance, Down's syndrome children failed to show any improvement after a 5 min rest, while both comparison groups showed a very marked improvement. Furthermore, in the finger tapping task, Down's syndrome children were abnormally slow compared to the other groups. Neither the level of mental development nor the degree of general mental retardation can account for these deficits. It is hypothesised that Down's syndrome is associated with specific difficulties in using long term motor programmes and that mongol children may therefore be dependent on simple feedback processes to perform motor tasks.
187 citations
181 citations
TL;DR: Henson and others have shown that granulocytes exposed to immune complexes in vitro release lysosomal enzymes while remaining viable, and presumably the same happens in Arthus reactions in vivo.
Abstract: IMMUNE complexes contribute to tissue damage in a variety of experimental and human diseases. Immune complexes induce arthritis1 and nephritis2,3 in laboratory animals while lupus glomerulonephritis4 and possibly rheumatoid arthritis5 are examples of their effects in man. The mechanisms by which damage is initiated and perpetuated are poorly understood. In the acute stage of inflammation resulting from immune complexes many granulocytes are present. These cells have abundant lysosomes rich in acid hydrolases which when released can degrade various tissue components. Enzyme release may result from cell death or exocytosis of granules from viable cells. Henson6 and others7,8 have shown that granulocytes exposed to immune complexes in vitro release lysosomal enzymes while remaining viable, and presumably the same happens in Arthus reactions in vivo.
TL;DR: It was concluded that much of the pre-implantation loss really stemmed from non-fertilization rather than from zygotic death, and suggested that reduced fertilization is likely to occur in mice whenever sperm counts fall to less than 10% normal.
Abstract: Adult male mice were given doses of 200 rad acute X-irradiation and mated at intervals to hybrid females over the next 9 weeks. Testis weights fell to 44% of normal during the 5th week and were still subnormal when observations ended in the 10th week. Epididymal-sperm counts fell in the 4th week (after a peak in the 3rd) and were very low in the 6th and 7th weeks, though still above zero. This reduction was followed by high frequencies of pre-implantation loss in females mated to these males and dissected on the 12th day of gestation. Examination of eggs 1–2 days after ovulation showed that there was also a sharp decrease (from the normal level of almost 100%) in the fertilization index, no eggs being fertilized in some females while others showed an intermediate rate. It was concluded that much of the pre-implantation loss really stemmed from non-fertilization rather than from zygotic death. This possibility has already been envisaged by Bateman and others, and reinforces the belief that an index of dominant lethality based on post implantation death should be used whenever the mutagenic treatment is likely to induce much germ-cell killing. The data suggested that reduced fertilization is likely to occur in mice whenever sperm counts fall to less than 10% normal.
TL;DR: The existence of two distinguishable guanine nucleotide binding sites per molecule of tubulin has been confirmed and the nucleotide used in this reaction comes from the medium and binds to a third site on tubulin itself or to another protein associated with it.
TL;DR: This agent has potential therapeutic value in the management of cardiovascular failure associated with low cardiac output after myocardial infarction or open heart surgery, whenever isoprenaline would currently be used.
TL;DR: An expression having a basic cubic form was derived to describe the in vitro release of drugs from slow-release tablets formulated with a homogeneous insoluble matrix and it was shown that the rate constants may be described in terms of the physicochemical properties of the tablet constituents and the degree of compression.
TL;DR: The brains of 18-day-old rats utilize glucose and ketone bodies and the rates of acetyl-CoA formation from these substrates and of glycolysis were determined in vivo from the labelling of intermediary metabolites after intraperitoneal injection.
Abstract: The brains of 18-day-old rats utilize glucose and ketone bodies. The rates of acetyl-CoA formation from these substrates and of glycolysis were determined in vivo from the labelling of intermediary metabolites after intraperitoneal injection of d-[2-14C]glucose, l(+)-[3-14C]- and l(+)-[U-14C]-lactate and d(−)-3-hydroxy[14C]butyrate. Compartmental analysis was used in calculating rates to allow for the rapid exchange of blood and brain lactate, the presence in brain of at least two pools each of glucose and lactate, and the incomplete equilibration of oxaloacetate with aspartate and of 2-oxoglutarate with glutamate. Results were as follows. 1. Glucose and ketone bodies labelled identical pools of tricarboxylate-cycle metabolites, and were in every way alternative substrates. 2. The combined rate of oxidation of acetyl-CoA derived from pyruvate (and hence glucose) and ketone bodies was 1.05μmol/min per g. 3. Ketone bodies contributed 0.11–0.53μmol/min per g in proportion to their concentration in blood, with a mean rate of 0.30μmol/min per g at 1.24mm. 4. Pyruvate and ketone bodies were converted into lipid at 0.018 and 0.008μmol/min per g respectively. 5. Glycolysis, at 0.48μmol/min per g, was more rapid in most rats than pyruvate utilization by oxidation and lipid synthesis, resulting in a net output of lactate from brain to blood. 6. Rates of formation of brain glutamate, glutamine and aspartate were also measured. Further information on the derivation of the models has been deposited as Supplementary Publication SUP 50034 (18 pages) at the British Library, Lending Division (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7QB, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973) 131, 5.
TL;DR: T-cell and B-cell markers have been studied in 30 patients with chronic lymphocytic leukaemia and found that a significant increase in leukaemic lymphocytes in all the cases had B- cell characteristics.
TL;DR: The results of an onchocerciasis survey of total populations aged 5 years and over in 16 heavily infected villages in Cameroon suggest that concomitant infections may influence the immunological response.
Abstract: The results of an onchocerciasis survey of total populations aged 5 years and over in 16 heavily infected villages in Cameroon rain-forest and savanna zones are reported. Using standardized parasitological and clinical techniques the same observers examined the intensity of infection and clinical manifestations in 1,098 cases in the rain-forest and compared them with those found in 1,128 cases in the savanna. The following Table summarizes the main findings:- Rainforest Savana Prevalence of nodules 80–90% 60–70% Mean number of nodules per person +++ ++ Microfilarial skin density ++ −++ Skin atrophy ++ +++ Shin depigmentation +++ + Groin lymphadenopathy +++ ++ Hanging groin ++ + Microfilarial invasion of cornea ++ +++ Microfilarial invasion of anterior chmaber +++ +++ Microfilarial invasion of vitreous + ++ Snowflake corneal opacities ++ + Sclerosing keratitis + +++ Iritis + +++ Optic atrophy + + Choroidoretinitis + + Blindness 2.0% 5.1% + =at low level ++ =at medium level +++ at high level It is suggested that the differences between rain-forest and savanna may be due to variations in host response resulting from differences in the intensity and patterns of transmission. Different pathogenicity of the rain-forest and savanna strains of parasite is also considered to be of importance, and it is suggested that concomitant infections may influence the immunological response. Hormonal factors are considered to be important in influencing the differences in the patterns and severity of infections between males and females.
TL;DR: Noise increases the interference between colours and conflicting colour names and this could be due to the overarousal produced by the noise, or to the perceptual isolation which the noise produces.
Abstract: : Noise increases the interference between colours and conflicting colour names. The interference increases with the time spent in the noise. This could be due to the overarousal produced by the noise, or to the perceptual isolation which the noise also produces. (Author)
TL;DR: The presence du 5α-androstene-16-3α-ol d'odeur musquee dans la fraction contenant les steroides libres de la sueur des aisselles, recueillie chez des hommes sains adultes, a ete etablie par chromatographie en gaz avec spectrometrie de masse, trouvee n'exclut pas la possibilite d'une fonction pheromonale de ce steroide as discussed by the authors.
Abstract: La presence du 5α-androstene-16-3α-ol d'odeur musquee dans la fraction contenant les steroides libres de la sueur des aisselles, recueillie chez des hommes sains adultes, a ete etablie par chromatographie en gaz avec spectrometrie de masse. La quantite d'androstenol trouvee n'exclut pas la possibilite d'une fonction pheromonale de ce steroide.
TL;DR: Variation in hours of sunshine is responsible for a seasonal variation in osteomalacia in femoral-neck-fracture cases and, possibly, in the elderly population as a whole.
TL;DR: The final preparation is composed almost exclusively from pre- and postsynaptic neuronal structures, and is consistent with the view that GAD activity is very high in the inhibitory Golgi terminals, and acetylcholine may be a transmitter only in a relatively small fraction of the mossy fibre terminals.
TL;DR: In this article, it was argued that even at a level of successful detection well below 100%, this form of prenatal diagnosis may be worth while for spina bifida, and six plasma samples taken between 15 and 18 weeks of pregnancy had distinctively abnormal A.F.P.
TL;DR: It is suggested that CNV resolution in the post-stimulus trace reflects selective attention paid to the stimulus, and may be responsible, through summation, for claims that N1-P2, and sometimes P300, does so.
TL;DR: No therapeutic action was demonstrated in a double-blind cross-over trial in depressive patients of intravenous thyrotrophin-releasing hormone and there was evidence that the T.R.H.S. was impaired in a proportion of the depressive patients.
TL;DR: The mammalian toxicity of NRDC 156 and NRDC 161 was assessed in albino female, rats 10 to 12 week old and the results confirmed the importance of knowing the carrier and removal status of canine coronavirus to protect against disease.
Abstract: THE mammalian toxicity of NRDC 156 and NRDC 161 (see accompanying paper1) was assessed in albino female, rats 10 to 12 week old.
Journal Article•
TL;DR: Reactive sulfur liberated during the oxidative desulfuration of several chemicals may become bound to cellular components and initiate toxic changes in the liver and account for the centrilobular hydropic degeneration seen in vivo.
Abstract: When liver microsomes from phenobarbitone-treated rats are incubated with carbon disulfide, a marked loss of cytochrome P-450 is observed only when NADPH is present. By employing 14 C- and 25 S-labeled CS 2 , it has been found that in the presence of NADPH labeled sulfur becomes covalently bound to microsomes: The binding of 35 S exceeds that of 14 C, indicating that sulfur itself becomes bound. A loss of cytochrome P-450 is also seen when parathion, phenylthiourea, or 1-naphthylisothiocyanate is incubated with liver microsomes in the presence of NADPH, whereas the oxygen-containing analogues of these compounds are all inactive. It is concluded that reactive sulfur liberated during the oxidative desulfuration of several chemicals may become bound to cellular components and initiate toxic changes in the liver. This may account not only for the loss of cytochrome P-450 but also for the centrilobular hydropic degeneration seen in vivo .
TL;DR: Francis Crick reviews the papers published 21 years ago on the structure of DNA and the reaction to them and concludes that the current understanding of DNA is closer than previously thought.
Abstract: Francis Crick reviews the papers published 21 years ago on the structure of DNA and the reaction to them.
TL;DR: The purpose of the present paper is to present the result of a study investigating the role of pyruvate dehydrogenase in the conversion of D-P-hydroxybutyrate and acetoacetate to acetyl-CoA in rat brain from birth to adulthood.