Showing papers by "Medical Research Council published in 1978"
TL;DR: Restriction enzymes Hpa II, Ava I, Hha I and Hae II have been found to distinguish Xenopus laevis somatic rDNA † from amplified rDNA, and the pattern of methylation in erythrocyte rDNA is studied.
410 citations
TL;DR: Using this improved method, ts and hr mutations in intact DNA have been rescued with restriction endonuclease fragments of DNA bearing the corresponding wild-type genetic markers and a number of mutations have been located unequivocally within the left quarter of the genome.
352 citations
351 citations
TL;DR: In this paper, the authors added approximately 20 g/day of concentrated dietary fibre from carrot, cabbage, apple, bran, and guar gum to the controlled basal diet of nineteen healthy volunteers.
338 citations
TL;DR: Four groups of postmen were trained to type alpha-numeric code material using a conventional typewriter keyboard, and it is suggested that where operationally feasible, keyboard training should be distributed over time rather than massed.
Abstract: Four groups of postmen were trained to type alpha-numeric code material using a conventional typewriter keyboard. Training was based on sessions lasting for one or two hours occurring once or twice per day. Learning was most efficient in the group given one session of one hour per day, and least efficient in the group trained for two 2-hour sessions. Retention was tested after one, three or nine months, and indicated a loss in speed of about 30%. Again the group trained for two daily sessions of two hours performed most poorly. It is suggested that where operationally feasible, keyboard training should be distributed over time rather than massed.
275 citations
TL;DR: Results indicate that any pattern of methylated and unmethylated paired CpGs in the genome of a cell will be inherited by descendants of that cell.
271 citations
TL;DR: Although emphasis on infant feeding is rightly being placed on breast-feeding, the need for safe weaning foods for the developing world must also receive its due attention.
195 citations
TL;DR: The ultrastructural organization of the mature gametocytes of Plasmodium falciparum isolated from the peripheral circulation of naturally infected Gambians is examined and compared with immature forms obtained from the central circulation of a chloroquine treated patient, suggesting that P. falcIParum is best considered as pre-dating the ‘malariae’ and ‘vivax’ groups and not as having evolved from them.
Abstract: The ultrastructural organization of the mature gametocytes of Plasmodium falciparum isolated from the peripheral circulation of naturally infected Gambians is examined and compared with immature forms obtained from the peripheral circulation of a chloroquine treated patient. The latter are recognized as the stage 2 and 3 developmental forms (Hawking, Wilson & Gammage 1971 Trans. R. Soc. trop. Med. Hyg. 65, 549-559) observed by light microscopy and are distinguished in the electron microscope by three characters; (i) they do not fill the host cell, (ii) they contain few, if any, osmiophilic bodies, (iii) they possess an extensive subpellicular tubule system. Maturation (capacitation) of these immature parasites takes many days and is followed by an extended period of maturity during which the gametocytes will exflagellate. Mature macro- and microgametocytes have numerous characters in common with the gametocytes of avian and reptilian Plasmodiidae, namely a tripartite pellicle, cristate mitochondria, a comparatively high density of osmiophilic bodies in the macrogametocyte, cytostomal feeding, Golgi body, and persistent nucleolus in the female gametocyte. These similarities together with the unexpected nuclear changes detected in macro-gametogenesis suggest that P. falciparum is best considered as pre-dating the 'malariae' and 'vivax' groups and not as having evolved from them. Light microscopy, scanning and transmission electron microscopy and videotape analyses of gamete formation were undertaken. Nuclei in the mature gametocytes are Feulgen negative but upon activation rapidly become Feulgen positive. The gametes also are Feulgen positive. The crescentic parasites swell to become large spherical cells and escape from the host cell by osmotic or enzymic activity. The microgametocyte undergoes three mitotic divisions during which the chromosomes are sequentially reduced in number such that ca. 7 are incorporated into each gametic nucleus. The microtubule organizing centre (m.t.o.c.), which in the mature gametocyte is associated with the intranuclear body, is attached to the centriolar plaque of the first division spindle. There it differentiates into kinetosomes which act as foci for the polymerization of axonemes. The kinetosomes and axonemes remain attached to the centriolar plaques during division and are segregated synchronously with the genome at each division. Subsequently one axoneme enters each haploid gamete at exflagellation. Exflagellation is accompanied by a significant reduction in microgametocyte volume which is associated with an increase in density of the cytoplasm. The female gametocyte does not decrease in volume but undergoes nuclear changes in which a single pole of an intranuclear spindle is detected. Comparisons are made with macrogametogenesis in avian malarial parasites from which it is suggested that this spindle, if not half of a normal mitotic spindle, is an atavistic trait. The possibility of a meiotic gametic division is discussed but discounted. The activity pattern of the microgamete was found to be similar to that of other malarial parasites, with states of high and low activity or immobility. High activity, which results in rapid movement through the medium, is produced by long wavelength (12 $\mu $m), low amplitude (1.1 $\mu $m) waves generated at ca. 12 waves per second; low activity, which results in contorted gyrating on the spot, is produced by long wavelength (14.1), high amplitude (2.3) waves produced at ca. 1 wave per second. Following an initial period of continuous activity the gamete usually alternates between high and low activity states. Subsequent low activity and immobility is in turn followed by death. Microgamete activity was profoundly affected by the plasma of some patients, presumably as a result of the antigametocyte antibodies present. The microgamete contains a single axoneme, at one end of which lies the kinetosome with the juxtakinetosomal sphere and granule. It is this end which emerges first from the parental gametocyte. A single nucleus is centrally located in many microgametes although 23% are anucleate.
183 citations
TL;DR: It is suggested that lipopolysaccharide triggers the release from the infiltrating mononuclear cells of factors toxic for hepatocytes, and certain parasitic and virus infections and graft-versus-host reactions can sensitise mice to the induction of hepatitis by exposure to small doses of lipopoly Saccharide.
170 citations
TL;DR: Reversed-phase, high-pressure liquid chromatography has been successfully applied to the analysis of peptides and proteins by the addition of hydrophilic or hydrophobic ion-pairing reagents to the mobile phase.
Abstract: Reversed-phase, high-pressure liquid chromatography has been successfully applied to the analysis of peptides and proteins by the addition of hydrophilic (for example, phosphoric acid) or hydrophobic (for example, hexanesulfonic acid) ion-pairing reagents, or both, to the mobile phase. Examples described included proteins such as insulin, glucagon, and 1-24 ACTH pentaacetate (ACTH is adrenocorticotrophic hormone).
168 citations
TL;DR: In this study, the mean plasma cholesterol level was found to be significantly lower on the plant protein diet, compared with the conventional diet.
TL;DR: The quantitative correlation found between isomalathion content and toxicity of many field samples of malathion has been confirmed by an examination of mixtures of pure compounds and impurities identified (trimethyl phosphorothioates) have been identified and have been shown to behave like isomalATHion in potentiating the toxicity ofmalathion.
Abstract: During a malaria eradication programme in Pakistan in 1976, out of 7,500 spraymen, 2,800 became poisoned and 5 died. The major determinant of this poisoning has been identified as isomalathion present as an impurity in the malathion. It seems almost certain that the isomalathion was produced during storage of the formulated malathion. The quantitative correlation found between isomalathion content and toxicity of many field samples of malathion has been confirmed by an examination of mixtures of pure compounds. Addition of known amounts of isomalathion to technical malathion indicates that other active substances are present. These impurities have been identified (trimethyl phosphorothioates) and have been shown to behave like isomalathion in potentiating the toxicity of malathion. Some preliminary work on their toxicological properties is reported. The mechanisms involved in the potentiation of the toxicity of malathion are discussed.
TL;DR: Single brief whole-body X-ray exposures have now proved to be effective in inducing myeloid leukaemia in male CBA/H mice, provided that the radiation dose is not too great.
Abstract: ABOUT two-thirds of the excess leukaemia in adult Japanese survivors of the atomic bombs is myeloid in type (acute plus chronic)1. Nevertheless, most of the extensive experimental work on leukaemia induction by ionising radiation in the past 25 yr has been concerned with the thymic leukaemia of the laboratory mouse2, a disease which may have no human counterpart. So far, only one series of systematic experiments has been reported on myeloid leukaemia in irradiated mice3,4, and this concerned RF mice, a strain which has this disease in the relatively high frequency of 2–6% in unirradiated controls. Single brief whole-body X-ray exposures have now proved to be effective in inducing myeloid leukaemia in male CBA/H mice, provided that the radiation dose is not too great. This possibly provides an important model for quantitative investigation of carcinogenic mechanisms and for use in the development of chemotherapy for the analogous human disease.
TL;DR: In this paper, a new set of conditions, namely, the addition of phosphoric acid to the mobile phase, has been found to have very real advantages in the analysis of underivatised peptides.
TL;DR: With progressive occlusion of the pattern stimulus from the central regions of the visual half-field, the ipsilateral positive wave was increasingly attenuated, while components of the contralateral complex were relatively unaffected, or, in some cases, enhanced.
TL;DR: Daily milk consumption was limited primarily by the amount delivered per feed, not the frequency of feeding, and other factors significantly influencing output were parity, month of lactation, baby's weight-for-age, season, and maternal diet.
TL;DR: There seems little advantage in routine monitoring of AT and NT, since variations in plasma-levels do not account for the considerable variation in therapeutic outcome, and no important correlations were found between steady-state plasma- levels and therapeutic outcome or corrected side-effects.
TL;DR: High pressure liquid chromatography for the rapid analysis at high sensitivity of peptide mixtures from proteolytic digestlon of proteins and the chromatographic system can be used to follow the progress of a digestion and to monitor the purity of the proteolytics enzyme.
TL;DR: The experiment shows that two portable and brief performance tests are sensitive indices of sleep loss and should be particularly useful for assessing levels of alertness in the field.
Abstract: The effects of one night's total sleep deprivation were examined using the Wilkinson vigilance task and four 10 min duration performance tests. A repeated measures design was used in which eight male subjects experienced one night of sleep loss, the order of sleep loss being balanced across subjects. The four short duration performance tests consisted of choice reaction time, simple reaction time, short-term memory, and a motor task, handwriting. The results confirm the effects of one night's sleep deprivation on the vigilance task and also show that performance on the two reaction time tests was significantly impaired by the loss of sleep, but not at such a high level as for the vigilance. The short-term memory test failed to show any adverse effects of sleep loss and similarly for the handwriting. The experiment shows that two portable and brief (10 min) performance tests are sensitive indices of sleep loss and should be particularly useful for assessing levels of alertness in the field.
TL;DR: It is concluded that these rodent studies do not implicate any specific inhalational anesthetic agent in fetal toxicity, and that the effects of additional factors, such as stress, must be considered.
Abstract: An animal model was used to investigate the comparative fetal toxicities of three inhalational anesthetics. Pregnant Sprague-Dawley rats were exposed for eight hours a day throughout the 21 days of gestation to graded concentrations of halothane (0.16-0.32 per cent), or nitrous oxide (1-50 per cent), or a nitrous oxide (10 per cent) and halothane (0.16 per cent) mixture, or methoxyflurane (0.01-0.08 per cent). High subanesthetic concentrations of all the inhalational anesthetics could cause fetal growth retardation (e.g., 3-21 per cent decreases in normal fetal weights), but this was unaccompanied by significant fetal loss (overall rate: 4.8 +/- 1.2 per cent, mean +/- SE, in anesthetic groups) or any evidence of skeletal or gross abnormalities related to treatment. It is concluded that these rodent studies do not implicate any specific inhalational anesthetic agent in fetal toxicity, and that the effects of additional factors, such as stress, must be considered.
TL;DR: It was shown that high levels of cytochrome P-450 could be maintained in liver cell culture in the face of high haem oxygenase activities.
TL;DR: A calorimeter for the continuous measurement of heat production and heat loss in the human subject, for at least 24 h, is described and problems associated with the calculation of evapoative heat loss and the estimation of the volume of incoming air in open-circuit systems are considered.
Abstract: 1. A calorimeter for the continuous measurement of heat production and heat loss in the human subject, for at least 24 h, is described. The calorimeter operated on the heat-sink principle for direct calorimetry and an open-circuit system for indirect calorimetry. 2. Sensible heat loss was measured using a water-cooled heat exchanger, and the temperature of water entering the heat exchanger was controlled to maintain a mean temperature gradient of zero across the chamber walls. 3. Evaporative heat loss was determined from ingoing and outgoing wet-and-dry bulb temperatures and air flow-rates. 4. Problems associated with the calculation of evapoative heat loss and the estimation of the volume of incoming air in open-circuit systems are considered. 5. The calibration, limits of accuracy, sources of error and experiments with subjects are discussed.
TL;DR: The hypothesis that the small increases in urinaryOxalate excretion which occur in some idiopathic calcium oxalate stone-formers are due to increased absorption of oxalates from the intestine, which may be due to a reduction in intraluminal calcium concentration, is compatible with the hypothesis.
Abstract: 1. The possible roles of the diet and of intestinal absorption in the increased excretion of oxalate by patients with renal calcium stones have been studied. 2. Dietary surveys showed that the mean daily intake of oxalic acid by stone-formers was not significantly different from that of non-stone-formers. 3. The mean urinary excretion of oxalate, expressed as an oxalate/creatinine molar ratio, was significantly reduced by fasting, the change being more marked in the stone-formers than in the normal subjects. Moreover, fasting abolished the difference in mean oxalate/creatinine ratios between stone-formers and control subjects. 4. These results are compatible with the hypothesis that the small increases in urinary oxalate excretion which occur in some idiopathic calcium oxalate stone-formers are due to increased absorption of oxalate from the intestine, which may be due to a reduction in intraluminal calcium concentration.
TL;DR: Three standard samples of amphibole asbestos were subjected to ball‐milling; the main effect of this procedure was to reduce the length of the fibres present in each sample, compared with the sizes of fibre previously reported to induce mesotheliomata when implanted into the pleural cavities of rats.
Abstract: Three standard (UICC) samples of amphibole asbestos were subjected to ball-milling; the main effect of this procedure was to reduce the length of the fibres present in each sample. The numbers of fibres in unit masses, and the distribution of fibre sizes in all the samples, both parent and milled, were estimated from electron micrographs. The ability of all the samples to reduce the plating efficiency of V79-4 cells is compared, on the basis of mass, fibre number and fibre number number above various length thresholds. This biological activity of all the samples correlated best with the number of fibres above a threshold length of 6.5 micron. This is compared with the sizes of fibre previously reported to induce mesotheliomata when implanted into the pleural cavities of rats.
TL;DR: Prophylaxis with co-trimoxazole is important in preventing or delaying the development of infection in neutropenic patients receiving therapy for acute leukaemia.
TL;DR: The mean intrapair variance of both total and cortical width was found to be four to five times higher in DZ than in MZ pairs, indicating a predominant genetic influence.
Abstract: The relative importance of genetic factors in the pathogenesis of age related bone loss has been investigated in a study involving 17 monozygotic (MZ) and 8 dizygotic (DZ) pairs of twins aged 64 to 75 years. Radiographic morphometry was performed at the midpoints of the 2nd, 3rd and 4th metacarpals of both hands and the mean total and cortical widths were evaluated. The heritability, h2, was calculated as the difference between the intrapair variances in same sexed DZ and MZ pairs divided by the intrapair variance in DZ pairs. The mean intrapair variance of both total and cortical width was found to be four to five times higher in DZ than in MZ pairs. The differences are highly significant with an h2 value between 0.7 and 0.8, indicating a predominant genetic influence. It is stressed that this result applies only to the population from which the twin sample was drawn.
TL;DR: The concentration of dolichol has been determined in various human tissues obtained at autopsy and the highest levels were found in testes, Liver and several other endocrine tissues contained about 1000 μg/g.
Abstract: The concentration of dolichol has been determined in various human tissues obtained at autopsy. The highest levels (∼3000 μg/g wet weight) were found in testes. Liver and several other endocrine tissues contained about 1000 μg/g. Lower levels were present in other tissues examined. Only a small proportion of the total dolichol in human tissues was esterified to fatty acids.
TL;DR: The very great majority of those who died, who would not have died if there had been no heat wave, were elderly people of both sexes and irrespective of color who had underlying organic disease.
TL;DR: It is suggested that the ratio neurotoxicity/lethality for trichlorphon is higher in man than in the hen, and laboratory tests to improve neurotoxicity screening are made.
Abstract: Progressive neuropathy developed in a man during 2--8 weeks after acute poisoning by a pesticide said to contain trichlorphon. The neuropathy was typical of that caused by organophosphorus esters in the delay and in the maintenance of normal conduction velocity in surviving nerve fibres. A sample alleged to be typical of the ingested material was not more active against hen brain neurotoxic esterase (NTE) than was pure trichlorphon. Delayed neuropathy has never been produced in hens by a single dose of trichlorphon. This incident and studies of human brain in vitro suggest that the ratio neurotoxicity/lethality for trichlorphon is higher in man than in the hen. Suggestion is made of laboratory tests to improve neurotoxicity screening.