Showing papers by "Medical Research Council published in 1979"

Severe impairments of social interaction and associated abnormalities in children : epidemiology and classification

Abstract: The prevalence, in children aged under 15, of severe impairments of social interaction, language abnormalities, and repetitive stereotyped behaviors was investigated in an area of London. A “socially impaired” group (more than half of whom were severely retarded) and a comparison group of “sociable severely mentally retarded” children were identified. Mutism or echolalia, and repetitive stereotyped behaviors were found in almost all the socially impaired children, but to a less marked extent in a minority of the sociable severely retarded. Certain organic conditions were found more often in the socially impaired group. A subgroup with a history of Kanner's early childhood autism could be identified reliably but shared many abnormalities with other socially impaired children. The relationships between mental retardation, typical autism, and other conditions involving social impairment were discussed, and a system of classification based on quality of social interaction was considered.

Recombinant Inbred Strains

Abstract: The development and use of recombinant inbred (RI) strains may prove to be one of the most significant advances in mammalian genetics since the development of congenic lines. These strains will probably lead to the identification and mapping of a large number of new polymorphic genetic loci and the further genetic analysis of a number of complex or difficult characteristics, such as skin graft rejection and susceptibility to spontaneous and infectious diseases.

Case study approach in neuropsychological research

Abstract: The contribution of the neurological case study approach for establishing the functional organisation of cognitive subsystems is assessed. A number of potential problems are considered, including “resource artefacts”, the nature of the lengthy clinical/experimental procedure used, statistical selection artefacts, reorganisation of function, atypical lateralisation, and the existence of associated deficits. It is argued that, despite these problems, the case study approach is the most promising neuropsychological technique for providing information on the functional organisation of cognitive subsystems.

Mutation and inactivation of cultured mammalian cells exposed to beams of accelerated heavy ions. II. Chinese hamster V79 cells.

Abstract: SummaryInactivation and mutation to thioguanine-resistance of V79 hamster cells were studied after irradiation with accelerated helium, boron or nitrogen ions covering a range of linear energy transfer from 28 to 470 keV µm−1. For all radiation qualities a dose-dependent increase in mutant frequency was found for doses giving surviving fractions greater than about 0·20. The effectiveness per unit dose for both inactivation and mutation induction increased with the linear energy transfer of the radiation to a maximum in the range 90–200 keV µm−1. However, the maximum mutagenic effectiveness relative to γ-rays was about two or more times that for inactivation. It is suggested that a proportion of the radiation-induced mutants suffer extensive genetic damage, and that some forms of this damage may be induced with high efficiency by radiations of high linear energy transfer.

Kinetics of blood‐brain barrier transport of pyruvate, lactate and glucose in suckling, weanling and adult rats

Abstract: — The kinetics of the uptake from blood to brain of pyruvate, lactate and glucose have been determined in rats of different ages. The carotid artery single injection technique was used in animals anaesthetized with pentobarbital. The rates of influx for each substrate were determined over a range of concentrations for the different age-groups. Data were analysed in terms of the Michaelis-Menten equation with a component to allow for non-saturable diffusion. Values are given for Km, Vmax and Kd. In suckling rats (15-21 days) the Vmax values for both pyruvate and lactate were 2.0 μmol g−1 min−1. In 28-day-old rats the Vmax values had fallen to one-half and in adults they were less than one-tenth. Km, values were higher in the younger animals. The rate of glucose transport in suckling rats was half that of 28-day-old and adults although there was no difference with age in the Km values. The results are discussed in relation to the net flux of these substrates in and out of brain during different stages of post-natal development.

Reduced thermogenesis in obesity

Abstract: IT is often claimed that there are obese patients who find it difficult to maintain a normal body weight because they have such low energy requirements that even normal intakes of energy result in weight gain and obesity. Studies of both children1 and adults2 show that there can be a twofold difference in energy intake between individuals despite apparently similar patterns of physical activity. An individual variability in the capacity to dissipate heat by metabolic changes has therefore been suggested3 but no physiological basis for the differences in thermogenesis has yet been established. In genetically obese ob/ob mouse there are two components involved in the deposition of excess body fat: hyperphagia and increased metabolic efficiency4,5. Metabolic efficiency is the major factor responsible for obesity when the animals are kept at 20 °C so these animals provide a model study of the link between metabolic rate and obesity. Pre-obese and obese ob/ob animals have an abnormality of thermoregulatory thermogenesis with a reduced thermogenic response to cooling6. A defect in non-shivering thermogenesis can be confirmed by monitoring the thermogenic response to maximum doses of nor adrenaline: the ob/ob mouse has only half the response of its lean littermate. The abnormal thermoregulatory thermogenesis quantitatively accounts for most of the metabolic efficiency of the obese animals as pair feeding at thermoneutrality rather than at 23 °C reduces the excess fat deposited by 65%7. We report here that obese adults with a family history of obesity have a reduced metabolic response to noradrenaline infusion compared with thin adults. As the reduced non-shivering thermogenesis is also found in subjects with familial obesity who remain at normal weight by persistent dieting, the defect in non-shivering thermogenesis appears to be constitutional and not a secondary consequence of obesity.

Prevalence of asthma: a comparative study of urban and rural Xhosa children.

Abstract: An epidemiological study was undertaken to determine the prevalence of asthma in young urban and rural black (Xhosa) children. One thousand three hundred and seventy five children were studied, 694 from a Cape Town african township and 671 from a rural area in Transkei. The exercise tolerance test which required free range running at maximum effort for 6 min was used to identify asthmatic subjects. A fall of 15% or more in the post-exercise FEV1 and PEFR values was regarded as a positive result. Twenty-three children were found to be asthmatic, twenty-two from the city area, but only one from the country, giving a prevalence figure for asthma of 3.17% in the first group and 0.14% for the second. Possible reasons for these differences are discussed. The exercise tolerance test was found to be a useful tool for epidemiological studies of asthma.

Ocular tilt reaction with peripheral vestibular lesion

Abstract: Following inadvertent destruction of the left vestibular labyrinth during stapedectomy, a patient developed a transient abnormality of posture consisting of leftward ocular counterrolling, leftward had tilting, and a right-over-left skew deviation. This postural pattern, known as the "ocular tilt reaction," is the normal compensatory response of the dependent utricle to tilting. In this patient, the unopposed action of the intact right utricle was presumably responsible for the appearance of a normal leftward ocular tilt reaction.

Inbred Strains of Mice

Abstract: Inbred mice have been used more extensively than those of any other species of laboratory mammal. A total of about 230 strains are listed here, but some of the more widely used strains have become divided into sublines among which there are detectable genetic differences. Some strains are recorded in the literature but are now extinct. Such strains have been excluded from this list.

Antibodies to Sporozoites: Their Frequent Occurrence in Individuals Living in an Area of Hyperendemic Malaria

Abstract: Serum samples from 158 West Africans were tested for antibodies against sporozoites, the vector stage of the malaria parasite. Antibodies specific for Plasmodium falciparum sporozoites were detected by means of the circumsporozoite precipitation assay and indirect immunofluorescence. More than 90 percent of the serum samples from adults gave positive immunofluorescent reactions against falciparum sporozoites, whereas most of the samples from children gave low or negative reactions.

Mutation and inactivation of cultured mammalian cells exposed to beams of accelerated heavy ions. III. Human diploid fibroblasts.

Abstract: SummaryThe induction of inactivation and mutation to thioguanine-resistance in cultured human diploid fibroblasts was studied after exposure to ionising radiations with LETs in the range 20–470keV µm−1. Unique r.b.e. values were obtained for inactivation and mutation induction with nine different qualities of radiation. The plot of r.b.e. versus LET gave humped curves for both endpoints; r.b.e. maxima were in the LET range 90–200keV µm−1 but the maximum r.b.e. value for mutation induction was almost twice that for inactivation. The accuracy of estimates of mutation induction are discussed with regard to possible selective effects against mutants during post-irradiation growth.

Antiepileptic properties of clobazam, a 1-5 benzodiazepine, in man.

Abstract: Clobazam is a benzodiazepine with special molecular structure (its nitrogen radicals are in positions 1 and 5, rather than 1 and 4 as in all other antiepileptic benzodiazepines), and it is rapidly effective--in a matter of hours or within a few days--against all varieties of epileptic seizures in 52% of subjects treated with it. Its effects are relatively mild. Unfortunately, its outstanding antiepileptic properties are exhausted after only a few weeks in one-third of all cases. The authors discuss the potential significance of this phenomenon, and stress the urgent need for intensive study of the basic mechanism governing exhaustion of the antiepileptic properties of the benzodiazepines in general and clobazam in particular.

Infant foods as a potential source of diarrhoeal illness in rural West Africa

Abstract: It is common practice in rural areas of The Gambia to prepare infant foods in quantities which are sufficient to meet the needs of the day rather than one meal. These are then stored at ambient temperatures for periods up to 12 hours for feeding to the child on demand The total viable counts and levels of Bacillus cereus, Clostridium welchii, Staphylococcus aureus and Escherichia coli were determined in 294 infant foods samples from nought to eight hours after preparation. The presence of Salmonella was determined in 10 g samples of food. In the first hour after preparation the proportion of foods dangerously contaminated was high during the rainy season, significantly more so than during the dry season. Foods not consumed fresh were very often hazardous and almost always so after 8 hours. This problem may be a causal factor in weanling diarrhoea which also shows marked seasonal variation in prevalence.

Gametocytogenesis of Plasmodium falciparum in vitro: the cell-cycle

Abstract: Reproducible growth of gametocytes of Plasmodium falciparum in vitro was obtained from ring-stages taken directly from naturally infected patients and from the same material following storage in liquid nitrogen. Progressive sexual differentiation in vitro was examined for a finite period of 9 days in microcultures and was, for convenience, divided into 5 stages using established morphological criteria (Hawking, Wilson & Gammage, 1971). This microculture system was adapted as a bioassay for various anti-metabolites. Drug activity was measured by observing the inhibition of the established pattern of sequential development in experimental as compared to control cultures. Inhibitors used were directed against DNA, RNA and protein metabolism and microtubule assembly. As a result of these studies it is proposed that the sexual cell-cycle of P. falciparum is characterized by 4 phases. (1) A G1 period which lasts only a few hours. (2) The S phase, where DNA synthesis occurs, occupies the remainder of the first 2 days of development - both G1 and S are confined to stage I and II gametocytes. (3) G2, which is subdivided into 2 sections: G2A, characterized by stage II and III gametocytes, in which significant RNA and protein synthesis continue to occur; and G2B, where there is a progressive increase in transcription control resulting in the depression of both RNA and protein synthesis. Nonetheless, continued morphological differentiation occurs in the latter section transforming the parasites to stage IV and the morphologically and functionally mature stage V. The final M phase is marked by the brief and exposive events of gametogenesis, during which further protein synthesis occurs de novo. The proposed cell-cycle is examined as a model for studies on the activity of gametocytocidal compounds.

Effects of lactation on fertility.

Abstract: A review of our current knowledge of the mechanism underlying lactation amenorrhoea suggests that there is a causal relationship between high prolactin levels and the absence of ovarian activity. During pregnancy blood levels of prolactin continually increase. After delivery among those women who breastfeed the level remains; however when breastfeeding is reduced to 3 or less episodes/day prolactin levels quickly return to normal. The follicle stimulating hormone (FSH) is suppressed during pregnancy but increases after birth. For lactating women FSH in the 1st year is in the high normal range and in the 2nd year it is in the normal range of the follicular phase. The luteinizing hormone (LH) remains low during lactation but at weaning LH concentrations increase as prolactin levels decrease. Apparently this low level of LH during lactation is not due to pituitary inability to respond to the gonadotrophin-releasing hormone but instead is due to the increased sensitivity of the hypothalamo-pituitary axis to the negative feedback effects of estrogen. In lactating women estradiol levels remain low as long as prolactin levels remain high. Despite an adequate store of releasable FSH and LH in the pituitary estrogen secretion does not occur and the ovaries remain inactive. In pathological hyperprolactinemia the high levels of prolactin also appear to be related to the absence of ovarian function. Many studies have shown that in some societies prolonged breast feeding accompanied by lactational infertility increases the birth interval and thus serves as a form of contraception. Other studies indicate that lactation is not associated with infertility for all women and that the number of suckling episodes introduces variation in the lactational maintenance of infertility. Further studies are needed concerning the relationship between suckling frequency and prolactin level. In addition there is a need to develop a reliable method for detecting the resumption of ovulation.

Hemisphere contributions to the composition of the pattern-evoked potential waveform

Abstract: The transverse distribution of scalp-recorded potentials evoked by pattern reversal stimulation was studied in 50 healthy subjects. In most individuals the full-field responses were symmetrical over the occipital scalp, but important variations in distribution, symmetry and waveform were recorded in some cases. Asymmetrical responses were similar for each eye (i.e., they were “uncrossed” or homonymous asymmetries). Full-field peak latencies and amplitudes in the lateral channels were more variable than those at midline electrodes. Half-field responses were markedly asymmetric with well-lateralised components widespread over occipital-parietal scalp. In contrast to the full-field responses, component values measured near the midline were less consistent than those from lateral channels due to waveform distortions in this area (“transitional zone”). Upper field stimulation is particularly likely to produce such midline waveform distortions. Activity recorded from the scalp contralateral to the half-field stimulated shows more inter-individual and inter-hemispheric variation than that recorded from ipsilateral electrodes. Variants in the full-field waveform can be accounted for by relative differences in amplitude and distribution of the ipsilateral and contralateral components from each half field. The algebraic sum of these half-field components does not differ significantly from the components of the separately recorded full-field response. Furthermore, responses from the surviving half-field in patients after total hemispherectomy contain all the ipsilateral and contralateral half-field components seen in healthy subjects.

Rapid aging of neurotoxic esterase after inhibition by di-isopropyl phosphorofluoridate

Abstract: 1. It was proposed [Johnson (1974) J. Neurochem.23, 785-789] that an essential step in the genesis of delayed neuropathy caused by some organophosphorus esters was aging of phosphorylated neurotoxic esterase, involving generation of a charged monosubstituted phosphoric acid residue on the protein. 2. Neurotoxic esterase of hen brain was inhibited with di-isopropyl phosphorofluoridate either unlabelled or mixed-labelled with (3)H and (32)P. 3. Reactivation of inhibited enzyme by KF was possible only immediately after a brief inhibition:aging at pH8.0 and 37 degrees C occurred with a half-life of about 2-4min. 4. When the radiolabelled enzyme was studied no loss of label was observed during the expected aging period, but a change in the nature of the bound radioisotopes occurred (half-life=3.25min). 5. Alkaline hydrolysis of labelled enzyme liberated di-isopropyl phosphate at early times after labelling, but increasing amounts of monoisopropyl phosphate plus a volatile tritiated compound (possibly propan-2-ol) at later times. 6. Treatment of labelled enzyme with KF released di-isopropyl phosphate and caused reactivation of enzyme to similar degrees. It is concluded that the chemical change from di-isopropyl phosphoryl-enzyme to mono-isopropyl phosphoryl-enzyme and the loss of reactivatibility are related. 7. The rate of aging is similar at pH5.2, 6.5 and 8. Aging is unaffected by addition of reduced glutathione and imidazole at pH5.2 or 8, and none of the transferred (3)H is trapped by these reagents. The mechanism of aging must be different from the better-known dealkylation aging of the cholinesterases.

On Training People to Recognize Faces

Abstract: Experiments were carried out in an attempt to validate the facial recognition element of a three-day training course in person recognition. In one experiment the subjects had to rely on memory. In two other experiments they were provided with an array of full-face photographs to match against different poses and expressions of the same faces. The performance of subjects who had received training was never reliably better than that of untrained subjects, and in one experiment was significantly worse. Ii is suggested that the emphasis on isolated facial features in the training course may be responsible for its lack of success, and that processing independent features is not a good basts for a model of facial recognition

The significance of proteinuria and haematuria in Schistosoma haematobium infection.

Abstract: The intensity and prevalence of proteinuria and haematuria were studied with urinanalysis reagent strips in a Gambian community in which the intensity of infection with Schistosoma haematobium was high. The level of proteinuria present was shown to be related to the intensity of infection. Follow-up for 12 months showed that infected subjects with heavy proteinuria had a good prognosis. These findings suggest that the urinary protein in such subjects is likely to originate from lesions in the bladder and ureters and that advanced glomerular pathology is probably rare. The relationship of the levels of proteinuria and haematuria to the egg count suggests they may be parameters which could have value as indications for chemotherapy. Detailed study showed that the effect of treating all the subjects who had both 30 mg/100 ml or more of protein and at least a trace of haematuria would have been very similar to treating all those with an egg count of 200 ova/10 ml or more. Since urinanalysis with reagent strips is very simple and rapid it could have a role in mass chemotherapy campaigns, particularly those aimed at the identification and treatment of heavily infected subjects.

Calcium measurements in serum and plasma--total and ionized.

Abstract: This article will review the methods currently employed for measuring the concentrations of total and ionized calcium in serum or plasma. As far as total calcium is concerned, various techniques such as atomic absorption spectrometry, spectrophotometry, fluorometry, complexometric titration, and flame photometry will be described and compared. Particular emphasis will be given to the accuracy and precision of each technique. Possible sources of error and interfering agents will be identified and the various procedures for the taking and handling of blood samples evaluated. Inter-laboratory variation in the measurement of calcium will be studied. An assessment will be made of a new reference method for measuring total calcium in serum using isotope-dilution mass spectrometry. The usefulness of the total calcium measurement in clinical medicine will be briefly discussed. Within the last decade the refinement of spectrophotometric techniques and the improvements in ion-selective electrode technology have revolutionized the measurement of ionized calcium in serum, such that it may now be possible to replace total calcium measurements with ionized calcium measurements on a routine basis. The various techniques currently in use for measuring ionized calcium will be described and evaluated. Particular attention will be paid to the preparation of standards, the procedures for taking blood samples, and the handling of the samples prior to and during measurement. An assessment of the relative value of measuring total and ionized calcium will be presented.

Selective chromatolysis of neurons in the gerbil brain: a possible consequence of "epileptic" activity produced by common carotid artery occlusion.

Abstract: Unilateral (50 to 118 minutes) and bilateral (2 to 33 minutes) carotid artery occlusion in gerbils resulted in two distinct types of neuronal alteration: ischemic cell change (ICC) in selectively vulnerable brain regions, and selective chromatolysis (SC) confined to the deeper layers of the cortex, the Sommer sector of zone h-1, and the paramedian region (PM) of the hippocampus. In typical SC the nucleus was eccentric and the Nissl substance was lost in the central eosinophilic cytoplasm. In electron micrographs this area of cytoplasm showed disruption of smooth and rough endoplasmic reticulum with disaggregation of polyribosomes and accumulation of mitochrondria and various dense bodies. SC was identified at 2 to 3 hours and was still recognizable at five days. When bilateral carotid artery occlusion lasted 5 to 6 minutes, SC was seen in the hippocampal Sommer sector and cerebral cortex, while ICC was restricted to the endfolium (h3-5). Unlike ICC, the frequency of SC was not related to the duration of ischemia but probably to the epileptic seizures (overt and subclinical) initiated by ischemia in the gerbil. These changes must be considered when the gerbil is employed as a model of experimental stroke.

Studies on the sibling species Anopheles gambiae Giles and Anopheles arabiensis Patton (Diptera: Culicidae) in the Kisumu area, Kenya.

Abstract: A study was undertaken of the seasonal abundance, feeding habits, resting habits and malaria infection rates of the sibling species Anopheles gambiae Giles and A. arabiensis Patton on the Kano Plain, Kenya, and the surrounding foothills. A. arabiensis was the dominant species on the plains and A. gambiae in the foothills. A. gambiae was highly anthropophilic with 92% feeding on man, whereas 59% of A. arabiensis fed on cattle. In both species, the choice of host was affected by the availability of cattle. A. arabiensis rested out of doors more commonly than A. gambiae. The sporozoite rate in A. gambiae was 5·33%, 15·98 times higher than the rate of 0·33% found in A. arabiensis.