Showing papers by "Medical Research Council published in 1981"

The influence of immaturity on hypoxic-ischemic brain damage in the rat

Abstract: Brain damage in the Levine preparation (unilateral common carotid artery ligation with hypoxia) consists of ischemic neuronal alterations in the ipsilateral forebrain. As the model has been restricted to adult animals, unilateral common carotid artery ligation was carried out in 7-day-postnatal rats. Four to 8 hours later the 25 pups were exposed to 8% oxygen at 37 degrees C for 3.5 hours. Controls consisted of littermates subjected to carotid ligation without subsequent hypoxia, hypoxia without prior ligation, and neither ligation nor hypoxia. After hypoxia the animals were returned to their dams and appeared normal for up to 50 hours. All pups were then killed by perfusion-fixation. Moderate to severe ischemic neuronal changes were seen in the ipsilateral cerebral cortex, striatum, and hippocampus in at least 90% of the animals and included infarction in 56% of the brains. Cortical damage was occasionally laminar but more often occurred in columns at right angles to the pial surface. Unlike adult animals, there was necrosis of white matter, greater ipsilaterally, originating in and spreading from myelinogenic foci. The evolution of ischemic cell change and the associated gliomesodermal reaction was more rapid than in the adult. In 22 additional pups subjected to carotid artery ligation and hypoxia, brains were analyzed for water content. Significant increases (0.6 to 3.3%) in water content of the ipsilateral hemispheres occurred in 11 of 22 brains (50%). Unilateral ischemia combined with hypoxia in developing rats therefore results in neuronal destruction in the same brain regions as in adult animals, but also causes necrosis of white matter. The incidence of increased water content was similar to that of overt infarction. Thus, as previously shown in the adult, brain edema is a consequence rather than a cause of major ischemic damage in the immature animal.

Sex ratios in early childhood autism and related conditions

Abstract: Children aged 0-14 on a specified census day, with impairments of verbal and nonverbal communication, social interaction and imaginative play, and with repetitive, stereotyped activities, were identified in an epidemiological study carried out in an area of southeast London. Sociable moderately, severely, and profoundly retarded children were included for comparison. An overall male:female ratio of 2.6:1 was found in those with language and social impairments, but, in the children of this group who were moderately, severely, or profoundly retarded, the ratio was 2.1:1, closely similar to that found in children in the same IQ range with Down's syndrome or cerebral palsy. The excess of males was much more marked in language and socially impaired children who were of higher ability, or who had a history of typical early childhood autism. The findings were linked to hypotheses of genetically greater variability in males, and to male-female differences in visuo-spatial and language skills.

Ketamine alone and combined with diazepam or xylazine in laboratory animals: a 10 year experience

Abstract: Ketamine alone or supplemented by diazepam or xylazine has been used and evaluated as an anaesthetic in a range of animals including snakes, tortoises, lizards, birds, ferrets, dogs, cats, pigs, sheep, goats, non-human primates, rabbits, guineapigs, rats, mice and hamsters. Ketamine alone has severe limitations in most species, but in combination has proved valuable.

High sequence specificity of micrococcal nuclease

Abstract: The substrate specificity of micrococcal nuclease (EC 3.1.4.7.) has been studied. The enzyme recognises features of nucleotide composition, nucleotide sequence and tertiary structure of DNA. Kinetic analysis indicates that the rate of cleavage is 30 times greater at the 5' side of A or T than at G or C. Digestion of end-labelled linear DNA molecules of known sequence revealed that only a limited number of sites are cut, generating a highly specific pattern of fragments. The frequency of cleavage at each site has been determined and it may reflect the poor base overlap in the 5' T-A 3' stack as well as the length of contiguous A and T residues. The same sequence preferences are found when DNA is assembled into nucleosomes. Deoxyribonuclease 1 (EC 3.1.4.5.) recognises many of the same sequence features. Micrococcal nuclease also mimics nuclease S1 selectively cleaving an inverted repeat in supercoiled pBR322. The value of micrococcal nuclease as a "non-specific" enzymatic probe for studying nucleosome phasing is questioned.

Pathogenic Mechanisms of Neisseria gonorrhoeae: Observations on Damage to Human Fallopian Tubes in Organ Culture by Gonococci of Colony Type 1 or Type 4

Abstract: The relative virulence of isogenic clones of colony type 1 (T1) (piliated) and colony type 4 (T4) (nonpiliated) gonococci was assessed in organ cultures of human fallopian tubes. The rate of damage to fallopian tube mucosa was determined by measurements of ciliary activity and was correlated with the sequential pathologic events observed by light and electron microscopy. During the first 24 hr of the infection, T1 gonococci attached to and damaged the mucosa more rapidly than did T4 gonococci. This damage was manifested primarily by sloughing of ciliated cells. The observation that gonococci attached almost exclusively to nonciliated cells but damaged primarily ciliated cells suggested that this damage was mediated by one or more toxic factors. After attaching, gonococci entered the nonciliated mucosal cells, increased in numbers inside them, and then invaded the subepithelial tissues. Thus, attachment of gonococci to the fallopian tube mucosa may facilitate effective delivery of one or more gonococcal toxins to target cells in the mucosa and may initiate a process by which gonococci traverse the mucosal barrier.

One process, not two, in reading aloud: Lexical analogies do the work of non-lexical rules

Abstract: It is widely held that there are two (non-semantic) processes by which oral reading may be achieved: (a) by known words visually addressing lexical storage of their complete orthography and phonology; (b) by parsing a letter string into graphemes which are translated by rule into phonemes. Irregular words (HAVE) rely on the former, new and non-words rely on the latter. Recent evidence casts doubt on this view; to meet some of this data a revised version is presented. An alternative view is that the phonology of both words and non-words, at each encounter, is retrieved by analogy with all known words having matching segments. In a mixed list of words and non-words, presented singly for pronunciation, phonologically ambiguous non-words (NOUCH) were preceded critically by words with the same ambiguous segments, either pronounced regularly (COUCH) or irregularly (TOUCH). Standard (and revised) dual-process theory predicts that preceding words will not affect pronunciation of non-words; analogy theory predicts...

Whither short-course chemotherapy?

Abstract: Our understanding of the mechanisms of short-course chemotherapy has largely, though not exclusively, been based on the Pasteur Institute (Paris) group’s experimental work in mice, the in vivo and in vi&o laboratory experimental work of Professor Mitchison’s unit and a number of large cooperative controlled clinical trials in several countries with which the Medical Research Council (MRC) has been closely involved. Each clinical trial, in addition to comparing the effectiveness of short-course regimens, was designed with the aim of measuring the contribution of individual drugs. The interfacing of all three groups’ activities has also been an important feature. The evidence from the mouse experiments has been summarized by Grosset (1978), the main points being: 1. Pyrazinamide and rifampicin are very potent sterilizing drugs in experimentally infected mice.

Patterns of Emotional Response in Relatives of Schizophrenic Patients

Abstract: In Chap. 2, Hooley succinctly summarizes the history of expressed emotion (EE) research and its principal findings to date. She reviews the considerable body of evidence which suggests that the EE index has predictive validity where relapse patterns in schizophrenia are concerned and refers to the content and concurrent validity studies which offer further proof that EE is conceptually sound. However, she also acknowledge the existence of unresolved questions and issues raised by the EE investigations. The intention of this chapter is to take up some of these questions and issues and explore them in the light of unpublished data from relatives’ interviews—rich sources of information concerning patterns of emotional response and family interaction in the months preceding a psychiatric admission. The material to be presented suggests some directions for further research and tentative guidelines for clinical interventions in the future.

Maintained Fertility in a Patient with Hyperprolactinemia due to Big, Big Prolactin

Abstract: The heterogeneity of serum PRL in a hyperprolactinemic but fertile woman (Patient A) was studied by gel chromatography. Ninety percent of her PRL eluted with the void volume as "big, big" PRL and only 6% coincided with monomeric "little" PRL. Sera from a woman who had hyperprolactinemia associated with infertility (Patient B) and a normal woman (Patient C) exhibited the usual heterogeneous distribution, where 5% and 19%, respectively, eluted as big, big PRL and 76% and 65%, respectively, eluted as little PRL. Serial dilutions of the serum from Patient A displayed nonparallelism to the lines obtained from similar dilutions of both PRL standard and serum from a normal woman, suggesting possible immunological differences among the three forms of the circulating hormone. This finding, together with reports that suggest big, big PRL has a low receptor affinity, may account for the apparent lack of any biological effect upon Patient A from her sustained hyperprolactinemia.

Human Manual Control

Abstract: The sections in this article are: 1 A Simple Model for Voluntary Control 1.1 Working Memory and Internal Rehearsal 1.2 Coding of Words in Working Memory 1.3 Computer of Limited Capacity 1.4 Single-Channel Input Selector 1.5 Long-Term Memory and Automation of Skill 1.6 Summary 2 Bias from Transfer 2.1 Central Tendency Bias 2.2 Asymmetric Transfer Bias 2.3 Avoiding Transfer Bias 2.4 Summary 3 Measures of Error 3.1 Relationships Between Measures of Error 3.2 Measures of Error in Tracking 3.3 Summary 4 Preprogramming and Error Correction 4.1 Quick Ballistic Movements 4.2 Craik's Ratio Rule 4.3 Preprogrammed Movements With Error Correction 5 Nonvisual Memory for Single Movements 5.1 Weber's Law for Accuracy of Movements 5.2 Contraction Bias 5.3 Uncontrolled Differences in Sizes of Movements 5.4 Forgetting and Spatial Reference Points 5.5 Interpolated Motor Activity Between Criterion Movement and Reproduced Movement 5.6 Location Better Remembered Than Distance 5.7 Active and Passive Preselected and Constrained Movements 5.8 Visual Cues Take Priority Over Nonvisual Cues 5.9 Summary 6 Reaction Time for Correcting a Limb Movement 6.1 Deliberate and Automatic Corrections 6.2 Kinesthetic Reaction Time 6.3 Visual Correction of Quick Movements 6.4 Reaction Time for a Correction in Tracking Steps 6.5 Advance Correction of Direction 6.6 Corrected Anticipatory Response 6.7 Difficulties of Interpretation 6.8 Additional Artifacts in Measuring Reaction Times to Steps 6.9 Summary 7 Preparation and Time Sharing 7.1 Reaction Times for Multiple Choices 7.2 Grouped Responses to Simultaneous Stimuli 7.3 Psychological Refractory Period 7.4 Holding Strategy in Tracking Steps 7.5 Apparent Elimination of Psychological Refractory Period by Simultaneous Strategy 7.6 Probe Reaction Time and Psychological Refractory Period 7.7 Reaction Time to a Probe Presented During a Movement 7.8 Interference Between Movements of Two Limbs 7.9 Time Sharing Between Two Tasks 7.10 Tracking in Two Dimensions 7.11 Optimum Combinations of Two Unrelated Tasks 7.12 Summary 8 Prediction and Preprogramming Replace Error Correction in Complex Skills 8.1 Prediction of Speed in Pursuit Tracking 8.2 Preprogramming of Response Frequency in Pursuit Tracking 8.3 Models for Prediction 8.4 Prediction and Error Correction in Tracking With Pursuit and Compensatory Displays 8.5 Preprogramming With Control Systems of High Order 8.6 Preprogramming and Error Correction in Complex Skills 8.7 Summary 9 Tracking by Eye 10 Overview

Analysis of antigenic types appearing in first relapse populations of clones of Trypanosoma brucei.

Abstract: Variant antigenic types (VATs) represented in a total of 47 first relapse populations of 6 clones of Trypanosoma brucei LUMP 227 were identified by immunofluorescent staining of living trypanosomes, using antiserum raised against purified surface antigens The relative growth rates of these 6 clones were measured both individually and when grown together in a mixed population, and were found to be different under these two sets of conditions A pattern emerged in the VATs represented in relapses of each clone, with some types being expressed more frequently than others and certain VATs being only very rarely expressed It is suggested that new VATs are expressed according to a statistically definable order of priority which is different for each parent VAT, and that some VATs may be able to change to certain others only after passing through an intermediate VAT The order of priority of appearance of VATs does not appear to correlate with growth rate measured either in individual clones or when clones are grown in a mixed population

The repair of potentially lethal damage in x-irradiated cultures of normal and ataxia telangiectasia human fibroblasts.

Abstract: SummaryThe repair of potentially lethal damage (PLD) after X-rays was studied in plateau phase cultures of nine normal and five ataxia telangiectasia (AT) strains of human fibroblasts. In the normal strains PLD repair was complete after 6 hours of post-irradiation incubation. There were differences in the form of the survival curves of normal strains after maximum PLD repair but the extent of post-irradiation recovery was similar in all strains. In contrast all AT strains were almost completely deficient in PLD repair even when post-irradiation incubation was extended to 18 or 24 hours. The relevance of the PLD repair-deficiency in cultured AT strains to in vivo radiotherapeutic observations in AT patients is briefly discussed.

Tests of efficacy of antidotes for removal of methylmercury in human poisoning during the Iraq outbreak

Abstract: Three complexing agents and a thiolated resin were tested for their ability to reduce the T 1/2 of methylmercury in blood during an outbreak of human poisoning. The slope of the line relating the natural logarithm of the blood concentration to time during treatment was calculated by a parametric (linear regression) and a nonparametric (two-point) method. The mean slope for each treatment group was calculated and the T 1/2 was calculated from the mean slope. Both the linear regression and two-point methods yield similar mean values. The "two-point" T 1/2 will be quoted here. The mean T 1/2 in six patients receiving no specific treatment was 65 days and in 10 patients receiving placebo was 61 days, and these values did not differ from those reported in the literature. All four treatments significantly reduced the mean T 1/2 values below the mean for the combined placebo and no treatment groups. Sodium 2,3-dimercaptopropane-1-sulfonate was the most effective agent, reducing the mean T 1/2 in 10 patients to 10 days. The thiolated resin given to eight patients produced a mean T 1/2 of 20 days. The penicillamines also produced a significant reduction in T 1/2 values; the mean T 1/2 for D-penicillamine in 12 patients was 26 days and N-acetyl-DL-penicillamine in 17 patients yielded a mean T 1/2 of 24 days. This is the first report of the effects of sodium 2,3-dimercaptopropane-1-sulfonate and resin in human subjects exposed to methylmercury. No adverse effects were observed in any of the treatment groups. A clinical trial was not possible but it is concluded that agents that reduce blood levels and accelerate excretion are probably clinically useful if given before irreversible damage has occurred.

Consistency and compatibility in human-computer dialogue

Abstract: To tackle problems of human-computer interaction the traditional scope of humanmachine studies needs extending to include the complex cognitive skills of understanding, communication and problem solving. This extension requires a fusion of the conceptual and empirical tools of human factors with those of cognitive psychology. A methodological approach to this fusion is outlined as a background for three studies of structured human-.computer dialogue. The studies involved a task in which secret messages were decoded in a number of discrete steps corresponding to computer commands. Each “command” required two numeric arguments. The study investigated underlying variables using questionnaire techniques in addition to user performance in an interactive version of the task. Three factors concerning the order of arguments in a command string were investigated: the consistent positioning of a recurrent argument, the relationship between argument entry order and their order in natural language, and the relationship between argument entry order and the position of argument values on a VDU. In Study I software specialists were asked to design command structures for the task and to give reasons for their choices. In Study II naive subjects were asked to choose between telegrams in which alternative argument orders were expressed in terms of alternative word orders. In the interactive version of the task, used in Study III, positionally consistent systems were most readily learned, but this depended on having the recurrent argument in the first position. With positionally inconsistent systems there were reliable effects due to the position of the direct object of individual command verbs.

Breast-milk fat concentrations of rural African women. 2. Long-term variations within a community.

Abstract: 1. Long-term variations in breast-milk fat concentration of mothers feeding on demand were studied in 120 rural West African women over a 12-month period. 2. The over-all mean 12 h breast-milk fat concentration was 39.3 g/l. 3. Mean breast-milk fat concentrations were affected by season in a manner which was correlated with seasonal changes in maternal subcutaneous fat stores (P less than 0.05) but which was unrelated to seasonal variations in maternal energy intake and breast-milk output. 4. Breast-milk fat concentrations were highest in early lactation, decreasing to a constant level during the first year. 5. There was significantly greater between-mother than within-mother variation in breast-milk fat concentrations measured in successive months, after correcting for season and stage of lactation (P less than 0.001). 6. Breast-milk fat concentrations were highest for primiparous mothers, decreasing to a constant level at parity 4 and higher. 7. A mother's relative breast-milk fat concentration was not correlated with her levels of dietary energy intake and breast-milk output but was positively correlated with her relative subcutaneous fat deposits (P less than 0.01).

Plasmodium falciparum gametocytogenesis stimulated by lymphocytes and serum from infected Gambian children.

Abstract: Using peripheral blood from six Gambian children (aged between nine months and two years) with Plasmodium falciparum infections, it is shown that lymphocytes and serum combine to increase the production of P. falciparum gametocytes in in vitro culture.

BCG vaccination of children against leprosy in Uganda: final results

Abstract: A total of 19 200 children, all contacts or relatives of known leprosy patients, and all free of visible leprosy lesions, were included in a controlled trial of BCG vaccination against leprosy in Uganda between 1960 and 1964. They were followed for an average of 8 years, during which time 261 developed early leprosy lesions. A less comprehensive follow-up was carried out for a further 5 years, when 8 more cases of leprosy were identified.In the main intake, between 1960 and 1962, 16 150 tuberculin-negative or weakly tuberculin-positive (Heaf Grades O-II) children were allocated by an effectively random process to either a BCG-vaccinated or an unvaccinated control group. Both groups were seen and examined in an identical fashion for leprosy at approximately 2-year intervals, and precautions were taken to ensure unbiased assessment of new cases of leprosy. After 8 years, 41 cases of leprosy had been identified in the BCG-vaccinated group, and 201 in the control group, a percentage reduction in the BCG-vaccinated group compared with the control group of 80%. The percentage reduction was similar for those initially tuberculin-negative, and for those initially weakly positive, and did not depend upon the age at vaccination. It was also similar for both sexes, for contacts of lepromatous and contacts of non-lepromatous leprosy, for children having contact with one or more than one patient, and for differing grades of physical contact and genetic relationship with a patient. The protective effect of BCG vaccination continued over the 8-year period, although it may have fallen off slightly at the end.In a group of 1074 strongly tuberculin-positive (Heaf Grades III-IV) children followed in parallel with the other two groups a total of 16 cases of leprosy were identified. When adjusted for age, this incidence is 58% lower than that in the unvaccinated control children who were initially tuberculin-negative, indicating a protective effect against leprosy of naturally-acquired strong tuberculin sensitivity.Between 1970 and 1975, one new case of leprosy was identified in a child who had initially been strongly tuberculin-positive and had therefore not been vaccinated, one in a BCG-vaccinated child, and 6 in control children. Although the follow-up in this period was less comprehensive than that in the main part of the trial, the ascertainment of cases was unlikely to have been biased towards either vaccinated or control children. These results indicate a continuing protective effect of BCG up to 12-13 years after vaccination.

Interactions between 17β-Estradiol and Progesterone in the Control of Luteinizing Hormone and Follicle-Stimulating Hormone Release in Rat Anterior Pituitary Cells in Culture

Abstract: After preincubation of rat anterior pituitary cells in culture for 48 h with 10-9 M 17β-estradiol (E2), basal LH release is increased 1- to 2-fold, while the concentration of LHRH required to induce a half-maximal stimulation (ED50) of LH release is approximately 50% reduced. The presence of 10-7 M progesterone (P) alone for 48 h has no effect on LH release, but it inhibits the sensitizing action of E2 on the LH response to LHRH. This inhibitory effect of P on the E2-induced increase of LH responsiveness to LHRH is similar to the effect of androgens. While not affecting the LHRH ED50 for FSH release, P stimulates both basal FSH release and the maximal FSH response to LHRH. This effect of P is potentiated by simultaneous incubation in the presence of E2. The stimulatory effect of E2 alone on LH release is exerted at an ED50 value of 1–2 × 1011 M.A similar ED50 value is found for the potentiating effect of E2 on the P-induced stimulation of FSH release. The stimulatory effect of E2 on LH responsiveness to L...