Showing papers by "University of London published in 1980"

Muscarinic suppression of a novel voltage-sensitive K + current in a vertebrate neurone

Abstract: Cholinergic excitation of vertebrate neurones is frequently mediated through the action of acetylcholine on muscarinic (atropine-sensitve) receptors. This type of excitation differs substantially from the better known nicotinic excitation. One difference is that, instead of an increased membrane conductance, a decreased conductance (to K+ ions) frequently accompanies muscarinic depolarisation. This has been detected in sympathetic, cortical and hippocampal neurones. Using voltage-clamped frog sympathetic neurones we have now identified a distinctive voltage-sensitive K+-current, separate from the delayed rectifier current, as the prime target for muscarinic agonists. We have termed this current the M-current, IM.

Protective effect of pretreatment with verapamil, nifedipine and propranolol on mitochondrial function in the ischemic and reperfused myocardium.

Abstract: To establish whether the prophylactic use of verapamil, nifedipine or propranolol protects heart muscle against the deleterious effects of global ischemia and reperfusion, rabbits were injected subcutaneously twice daily with 2.0 mg/kg of one of these drugs for 4 to 5 days. The hearts were then isolated, paced and either perfused aerobically, made totally ischemic for 90 minutes or made ischemic for 90 minutes and then reperfused. At the end of this time some of the hearts were assayed for adenosine triphosphate (ATP), creatine phosphate (CP) and calcium (Ca ++ ). Other hearts were homogenized, the mitochondria harvested and monitored for oxidative phosphorylating and ATP-generating capacity and Ca ++ content. The effect of Ca ++ on the ATP-generatlng capacity of cardiac mitochondria was also determined. Hearts that were made ischemic gained Ca ++ . The endogenous stores of ATP and CP were depleted; the mitochondria accumulated Ca ++ and the oxidative phosphorylating activity (respiratory control index and oxygen quotient) was impaired. During reperfusion, tissue and mitochondrial Ca ++ was substantially increased, the capacity of the mitochondria to use O 2 for state III respiration was further impaired and the ATP-generating capacity reduced. Resting tension increased and there was only a small recovery of active tension generation. Hearts from the rabbits treated with propranolol, verapamil or nifedipine were protected against ischemia, and ischemia with reperfusion-induced decline in the ATP-generating and O 2 -utillzing capacity of the mitochondria. There was also a less marked increase in tissue and mitochondrial Ca ++ and the systolic tension-generating capacity of the hearts was better maintained.

On closure and factorization properties of subexponential and related distributions

Abstract: For a distribution function F on [0, ∞] we say F ∈ if {1 – F(2)(x)}/{1 – F(x)}→2 as x→∞, and F∈, if for some fixed γ > 0, and for each real , limx→∞ {1 – F(x + y)}/{1 – F(x)} ═ e– n. Sufficient conditions are given for the statement F ∈ F * G ∈ and when both F and G are in y it is proved that F*G∈pF + 1(1 – p) G ∈ for some (all) p ∈(0,1). The related classes ℒt are proved closed under convolutions, which implies the closure of the class of positive random variables with regularly varying tails under multiplication (of random variables). An example is given that shows to be a proper subclass of ℒ 0.

Sexual Selection and the Evolution of Complex Songs Among European Warblers of the Genus Acr Ocephal Us

Abstract: An attempt has been made to explain why the songs of Acrocephalus warblers have become so complex during their evolution. A considerable body of evidence has implicated sexual selection, and two predictions from sexual selection theory have been tested. First, males with more complex songs should attract females for pairing before their rivals with simpler songs. This prediction has been confirmed, when a strong inverse correlation between syllable repertoire size (song complexity) and pairing date (female choice) was obtained in a population of sedge warblers. No significant correlation was obtained between male arrival date and pairing date. Assuming that the first (usually older) males back should select the best territories, then territory quality appeared to have little or no significant effect upon female choice. The second prediction tested was that due to increased sexual selection pressure, males of polygynous species should have evolved more comples songs than males of monogamous species. Of the six common European Acrocephalus species studied, four are monogamous and two polygynous. The prediction was not upheld, as the four monogamous species had long, complex and variable songs, and the two polygynous species had shorter, simpler and less variable songs. The explanation for this apparent paradox can be found in the different relationships between female choice, feeding ecology and parental investment in monogamous or polygynous Acrocephalus species. In polygynous species, a female must ensure the territory contains enough resources to enable her to feed the young and should base her choice primarily upon territory quality. In monogamous species, a female must select a male who will help her to feed the young, and should base her choice more directly upon male quality. The songs of polygynous species have therefore evolved primarily through indirect (intrasexual) sexual selection pressure, which has produced shorter, simpler and more stereotyped songs more suited to male-male interactions and a territorial function. The songs of monogamous species have evolved primarily through direct (intersexual) selection pressure, which has produced the long, complex and variable songs which females find more attractive.

The reduced major axis of a bivariate sample

Abstract: SUMMARY In situations such as allometry where a line is to be fitted to a bivariate sample but where an asymmetric choice of one or other variable as regressor cannot be made, the reduced major axis is often used. Existing tests of the slope of this line, particularly between samples, are not sufficiently accurate in view of the scarcity of the material to which such methods are often applied. Alternative test statistics are suggested and some of their properties derived from a computer implementation of k statistics. One often wishes to describe the relationship between two observed random variables without, in the usual regression terminology, having to specify one as dependent on the other. A typical case, in fact the one which led to this paper, is in allometry where the variables are anatomical measurements, the relationship between which determines shape and may be used as a basis for comparison between species. After suitable transformations, usually logarithmic, have been applied, some measure of the slope of the bivariate scatter plot is required that treats both variables symmetrically. Unless there are sufficient grounds for specifying an underlying model with estimable parameters a possible choice is the line whose sum of squared perpendicular distances from the sample points is a minimum, and it is well known that this is given by the eigenvector corresponding to the larger eigenvalue of the sample dispersion matrix, the smaller eigenvalue in this two variable case being the minimized sum of squares. For the bivariate normal distribution this line is the major axis of the ellipses of constant probability, and so has come to be called the major axis of the bivariate sample. Although invariant under rotation the major axis is altered in a complicated way by changes of scale and in practice preference in the specialist literature on allometry has been given to the line obtained by normalizing the variables to unit standard deviations, finding the major axis, and transforming back to the original scales of measurement. This has come to be called the reduced major axis. The purpose of this paper is to suggest some more precise methods of testing simple hypotheses about the reduced major axis than have hitherto been available.

Numerical analysis of enzyme polymorphism: a new approach to the epidemiology and taxonomy of trypanosomes of the subgenus Trypanozoon.

Abstract: Publisher Summary The subgenus Trypanozoon contains several kinds of trypanosome, which are morphologically indistinguishable but differ in their behavior. At various times specific or subspecific status has been accorded to each kind, but, in recent years, those cyclically transmitted by tsetse in Africa have been separated into subspecies of Trypanosoma brucei , while the others, transmitted non-cyclically outside the African tsetse belts, have retained separate species status. However, although such new terminology may be more correct taxonomically, the practical problems of distinguishing the trypanosomes remain. Enzyme electrophoresis is being used on an increasingly wide scale for the intrinsic characterization. However, as the number of enzyme systems being used for identification grows, comparison of stocks becomes increasingly difficult and intricate, particularly when an enzyme occurs in a multibanded form after electrophoresis. After using 12 enzyme systems to characterize 160 Trypanozoon stocks, the results have been analyzed to establish the degree of relatedness of each of the 59 zymodemest encountered. The detailed analysis is presented in this chapter.

Malignant mesothelioma in North America

Abstract: Ascertainment, through 7,400 pathologists, of all fatal malignant mesothelial tumors in Canada (1960-75) and the U.S.A. (1972) gave a total of 668 cases (272 in 1972). In Canada, the annual number of male cases rose from about 17 in 1966 to 25 in 1972 but the number of female cases remained fairly steady at a much lower level. The annual incidence in North America in 1972 was estimated at 2.8 per million males and 0.7 per million females aged 15 years and over. Occupational histories were obtained "blind" for 480 of the 557 cases through 1972, and their matched controls; relative risks were as follows: insulation work, 46.0 asbestos production and manufacture, 6.1, heating trades (other than insulation) 4.4. For nearly half the male cases and for about 5% of female cases, the tumor could be attributed to occupational exposure to asbestos, of which a fifth were in shipyards. No indication was found of other possible causes (including man-made mineral fibers, tobacco smoking, or residence near zeolite deposits). Four subjects were men who had been employed in Quebec chrysotile mines and 3 were children of employees, but no other subject had lived in the mining area. The findings remain consistent with a much greater mesothelioma-producing potential for crocidolite and amosite than for chrysotile; however, further studies of factory workers exposed to chrysotile only are needed to confirm this. Mineral fiber analysis of lung tissue from patients and controls is in progress.

Wasted skills: a general overview.

Abstract: HE MAIN purpose of this contribution is to take a broad approach to the problem of physical handicap in those aged 16 years and over..The physically handicapped include a range of conditions whichvary in origin, age of onset and have differing prognostic outlooks. They vary in their needs’ for services and for family and community support. Nevertheless there is every justification for categorising them in a single group because all share the’same disadvantage: restriction of physical or social function due to their handicaps. ’

Further enzymic characters of Trypanosoma cruzi and their evaluation for strain identification.

Abstract: Starch-gel electrophoresis of 38 enzymes was attempted with extracts of Trypanosoma cruzi culture forms. 18 of the enzymes that gave discrete electrophoretic bands were selected for routine characterization of T. cruzi stocks; the enzymes were: aspartate aminotransferase (E.C. 2.6.1.1, ASAT); alanine aminotransferase (E.C.2.6.1.2, ALAT); phosphoglucomutase (E.C.2.7.5.1, PGM); glucosephosphate isomerase (E.C.5.3.1.9, GPI); malate dehydrogenase (oxaloacetate decarboxylating) (NADP+) (E.C.1.1.1.40, ME); glucose 6-phosphate dehydrogenase (E.C.1. 1.1.49, G6PD); malate dehydrogenase (E.C.1.1.1.37, MDH); aconitate hydratase (E.C.4.2.1.3, ACON); isocitrate dehydrogenase (NADP+) (E.C.1.1.1.42, ICD); alcohol dehydrogenase (NADP+) (E.C.1.1.1.2, ADH); lactate dehydrogenase (E.C.1.1.1.27, LDH); aminopeptidase (cytosol) (E.C.3.4.11.1, PEP); pyruvate kinase (E.C.2.7.1.40, PK); phosphoglycerate kinase (E.C.2.7.2.3, PGK); enolase (E.C.4.2.1.11, ENO); hexokinase (E.C.2.7.1.1, HK); mannosephosphate isomerase (E.C.5.3.1.8, MPI); and glutamate dehydrogenase (E.C. 1.4.1.2, GD). ADH (NADP+) in the genus Trypanosoma, and PGK, MPI and ENO, in T. cruzi, were apparently demonstrated for the first time. Between six and 18 enzymes were used to characterize more than 250 T. cruzi stocks, newly isolated from a wide range of sources in northern and central Brazil. All stocks were identified as belonging to T. cruzi zymodemes 1, 2 or 3, as originally defined—that is, by combination of electrophoretic patterns of ASAT, ALAT, PGM, GPI, ME and G6PD. The composite range of results with all enzymes confirmed the presence of three principal T. cruzi zymodemes, but some enzymic characters overlapped between zymodemes and others suggested subgroups within individual zymodemes. Seven (MDH, ACON, LDH, PK, PGK, ENO, HK) of the 18 enzymes did not distinguish the three zymodemes; five (ASAT, PGM, GPI, ICD, PEP) distinguished all three zymodemes; 10 (ASAT, ALAT, PGM, GPI, ME, G6PD, ICD, ADH, PEP, GD) distinguished zymodemes 1 and 2, of which seven plus MPI and eight plus MPI separated zymodemes 1 from 3 and 2 from 3 respectively. T. cruzi stocks were taken from a small area of the natural species distribution; the full range of enzymic characters within the species T. cruzi is expected to be far more complex. The epidemiological distribution of the zymodemes continued to accord with local transmission cycles and supported the hypothesis that distinct T. cruzi strains might be responsible for the enigmatic distribution of chronic Chagas's disease. Some of the difficulties in the empirical selection of new electrophoretic methods and the interpretation of results were presented, and the present and prospective significance of T. cruzi enzymic characters was discussed. Until the stability and genetic basis of T. cruzi enzymic characters are better understood it is recommended that isoenzymic profiles be confirmed routinely, both before and after stocks are used experimentally, as representative of a given zymodeme. A multiple biochemical approach to T. cruzi strain identification is recommended, using characters suitable for a numerical taxonomy.

The estimation of late fetal and perinatal age from limb bone length by linear and logarithmic regression

Abstract: SummaryThis paper describes an attempt that was made to confirm the suggestion that limb bone length may be a good indicator of perinatal age. Gestational (menstrual) age was regressed on: (i) the lengths of the ossified shafts of the femur, humerus and radius of 17 subjects of mixed sex aged between 27 and 46 weeks; and (ii) the femur, tibia, humerus, radius and ulna of a second, larger, sample of 65 subjects (29 male; 36 female) aged between 24 and 40 weeks. Age was regressed on single bones and combinations thereof, e.g. humerus, radius and ulna. The data were analysed both in their raw form and as logarithms, the latter yielding very slightly, but not significantly, better results than the former in the case of sample (ii) but not in (i).

The Communication of ELISA Data from Laboratory to Clinician

Abstract: The data generated by quantitative enzyme-immunoassay of antibody activity are unsuitable for direct communication from the laboratory to clinician. In this paper, the fundamental problems of reporting ELISA results are highlighted and a list of desirable characteristics is set out for such reports. The available methods for processing ELISA data are reviewed in relation to these ideal requirements and the deficiencies and advantages of each method are discussed. The performance of each method is demonstrated by the use of actual test data from a model ELISA system. No single method has been found which satisfies all criteria.

Evidence for a GABAergic nigrothalamic pathway in the rat. I. Behavioural and biochemical studies.

Abstract: Unilateral stereotaxic microinjection of muscimol into the caudal region of the substantia nigra (SN) evoked tight, dose-related contralateral locomotor asymmetry and stereotypy. These behaviours were partially attenuated by various pretreatments, including 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway, intraperitoneal (i.p.) haloperidol, and inhibition of thalamic GABA-transaminase activity by local intrathalamic injection of ethanolamine-O-sulphate. Electrolytic or kainic acid lesions of the medial thalamic nuclei (MTN) partially reduced the contraversive rotation to intranigral muscimol, and completely abolished the similar behaviour elicited by apomorphine (25 microgram) injected into the ipsilateral caudate nucleus. Contraversive turning to intranigral muscimol was completely inhibited by kainic acid lesions of the ipsilateral SN, but potentiated by intrahalamic injection of picrotoxin. Muscimol (40 ng--4 microgram) administered to the MTN complex in one hemisphere stimulated rats to move in ipsilateral circles that were unaffected by haloperidol. The results of these behavioural experiments suggest that the nigrostriatal dopamine pathway, the nigrothalamic projection and possibly other non-dopaminergic SN efferents all play important roles in mediating the influences of the SN on motor and stereotyped behaviours. Disruption of the nigrothalamic pathway following electrical or chemical injury to the SN was accompanied by falls in GABA and its synthesising enzyme in the corresponding MTN. These data, together with the findings of our electrophysiological study presented in the following paper, are consistent with the nigrothalamic system having a GABAergic inhibitory function.

Procedures for testing the viability of human hydatid cysts following surgical removal, especially after chemotherapy

Abstract: The basic problems involved in assessing the viability of hydatid material following surgical removal from human cases are outlined and the use of enzyme digestion techniques is shown to provide a rapid and relatively simple diagnostic procedure. The method is described in detail and examples of its practicability are cited. Infection in laboratory animals provides a back-up diagnostic procedure but cyst development in them is too slow to be of value for most clinical work.

Influence of H-2 complex on acquired resistance to Leishmania donovani infection in mice.

Abstract: Innate susceptibility to Leishmania donovani infection in mice (measured over 2–4 weeks) is under the control of a single autosomal gene (Lsh) segregating for incompletely dominant resistant (r) and recessive susceptible (s) alleles1. This locus maps2 away from the known histocompatibility loci to a position between the centromere and Id–1 on the chromosome 1 of the mouse. Amongst homozygous recessive Lshs strains of mice two patterns of recovery are observed3 when the course of infection is followed over a longer term. In some strains a dramatic fall in parasite numbers with histological liver damage occurs while other strains maintain immense parasite loads for up to two years involving mononuclear phagocytes throughout the body. We now present evidence which suggests that this difference in long-term response is largely controlled by a gene(s) within, or closely adjacent to, the major histocompatibility complex (H–2) of the mouse.

Increased pulmonary alpha-adrenergic and reduced beta-adrenergic receptors in experimental asthma.

Abstract: The role of adrenergic mechanisms in the pathogenesis of asthma is controversial. Increased airways resistance in asthmatics is reversed by β-adrenergic receptor agonists such as isoprenaline, and it has been suggested that β-adrenergic activity is diminished in this condition1. This is supported by studies showing reduced metabolic responses to β-adrenergic agonists2,3 and fewer lymphocyte β-adrenergic receptors in asthmatics than in normal subjects4. However, the main contributory factor to diminished β-receptor responsiveness is probably a history of treatment with β-adrenergic agonists, resulting in tachyphylaxis5,6. Nevertheless, similar but less pronounced changes have been observed in untreated asthmatic patients7, α-Adrenergic agonists produce bronchoconstriction in asthmatic patients, but not in normal subjects8,9. Similarly, in vitro studies show α-adrenergic receptor-mediated constriction of bronchial smooth muscle from patients with increased airways resistance, but not from normal controls10,11. In addition increased α-adrenergic receptor-mediated responses in vascular and pupillary smooth muscle have been reported in asthmatics12. Using radioligand binding techniques, we have investigated the possibility that changes in numbers of α- and β-adrenergic receptors or their affinity are associated with the changes in adrenergic responsiveness observed in asthma. We report here that increased α- and fewer β-adrenergic receptors were observed in pulmonary homogenates of an animal model of chronic asthma than in those from controls.

Hyperkinetic and conduct problem children in a primary school population: some epidemiological considerations

Abstract: SUMMARY An epidemiological survey designed to investigate the possible causal influence of biological and psychological factors on hyperactivity and conduct disturbance among 226 primary school boys is provided. The background variables investigated were: adverse perinatal events, neurodevelopmental abnormalities, minor physical anomalies and a combination of psychosocial disadvantage factors. Hyperactivity and conduct disturbance were measured by parent and teacher questionnaires, the disturbed groups being taken as the top 10 per cent. Teachers and parents largely identified separate children as disturbed. The teacher questionnaires failed to distinguish between the two conditions but disturbance was significantly related to high social disadvantage. The parent questionnaire distinguished the two groups better and disturbance of either kind was markedly associated with maternal mental distress, and this far outweighed the contribution of any other background variable.

Solute movement in submerged angiosperms

Abstract: CONTENTS

Functional changes in autonomic nervous responses with ageing.

Abstract: The effects of ageing on autonomic nervous responses have been investigated in 29 young adults, 64 healthy elderly in the age range 66 to 86 years, and 20 elderly in-patients with hypothermia, instability of bladder function or marked orthostatic hypotension. In the healthy elderly group, the beat-to-beat variation in response to postural change was significantly diminished, the vasoconstrictor response to cooling reduced and baroreflex sensitivity during lower-body negative pressure was decreased compared with young adults. Patients with an atronic bladder, determined by urodynamic tests, showed an even more marked decrease in baroreflex sensitivity. The multisystem nature of these autonomic disturbances suggests that physiological impairment may occur in autonomic neural pathways with ageing.