Showing papers by "Medical Research Council published in 1983"

Detection of Intermodal Numerical Correspondences by Human Infants

Abstract: Infants prefer to look at an array of objects that corresponds in number to a sequence of sounds. In doing so, infants disregard the modality (visual or auditory) and type (object or event) of items presented. This finding indicates that infants possess a mechanism that enables them to obtain information about number.

Prosody: Models and measurements

Abstract: 1. Introduction. Models and Measurements in the Study of Prosody.- 1.1 Concrete and Abstract Accounts of Prosody.- 1.2 Illustrating the Two Approaches.- 1.2.1 Intonation.- 1.2.2 Stress.- 1.3 Implications of the Two Approaches.- 1.4 The Contributions.- 1.5 The Purpose of an Interdisciplinary Volume.- 2. A Generative Model of Intonation.- 2.1 The Model.- 2.2 Application to Swedish, Greek and French.- 2.3 Comparison.- 2.3.1 Intonation and Boundaries.- 2.3.2 Accentuation.- 2.4 The Model Applied to Questions and Pragmatic Effects.- 3. Two Issues in the Prosody of Standard Danish.- 3.1 Introduction.- 3.2 Sentence Accent.- 3.3 The Representation of Sentence Intonation.- 3.3.1 The Tone Sequence Approach.- 3.3.2 Problems with the Tone Sequence Approach in Standard Danish.- 4. Peak Features and Overall Slope.- 4.1 Introduction.- 4.2 The Peak-Feature Model.- 4.2.1 Background.- 4.2.2 Some Details.- 4.3 Cross-Classification and Functional Relatedness.- 4.4 Peak Scaling and Declination.- 4.4.1 Declination in Questions.- 4.4.2 Declination and Downstep.- 4.4.3 Deviations from Regression Lines.- 4.5 Summary.- 5. Language-Independent Prosodic Features.- 5.1 Introduction.- 5.2 Language-Independent Similarities.- 5.2.1 Pauses.- 5.2.2 Fundamental Frequency Features.- a) The Declination Tendency.- b) Resetting of the Baseline.- c) Normal Frequency Range and the Control of Range.- d) Rising Versus Falling F0 Movements.- 5.2.3 Durational Features and Intensity Phenomena.- a) Final Lengthening.- b) Other Lengthening Phenomena.- 5.2.4 Intensity and the Syllable.- 5.3 Prosodic Differences Among Languages.- 5.3.1 Differences in Timing.- 5.3.2 Different Orders of Priorities.- 5.3.3 Different Relationships Between F0, Duration and Intensity.- 5.4 Conclusion.- 6. Prosodic Structure and the Given/New Distinction.- 6.1 The Given/New Distinction.- 6.2 Extensions of the Given/New Distinction.- 6.3 An Experimental Study of Intonation and Information Structure.- 6.3.1 The Data.- 6.3.2 Formal Realisations in the Data.- 6.4 Conclusion.- 7. Speakers' Conceptions of the Function of Prosody.- 7.1 Introduction.- 7.2 The Prosody of Repair.- 7.3 The Repair of Prosody.- 7.4 Conclusion.- 8. Structures and Categories in Prosodic Representations.- 8.1 Intonation and Universal Grammar.- 8.2 Phonetic Representations of Intonation.- 8.3 Phonological Representations.- 8.3.1 Phonological Tones.- 8.3.2 Phonological Structure.- 8.3.3 Underlying Tonal Representations.- 8.3.4 Phonetic Implementation.- 8.4 Conclusion.- 9. Temporal Predictability in the Perception of English Speech.- 9.1 Stress and Rhythm.- 9.2 P-Centres and Rhythm.- 9.3 Rhythm and Temporal Predictability.- 9.4 Modelling Rhythmic Structure.- 9.5 Summary.- 10. Prosodic Structure Above the Word.- 10.1 Introduction.- 10.2 Construction of Prosodic Categories.- 10.3 Intonation Phenomena.- 10.4 Ambiguity and Potential for Disambiguation.- 10.4.1 Syntactic Versus Prosodic Constituents, and the Resolution of Ambiguity.- 10.4.2 Perception Test.- a) Material.- b) Subjects.- c) Procedure.- d) Results.- 10.5 Conclusions.- 11. Comparative Notes on Terms and Topics in the Contributions.- 11.1 Accents.- 11.2 Domains.- 11.3 Grids.- 11.4 Lines.- 11.5 Tones.- References.- Name Index.

Analysis of resonant coupled coils in the design of radio frequency transcutaneous links

Abstract: A theory of coupled resonant coils has been developed which makes possible the design of radio frequency transcutaneous links of simultaneously high overall efficiency and good displacement tolerance while keeping circuitry simple (particularly in the implanted receiver). Series-tuned transmitter coils were used, obtaining high efficiency. In the first example a stimulator which has excellent displacement tolerance because it works at critical coupling is designed. The second example shows how the theory was used when the voltage in the implant was regulated. The design process involvesad hoc compromises between disparate quantities (e.g. efficiency against voltage transfer ratio), rendering a standard design procedure unsuitable. Fortunately, the derived theoretical formulae are simple enough for every design to be considered from fundamentals, based on coil parameters. Extensive coil loss data are presented here for the frequency band 0·2 to 20 MHz.

Protein structural domains in the Caenorhabditis elegans unc-54 myosin heavy chain gene are not separated by introns.

Abstract: The 1,966-amino acid unc-54 myosin heavy chain sequence was determined from DNA sequence studies of the cloned gene. The gene is split by eight short introns, 48-561 base pairs long, and appears to lack a "TATA" box at its promoter. The physical map of the gene was aligned with the genetic map by locating two point mutations and three internal deletions: 0.01 map units correspond to approximately 5 kilobases. Comparison of the unc-54 protein sequence with the sequence of a second myosin heavy chain from nematode, indicates that the globular head sequence S-1 is more highly conserved than the alpha-helical coiled-coil rod. Major sites of proteolysis in S-1 are associated with variable sequences that have the characteristics of surface loops. In both genes there is no correlation between the positions of introns and the major protein structural domains.

Progressive change in cerebral blood flow during the first three weeks after subarachnoid hemorrhage

Abstract: Cerebral blood flow (CBF) was estimated from each cerebral hemisphere by the 133Xe inhalation method. Daily estimates were made during the first 3 weeks after subarachnoid hemorrhage (1265 studies in 116 patients). Some of the patients were taking adrenergic blocking drugs (propranolol and phentolamine), others were taking tranexamic acid, and the rest were taking no drugs. CBF was also studied in 67 normal subjects. The resting CBF was related inversely to age not only for normal subjects but also for patients after subarachnoid hemorrhage (SAH). The CBF fell progressively during the first 2 weeks after SAH and was abnormally low throughout the 3 weeks after hemorrhage. For any 1 day after SAH, those patients who were fully alert had the smallest reduction in CBF. The progressive changes in CBF occurred whether or not an aneurysm was present on angiograms. For aneurysms situated to one side of the midline, the changes in CBF affected both sides of the brain. The progressive decline in CBF was least in those patients who subsequently made the best clinical recovery. Arterial pCO2 seemed to influence CBF throughout the 3 weeks after SAH. During the 2nd week, CBF was especially low in SAH patients treated with tranexamic acid. The serial changes in CBF are discussed in relation to current views concerning the timing of operation for ruptured aneurysms.

Regional Brain Blood Flow, Blood Volume, and Haematocrit Values in the Adult Rat:

Abstract: Measurements of red cell volume, plasma volume, and tissue haematocrit (Hct) were made in 14 brain regions in adult rats using 51Cr-tagged red cells and 125I-labeled human serum albumin. The mean large vessel (systemic artery) Hct was 41.8, total body Hct was 35.3, and of the brain regions, the lowest value (septal nucleus) was 25.91 and the highest (visual cortex) was 32.05. The lowest blood volume was 6.29 microliters g-1 (caudate putamen) and the highest was 14.44 microliters g-1 (inferior colliculus). There was a significant difference between regions in both blood volume and tissue blood Hct. When brain regions were ranked in order of blood volume, this did not coincide with the order for blood flow.

Relationships between Extraction and Metabolism of Glucose, Blood Flow, and Tissue Blood Volume in Regions of Rat Brain:

Abstract: Studies were made on the relationships between the rate of glucose metabolism, the transport of glucose between plasma and brain, cerebral blood flow, and blood content. Conscious control rats were compared with rats with intense tremors induced with cismethrin. The influence of plasma glucose concentration was studied by fasting some animals overnight prior to the induction of tremors. Mean plasma glucose was 8.83 mM in controls, 12.57 mM in fed rats with tremors, and 4.94 mM in rats fasted overnight prior to induction of tremors. Of 12 brain regions studied, nine showed an increased rate of glucose utilization in both fed and fasted trembling rats. Cerebellum had the highest percentage increase (200%). Rates of unidirectional glucose influx in fed trembling rats were significantly greater than those in controls in eight regions. In fasted animals, rates were the same as in controls, except in cerebellum, where it was 1.6 times higher. These high rates of glucose influx at low plasma glucose concentrations were indicative of a change in kinetic parameters of glucose transport. Unidirectional glucose influx rates were transformed to estimates of maximal transport rates (Tmax), based on the Michaelis-Menten equation. Average plasma glucose concentrations in regional capillaries (c) were calculated and shown to be maintained at values close to arterial plasma glucose concentrations (Ca), in all brain regions of each group. In trembling rats, Tmax for each brain region was higher than that in controls. In fasted rats with tremors, Tmax was higher in several brain regions than in fed rats. Tmax in cerebellum was 3.37, 4.71, and 7.89 mumol g-1 min-1 in control, fed trembling, and fasted trembling rats, respectively. Blood flow increased significantly in all regions in rats with tremors and was higher in fasted than in fed animals. There was only a weak correlation between blood flow and Tmax. Blood content of several regions increased in rats with tremors, and there was a strong correlation between Tmax and tissue blood volume. Results are consistent with localized regulatory links between blood flow, capillary surface area, and glucose transport in response to metabolic demand and hypoglycaemia. These involve changes in the linear velocity of blood through capillaries and in the extent of capillary recruitment.

The termination of primary afferents within the rat dorsal horn: evidence for rearrangement following capsaicin treatment.

Abstract: The mode of termination of primary afferent fibres within the superficial dorsal horn of the spinal cord was studied with anterograde tracing methods in normal rats and in animals which had been treated with capsaicin (50 mg/kg. s.c.) shortly after birth. In normal animals following injections of horseradish peroxidase (HRP) into lumbar dorsal root ganglia L4, L5, L6, a Golgi-like filling of primary afferent fibres was seen consistently within laminae I, II, and III of the dorsal horn. Several types of lamina related arborisations were observed, depending upon the survival time after HRP injection. At the earliest survival time (1–2 days) a punctate granular labelling was found in laminae I and II inner (IIi). At 3 days survival a Golgi like labelling of primary afferent axons occurred and three tiers of arborisation were seen within laminae I, II outer (IIO), and II inner (IIi), respectively. By 7 days after injection this pattern was considerably reduced and there was coarser fibre labelling within laminae I, IIO, and III. When these tracing experiments were repeated in capsaicin-treated rats in which up to 90%of unmyelinated fibres had been destroyed, evidence for a considerable loss of some inputs and rearrangement of the remaining fibres was found. At 3–5 days survival the axonal labelling within laminae I and IIi was severely depleted yet some input, particularly to lamina IIO, was present. At 7 days survival deep fibre labelling within lamina III now extended well into lamina II. Mapping of the primary afferent input following 3H-proline injections into the dorsal root ganglion and subsequent autoradiographic processing confirmed that primary afferents terminated throughout the dorsal horn but most heavily in two bands within laminae I and IIi. These two dense layers of termination were not present in capsaicin-treated animals, suggesting that they corresponded to areas of unmyelinated primary afferent fibre input. These data, taken together with histochemical observations on the distribution of substance P and fluoride-resistant acid phosphatase (FRAP)-containing primary afferents, suggests that the earliest-labelled fibre systems (3days) were unmyelinated and replaced at 7 days by predominantly A6 myelinated fibres. It is further suggested that of the three tiers of C fibre terminations seen at 3 days, the most superficial corresponds in part to those primary afferents that can be stained for substance P within lamina I while the most ventral tier within lamina IIi are those primary afferents containing FRAP. The presence of the two temporally distinct fibre systems also suggests that laminae I and IIo, receive both C and A6 primary afferent input while lamina IIi, receives only C fibre input.

Role of endogenous substance P in stress-induced activation of mesocortical dopamine neurones

Abstract: The dopamine (DA) innervation to the forebrain arises from subpopulations of midbrain DA neurones broadly classified as nigrostriatal, mesolimbic and mesocortical1. Significant differences in the autoregulatory mechanisms and neuronal inputs of these DA pathways may account for their differences in physiological and pharmacological responsiveness2. For example, foot-shock stress can activate rat mesocortical DA cells but does not alter nigrostriatal DA turnover3–5, while also decreasing substance P (SP) concentrations in the midbrain interpeduncular nucleus and in the adjacent ventral tegmental area (VTA), but not in the substantia nigra (SN)6. This suggested that the activation of the SP input to the VTA6 may mediate activation of certain DA systems by footshock stress (Fig. 1); behavioural studies also had suggested an excitatory effect of SP on DA cells in the VTA7. SP antagonists now available are neurotoxic8 and of questionable efficacy9, we therefore used monoclonal antibody against SP. Antibody microinjected into the VTA prevented normal footshock-induced activation of mesocortical DA neurones, suggesting mediation by SP input to the VTA. The in vivo application of antibodies may prove valuable in studies of neuropeptides in the central nervous system (CNS).

Sexual responsiveness in diabetic women

Abstract: Sexual responsiveness in 82 Type 1 (insulin-dependent) diabetic women was compared with that of 47 normal control subjects, using an interview method for rating various aspects of sexual response, and attitude questionnaires. The diabetic women were questioned about symptoms of autonomic neuropathy, and cardiovascular autonomic nerve function tests were performed. There were differences between the two groups in the reports of vaginal lubrication, but in most other respects the groups were similar. The diabetic women were not less orgasmic, and reported significantly fewer unpleasant feelings during sexual intercourse. They saw themselves and their husbands as less 'potent' than did the normal subjects. The possible enhancing effect of diabetes on the marriage of some diabetic women possibly counteracted the relatively mild physiological deficits involved. There was very little difference in sexual response between women with and without symptomatic autonomic neuropathy.

Fragments from both termini of the herpes simplex virus type 1 genome contain signals required for the encapsidation of viral DNA

Abstract: A 535 base pair DNA fragment which maps entirely within the IRS/TRS regions of the herpes simplex virus type 1 (HSV-1) genome and contains all the cis-acting signals necessary for it to function as an origin of viral DNA replication has previously been identified (N.D. Stow and E.C. McMonagle, Virology, in press). When BHK cells were transfected with circular plasmid molecules containing cloned copies of this DNA fragment, and superinfected with wt HSV-1 as helper, amplification of the input plasmid was detected. Two observations indicated that the amplified DNA was not packaged into virus particles. Firstly, when the transfected cells were disrupted the amplified DNA was susceptible to digestion by added DNase, and secondly, it was not possible to further propagate the DNA when virus from the cells was passaged. Fragments from the joint region and from both termini of the viral genome were inserted into origin-containing plasmids and the resulting constructs analysed. In all cases the inserted fragment allowed the amplified DNA to be further passaged, and a proportion to become resistant to digestion with DNase. These observations suggest that signals required for the encapsidation of HSV-1 DNA are located within DNA sequences shared by the inserted fragments and therefore lie within the reiterated 'a' sequence of the viral genome.

Metabolically Active Synaptosomes Can Be Prepared from Frozen Rat and Human Brain

Abstract: Nerve ending particles (synaptosomes) were prepared from pieces of rat and human brain and from brain homogenate that had been frozen and thawed under a variety of conditions. Their purity, as judged by electron microscopy, and performance in terms of a number of metabolic and functional parameters [accumulation of tissue potassium, respiration, release of transmitter amino acids, and the responses on these indices to depolarisation by veratrine (VX)] were compared with those of fresh tissue-derived synaptosomes. It was found that rapid freezing and/or slow thawing severely impaired the subsequent performance of incubated synaptosomes. In contrast, synaptosomes from tissue frozen slowly and thawed rapidly showed relatively good retention of morphology and metabolic performance. It was better to use whole (1-5 g) pieces of tissue than tissue homogenate: the synaptosome fraction from frozen tissue pieces contained 80% of the proportion of identified synaptosomes found in the fresh tissue synaptosome fraction, its respiratory rate was 65%, and its tissue potassium content 70% of that of fresh controls. Moreover, it responded to VX or potassium stimulation by showing increased respiratory rate, decreased tissue potassium, and increased release of neurotransmitter amino acids, to an extent that was comparable to that of fresh tissue fractions. Thus, preparations from frozen rat and human brain were shown to be metabolically and functionally active, and can be used for a variety of neurotransmitter-related studies.

Functional analysis of a herpes simplex virus type 1 promoter: identification of far-upstream regulatory sequences

Abstract: We have performed a functional analysis of DNA sequences upstream from the gene for IE mRNA3 of herpes simplex virus type 1. Nucleotide sequences involved in initiation and positive regulation of transcription have been defined by construction of specific deletions in vitro. Transcription was assayed in vivo by microinjection into Xenopus oocytes, or by introduction of plasmid DNA into tissue culture cells and measurement of transient expression. Three functional promoter elements have been defined: i) Sequences between -16 and -37 which are not essential for transcription but are required for accurate initiation. ii) Proximal promoter sequences which are sufficient for transcription initiation in the absence of upstream sequences. iii) Far-upstream promoter sequences (more than 108bp upstream) which increase transcription in oocytes, and contain positive regulatory sequences (-174 to -331) which respond strongly to a factor in the virus inoculum.

Studies on the prevalence and epidemiology of urinary stone disease in men in Leeds.

Abstract: Summary— A postal survey among 2% of men in Leeds showed that the prevalence of urinary stone disease is 3.8%. The prevalence of upper urinary tract and spontaneously passed stones increases progressively from 0.7% in social class 5 to 5.0% in social class 1 but that of bladder stones (0.7% in the group as a whole) is independent of social class. There is an initial peak of upper urinary tract and spontaneously passed stones commencing at age 20 and having a projected prevalence at age 90 of 5.7% and a second peak of bladder stones, commencing about age 50, with a projected prevalence of 1.9%. The prevalence of stone disease increases according to the order: single < divorced/separated < married < widowed men. A family history of stones tends to be higher amongst relatives of stone-formers than amongst the corresponding relatives of control subjects, the male/female ratio being 2:1. The occurrence of urinary stones is significantly associated with that of gallstones, high blood pressure, backache, arthritis and gout but not with that of peptic ulcer, diabetes, thyroid disease or bronchitis.