Showing papers by "Medical Research Council published in 1982"
TL;DR: The unique delay in onset of ischemic cell change and the protracte increase in its incidence between 24 and 72 hours could reflect either delayed‐appearance of isChemic change in previously killed neurons or a delayed insult that continued to jeopardize compromised but otherwise viable neurons during the postischemic period.
Abstract: This study examined the temporal profile of ischemic neuronal damage following transient bilateral forebrain ischemia in the rat model of four-vessel occlusion. Wistar rats were subjected to transient but severe forebrain ischemia by permanently occluding the vertebral arteries and 24 hours later temporarily occluding the common carotid arteries for 10, 20, or 30 minutes. Carotid artery blood flow was restored and the rats were killed by perfusion-fixation after 3, 6, 24, and 72 hours. Rats with postischemic convulsions were discarded. Ischemic neuronal damage was graded in accordance with conventional neuropathological criteria. Ten minutes of four-vessel occlusion produced scattered ischemic cell change in the cerebral hemispheres of most rats. The time to onset of visible neuronal damage varied among brain regions and in some regions progressively worsened with time. After 30 minutes of ischemia, small to medium-sized striatal neurons were damaged early while the initiation of visible damage to hippocampal neurons in the h1 zone was delayed for 3 to 6 hours. The number of damaged neurons in neocortex (layer 3, layers 5 and 6, or both) and hippocampus (h1, h3-5, paramedian zone) increased significantly (p less than 0.01) between 24 and 72 hours. The unique delay in onset of ischemic cell change and the protracted increase in its incidence between 24 and 72 hours could reflect either delayed appearance of ischemic change in previously killed neurons or a delayed insult that continued to jeopardize compromised but otherwise viable neurons during the postischemic period.
2,729 citations
TL;DR: Oligonucleotide primers have been used to generate a cDNA library covering the entire tobacco mosaic virus (TMV) RNA sequence and analysis of these clones has enabled us to complete the viralRNA sequence and to study its variability within a viral population.
Abstract: Oligonucleotide primers have been used to generate a cDNA library covering the entire tobacco mosaic virus (TMV) RNA sequence. Analysis of these clones has enabled us to complete the viral RNA sequence and to study its variability within a viral population. The positive strand coding sequence starts 69 nucleotides from the 5' end with a reading frame for a protein of Mr 125,941 and terminates with UAG. Readthrough of this terminator would give rise to a protein of Mr 183,253. Overlapping the terminal five codons of this readthrough reading frame is a second reading frame coding for a protein of Mr 29,987. This gene terminates two nucleotides before the initiator codon of the coat protein gene. Potential signal sequences responsible for the capping and synthesis of the coat protein and Mr 29,987 protein mRNAs have been identified. Similar sequences within these reading frames may be used in the expression of sets of proteins that share COOH-terminal sequences.
639 citations
TL;DR: The logrank test is commonly used in the analysis of clinical trials in chronic diseases such as cancer and the numbers required are considerably smaller than those in existing tables when the event-free proportions are small, but otherwise comparable.
Abstract: The logrank test is commonly used in the analysis of clinical trials in chronic diseases such as cancer. Existing tables for the number of patients required in such trials are based on the direct comparison of two proportions. This paper presents tables of numbers required in clinical trials using the logrank test and describes their use. The numbers required are considerably smaller than those in existing tables when the event-free proportions are small, but otherwise comparable.
604 citations
TL;DR: The data are consistent with a predominant loss in Alzheimer's disease of the diffuse cholinergic projection from the brainstem and basal forebrain.
Abstract: Choline acetyltransferase (ChAT) activity and gamma-aminobutyric acid (GABA) concentration were measured in 19 cerebral cortical areas and 22 subcortical areas of brains from 26 control and 25 histologically proven cases of Alzheimer's disease. Reduced ChAt activity was observed in all the cortical areas examined in the Alzheimer cases dying before the median age of 79 years. In the Alzheimer cases aged greater than 79 years at death, 7 out of the 9 frontal cortical areas had a normal ChAT activity when compared with controls. Significant reductions in GABA concentrations in the Alzheimer cases were confined to the temporal cortex. Significant reductions in ChAT activity in subcortical areas were confined to 8 of the 22 regions examined. Notably these included the septal nuclei and substantia innominata, the proposed origins of the cholinergic projections to the hippocampus and neocortex, respectively. There were no reductions in GABA concentrations outside the cerebral cortex. Four multi-infarct cases and 6 cases with normal histology were found to have a small reduction in ChAT activity confined to only a few areas. The data are consistent with a predominant loss in Alzheimer's disease of the diffuse cholinergic projection from the brainstem and basal forebrain.
463 citations
TL;DR: In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone.
Abstract: In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, but changes in Bmax for tritiated spiperone reflect genuine changes in receptor numbers. The increases in receptors were seen only in patients in whom neuroleptic medication had been maintained until the time of death, indicating that they may be entirely iatrogenic. Dopamine measurements for a larger series of schizophrenic and control cases (n greater than 60) show significantly increased concentrations in both the nucleus accumbens and caudate nucleus. The changes in dopamine were not obviously related to neuroleptic medication and, unlike the receptor changes, were most severe in younger patients.
386 citations
TL;DR: A double-stranded cut at the MAT locus appears to initiate cassette transposition-substitution and defines MAT as the recipient in this process, suggesting that cutting initiates the switching process.
367 citations
TL;DR: In contrast to SP and physalaemin, both eledoisin and a metabolically stable SP analogue, [pGlu5, MePhe8, Sar9]-SP5-11 exhibited differential recovery from SP tachyphylaxis in the guinea pig ileum, and part of their spasmogenic action in this preparation was atropine-sensitive.
Abstract: 1.
The possible existence of multiple receptors for substance P (SP) was investigated by examining the relative pharmacological potencies of SP and related peptides in contracting guinea pig ileum, in potentiating electrically evoked contractions of rat vas deferens preparations and in competing for 3H-SP receptor binding in rat brain membranes, and by comparing the extent of cross-tachyphylaxis of various analogues with SP in the guinea pig ileum.
2.
Different rank orders of potencies were observed among SP, its C-terminal fragments, analogues and related tachykinins in the different test systems, and these could not be explained by differential access to the target organ receptors.
3.
In contrast to SP and physalaemin, both eledoisin and a metabolically stable SP analogue, [pGlu5, MePhe8, Sar9]-SP5-11 exhibited differential recovery from SP tachyphylaxis in the guinea pig ileum, and part of their spasmogenic action in this preparation was atropine-sensitive.
4.
The results suggest the possible existence of multiple SP receptors, and the specificity of those in the brain may be different from those in the gut. The structural and pharmacological basis for subdividing tachykinins into SP-physalaemin and eledoisin-kassinin families is also discussed.
336 citations
TL;DR: The results suggest the existence of a population of fluoride-resistant phosphatase-positive sensory neurones which is distinct from neurones containing either of these peptides.
259 citations
TL;DR: Investigation of the coexistence of two neuronally-localised peptides, substance P and thyrotropin-releasing hormone, in descending serotoninergic nerve fibres to the spinal cord found that substance P was unaffected by 6-hydroxydopamine, a drug known to destroy catecholamine-containing neurones.
235 citations
TL;DR: Though relatively few people work on these minor, but very active, lipids at present, recent observations should soon attract others into this field and ideas and strictures that might inform future work are collected.
208 citations
TL;DR: Of the conventional parameters of semen analysis examined, the most revealing was the morphologic character of the sperm, which was significantly poorer in the group with unexplained infertility than in the normal fertile control group and also showed a significant relationship with the presence of subnormal fertilizing capacity in the hamster egg assay.
TL;DR: A portable, unprepared simple reaction time (USRT) test is described, particularly suitable for assessing performance in the field as a function of arousal-related stress.
Abstract: A portable, unprepared simple reaction time (USRT) test is described. This test is particularly suitable for assessing performance in the field as a function of arousal-related stress. The test, which is housed in a small, battery-powered cassette recorder, presents a visual stimulus at quasi-random intertrial intervals ranging from 1 to 10 s. The subject responds by pressing a button as quickly as possible, whereupon the reaction time is displayed. The duration of the test is limited only by the cassette tape on which the data are recorded, but 10 min is recommended. Reviewed are studies illustrating the test's brief practice curve and its sensitivity to arousal-related stress.
TL;DR: It is clear that the majority of rat central nervous system neurotensin‐like immunoreactivity is indistinguishable from the synthetic tridecapeptide, however, smaller amounts of carboxy‐ and amino‐terminal neurotensIn‐like Immunoreactivity were detected.
Abstract: Carboxy- and amino-terminal specific neurotensin antisera have been characterized and used to determine the nature of neurotensin-like immunoreactivity in the rat central nervous system. Using these antisera, together with the separation of neurotensin-like immunoreactivity on reversephase HPLC columns, it is clear that the majority of rat central nervous system neurotensin-like immunoreactivity is indistinguishable from the synthetic tridecapeptide. However, smaller amounts of carboxy- and amino-terminal neurotensin-like immunoreactivity were detected, which may correspond to carboxy- and amino-terminal fragments of neurotensin. In addition, using the amino-terminal directed neurotensin antiserum, a detailed distribution of neurotensin-like immunoreactivity in the rat central nervous system is described. Highest amounts were found in the hypothalamus, central amygdaloid nucleus, bed nucleus of the stria terminalis and the substantia gelatinosa of the spinal cord and of the trigeminal region.
TL;DR: Small injections of horseradish peroxidase were made into the various regions of the midbrain periaqueductal gray of monkey, cat, and rat PAG to see which of the forebrain areas directly influence the PAG.
Abstract: There is considerable evidence that the midbrain periaqueductal gray (PAG) is involved in visceral, emotive, and sexual responses and in endogenous analgesic effects. To see which of the forebrain areas directly influence the PAG, small injections of horseradish peroxidase were made into the various regions of monkey, cat, and rat PAG. Despite the fact that regions of the PAG were injected in separate animals the majority of the forebrain areas labeled remained constant. Retrogradely filled pyramidal neurons in layer V were found in the frontal lobe in areas 6, 8, 9, 10, 13, and 24. Labeled neurons also appeared in the amygdala, preoptic area, and the anterior, dorsal, periventricular, ventromedial, periarcuate lateral, and posterior hypothalamic nuclei. The main route for the hypothalamic leads to PAG projection appeared to be via the periaqueductal bundle which immediately borders on the cerebral aqueduct. Labeled neurons were also observed in the zona incerta, mesencephalic reticular formation, deep layers of the superior colliculus, and the nucleus cuneiformis. Most labeling was ipsilateral to the injection site although a small but consistent contralateral labeling was present. Therefore a strict subdivision of the PAG based on each subnucleus having its own unique set of connections seems inappropriate. There were few striking differences found in the forebrain areas that project to the PAG in the three species examined. These results are discussed in terms of the possible contribution these forebrain areas have in regulating the PAG with regard to its functions as a visceral, nociceptive, and cognitive integrator.
TL;DR: Reliability of the results of bio‐medical research clearly depends upon the animals used showing as standard responses as is possible, according to I.I.
Abstract: Summary
I. Reliability of the results of bio-medical research clearly depends upon the animals used showing as standard responses as is possible.
2. The majority of animals used in this field are small, homoiothermic mammals which have sensitive and strong homeostatic mechanisms. If a change in ambient conditions is of sufficient magnitude to unbalance homeostasis, then the neuroendocrine system is stimulated so as to restore it, and this can interfere with the response to test conditions or agents.
3. The homeostatic effectors involved are diverse and can include both physiological and behavioural changes in the animal. These can affect metabolic rate, body temperature, activity, food consumption, hormone concentration, wake/sleep patterns, maturation, posture, lactation and many other bodily functions. Any of these changes is potentially capable of influencing experimental results.
4. The evidence presented shows how environmental factors may affect the outcome of experiments in the fields of animal behaviour, cancer research, immunology, pathology, pharmacology, psychology, reproduction, teratology and toxicology; particular attention is paid to the effects of ambient temperature, relative humidity, air movement and quality, light and sound.
5. While a constant, reproducible environment would be ideal, there is little possibility of controlling all the variables; nevertheless all investigators should minimize those environmental variables that have been shown to be important.
6. To enable other investigators to repeat experiments or carry out comparative studies, environmental conditions pertaining during an experiment should be adequately described in any publications.
TL;DR: The aim has been to detail quantita tive data for several animal species without neces sarily implying that all such data are directly rele vant to man.
Abstract: Since the realization over a decade ago (Owen et aI., 1967) that the brain of the human adult can function, apparently normally, when up to two thirds of the substrates supplied are ketone bodies rather than glucose, consideration of substrate utili zation has to take into account which substrates are being used, as well as how much of each is being used. These questions have particular relevance throughout the period of brain development, both preand postnatally, since circumstances may arise under which an adequate supply of blood-borne glucose is compromised. Previous reviews on energy metabolism in the developing brain have emphasized the human baby and possible problems of adequate nutrition (Schwartz and Kalhan, 1975; Jones, 1979; Pratt, 1979; Wasterlain et aI., 1980; Cremer, 1981). In the present review, the aim has been to detail quantita tive data for several animal species without neces sarily implying that all such data are directly rele vant to man. Fortunately, information available on young babies and children is sufficiently com prehensive to allow a direct comparison with other species.
TL;DR: Withdrawal of anxiolytic agents such as ethanol, barbiturates, and benzodiazepines may result in a syndrome characterised in its most severe form by delirium and seizures, which could underlie the severe symptoms associated with tranquilliser withdrawal.
TL;DR: The results demonstrate that the apparent fertility of normal fertile men is compatible with a wide range of intrinsic sperm quality as reflected by penetration rates ranging from 14% to 90% and differences in the minimum concentration of motile spermatozoa required to initiate penetration.
TL;DR: The autoradiographic localizations of opiate and histamine H1-receptors were studied quantitatively and compared following dorsal root section in the primate spinal cord.
TL;DR: In this article, the authors linked information on the risk of tuberculous infection in the Netherlands with information on incidence of tuberculosis, in an attempt to estimate the risks of developing the disease following infection or reinfection.
01 Jan 1982
TL;DR: It is perhaps fitting that some of the present knowledge of the physiological actions of capsaicin is owed to the insight of the Hungarian scientist N. Jancso, who embarked on investigations of this substance in the late 1940s and continued until his death in 1966.
Abstract: Capsaicin is a principle constituent in a large variety of red peppers (e.g., Capsicum annuum, Capsicum frutescens), and it is to this and closely related substances that the pungency of these condiments is attributed. Peppers are routinely consumed by the people of a variety of nations and among these are the Hungarians, their cuisine being famous or, according to the palates of some, notorious for the generous use of paprika. It is perhaps fitting therefore that we owe some of the present knowledge of the physiological actions of capsaicin to the insight of the Hungarian scientist N. Jancso, who embarked on investigations of this substance in the late 1940s and continued until his death in 1966. The impetus he provided is attested to by the incisive work conducted subsequently by his colleagues. A review of literature on capsaicin, therefore, cannot preclude a separate acknowledgment of these investigators for it is some of their work that has stirred the current interest in capsaicin.
TL;DR: The nature of the association of substance P (SP) with taste buds in the rat tongue was investigated by immunohistochemical and radioimmunoassay techniques and both the circumvallate and fungiform papillae were found to receive a rich innervation by substance P-containing fibres.
TL;DR: Double labelling studies established that enkephalin and serotonin co-exist within some neurons in NRM and NRP, and beta-Lipotropin-positive cell bodies were found principally within NRP and within the ventrolateral reticular formation in PGL and LRM.
TL;DR: Four patients had central retinal artery occlusions after retrobulbar anesthesia with lidocaine HCl was administered before photocoagulation and it is thought that direct trauma to the central retina artery behind the globe, the pharmacologic or compressive effects of the injected solution, or both caused the occlusion.
TL;DR: The present data suggest that the neuronal organization of the PAG could be described as a mosaic of clusters of functional related neurons rather than as three distinct subnuclei, each with its own unique cytoarchitecture and connectivity.
Abstract: Anatomical staining methods including Nissl, Weil, Golgi, and horseradish peroxidase stain have been used to elucidate the cyto- and myeloarchitectural organization of the periaqueductal gray in monkey, cat, and rat. From these various staining methods it appears that the periaqueductal gray is composed of a tightly packed group of cells, which show a slight increase in soma size, dendritic diameter, and degree of myelinization from central to peripheral borders. This central gray region contains a wide variety of cell types including multipolar, fusiform, stellate, and pyramidal neurons. Clearly delineated subnuclei, distinguished on the basis of soma size, dendritic arborizations, pigmentation, or evidence of cytological individuality could not be discerned in this study. Together with the immunohistochemical and connectivity studies the present data suggest that the neuronal organization of the PAG could be described as a mosaic of clusters of functional related neurons rather than as three distinct subnuclei, each with its own unique cytoarchitecture and connectivity.
TL;DR: The results suggest that malignant gliomas contain a population of B lymphocytes which may be involved in host defence against the tumour.
TL;DR: Methods of survival analysis for long-term follow-up studies are illustrated by a study of mortality in 3878 breast cancer patients in Edinburgh followed for up to 20 years, and an additive hazard model is developed to incorporate covariates in the analysis of relative survival and curability.
Abstract: Methods of survival analysis for long-term follow-up studies are illustrated by a study of mortality in 3878 breast cancer patients in Edinburgh followed for up to 20 years. The problems of life tables, advantages of hazard plots and difficulties in statistical modelling are demonstrated by studying the relationship between survival and both clinical stage and initial menopausal status at diagnosis.
To assess the ‘curability’ of breast cancer, mortality by year of follow-up is compared with expected mortality using Scottish age-specific death rates. Techniques for analysing such relative survival data include age-corrected life tables, ratio of observed to expected deaths and excess death rates. Finally, an additive hazard model is developed to incorporate covariates in the analysis of relative survival and curability.
TL;DR: The resumption of post‐partum menstruation and ovulation was studied in ten bottle feeding and twenty‐seven breast feeding mothers.
Abstract: The resumption of postpartum menstruation and ovulation was studied in 10 bottlefeeding and 27 breastfeeding mothers. 1st menstruation occurred at 8.1 weeks (+or- 1.0 SE) in bottlefeeders and 32.5 weeks (+or- 2.5 SE) in breastfeeders (P<0.001); 1st ovulation occurred at 10.8 weeks (+or- 1.0 SE) in bottlefeeders and 36.4 weeks (+or- 2.5 SE) in breastfeeders (P<0.001). In bottlefeeders ovulation preceded 1st menses only in 2/10 (20%) of mothers but was regularly established thereafter occurring in 17/18 (94%) of 2nd and subsequent cycles. Breastfeeding did not postpone ovulation indefinitely because 13/27 of the breastfeeding mothers ovulated while still lactating; ovulation occurred in 9/27 (33%) of breastfeeding mothers during the phase of lactational amenorrhea but was followed by menstruation in every case. In breastfeeding mothers the frequency of ovular cycles progressively increased with time ovulation being observed in 9/20 (45%) of the 1st cycles during lactation 20/30 (66%) of later cycles during lactation 16/23 (70%) of 1st cycles after lactation and 26/31 (84%) of later cycles after lactation. There was a disruption of menstrual rhythms during lactation the mean interval between the 1st day of consecutive menstrual cycles being 37.0 days +or- 3.3 SE during lactation compared with 29.8 days +or- 1.0 SE after lactation and 29.5 days +or- 1.0 SE in bottlefeeding mothers. This study shows that bottlefeeding is associated with an early resumption of postpartum menstruation and ovulation. In breastfeeding mothers there is complete suppression of ovulation during the greater part of lactational amenorrhea but ovualtion will return in a proportion of mothers just before the 1st menses. After return of menstruation during lactation the frequency of ovular cycles progressively increases but does not return to normal until complete weaning has taken place. (authors)
TL;DR: Analysis of the inversion polymorphism of Anopheles gambiae s.str.
Abstract: Analysis of the inversion polymorphism of Anopheles gambiae s.str. in The Gambia and surrounding zones of Senegal (Saloum and Casamance) shows, in samples from the central part of the study area, highly significant and temporally stable departures from Hardy-Weinberg equilibrium with deficits of the hetero-karyotypes. This situation and the general pattern of karyotype distribution are consistent with the hypothesis of two chromosomally differentiated populations of A. gambiae which show partial reproductive isolation and incomplete intergradation in the contact zone.
TL;DR: This increased nitrite production in vitro was associated with methaemoglobinaemia following the oral administration of nitrate to rats fed the diet containing pectin, and animals receiving the basal fibre-free diet were unaffected by nitrate.
Abstract: 1. A semi-synthetic diet, the semi-synthetic diet plus pectin, and a stock diet were fed to rats, and three metabolic functions of the caecal bacteria (reduction of amaranth, p-nitrobenzoic acid and nitrate) were measured in vitro. 2. No consistent differences were noted between diets for the reduction of amaranth and p-nitrobenzoic acid. 3. No consistent differences in nitrate reductase activity were noted for rats maintained on a stock diet or a fibre-free diet. However, the addition of 5% pectin to the latter diet resulted in a several-fold increase in nitrite production. 4. This increased nitrite production in vitro was associated with methaemoglobinaemia following the oral administration of nitrate to rats fed the diet containing pectin. Animals receiving the basal fibre-free diet were unaffected by nitrate.