GABA and nucleus accumbens glutamate neurotransmission modulate ethanol self-administration in rats.
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2-Amino-5-phosphonovalerate↗
Biomedical subjects
E Riley
Publications and source records attributed to E Riley.
HLA polymorphisms and evolution.
Polymorphisms within the human MHC are of interest to immunologists, for their functional significance, and to geneticists, as markers of populations. Here, Eleanor Riley and Olle Olerup describe how molecular analysis of the HLA complex is beginning to reveal the true extent of class II diversity, and demonstrate the use of this information to clarify the historical relationships between different human populations.
Africa↗
Primary structure and localization of a conserved immunogenic Plasmodium falciparum glutamate rich protein (GLURP) expressed in both the preerythrocytic and erythrocytic stages of the vertebrate life cycle.
A gene coding for a 220-kDa glutamate rich protein (GLURP), an exoantigen of Plasmodium falciparum, was isolated and its nucleotide sequence was determined. The deduced amino acid sequence contains 2 repeat regions. The sequence of one of these was shown to be conserved among geographically dispersed isolates, and a fusion protein containing that sequence was able to stimulate B- and T-cells. Antibodies against GLURP stained erythrocytic stages of the parasite as well as the hepatic stage as detected by electron microscopy.
Amino Acid Sequence↗
Failure to detect MHC class II associations of the human immune response induced by repeated malaria infections to the Plasmodium falciparum antigen Pf155/RESA.
Available evidence suggests that human T and B cell responses to a major Plasmodium falciparum malaria antigen (Pf155/RESA) in individuals primed by repeated infections are genetically regulated. In the present study we have attempted to establish whether these regulations reflect genetic restrictions imposed on the immune response by class II molecules of the donor's MHC system. T cell activation (proliferation and IFN-gamma release in vitro) and antibody activity (ELISA) were assayed with synthetic peptides corresponding to major Pf155/RESA epitopes. To associate T cell and antibody responses with the donors' MHC class II genotypes, leukocytes from 145 donors living in holo- or hyperendemic regions of Africa (Liberia, Gambia, Madagascar) were used for genomic HLA class II typing of their DRB-DQA and DQB genes by means of restriction fragment length analysis (RFLP). No associations between T cell responses and HLA-DR or -DQ alleles or DRB-DQA-DQB haplotypes were seen among the West Africans even when the donors were divided into high, medium or low responders. This was also true for a small group of HLA class II identical Malagasy donors including three pairs of twins. However, while the T cell responses between the twin pairs varied, those within the pairs were similar. Very similar findings were made with antibodies binding to Pf155/RESA peptides. Our data imply that the impact of MHC class II gene products on specific immune responses to Pf155/RESA epitopes is weak and hard to demonstrate in outbred human populations naturally primed by infection. This may be due to genetic regulations by other, non-HLA class II coded factors superimposed on possible HLA class II restrictions.
Adult↗
Epitopes of the Plasmodium falciparum clustered-asparagine-rich protein (CARP) recognized by human T-cells and antibodies.
Linear B- and T-cell epitopes have been identified in the Plasmodium falciparum clustered-asparagine-rich-protein (CARP). Twenty-six synthetic peptides, 15-25 amino acids in length, were assayed for their ability to stimulate purified, human T-cells primed to P.falciparum by natural infection to proliferate and/or secrete gamma-interferon (IFN gamma). The plasma of malaria exposed individuals were tested for antibody reactivity with peptides coupled to bovine serum albumin in a semiquantitative ELISA. Two of the peptides (NNFMNRNMKNKNMN/NAKNVNDMYRDGEMS) induced T-cells from many malaria exposed donors to proliferate and/or secrete-IFN gamma. Six peptides bound antibodies from a large number of the plasma samples, the amounts ranging from ten to more than 200 micrograms specific antibody/ml. T-cell activation was most pronounced when the T-cells were from highly immune donors. In contrast, high anti-peptide specific antibody levels were usually detected in the plasma of less immune donors, recently exposed to infection. One short sequence (NAKNVNDMYRDGEMS) was found to contain both T- and B-cell epitopes. Thus, CARP includes both T- and B-cell reactive elements recognized by the human immune system following exposure to the parasite by natural infection.
Amino Acid Sequence↗
Clinical significance of the V-shaped space in the subluxed shoulder of hemiplegics.
Recently, it has been proposed that shoulder subluxation in hemiplegia is accompanied by 1) the appearance of a V-shaped articular configuration occurring between the humeral head and glenoid fossa and 2) the presence of chronic pain. The main purpose of this study was to investigate the validity of these statements. We evaluated 40 hemiplegic subjects over 3 months. Radiographs of the affected and nonaffected shoulders were taken at both a frontal plane (0 degree) and a 45 degree incidence. From these patients, subluxed (n = 19) and nonsubluxed (n = 21) groups were formed. Pain was evaluated using the Present Pain Intensity index of the McGill Pain Questionnaire. On these x-ray films, measurements were taken of the V-shaped space, abduction of the arm, and rotation of the scapula. The statistical analysis (analysis of variance for repeated measures) contrasted the results obtained from the nonaffected side with those from the affected side over the 3 months studied. At the 45 degree angle, which better exposes the articular configuration of the shoulder, the difference in the V angle between the affected and nonaffected shoulders was significant for the subluxed group (p less than 0.01), indicating that such a V-shaped space can be identified. The measures taken also indicate that a downward subluxation of the humeral head occurs relative to the scapula without any systematic abduction of the humerus or downward rotation of the scapula. None of the results obtained from the frontal plane x-ray films was significant. Finally, no significant relation was found between subluxation and shoulder pain.
Adult↗
Measuring cellular immune responses to malaria antigens in endemic populations: epidemiological, parasitological and physiological factors which influence in vitro assays.
Measurements of in vitro cellular immune responses to malaria antigens are influenced by a variety of external factors. The physiological status of the donor, which is affected by, for example, malaria infection, intercurrent illness and pregnancy, can influence the lymphoproliferative response to specific antigens. Prior exposure to malaria antigens, determined by malaria endemicity, seasonal variations in transmission and the degree of polymorphism of the particular antigen, will also affect the prevalence and intensity of responses. Malaria-related immunosuppression may be both generalised and antigen specific. Although in vitro responses to malaria antigens are profoundly suppressed in acutely infected individuals, there is evidence that lymphocyte activation does occur in vivo. We conclude that longitudinal studies, correlating specific immune responses with subsequent malaria morbidity are required, to identify potentially protective antigens and appropriate effector mechanisms.
Acute Disease↗
Prourokinase activation on the surface of human rhabdomyosarcoma cells: localization and inactivation of newly formed urokinase-type plasminogen activator by recombinant class 2 plasminogen activator inhibitor.
Recombinant class 2 plasminogen activator inhibitor (PAI-2) was used in an approach to probe the formation and location of enzymatically active urokinase-type plasminogen activator (u-PA) sites on the surface of cultured human rhabdomyosarcoma cells (RD cells). Activation of pro-u-PA on the cell surface and consequent binding of PAI-2 was dependent on the addition of native plasminogen to serum cultures of the cells. Inhibition of the enzyme activity of surface-bound u-PA by the added PAI-2 resulted in a 79% reduction in the capacity of the RD cells to generate cell surface-associated plasmin activity from bound plasminogen. Under these conditions, the PAI-2 probe was localized at focal adhesions of RD cells, where it colocalized with both extracellular u-PA and intracellular vinculin antigens in double immunofluorescence labeling. Specificity of the probe's interaction with cell surface-bound u-PA was confirmed by blocking with a monoclonal antibody to human u-PA, which could also inhibit the formation of bound plasmin activity. These results showed the assembly of the plasmin-generating system at focal adhesions and the accessibility of bound u-PA on which it depends to added PAI-2. Therefore, PAI-2 has the potential both to localize at sites of tumor expression of functionally active u-PA and simultaneously to inhibit cell surface plasminogen activation.
Cell Line↗
Geographical distribution of Plasmodium falciparum erythrocyte rosetting and frequency of rosetting antibodies in human sera.
Uninfected erythrocytes bind spontaneously to those infected with certain strains of Plasmodium falciparum. This is known as spontaneous erythrocyte rosetting. We have studied the occurrence and frequency of rosetting in 75 fresh patient isolates and have identified rosetting strains from Africa, South America, and Asia. Rosetting was present in 49% of the isolates tested; the frequency of rosetting red blood cells (RBC) in individual isolates was 0-75% when scored during the first cycle of in vitro growth. Rosetting antibodies were found in 15 out of 73 (21%) Liberian sera as measured by disruption of rosettes in vitro. However, antibodies able to inhibit CD36 dependent cytoadherence of P. falciparum-infected RBC were not detected in these sera. Erythrocyte rosetting is a geographically widespread phenomenon. Rosetting antibodies seem to be induced by natural infection and the molecular mechanism of rosette formation seems distinct from that of endothelial cytoadherence.
Africa↗
First year after stroke: tracking cognitive and affective deficits.
A total of 58 cerebrovascular accident (CVA) rehabilitation inpatients with lateralized brain damage were assessed at two time points (T1 = admission to rehabilitation facility, about 7 weeks post-CVA, and T2 = 10 months post-CVA) in the following domains: hemispatial neglect, reaction time, depression, and affect comprehension. Performance was compared with 22 age-matched control subjects. Repeated measures ANOVAs were performed with patients subdivided into groups by laterality of lesion and visual field status (a strong predictor of psychometric performance, particularly in the hemispatial-neglect domain). During this initial year after stroke onset, significant improvements were observed in hemispatial neglect and affect comprehension in the two right-brain-damaged groups, but not the left-brain-damaged group. There was also a trend for improvement in observer rating of depression in all three groups. However, there was poor resolution of reaction time and self-reported depression in all three groups. These findings suggest that these latter domains should be targeted for more aggressive therapeutic intervention. An important component of such intervention, in addition to direct treatment of deficits, should be education of both patient and family as to the nature of deficits, expectations regarding resolution, and appropriate attributions of changed behavior after stroke.
Affect↗
Predictors of patient assault on acute inpatient psychiatric units: a pilot study.
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Dangerous Behavior↗
An evaluation of the hemiplegic subject based on the Bobath approach. Part II: The evaluation protocol.
A protocol of evaluation of the hemiplegic patient based on the Bobath approach to treatment is presented. Six parameters are evaluated: sensorium, muscle tone, reflex activity, active movement, postural reactions and pain. The first and last of these are included because of their possible effects on the motor recovery process of the hemiplegic patient. The other four are directly borrowed from the Bobath modality of treatment. For each of these parameters, the procedures are given for its evaluation along with its respective rating scales. These scales are of an ordinal nature ranging from 0 to 3. It is suggested that this new evaluation protocol is fully compatible with the therapeutic modality developed by Bobath and as well is adequate to quantify patient progress in the principle aspects treated by this well used rehabilitation approach.
Disability Evaluation↗
Studies in vivo to investigate the status of 4-N-pyrrolidinylazobenzene as a pure cancer initiating agent to the rat liver.
4-N-Pyrrolidinylazobenzene (4N) has been described sequentially as a potential rat hepatocarcinogen, a non-hepatocarcinogen to the rat, a possible pure initiating agent to the rat liver and as unlikely to be either a rat hepatocarcinogen or a cancer initiating agent. Given the importance of defining a pure initiating agent to the rodent liver we have conducted experiments to evaluate the status of 4N in this respect. By histopathological criteria 4N is non-hepatotoxic to the rat liver following daily oral gavage for 6 weeks, but it can be detected unbound in the rat liver following a single exposure via oral gavage and methaemoglobin is evident in peripheral blood. In addition, it fails to bind covalently to hepato-proteins or to initiate unscheduled DNA synthesis in the rat liver following oral dosing. Under similar conditions of bioassay, the rat liver carcinogen 3'-methyl-4-dimethylaminoazobenzene (3'M) gave a positive response on each count. Further, no evidence of histopathological change was observed in the rat liver following daily intraperitoneal injection of 4N for 2 weeks. It is concluded that 4N is both non-toxic and non-genotoxic to the rodent liver in vivo in all respects studied, and that it is therefore very unlikely to possess cancer initiating activity in this tissue.
Animals↗
Congenital horizontal gaze palsy and kyphoscoliosis in two brothers.
In a sibship of 11, two brothers with a congenital complete horizontal gaze palsy developed severe kyphoscoliosis. No-one else in the family has a gaze palsy or comparable skeletal abnormalities. Since the parents are first cousins, an autosomal recessive mode of inheritance seems likely.
Adult↗
Diaphragmatic fatigue [proceedings].
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Animals↗
Inherited parkinsonism.
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Genes, Dominant↗
Aerosolized or intravenous catecholamines: cardiovascular effects in awake rats.
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Aerosols↗
Sustained pressore responsiveness to prolonged hypothalamic stimulation in awake rats.
Whether or not pressor responsiveness changes in unanesthetized rats during recurrent sympathetic excitation was determined by recording blood pressure and heart rate continuously while the posterior hypothalamus was stimulated repeatedly with constant currents. Because preliminary tests showed that telestimulation with a radio-controlled stimulator produced erratic responses, awake rats were routinely stimulated in a conventional manner by connecting them through wires to a square-wave stimulator. Although tachycardia was the most common chronotropic effect, bradycardia also occurred, and both responses were occasionally seen in the same rat at different times. Inhibition of chronotropic responses by combined pharmacologic blockage with propranolol and atropine did not affect corresponding pressure responses in normotensive rats. Renal and spontaneously hypertensive rats always had larger pressor responses than normotensive ones, and, in spite of individual variations, responsiveness generally remained unaltered during 3-6 h of repeated hypothalamic stimulation. These results indicate that in awake normotensive or hypertensive rats cardiovascular responses to posterior hypothalamic stimulation continue unabated even when stimulation is repeated for hours.
Animals↗