Meningitis: ousting the organism.
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Adolescent↗
Biomedical subjects
P Robinson
Publications and source records attributed to P Robinson.
Differential effects of spermine on aggregation, inositol phosphate formation and protein phosphorylation in human platelets in response to thrombin, arachidonic acid and lysophosphatidic acid.
Platelet aggregation stimulated by thrombin, arachidonic acid or lysophosphatidic acid is associated with rapid phosphorylation of two platelet proteins, myosin light chain and a 47 kDa protein. The polyamine, spermine, inhibited platelet aggregation stimulated by all three agents. Spermine inhibited thrombin-stimulated phosphorylation of myosin light chain and the 47 kDa proteins as well as thrombin-induced production of the inositol phosphates and phosphatidic acid. In contrast, spermine did not inhibit phosphorylation of either protein or the formation of inositol phosphates and phosphatidic acid in response to arachidonic acid or lysophosphatidic acid. Although spermine has been demonstrated to inhibit both phosphatidylinositol-specific phospholipase C and calcium-dependent protein kinases in cell free systems, these results suggest that, in the intact platelet, spermine does not directly inhibit these enzymes. Inhibition of aggregation stimulated by arachidonic acid and lysophosphatidic acid is secondary to interference with platelet-platelet interaction but not with platelet activation. In contrast, spermine inhibits thrombin-induced platelet activation. This thrombin-specific inhibition may be related to interference with the binding of thrombin to its receptor or to its catalytic substrate on the cell surface.
Arachidonic Acid↗
Gag reflex in bulimia nervosa.
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Feeding and Eating Disorders↗
The development of the ovine small intestine.
Intestinal development was noted from 27 days gestation. By 50 days gestation the ovine small intestine shows the beginning of villus formation. The lumen becomes patent by 70 days. Proximal regions mature earlier than distal regions. Vacuolation of enterocytes occurs in all regions of the small intestine at some stage during development. Mature-looking enterocytes can be found in proximal regions by 125 days gestation while in distal regions immature vacuolated cells can still be found just prior to birth. Enterocytes lining the villi are more mature at the villus tip than those at the base in all regions. This gradient of maturation is consistent with a suggestion of the early establishment of adult patterns of proliferation and migration of enterocytes in the sheep fetus.
Animals↗
Can follow-up sclerotherapy for oesophageal varices be improved? Early results of a new technique.
To help correctly identify varices as patent or thrombosed during follow-up sclerotherapy, a simple pressure device has been used to obtain intravariceal pressure. A high pressure denotes thrombosis and a low pressure (less than 50 mmHg) denotes patency. In 217 variceal assessments, conventional and pressure assessments agreed in 179 (82%). Over the 7 month study, a significant improvement was noted in correctly diagnosing thrombosed varices (p less than 0.01). No ulcers, bleeding or complications occurred. Pressure assessment of varices is simple and avoided 38 (18%) incorrect diagnoses and their consequences.
Esophageal and Gastric Varices↗
Sir John Russell Reynolds: 1828-1896.
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History, Modern 1601-↗
Chlamydial antibody crossreactivity with peripheral blood mononuclear cells of patients with ankylosing spondylitis: the role of HLA B27.
We have previously reported the association of Chlamydia trachomatis with HLA B27+ related diseases. To investigate the possibility that chlamydial antibodies serve to localize the immune response in such diseases, we examined the crossreactivity of chlamydial antibodies (rabbit anti-D and anti-L2 serotypes) with peripheral blood mononuclear cells of patients with ankylosing spondylitis (AS) and anterior uveitis (AU) and with human and bovine ocular tissue and cells in culture. Our results indicate a significantly increased percentage binding of chlamydial antibody (D serotype) to the mononuclear cells of HLA B27+ patients with AS when compared with HLA B27- patients with AS (12.9% +/- 2.2 versus 5.4% +/- 2.2), B27+ controls (5.5% +/- 1.5) and B27- controls (6.1% +/- 1.0). There was no significant difference between controls and HLA B27+ patients with AU (6.6% +/- 1.9) and B27- patients with AU (8.7% +/- 1.1). This crossreactivity could not be blocked by monoclonal HLA B27 antibody. Chlamydial antibodies (D and L2) crossreact with human and bovine conjunctiva but not uvea, tissue culture derived iris fibroblasts or smooth muscle cells. Our results provide additional support for the concept of crossreactivity between antibodies to microbial agents and peripheral blood mononuclear cells of patients with HLA B27+ AS.
Adolescent↗
Activation of permeabilized platelets by inositol-1,4,5-trisphosphate.
The effect of inositol 1,4,5-trisphosphate (IP3) was studied using human platelets permeabilized with saponin and suspended in a high potassium, Ca2+-free buffer containing 40 microM EGTA and 1.2 mM magnesium. Under these conditions IP3 stimulated aggregation at a concentration of 0.5 microM with maximum aggregation at 5.0 microM. Aggregation was associated with phosphorylation of myosin light chain and a 47,000 dalton protein, and with a change in platelet shape including granule centralization and pseudopod formation similar to changes seen when cytoplasmic calcium is raised by other means. IP3 stimulated [14C]-serotonin release from platelet dense granules, [14C]-arachidonic acid release from platelet phospholipids and production of thromboxane B2. Preincubation of platelets with aspirin which blocked thromboxane formation also inhibited protein phosphorylation, serotonin secretion and partially inhibited aggregation. These results support the concept that IP3 is a major intracellular messenger in platelets and suggests that its effects are mediated both through Ca2+ flux and thromboxane formation.
Arachidonic Acid↗
Mepacrine (quinacrine) inhibition of thrombin-induced platelet responses can be overcome by lysophosphatidic acid.
Addition of thrombin to human platelets results in production of lysophosphatidic acid. Such synthesis of lysophosphatidic acid can be inhibited by mepacrine, an inhibitor of the phospholipase A2 which attacks phosphatidic acid to give lysophosphatidic acid. In the present study, mepacrine was used at a concentration of 2.5-20 microM, sufficient to block aggregation and lysophosphatidic acid formation induced by 0.1 U/ml thrombin. Mepacrine, at this concentration, also blocked thrombin-induced phosphorylation of platelet myosin light chain and a 47 kDa protein, thrombin-induced secretion and thrombin-induced release of arachidonic acid from platelet phospholipids. However, mepacrine also partly inhibited the formation of phosphatidic acid in response to thrombin, consistent with some simultaneous inhibition of phospholipase C. Lysophosphatidic acid (2.5-22 microM) overcame the mepacrine block in thrombin-stimulated aggregation, protein phosphorylation and secretion without stimulating the release of arachidonic acid from platelet phospholipids or the formation of lysophosphatidic acid, and only slightly increasing phosphatidic acid formation. The results suggest that lysophosphatidic acid primarily acts distal to mepacrine inhibition of phospholipase A2 and phospholipase C and are consistent with the possibility that lysophosphatidic acid might be a mediator of part of the effects of low-dose thrombin on human platelets.
Arachidonic Acid↗
Platelet protein phosphorylation.
As can be seen from this review, protein phosphorylation appears involved in both positive and negative regulation of platelets. To date, good evidence has been presented for the involvement of protein phosphorylation in the regulation of granule centralization (i.e. myosin light chain phosphorylation). It is probable that protein phosphorylation may also be involved in granule labilization, pseudopod formation and ATP synthesis. Protein phosphorylation in association with platelet activation appears mediated through calcium flux, in the case of myosin light chain phosphorylation, and through diglyceride or other substances in the case of 47P phosphorylation. A summary scheme is shown in Figure 1.
Actin Cytoskeleton↗
Anorexia nervosa in American blacks.
Five cases of anorexia nervosa in black American patients are presented. All had lost parents by death or divorce. Three had a family history of obesity and of a physical illness related to obesity. Two were male and both of these had a previous history of serious psychiatric disturbance. Three patients had a first or second degree relative with affective disorder. Two patients showed a primary lack of sexual interest and one male was bisexual. Four of the patients came from social classes 3-5.
Adolescent↗
Analysis of a region in plasmid R386 containing two functional replicons.
A miniplasmid has been obtained from R386 by ligating EcoRI fragments with a fragment carrying a kanamycin-resistance gene. It contains a 6.8-kb Eco fragment of R386 which hybridizes strongly with several IncFI plasmid DNAs but not with the primary or secondary replicons of the F plasmid. This mini-R386 is incompatible with certain IncFI plasmids, and it appears to be one example of a previously unidentified replicon widely distributed in the IncFI group. A region of R386 not closely linked to the 6.8-kb fragment is involved in copy number control of the mini-R386, and a sequence in the same region interacts with mini-F partition functions to cause incompatibility. The 6.8-kb fragment also restricts growth of T7 bacteriophage, and an adjacent fragment restricts phage T4 growth. A further R386 sequence, sharing homology with the F secondary replicon, is capable of autonomous replication. Hence R386, like F, contains at least two functional replicons.
Cell Division↗
Characterization of an extracellular matrix-degrading protease derived from a highly metastatic tumor cell line.
A proteolytic activity associated with the microsomal fraction of L-5178Y/Esb tumor cells has been characterized. The enzyme has a molecular weight of 80-90 kD as determined by affinity-labelling with [3H]DFP and SDS-gel electrophoresis. It cleaves ester substrates at the carboxyl position of lysine and arginine and can activate the proenzyme plasminogen. The enzyme is found to be associated with the plasma membranes of high and low metastatic tumor cell lines and is shed in high-molecular-weight form mainly by the high metastatic variant. The pH optimum for esterase and protease activities was 7.5-8.5. Although similar to trypsin in substrate specificity, the enzyme was not inhibited by lima-bean trypsin inhibitor but was inhibited by DFP, PMSF, aprotinin and leupeptin. Partially purified preparations of the protease can alone degrade 125I-labelled endothelial cell extracellular matrix, pointing at the putative role of this enzyme in tumor invasion.
Animals↗
The effect of nucleotides on the rate of spontaneous quantum bumps in Limulus ventral photoreceptors.
The effect of intracellular nucleotides on the rate of spontaneous quantum bumps in Limulus ventral photoreceptors has been examined. Internal dialysis of photoreceptors with solutions lacking nucleotide leads to an elevation of the quantum bump rate that can be reversed by introduction of nucleotide. Similarly, elevation occurs after treating intact cells with the metabolic inhibitor 2-deoxyglucose. This effect can be reversed by intracellular injection of ATP. The rate of spontaneous quantum bumps in unpoisoned cells can be reduced to below normal levels by injection of ATP. These results support the hypothesis that high-energy nucleotides suppress the rate of spontaneous quantum bumps.
Alkaline Phosphatase↗
Decreased chemiluminescent associated phagocytic response of peripheral blood mononuclear cells to Chlamydia trachomatis in patients with HLA-B27+ anterior uveitis.
The chemiluminescent (CL) associated phagocytic response of peripheral blood monocytes to two serovars of Chlamydia trachomatis, Shigella flexneri and zymosan was assessed in a group of 26 patients with anterior uveitis (AU). HLA-B27+ patients with AU, when compared to HLA-B27- patients with AU and appropriate controls, had a significantly decreased CL response to C. trachomatis but no difference between groups in the response to S. flexneri and zymosan. The decreased chemiluminescent (phagocytic) response of mononuclear phagocytes to Chlamydiae may indicate an important abnormality in the pathogenesis of HLA-B27+ AU.
Adolescent↗
Freud under siege.
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History, Modern 1601-↗
Ontogeny of gastric acidity in the ovine fetus.
Hypoacidity and hypergastrinaemia have been reported in the newborn human. However, little is known about in utero gastric acid secretion, and the relationship to fetal plasma gastrin levels. The longitudinal pattern of development of basal and stimulated gastric acid secretion in the non-anaesthetized fetal sheep has been studied during the last 45 days of gestation. Fetuses had cannulae inserted into the jugular vein, carotid artery and stomach. Gastric juice and blood was sampled daily from 101 days gestation until birth (145 days). Intermittent basal acid secretion began between 120 and 133 days of gestation. These fluctuations in gastric juice pH continued until birth. Overall there was a decline in gastric pH from 7.5 +/- 0.2 (SEM), for fetuses 101-105 days to 4.3 +/- 0.5 by 131-135 days. Mean fetal plasma gastrin was higher than maternal levels after 111-115 days but no correlation between fetal plasma gastrin levels and gastric pH could be demonstrated. Pentagastrin and histamine infusion did not stimulate acid secretion in fetuses younger than 115 days. After this age the fetuses became responsive to both pentagastrin and histamine. In contrast, cholinergic stimulation, using bethanechol, did not stimulate acid production until 10 to 15 days later, suggesting a hierarchy in the development of the control of acid secretion in the fetus. The lack of response to endogenous gastrin and the hierarchy in the control of acid secretion suggest either a lack of receptors on the parietal cell or the presence of an inhibitor of acid secretion. These studies are relevant to human physiology since the present findings show that the sheep and human have a similar gastrin/acid profile at birth.
Animals↗