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P Robinson
Publications and source records attributed to P Robinson.
The chemiluminescence response of normal human leukocytes to chlamydia trachomatis.
The aim of the present study was to investigate the phagocytic response of normal human polymorphonuclear leukocytes (PMN) and monocytes (MN) to eight serotypes of C trachomatis (B,C,D,E,F,I,J, and L2) using a chemiluminescence (CL) assay, with luminal and lucigenin as amplifiers. The magnitude of the phagocytic cell CL response was proportional to the phagocyte-to-chlamydiae ratio, with a poor CL response detected at a ratio of 1:125 and progressively larger CL responses up to ratios of 1:50,000. The durations of the CL responses to all chlamydiae serotypes tested were considerably longer than that for zymosan. The PMN demonstrated a relatively greater CL response to all chlamydiae serotypes tested when compared with MN. The PMN and MN CL responses to "genital serotypes" (D,E,F,I, and J) (as well as lymphogranuloma venereum serotype L2) were greater than that for "ocular" serotypes (B and C). Inactivation of serum complement and specific chlamydial antibody absorption reduced the CL responses of both PMN and MN. This is the first study to characterize the CL responses of normal human PMN and MN cells to C trachomatis, and it indicates the important role of oxygen dependent antimicrobial systems in the phagocytosis of this common human pathogen.
Lysophosphatidic acid can activate platelets without increasing 32P-labelling of phosphatidic acid.
Stimulation of platelets by thrombin produced a rise in [32P]phosphatidic acid labelling of platelets which was greater in medium without added calcium than in medium with 2.5 mM calcium. A rise in [32P]lysophosphatidic acid was also seen in platelets stimulated by thrombin in the presence of 2.5 mM extracellular calcium, though it was of lesser magnitude (average 35%) than the rise in phosphatidic acid. In platelets resuspended without added calcium no change in [32P]lysophosphatidic acid was seen in response to thrombin. Lysophosphatidic acid can itself induce platelet aggregation. Similarly to the calcium ionophore A23187, lysophosphatidic acid produced minimal change (in medium with no added calcium) to no change (in medium with 2.5 mM external calcium) in [32P]lysophosphatidic acid. The endoperoxide analog U46619 produced changes in 32P-labelling of platelet phosphatidic and lysophosphatidic acid similar to those produced by thrombin but of lesser magnitude. The results of these studies show that the action of lysophosphatidic acid on platelets differs from the action of thrombin, U46619 and platelet-activating factor, which produce a rapid rise in [32P]phosphatidic acid, and suggests that lysophosphatidic acid, like A23187, largely bypasses the initial receptor-coupled breakdown of phosphoinositides leading to formation of diacylglycerols and phosphatidic acid.
Evidence for a projection from the lateral preoptic area and substantia innominata to the 'mesencephalic locomotor region' in the rat.
A series of anatomical and electrophysiological experiments have been carried out to examine the organization of a direct projection from the substantia innominata and the lateral preoptic area of the hypothalamus, referred to collectively as the subpallidal region, to the pedunculopontine nucleus and adjacent parts of the dorsal midbrain in the adult rat. In the first series of experiments, the retrogradely transported fluorescent tracer SITS, which does not appear to be taken up by fibers-of-passage, was injected into the pedunculopontine nucleus, and the distribution of labeled neurons was plotted in the substantia innominata and lateral preoptic area, as well as in adjacent regions including the medial preoptic area, the bed nucleus of the stria terminalis and parvocellular parts of the paraventricular nucleus. Then, the anterogradely transported lectin PHA-L, which also does not appear to be taken up in effective amounts by fibers-of-passage, was injected into parts of the substantia innominata and lateral preoptic area that project directly to the pedunculopontine nucleus. These experiments demonstrated that fibers from both regions descend through the medial forebrain bundle and give rise in the pedunculopontine nucleus to a terminal field that contains many structures with the appearance of terminal boutons. They also indicated that individual fibers from the subpallidal region innervate both the pedunculopontine nucleus and adjacent parts of the central gray, and that the pathway innervates areas along the length of the medial forebrain bundle on its way to the dorsal midbrain. In a third series of experiments the retrogradely transported fluorescent tracer True Blue was injected into upper thoracic levels of the spinal cord, and it was found that the region of the pedunculopontine nucleus that receives the densest input from the subpallidal region contained many retrogradely labeled neurons on both sides of the brain. And finally, a series of electrophysiological experiments demonstrated that single-pulse stimulation of the substantia innominata and the lateral preoptic area altered the firing rate of a majority of the neurons in and around the pedunculopontine nucleus, and that excitatory and inhibitory responses occurred about equally. These results clearly suggest that the subpallidal region projects directly to the pedunculopontine nucleus and adjacent regions including the central gray and the superior colliculus.(ABSTRACT TRUNCATED AT 400 WORDS)
The GH response to clonidine in endogenous as compared with reactive depression.
The growth hormone (GH) response to clonidine was measured in 10 patients meeting standardized criteria for 'endogenous' depression and in 10 patients individually matched for age and sex but meeting the corresponding criteria for 'reactive' depression. In a paired comparison of patients with reactive and endogenous depression (matched for age and sex), the GH response to clonidine was less in the endogenous member of the pair in 8 out of 10 cases. These findings are interpreted as evidence of a defect at alpha 2 adrenoceptors in neuroendocrine systems in endogenous as compared with reactive depression.
Radionuclide imaging.
Recent advances in nuclear cardiology have included the application of radionuclide imaging techniques to the detection of coronary artery disease. Exercise Thallium-201 myocardial imaging has proved a sensitive and specific test for the detection of significant coronary artery disease and allows differentiation between myocardial ischaemia and infarction. Other conditions affecting the myocardium may produce abnormal myocardial images but, with recognition of this and the variations seen in normal subjects, the diagnostic accuracy of Thallium-201 myocardial imaging compares favourably with exercise electrocardiography. The technique is particularly useful where the exercise electrocardiogram is non-diagnostic or equivocal. Preliminary results from application to screening asymptomatic subjects have been encouraging. Radionuclide ventriculography allows the assessment of global and regional left ventricular function. The development of new regional wall motion abnormalities during stress is a highly specific indicator of the presence of myocardial ischaemia, and combined with analysis of the left ventricular ejection fraction response to exercise provides a sensitive test for the detection of significant coronary artery disease. Probability theory allows consideration of the place of these techniques in the investigation of the individual with proven or suspected coronary artery disease.
Chemiluminescent response to pathogenic organisms: normal human polymorphonuclear leukocytes.
Chemiluminescence (CL) is a sensitive indicator of phagocytosis and intracellular killing; however, little is known of the normal CL response by human polymorphonuclear leukocytes to different pathogenic microorganisms. We investigated the luminol-enhanced CL response of normal polymorphonuclear leukocytes to a number of common bacterial pathogens and two yeasts. We analyzed the CL response to viable and heat-killed microorganisms at 25 and 37 degrees C. The CL response to all microorganisms was greater and more rapid at 37 degrees C. Variable responses were observed with viable and heat-killed microorganisms; some were unaffected, whereas other demonstrated reduced CL. Each microorganism caused a reproducible response pattern, which could be placed into two general categories. In the first category were those which caused a rapid exponential rise and decay in CL: Enterobacter cloacae, Salmonella typhimurium, Shigella flexneri, Staphylococcus aureus, Candida albicans, and zymosan. In the second category were those which rose slowly over a longer time course to a poorly defined peak: Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and Streptococcus pyogenes. The CL response also reflected serum opsonic activity. The effect of inactivated complement, factor B, and removal of specific antibody were investigated. Increasing the concentration of zymosan gave a proportional rise in peak CL; however, a strain of E. coli caused a variation in peak time rather than peak height. Different CL kinetics were shown for three strains of K. pneumoniae, possibly a result of each having different membrane or cell wall characteristics. This study defines the nature and factors affecting the normal CL response to a variety of common pathogenic microorganisms.
Saccharomyces cerevisiae synthesizes proteins related to the p21 gene product of ras genes found in mammals.
A family of normal vertebrate genes and oncogenes has been called the ras gene family. The name ras was assigned to this gene family based on the species of origin of the viral oncogenes of the rat-derived Harvey and Kirsten murine sarcoma viruses. There are now three known functional members of the ras gene family, and genes homologous to ras genes have been detected in the DNA of a wide variety of mammals and in Drosophila melanogaster. Prior experiments have detected proteins coded for by ras genes in a large number of normal cells, cell lines, and tumors. We report here the detection of ras-related proteins in D. melanogaster, a result predicted by the earlier detection of ras-related genes in the Drosophila genome. We also report for the first time the detection of ras-related proteins in a single-cell eucaryocyte, Saccharomyces cerevisiae. These proteins, approximately 30K in size, are recognized by both a monoclonal antibody which binds to the p21 coded for by mammalian ras genes and a polyclonal rat serum made by transplanting a v-Ha-ras-induced tumor in Osborne-Mendel rats. The p21 of v-Ha-ras and the 30K proteins from S. cerevisiae share methionine-labeled peptides as detected by two-dimensional tryptic peptide maps. The results indicate that S. cerevisiae synthesizes ras-related proteins. A genetic analysis of the function of these proteins for yeast cells may now be possible.
Obsessive-compulsive neurosis following head injury. A report of four cases.
Four cases of obsessive-compulsive neurosis following head injury are described, three of which are from a consecutive series and the fourth from a discordant monozygotic twin pair. The aetiological significance of head injury in this disorder is discussed in the context of the clinical findings and of previous series of brain injured patients.
Double-blind comparisons of slow-release theophylline, ketotifen and placebo for prophylaxis of asthma in young children.
Clinical trials of slow-release theophylline and ketotifen as prophylaxis against asthma in 18 young children suggested that both drugs had some efficacy. The theophylline was more effective and produced reduction in salbutamol usage as well as an increase in peak expiratory flow rates. Transient nausea and vomiting was commoner during theophylline treatment but did not usually necessitate discontinuing therapy.
Outbreak of itching and rash. Epidemic hysteria in an elementary school.
Fifty-seven of 159 rural elementary school students had an explosive spread of pruritus and rash--a rarely described manifestation of epidemic hysteria. In a sample of 13 children (23%), each child examined had irregular, macular, erythematous lesions that were excoriated and actively changed during examination. Rash occurred only at sites readily accessible to hands. The symptoms disappeared promptly when the children left school and recurred each morning when they returned. There were no secondary family cases in sample children. School-wide attack rates were higher in girls and younger children. The outbreak resolved after two to three weeks, with identification of its nature and resumption of normal activities. Academic stresses were circumstantially linked to the outbreak.
A mouse hepatocyte carbohydrate-specific receptor and its interaction with liver-metastasizing tumor cells.
Spontaneous high-metastatic variants (ESb) of the DBA/2 mouse lymphoma L5178Y which show heavy liver involvement were found to form rosettes in vitro with isolated autologous hepatocytes, whilst low-metastatic sublines of the same tumor (Eb) did not. An analysis of the molecules involved in the hepatocyte:tumor cell interaction was performed by affinity adsorption and SDS-polyacrylamide gel electrophoresis of 125I-labelled membrane components from either the hepatocytes or the tumor cells. The hepatocytes were found to bind ESb tumor cells through lectin-like hepatic binding proteins (HBP) with molecular weights of 52, 56 and 110 Kd and specificity for D-galactosyl and N-acetyl-D-galactosaminyl residues. More than 10 different cell surface glycoproteins of ESb tumor cells and none of Eb-type tumor cells served as ligands in the hepatocyte interaction. The low-metastatic subline Eb formed hepatocyte rosettes only after neuraminidase pretreatment, indicating that lectin binding carbohydrate structures existed in a cryptic form masked on these cells by sialic acid. Although lectin-carbohydrate interactions have been found to play a crucial role in many intercellular recognition processes, this apparently is the first molecular description of such an interaction between organ-derived normal parenchymal cells and tumor cells. The possible relevance of such an interaction for cancer metastasis is suggested by the finding that spleen-selected ESb sublines differed from liver-selected ones in their organotropism as well as in their ability to form hepatocyte rosettes.
Doppler ultrasound probe for assessment of blood-flow in oesophageal varices.
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Regulation of plasminogen-activator in mastocytoma cells by lymphokines.
Culture supernatants from mitogen-stimulated splenocytes were found to stimulate protease production in P815Y mastocytoma cells. Such supernatants increased cell-associated plasminogen activator levels in a dose-dependent fashion, and under serum-free conditions. In contrast to peritoneal exudate cells, tumor-cell plasminogen activator was not enhanced by the mitogen ConA alone. The tumor cell line P815Y may, thus, be used as a homogeneous cell source for the quantitation of lymphocyte factors which activate or inhibit plasminogen activator activity.
Comparison of allogeneic and xenogeneic determinants on the H-2Kk molecule.
Two monoclonal rat anti-H-2 antibodies were derived by cell fusion from a rat immunized with mouse CH-1 lymphoma cells. Both antibodies recognize polymorphic H-2 determinants expressed on most haplotypes. Competitive binding studies on H-2Kk show that one rat antibody, R1-9.6, detects a determinant that is distant from the allodeterminants defined by 12 different mouse monoclonal anti H-2 antibodies. In contrast, the rat antibody R1-21.2 inhibits the binding of most mouse monoclonal anti H-2 antibodies to H-2k cells, possibly by causing a conformational change in the H-2 molecule. Both antibodies bind strongly to H-2 molecules and can be used for structural and biochemical studies.
A controlled comparison of slow-release theophylline, ketotifen and placebo in the prophylaxis of asthma in young children.
A double blind crossover comparison of slow-release theophylline, ketotifen and placebo was carried out in 18 young children with perennial asthma. Theophylline significantly reduced symptoms and increased the mean peak expiratory flow rate. Transient nausea and vomiting was commoner during theophylline treatment but did not usually necessitate discontinuance of therapy.
Immunological features of HLA-B27 anterior uveitis.
Analysis of the immunological features of anterior uveitis (AU) revealed a dichotomy of abnormalities defined in terms of the HLA-B27 status of the patient. HLA-B27-positive AU was characterised by the occurrence of iris autoantibodies and an absolute T cell lymphopenia during active disease which returned to normal with recovery. This phenomenon was not observed in HLA-B27-negative AU or in controls and could not be attributed to antilymphocyte antibodies as these were not detected. Furthermore, there were no changes in T-cell subsets (helper and suppressor T lymphocytes). Compared with HLA-B27-positive AU patients, the HLA-B27-negative group demonstrated elevated IgE levels and increased prevalence of smooth muscle autoantibodies.
Different patterns of lectin binding and cell surface sialylation detected on related high- and low-metastatic tumor lines.
We have analyzed cell surface-bound carbohydrates in two different model systems for metastasis composed of closely related tumor cell lines with differing metastatic potential. The first system studied was that of the DBA/2-derived T-lymphoma lines (Eb/ESb) and some recently established sublines of ESb with altered metastatic behavior (ESb-M and ESb-MR). The second system consisted of the highly metastatic MDAY-D2 cells, a wheat germ agglutinin-resistant low metastatic subline MDW40, and two metastatic revertants from the latter. The cells were stained with fluorescein isothiocyanate-conjugated lectins and analyzed by flow cytofluorography. All low-metastatic tumor lines expressed receptor sites for the lectins soybean agglutinin (SBA) and Vicia villosa (VV). The metastatic lines had the respective lectin binding sites blocked by sialic acid (SA). A good correlation was found within the cell lineages Eb leads to ESb leads to ESb-M leads to ESb-MR and MDAY-D2 leads to MDW40 leads to MDW40M1 between reactivity of SBA and VV and metastatic potential. The amount of neuraminidase-accessible SA was similar for all cell types (except MDW40) indicating differences in the positioning of SA. For high-metastatic ESb cells, the sialylation of SBA and VV receptor sites was paralleled by a relative decrease of SA associated with receptor sites for peanut agglutinin. Low-metastatic Eb cells, in contrast, had their peanut agglutinin receptor sites sialylated but expressed asialylated SBA and VV receptor sites. Eb cells were also found to have 2-fold higher activities in galactose-specific sialyltransferases. It is proposed that the differences in positioning of SA on the cell surface leading to masking or unmasking of terminal sugars could influence the metastatic potential of tumor cells.