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Biomedical subjects

C Robinson

Publications and source records attributed to C Robinson.

At least 397 records · Page 22Linked to original sources
PubMed1985

Industrial hygiene characterization of automotive wood model shops.

A suspicion of an excess cancer risk in automotive model shops prompted the Industrywide Studies Branch, NIOSH, to conduct a proportionate mortality study and an industrial hygiene characterization of operations in these shops. The mortality study showed a statistically significant excess proportion of deaths due to colon cancer and leukemia (for woodshops only). The materials used in the model shops include various natural woods, laminated woods, plastics, resins, varnishes, putties and paints. Personal breathing zone samples were collected for total and respirable dust, amines, various hydrocarbons (including styrene, and toluene), formaldehyde, and nitrosamines. Particle size distribution studies were conducted on the wood dust and bulk airborne samples of dusts were subjected to various mutagenicity test systems. Work practices, ventilation and general housekeeping were checked. Total wood dust samples ranged from 0.03 to 25 mg/m3 with an average around 1.0 mg/m3. The percent respirable dust ranged from 19 to 38% as measured with Andersen impactors. Solvent exposure samples ranged from non-detectable to about 10% of the OSHA Permissible Exposure Levels. Relevant recommendations for improvement of contaminant control were made.

Air Pollutants, Occupational↗
PubMed1985

Oxidative transformations of arachidonic acid in human dispersed lung cells: disparity between the utilization of endogenous and exogenous substrate.

Eicosanoid release from human dispersed lung cells (HDLC) containing ca 5% mast cells was studied before and after cell activation with ionophore A23187 or anti-IgE. Basal release of eicosanoids synthesized from endogenous arachidonate was measured by radioimmunoassay. In descending order of abundance the products were: 5-hydroxyeicosatetraenoic acid (5-HETE) greater than thromboxane B2 (TXB2) greater than prostaglandin F2 alpha (PGF2 alpha) approximately immunoreactive (i)-PGE2 greater than PGD2 greater than 6-keto-PGF1 alpha approximately i-LTC4. Stimulation of HDLC with ionophore A23187 or, after passive sensitization, with anti-IgE resulted in 2-10 fold increases in the generation of individual eicosanoids. In terms of net generation the most abundant products were PGD2 and TXB2 with either stimulus. Activation with A23187 caused net release of i-LTC4 and 5-HETE, but these products were not measured after immunological activation. A more complete profile of lipoxygenase products released from HDLC dispersed from one lung was obtained after separation by high performance liquid chromatography combined with ultra violet spectroscopy and bioassay. The major products released from the cells from this lung with ionophore stimulation were 13-hydroxylinoleic acid greater than LTB4 greater than 5-HETE greater than 12-HETE greater than LTC4 greater than 15-HETE greater than 11-HETE approximately 9-HETE. When the utilization of exogenous [14C]-arachidonic acid for prostanoid biosynthesis was compared to that of endogenous unlabelled arachidonate the formation of TXB2 was consistently underestimated. These results imply compartmentalization of arachidonic acid utilization in Ca2+-activated HDLC. In unstimulated cells the proportional formation of PGD2 was overestimated when exogenous arachidonic acid was substrate. After activation with A23187 the proportions of PGD2 were similar with both substrate sources. The large proportions of PGD2 and TXB2 generated by HDLC further supports the view that these eicosanoids may be important inflammatory mediators in lung tissue.

Arachidonic Acid↗
PubMed1985

Relationship between mediator release from human lung mast cells in vitro and in vivo.

There is now compelling evidence to incriminate bronchial mast cells in the pathogenesis of bronchoconstriction of allergic asthma. Human mast cells isolated from lung tissue or bronchoalveolar lavage release histamine and generate eicosanoids upon IgE-dependent activation. In this paper we present data that raise doubts about the significance of phospholipid methylation in IgE-dependent activation-secretion coupling and provide evidence that drugs such as 3-deazaadenosine inhibit mediator secretion by inhibiting phosphodiesterase, in addition to inhibiting putative methylation pathways. Activation of human mast cells and basophils also stimulates adenylate cyclase to increase levels of cyclic AMP, which, on the basis of pharmacological manipulation with purine nucleosides, we believe is involved in the progression of the secretory response. Human lung cells also generate both cyclo- and lipoxygenase products of arachidonate upon Ca++-dependent stimulation with complex interactions occurring between these pathways in the presence of the leukotriene inhibitor, Piriprost. The role of mast cells in the immediate airway response to inhaled allergens in asthma was demonstrated by showing an interaction between nonspecific bronchial reactivity and mast cell reactivity in predicting the airway response upon antigen inhalation. Further confirmation of this concept was obtained by showing an inverse relationship between the release of histamine and neutrophil chemotactic factor (NCF) into the circulation induced by antigen challenge, and nonspecific airway reactivity. The identification of significant increases in circulating mediators following antigen provocation of patients with seasonal asthma enabled the effects of drugs used in the treatment of asthma to be compared on airway calibre and mast cell mediator release. Sodium cromoglycate partially inhibited the airway and plasma histamine responses with antigen, but totally inhibited the increases in NCF. Salbutamol completely inhibited all responses, while ipratropium bromide, which produced the same bronchoconstriction as achieved with salbutamol, had no effect. The potent H1-antagonist astemizole partially inhibited bronchoconstriction without affecting histamine release. Antigen provocation produced a significant increase in circulating levels of the 13,14-dihydro-15-keto metabolite of PGF2 alpha which could originate from mast cell-derived PGD2. In both retrospective and prospective studies, a close relationship was shown between nonspecific bronchial reactivity and resting airway calibre in asthma.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Airway and cardiovascular responses to inhaled prostacyclin in normal and asthmatic subjects.

Prostacyclin (PGI2) is one of several prostanoids released after antigen challenge of human lung fragments. To define its activity on human airways, we studied the effect of inhaled PGI2 in 10 normal and 8 asthmatic subjects. In random order, PGI2, 1 mg/ml, its hydrolysis product, 6-oxo-PGF1 alpha, 1 mg/ml, and glycine vehicle were given on separate occasions by nebulizer. Measurements of specific airway conductance (SGaw), blood pressure (BP), heart rate (HR), plasma 6-oxo-PGF1 alpha, and cyclic AMP levels were made at frequent intervals for as long as 45 min after nebulization. Prostacyclin and 6-oxo-PGF1 alpha caused cough and retrosternal discomfort. None of the drugs had any significant effect on SGaw in either the normal or asthmatic subjects, though 2 asthmatics showed consistent bronchodilatation with prostacyclin. Prostacyclin caused a marked fall in diastolic blood pressure (mean 20 +/- 3 mmHg) and increase in heart rate (29 +/- 3 beats X min-1) with a small late fall in systolic blood pressure (8 +/- 2 mmHg). This was associated with a 12- to 15-fold increase in plasma 6-oxo-PGF1 alpha levels maximal at 1 min, and in normal subjects only, a later twofold increase in plasma levels of cyclic AMP maximal at 5 min. Thus, inhaled PGI2 at concentrations that had pronounced cardiovascular activity produced no consistent effect on airway caliber in normal or asthmatic subjects.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

The bronchoconstrictor effect of inhaled prostaglandin D2 in normal and asthmatic men.

Although prostaglandin D2 is the most abundant prostanoid generated by human lung mast cells and causes bronchoconstriction in animals, its effects have not been studied in human beings. We have compared the effects of inhaled prostaglandin D2 and prostaglandin F2 alpha on specific airway conductance in seven normal subjects and seven patients with mild allergic asthma. In dose-response studies in normal subjects, prostaglandin D2 caused a significant (20 +/- 6 per cent) fall in specific airway conductance after the two highest concentrations (250 and 500 micrograms per milliliter), whereas prostaglandin F2 alpha had no effect. In the asthmatic subjects, both prostaglandin D2 and prostaglandin F2 alpha caused a dose-related fall in specific airway conductance, starting at the lowest concentration of 4 micrograms per milliliter. Prostaglandin D2 was 3.5 times more potent than prostaglandin F2 alpha. In a single-dose study of both drugs (250 micrograms per milliliter), a minor fall in specific airway conductance occurred with prostaglandin D2 in the normal subjects, and a larger fall occurred with both drugs in the asthmatic subjects. Maximum effects were seen at three minutes: there was a 75 +/- 5 per cent fall with prostaglandin D2 and a 33 +/- 8 per cent fall with prostaglandin F2 alpha. These results suggest that prostaglandin D2 may be involved in the pathogenesis of bronchoconstriction in allergic asthma.

Adult↗
PubMed1984

Transport of proteins into chloroplasts. Partial purification of a chloroplast protease involved in the processing of important precursor polypeptides.

We have partially purified a soluble protease from Pisum sativum chloroplasts involved in the processing of precursor polypeptides imported into the organelle. The enzyme processes precursors of both stromal and thylakoid proteins to the mature size, but is inactive against all proteins so far tested other than precursors destined for the chloroplast. The enzyme processes precursors from wheat and barley, and is therefore not species-specific. It has a relative molecular mass of about 180 000 and a pH optimum near 9. The enzyme is inhibited by ethylenediamine tetraacetate and 1,10-phenanthroline but not by serine- or thiol-protease inhibitors.

Biological Transport↗
PubMed1984

Transport of proteins into chloroplasts. The precursor of small subunit of ribulose bisphosphate carboxylase is processed to the mature size in two steps.

The precursor of the small subunit of ribulose bisphosphate carboxylase in Pisum sativum (relative molecular mass 20 000) is processed to the mature size (relative molecular mass 14 000) by the purified processing enzyme in two steps. The maturation proceeds via an intermediate of Mr 18 000. Both processing reactions may be carried out by the same enzyme although different residues are involved in the two cleavage sites. The second cleavage is inhibited if the precursor is pre-incubated with iodoacetate. The processing intermediate cannot be detected during the uptake of the precursor by intact isolated chloroplasts but iodoacetate-treated precursor is taken up and converted to a number of polypeptides of Mr 18 000 and below.

Biological Transport↗
PubMed1984

Alterations in regulatory and locomotor behaviors following trimethyltin exposure in the rat: a time and dose analysis.

Adult male hooded rats were tested pretreatment for spontaneous alternation and open-field behaviors. Animals were then intubated with either 5 or 7 mg/kg trimethyltin chloride (TMT Cl) or the isotonic saline vehicle. Post-treatment, animals were again tested for spontaneous alternation and open-field behaviors during three separate 5-day periods: days 14-18, days 56-60 and days 106-110. Additionally, both body weight and water intake were assessed. The larger dose of TMT Cl resulted in significant, but temporary reduction in body weight, elevated water intake for approximately 3 weeks, and a persistent increase in open-field activity. The smaller dose of TMT Cl resulted in elevated water intake for approximately 3 weeks and a temporary increase in open-field activity. Since the tendency to enter choice arms decreased in all groups across testing sessions, the effects of TMT Cl on spontaneous alternation could not be accurately assessed.

Animals↗
PubMed1984

Total profiling by GC/NICIMS of the major cyclo-oxygenase products from antigen and leukotriene-challenged guinea-pig lung.

Separation and quantitation of all the major cyclo-oxygenase products in perfused guinea-pig lungs challenged with antigen or leukotrienes C4 and D4 were achieved using a novel combined capillary column gas chromatography/negative ion chemical ionization mass spectrometric (GC/NICIMS) method. In descending order of magnitude, unchallenged lungs released thromboxane B2 (TXB2) plus its pulmonary metabolite (TXDK) greater than 6-keto-PGF1 alpha plus its 13,14-dihydro-15-keto metabolite (K2H1F1 alpha) greater than PGE2 plus PGF2 alpha greater than PGD2; after ovalbumin anaphylaxis there were increases of X 26 in TXB2 plus TXDK, X 28 in PGD2 and histamine (measured fluorometrically) but of only X 3 in 6-keto-PGF1 alpha plus K2H2F1 alpha and PGE2 plus PGF2 alpha. FPL55712 treatment greatly reduced the release of TXB2 and 6-keto-PGF1 alpha and their metabolites (showing this to be a secondary effect mediated by leukotriene action) but did not affect PGD2 output. LTC4 and LTD4 themselves induced the release of TXB2 and TXDK, as did bradykinin, but neither substance caused appreciable PGD2 release. Aside from illustrating the great value of the GC/NICIMS method for simultaneously determining all cyclooxygenase products, the main conclusions are: (i) PGD2 may be an in vitro marker for activation of lung inflammatory cells; (ii) prostacyclin and thromboxanes are actively metabolized in situ in the lung; and (iii) 'pathological subversion' of pulmonary function by anaphylaxis, leukotrienes or bradykinin principally causes thromboxane release from unknown target cells, with a smaller release of prostacyclin which may be compensatory in nature.

Anaphylaxis↗
PubMed1984

Quantitative analysis of prostanoids in biological fluids by combined capillary column gas chromatography negative ion chemical ionization mass spectrometry.

An assay for the quantitative analysis of six biologically important prostanoids based on combined gas chromatography negative ion chemical ionization mass spectrometry has been developed. Prostanoids were extracted from biological fluids by liquid chromatography on Sep-Pak cartridges and converted to pentafluorobenzyl ester derivatives. Samples were injected on capillary column by the splitless technique and injections were made in a high boiling hydrocarbon solvent (n-dodecane) in order to minimize chromatographic run times. Quantification was carried out using selected ion monitoring of the appropriate [M-pentafluorobenzyl]- anion. The assay has been used for profiling cyclooxygenase metabolites of arachidonic acid in guinea pig lung perfusate after induction of anaphylaxis and platelet rich plasma after collagen-stimulated aggregation.

Animals↗
PubMed1984

Distribution and uptake of magnesium by developing deciduous bovine incisor enamel.

Magnesium concentrations determined in deciduous bovine enamel at different stages of development were similar to those previously published for human and rat enamel ranging from 0.1 to 0.4 per cent. Highest concentrations, i.e. greatest uptake, occurred after secretion, in the transitional and maturing enamel. Uptake had occurred throughout the tissue thickness and was not confined to the surface. Magnesium probably enters enamel in the tissue fluid which replaces the organic matrix. Some magnesium is lost as fluid is replaced by calcium and phosphate but part is retained probably on or near crystal surfaces.

Animals↗
PubMed1984

6,9-deepoxy-6,9-(phenylimino)-delta 6,8-Prostaglandin I1, (U-60,257) stimulates prostaglandin D2 and inhibits thromboxane B2 release from ionophore challenged human dispersed lung cells.

6,9-deepoxy- 6,9-(phenylimino)-delta 6,8-Prostaglandin I1 (U-60,257), a prostaglandin analogue known to inhibit leukotriene formation in a number of cell systems, potentiates mast cell release of prostaglandin D2 from human dispersed lung cells activated with ionophore A23187. Over the same concentration range of 30-300 microM there was a related inhibition of ionophore-induced generation of thromboxane B2 (r = 0.93, P less than 0.01). As both prostaglandin D2 and thromboxane A2 are potent bronchoconstrictors, these observations may be relevant to the potential of this drug in the treatment of asthma.

Calcimycin↗