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Biomedical subjects

C Robinson

Publications and source records attributed to C Robinson.

At least 379 records · Page 21Linked to original sources
PubMed1986

Decreased microsomal membrane fluidity in the development of cholesterol-induced atherosclerosis in the rabbit.

The hypothesis was examined that arterial microsomal membrane fluidity is decreased in atherosclerosis. To investigate this hypothesis, the fluorescence anisotropy (r) of 1,6-diphenylhexa-1,3,5-triene was measured in aortic microsomes isolated from normal and atherosclerotic rabbits. A decrease in membrane fluidity, as indicated by a significant increase in r, was observed in microsomes from atherosclerotic rabbits. Notably, the increase in r occurred prior to macroscopic lesion development. The data support the hypothesis that membrane fluidity is decreased in atherosclerosis and indicate that this decrease occurs early in the atherogenic process. The hypothesis that decreased microsomal membrane fluidity contributes to the increased activity of acyl-CoA:cholesterol acyltransferase (ACAT) in atherosclerosis was also investigated. The hypothesis was rejected on the basis that enrichment of microsomes from normal rabbits with exogenous cholesterol to achieve r values equal to that of microsomes from atherosclerotic rabbits did not result in comparable ACAT activity.

Animals↗
PubMed1986

The combined effects of two pairs of mediators, adenosine with methacholine and prostaglandin D2 with histamine, on airway calibre in asthma.

Mediators released from mast cells and secondary effector cells in the airways contribute to bronchoconstriction of allergic asthma. This study investigates methods for defining the effect of two inflammatory mediators on airway calibre in asthma. In an initial study on three asthmatic subjects, subconstrictor (subthreshold) concentrations of two mast cell derived mediators, histamine and prostaglandin (PG) D2, produced similar displacement to the left of a histamine concentration-specific airways conductance (sGaw) response curve. With both agonists enhancement of histamine-induced bronchoconstriction was greater at low histamine concentrations. Since potentiation of histamine-induced bronchoconstriction was independent of the class of subconstrictor agent given, it is likely to represent a physiological rather than a pharmacological interaction. During provoked asthma different constrictor mediators are likely to be released simultaneously into the airways. A method was therefore devised to investigate the combined effect of equiconstrictor concentrations of two mediators on airway calibre. Two pairs of inhaled bronchoconstrictor agonists were chosen for study: adenosine with methacholine and PGD2 with histamine. For each agonist, concentration-sGaw response curves were constructed, from which were derived the provocation concentrations of agonist causing a 25% fall in sGaw from baseline (PC25) and required to further this to 50% (PC50-25). On separate days, eight subjects received paired inhalations of methacholine-adenosine, methacholine-methacholine and adenosine-adenosine. The concentration used for the first inhalation was the PC25 value and for the second inhalation the PC50-25 value. Before, immediately after the first inhalation, and at regular intervals after the second inhalation, sGaw was followed for 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1986

Trans regulation of the phosphoenolpyruvate carboxykinase (GTP) gene, identified by deletions in chromosome 7 of the mouse.

Livers from newborn mice homozygous for either one of the lethal deletions c14CoS or c3H in chromosome 7 have drastically reduced levels of cytosolic phosphoenolpyruvate carboxykinase (GTP) [GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32] activity when compared with normal littermates. The structural gene for the enzyme maps on chromosome 2 and appears intact and not grossly rearranged in deletion homozygotes. These mice also have negligible levels of hepatic mRNA encoding this enzyme. Studies of the transcription rate of the gene showed that it was reduced to 25-50% of normal in hepatic nuclei obtained from mice homozygous for either deletion. We suggest that, in addition to the reduction in the level of transcription, the deletions in chromosome 7 may also cause alterations in messenger stability, processing, or transport from the nucleus.

Animals↗
PubMed1986

Evidence against the formation of 13,14-dihydro-15-keto-prostaglandin F2 alpha following inhalation of prostaglandin D2 in man.

There is evidence that an important step in the metabolism of prostaglandin D2 (PGD2) involves 11-keto-reduction and that such a conversion might account for the reported increase in plasma concentrations of 13,14-dihydro-15-keto-PGF2 alpha in allergic asthmatic subjects challenged with inhaled allergen. Plasma concentrations of immunoreactive 13,14-dihydro-15-keto-PGF2 alpha were measured by specific radioimmunoassay both before and after inhalation of PGD2 and PGF2 alpha in 7 normal and 7 asthmatic men. In both groups of subjects, PGF2 alpha produced an approximate two fold increase in plasma concentrations of 13,14-dihydro-15-keto-PGF2 alpha that was maximal 5-7 min after inhalation. There was no significant difference in response between the normal and asthmatic subjects. In contrast, PGD2 failed to produce a change in plasma 13,14-dihydro-15-keto-PGF2 alpha concentration in either group. These results provide evidence that the conversion of PGD2 to PGF2 alpha with subsequent metabolism to 13,14-dihydro-15-keto-PGF2 alpha is unlikely to occur when PGD2 is released from mast cells in the airways.

Adult↗
PubMed1986

Effect of inhaled piriprost (U-60, 257) a novel leukotriene inhibitor, on allergen and exercise induced bronchoconstriction in asthma.

The leukotrienes, a group of oxidative metabolites of arachidonic acid, have potent pharmacological actions on human airways. We have investigated the effects of a leukotriene synthesis inhibitor, piriprost (U-60, 257) administered by inhalation on allergen and exercise induced bronchoconstriction in 12 subjects with allergic asthma. Subjects underwent diagnostic challenges with allergen and treadmill exercise to define the strengths of the stimuli required to reduce the FEV1 to about 25% of baseline (PS25). On separate study days subjects inhaled either piriprost 1 mg or vehicle placebo, followed 15 minutes later by the PS25 allergen or exercise. The FEV1 was measured at regular intervals before and after challenge up to 60 minutes. After allergen challenge in six subjects peak expiratory flow (PEF) was measured for the following 20 hours. When compared with placebo, inhalation of piriprost had no significant protective effect on the fall in FEV1 at any time point within 60 minutes of allergen or exercise challenge. In the four subjects with a documented late asthmatic reaction 2-12 hours after allergen challenge piriprost had no protective effect when compared with placebo. In the subjects who recorded PEF over 20 hours after allergen challenge there was no significant difference between piriprost and placebo. Piriprost was appreciably more irritant to the respiratory tract than was placebo. On the assumption that inhaled piriprost was bioavailable in the airways, this study casts doubt on any theory of a pivotal role for leukotrienes in the pathogenesis of acute exercise and allergen induced airway bronchoconstriction in asthma.

Administration, Inhalation↗
PubMed1986

A comparative trial of depot pipothiazine.

Thirty-nine chronic schizophrenic patients were selected for a 12-month double-blind evaluation of the effectiveness of pipothiazine palmitate (PPT) and flupenthixol decanoate (FPX) in the maintenance management of their illness. Allocation was at random and, in order to allow constant injection intervals, the patients typically received every 2 weeks either 40 mg of flupenthixol decanoate or alternating injections of 100 mg of pipothiazine palmitate and placebo. At monthly intervals the patients were assessed using both a battery of rating scales (which included the Brief Psychiatric Rating Scale (BPRS), the Extrapyramidal Symptoms Rating Scale (EPS] and a general side-effects evaluation. At 3-monthly intervals they were also rated on the Comprehensive Psychiatric Rating Scale (CPRS) and the Zung Depression Scale. Haematological and biochemical tests were performed every 3 months. Both drugs provided good control of psychotic symptoms and side-effects were not troublesome. No substantial difference was detected on the CPRS and the Zung scales. There was a trend in favour of PPT on the BPRS survey, detectable at 6 months and reaching statistical significance by 12 months. We conclude that the PPT regime is at least as effective as the FPX treatment and probably more so. It is possible that even longer periods of control could be obtained with PPT.

Adult↗
PubMed1986

Design and evaluation of a nitrous oxide scavenging system for use in nontraditional hospital settings.

Analgesic use of nitrous oxide (N2O) in nontraditional settings requires safe and effective scavenging systems to rid the work area of hazardous waste gas. Significant health risks to health care workers are associated with repetitive exposure to excessive levels of N2O. Regulations limit the exposure level to 25 parts per million and also require the use of effective scavenging systems. We tested the existing room ventilation and a suction-powered scavenging system in our burn unit's hydrotherapy room and found them to be inadequate in maintaining safe room air levels. We therefore developed a fan-powered scavenging system using a ceiling-mounted hood, under which N2O is administered, and found it to maintain safe levels while requiring little patient cooperation and allowing complete access to the patient.

Burn Units↗
PubMed1986

The generation of prostaglandins by human lung and their effects on airway function in man.

Human dispersed lung cells containing 5-10% mast cells synthesised and released large quantities of prostaglandin D2 (PGD2) and thromboxane B2 (TXB2), with either IgE-dependent activation or ionophore A23187 challenge. The generation of these prostanoids and the release of histamine was related to the strength of activation stimulus. After activation the release of histamine and PGD2 proceeded in parallel, and the significant correlation between the release of these mediators suggests a common mast cell origin. This hypothesis is supported by cell enrichment experiments using Percoll density gradients. Prostaglandin D2 and histamine release was always associated with those fractions containing mast cells, whereas the generation of TXB2 was mainly associated with cells of the monocyte-macrophage series. The putative 5-lipoxygenase inhibitor 6,9-deepoxy-6, 9-(phenylimino)- 6,8-prostaglandin I1 (U-60,257, Piriprost) had complex inhibitory and potentiating effects on immunoreactive leukotriene C4 generation from ionophore activated human lung cells. The drug also had a surprising potentiating action on PGD2 release, while simultaneously inhibiting the generation of TXB2. The release of prostanoids from human lung cells is discussed in relation to the putative role of prostaglandins in asthma, with particular emphasis on the pharmacological actions of PGD2 on human airway function in vivo.

Airway Resistance↗
PubMed1985

Transport of proteins into chloroplasts. The effect of incorporation of amino acid analogues on the import and processing of chloroplast polypeptides.

We have synthesized abnormal precursors of imported chloroplast proteins by incorporating amino acid analogues during translation in a cell-free wheat germ system. Incorporation of analogues of either proline, arginine or leucine markedly inhibits both the import of Pisum sativum ribulosebisphosphate carboxylase small subunit precursor by isolated chloroplasts and processing to the mature size by the purified processing enzyme. One effect of the arginine analogue is to remove a positive charge(s) in the precursor essential for efficient recognition by the processing enzyme. Incorporation of a lysine analogue results in moderate inhibition of the import of small subunit precursor but complete inhibition of import of the chlorophyll a/b-binding polypeptide precursor. The effect of carboxymethylation on the import of chloroplast proteins is also analyzed. The results indicate that residues essential for transport of the imported proteins by the chloroplast vary among different protein precursors.

Amino Acids↗
PubMed1985

Distribution of fluoride in human cementum.

Fluoride and phosphorus concentrations were determined in layers of cementum and dentine serially-abraded from the root surface, passing through the cementum-dentine junction and into the underlying dentine, using silicon carbide-impregnated film. The concentrations of F in the cementum mineral were variable but consistently maximal at or near to the external surface of the root and tending to fall towards the interior and across the cementum-dentine junction into the underlying dentine. The F content in the cementum tended to increase with age.

Adolescent↗
PubMed1985

Pulmonary synthesis, release, and metabolism of prostaglandins.

Immunologic or calcium-dependent activation of proteolytically dispersed human lung cells containing 5% mast cells causes the release of large amounts of PGD2 and TxB2. In cell purification experiments, only those fractions containing mast cells had the capacity to generate PGD2 and release histamine with IgE-dependent activation. The cells of origin of T X B2 are likely to be cells of the monocyte-macrophage series, although additional eicosanoid release may occur from immunologically activated lymphocytes and eosinophils. In men who have asthma, inhalation of low concentrations of PGD2 results in bronchoconstriction, whereas higher concentrations of PGD2 are needed to produce bronchoconstriction in normal subjects. Subjects with asthma exhibited 3.5-fold greater responsiveness to inhaled PGD2 than to PGF2 alpha. These observations demonstrate that PGD2 is the most potent bronchoconstrictor prostanoid tested in man. In both normal subjects and subjects with asthma, a single inhalation of PGF2 alpha resulted in a doubling in plasma levels of 13,14-dihydro-15-keto-PGF2 alpha. Plasma levels of this metabolite did not change after PGD2 inhalation. These results indicate that the 11-keto reduction of PGD2 to PGF2 alpha with subsequent inactivation is not important in the initial metabolism of PGD2.

Airway Resistance↗