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A Gibson

Publications and source records attributed to A Gibson.

At least 127 records · Page 7Linked to original sources
PubMed1990

Movement of internalized ligand-receptor complexes along a continuous endosomal reticulum.

Complexes of cell-surface receptors and their ligands are commonly internalized by endocytosis and enter a prelysosomal endosomal pathway for further processing. Fluorescence microscopy and video recording of living cells to trace the passage of ligand-receptor complexes has identified the endosomal compartment as an extensive network of tubular cisternae. Endocytosed material entering this reticulum enters discrete swellings, identified as multivesicular bodies by electron microscopy, which move along the reticulum towards the pericentriolar area.

Biological Transport↗
PubMed1990

Characterization of aminopeptidases in human kidney soluble fraction.

Fractionation of human kidney soluble extract (with which the majority of cellular aminopeptidase activity is associated) via anion exchange chromatography resolved four types of separable aminopeptidase (relative activity in parenthesis): alanyl aminopeptidase (EC 3.4.11.14; 50%); arginyl aminopeptidase (EC 3.4.11.6; 30%); leucyl aminopeptidase (EC 3.4.11.1; 18%) and pyroglutamyl aminopeptidase (EC 3.4.19.3; 2%). The further purification (via gel filtration chromatography and preparative electrophoresis) and characterization of each aminopeptidase has been described; the aminopeptidase tissue profile for human kidney was found to be similar to that previously obtained for human skeletal muscle and brain tissue using a similar experimental approach, i.e. the same enzymes, with corresponding similar characteristics, are present in each tissue. These results suggest that soluble aminopeptidases may be of fundamental importance in general cell protein catabolism. Degradation of the following aminoacyl-AMC derivatives via kidney soluble extract has been shown to be due principally to hydrolysis by alanyl aminopeptidase: glutamyl, glycyl, isoleucyl, methionyl, ornithyl, phenylalanyl, prolyl, seryl, tyrosyl and valyl. We would suggest that measurement of the soluble extract-derived aminopeptidases described in this paper in urine may lead to an improvement upon existing assay procedures for early detection of kidney damage.

Aminopeptidases↗
PubMed1990

Isolation and preliminary characterization of the major membrane boundaries of the endocytic pathway in lymphocytes.

Plasma membrane, coated pits, endosomes, and lysosomes were isolated from a mouse T lymphoma cell line using a density shift protocol in which these compartments were selectively loaded with gold conjugates. The plasma membrane was prepared after selective labeling for 1 h at 2 degrees C with gold-ricin and gave a yield of 40% according to enzymatic and antigenic markers. Endosomes were obtained by loading the cells for 2 h at 22 degrees C with gold complexed to an antimouse transferrin receptor mAb. Coated pits were isolated using a similar procedure, but after an incubation at 10 degrees C, which allowed deep invagination of the pits but prevented internalization. The yield (calculated using the recovery of [125I]transferrin) was 32% for endosomes and 10% for coated pits. Finally lysosomes were prepared by loading the cells for 18 h at 37 degrees C with gold low density lipoproteins (LDLs) followed by a 3-h chase at 37 degrees C with LDL alone. The final lysosome yield (based on the recovery of lysosomal enzymes) was 16%. Studies of the protein composition of these cellular compartments on two-dimensional gels showed that while some major proteins are present throughout the pathway, specific proteins can be identified in each of the isolated fractions. The greatest change in the pattern of protein constituents seen along the pathway was between endosomal and lysosomal preparations.

Animals↗
PubMed1990

L-NG-monomethyl arginine and L-NG-nitro arginine inhibit non-adrenergic, non-cholinergic relaxation of the mouse anococcygeus muscle.

1. The effects of L-NG-monomethyl arginine (L-NMMA) and L-NG-nitro arginine (L-NOARG) on non-adrenergic, non-cholinergic (NANC) relaxations of the mouse anococcygeus were investigated. 2. L-NMMA (10-200 microM) produced a concentration-related inhibition of the NANC response; the inhibitory effect of 50 microM L-NMMA was completely reversed by L-arginine but not D-arginine (both 100 microM). 3. L-NOARG (1-50 microM) also produced a concentration-related inhibition of the NANC response and was some 30-50 times more potent than L-NMMA; again, the effects of 10 microM L-NOARG were reversed by 100 microM L-, but not D-, arginine. By itself 100 microM L-arginine did not relax the tissue, but did cause a slight potentiation of the NANC response. 4. Sodium nitroprusside (0.01-10 microM), hydroxylamine (0.1-100 microM), sodium azide (1-100 microM) and nitric oxide (3-120 microM) all relaxed carbachol-induced tone; relaxations to submaximal concentrations of these nitrovasodilators were unaffected by either 50 microM L-NMMA or 10 microM L-NOARG. 5. L-NOARG 10 microM did not inhibit, but rather potentiated, contractions of the mouse anococcygeus due to stimulation of its sympathetic nerves. 6. The inhibitory effects of 10 microM L-NOARG on NANC relaxations were reversed by L-arginine (by 131%), L-citrulline (by 75%), L-arginine methyl ester (by 46%) and L-homoarginine (by 22%), but were unaffected by a variety of other amino acids and their derivatives (all at 100 microM). 7. The results provide strong evidence that NANC relaxations of the mouse anococcygeus are mediated by an endogenous nitrate material, probably derived from L-arginine, and confirm that L-NOARG provides a very useful and potent drug for the investigation of endogenous nitrate function.

Animals↗
PubMed1990

L-NG-nitro arginine inhibits non-adrenergic, non-cholinergic relaxations of guinea-pig isolated tracheal smooth muscle.

The effects of L-NG-nitro arginine (L-NOARG) on alpha-chymotrypsin-resistant, non-adrenergic, non-cholinergic (NANC) relaxations of guinea-pig tracheal smooth muscle have been examined. L-NOARG (1-100 microM), but not D-NOARG (100 microM), inhibited the NANC relaxations in a concentration-related manner. The effects of L-NOARG were partially reversed by L-arginine but not D-arginine. L-NOARG was without effect on acetylcholine-induced contractile responses of the trachea or on relaxations produced by vasoactive intestinal peptide, sodium nitroprusside or isoprenaline. These results suggest that an endogenous nitrate may contribute to NANC relaxations of tracheal smooth muscle.

Acetylcholine↗
PubMed1990

L-NG-nitro-arginine and its methyl ester are potent inhibitors of non-adrenergic, non-cholinergic transmission in the rat anococcygeus.

1. The effects of L-NG-nitro-arginine (L-NOARG) and some other arginine analogues on non-adrenergic, non-cholinergic (NANC) relaxations of the rat anococcygeus muscle were investigated. 2. L-NOARG (5-200 microM) produced concentration-related inhibition of the NANC response; 100 microM L-NOARG produced 90% inhibition. 3. L-Arginine (5-200 microM) produced a concentration-related reversal of the inhibitory effect of 20 microM L-NOARG; a five fold excess of L-arginine (100 microM) was required to obtain the maximum reversal of 90%. D-Arginine (100 microM) produced no such reversal, but significant reversal was produced by L-citrulline, L-arginine-L-aspartate, L-homoarginine and L-arginine-methyl-ester (all at 100 microM). 4. L-NG-nitro-arginine-methyl-ester (L-NAME; 5-200 microM) also reduced NANC relaxations, with a potency similar to that of L-NOARG; both L-NOARG and L-NAME were some ten times more potent than L-NG-monomethyl-arginine (L-NMMA). Like L-NOARG, the effects of L-NAME (20 microM) were reversed by 100 microM L- but not D-arginine. 5. Neither L-NOARG nor L-NAME (both 20 microM) affected submaximal relaxations induced by 10 microM sodium nitroprusside or 20 microM hydroxylamine. 6. D-NOARG, L-NG-tosyl-arginine and L-N alpha-(t-butyl-oxycarbonyl)-NG-nitro-arginine (all at 100 microM) had no effect on NANC relaxations. 7. Thus, in the rat anococcygeus, L-NOARG and L-NAME are more potent than L-NMMA as prejunctional inhibitors of NANC transmission. The reversibility of the effect of L-NOARG by arginine analogues suggests that the NANC system of the anococcygeus shows similarities to the endogenous nitrate system recently described in the brain.

Animals↗
PubMed1990

L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro.

1. The effect of L-NG-nitro arginine (L-NOARG) was compared with that of L-NG-monomethyl arginine (L-NMMA) on vasodilatation of the isolated aorta of the rabbit and perfused mesentery of the rat in response to acetylcholine (ACh) and sodium nitroprusside (NP). 2. L-NOARG (1.5-100 microM) and L-NMMA (3-100 microM) produced concentration-related contraction of the rabbit aorta precontracted with phenylephrine (700-900 nM). Similarly, L-NOARG (10-200 microM) and L-NMMA (30-100 microM) elevated perfusion pressure of the noradrenaline (NA, 0.6-2.5 mM)-preconstricted rat mesentery preparation. 3. L-NOARG (1.5-100 microM) and L-NMMA (3-100 microM) caused concentration-related inhibition of the vasodilator effect of ACh (0.01-1.0 microM) on the rabbit aorta without influencing responses to NP (0.03-0.5 microM). L-NOARG methyl ester (30 microM) also inhibited ACh-induced vasorelaxation with similar potency to NOARG. L-arginine (30-150 microM) but not D-arginine (100 microM) caused graded reversal of the inhibitory effect of both L-NOARG (15 microM) and L-NMMA (30 microM). Complete reversal of the effect of both inhibitors was achieved with 150 microM L-arginine. L-Alanine (50 microM), L-arginosuccinic acid (5 microM), L-citrulline (50 microM), L-methionine (50 microM) and L-ornithine (50 microM) failed to reverse the inhibitory effect of L-NOARG (15 microM). 4. L-NOARG (10-200 microM) and L-NMMA (30-100 microM) inhibited the vasodilator effect of ACh (0.006-18.0 nmol) in the rat mesentery without affecting vasodilatation due to NP (1.1-11.1 nmol). L-Arginine (100 microM) but not D-arginine (100 microM) produced partial reversal of the effect of L-NOARG (30 microM) and L-NMMA (30 microM). 5. L- and D-N'-butyloxycarbonyl No-nitro arginine (100 microM) produced modest (approximately 20%) inhibition of the effect of ACh on the rabbit aorta; this effect was not reversible with L-arginine (100 microM). L-Namonocarbobenzoxy arginine (L-NMCA, 5O microM), L-N-NG-dicarbobenzoxy arginine (L-NDCA, 5 microM) and L-NG-tosyl arginine (50 microM) were inactive. 6. These results identify L-NOARG as a potent, L-arginine reversible inhibitor of endothelium-dependent vasodilatation. The available data suggests that L-NOARG, like L-NMMA, inhibits endothelial nitric oxide (NO) biosynthesis.

Acetylcholine↗
PubMed1990

The distribution of immunoreactive interferon-alpha in formalin-fixed paraffin-embedded normal human foetal and infant tissues.

Human foetal and infant tissues were studied to test the hypothesis that microbes have a role in switching on interferon-alpha (IFN-alpha) synthesis. Foetal tissues were essentially 'germ free', while the infants had been exposed to a normal microbial environment in life. IFN-alpha was first seen at 9 weeks gestation in macrophages in the liver and thereafter was seen in macrophages in most other organs. When infant lungs were compared with foetal lungs, a statistically significant increase in the number of macrophages and the percentage of these cells expressing IFN-alpha was noted in the infant lungs. No such change was observed in spleen, liver and thymus following birth. These findings suggest that there is a basal production of IFN-alpha by macrophages that is not dependent on microbial products, but that such products can enhance synthesis of this cytokine.

Child, Preschool↗
PubMed1989

N-methylhydroxylamine inhibits and M&B 22948 potentiates relaxations of the mouse anococcygeus to non-adrenergic, non-cholinergic field stimulation and to nitrovasodilator drugs.

1. The effects of N-methylhydroxylamine (NMH) and of M&B 22948 on relaxations of the mouse anococcygeus to non-adrenergic, non-cholinergic (NANC) field stimulation and to a number of smooth muscle relaxant drugs were investigated. 2. Relaxations to NANC field stimulation (10 Hz; 60 s train) were reversibly blocked by NMH (1-5 mM), which also caused weak, transient reductions of carbachol (50 microM)-induced tone. N,N-dimethylhydroxylamine (2 mM) and hydroxylamine (5 microM) reduced tone to the same extent as NMH, but neither produced any inhibition of NANC relaxations. 3. M&B 22948 10 microM, which by itself reduced tone by 12%, potentiated submaximal but not maximal relaxations to NANC field stimulation; overall the log frequency-response curve was displaced to the left by a factor of 2. 4. Sodium nitroprusside (0.01-1 microM), hydroxylamine (0.5-100 microM), and nitric oxide (2-200 microM) all relaxed carbachol-induced tone; relaxations to submaximal concentrations of these nitrovasodilators were reduced in the presence of 2 mM NMH, and potentiated in the presence of 10 microM M&B 22948. 5. Neither NMH (2 mM) nor M&B 22948 (10 microM) affected relaxations induced by submaximal concentrations of vasoactive intestinal peptide (VIP; 1 microM), papaverine (10 microM), 3-isobutyl-1-methyl-xanthine (10 microM), or 8-bromo-cyclic guanosine monophosphate (100 microM); relaxations to adenosine 5'-triphosphate (ATP, 2 mM) were unaffected by M&B 22948, but were potentiated by NMH. 6. The selective inhibition by NMH, and potentiation by M&B 22948, of NANC and nitrovasodilator-induced relaxations of the mouse anococcygeus suggests that the NANC transmitter is neither VIP nor ATP, but resembles the nitrovasodilator drugs in its mode of action. The NANC transmission system is therefore similar to that recently described in the bovine retractor penis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

The effect of Ca deprivation and of Ca-blocking drugs on oxytocin-induced contractions of the male mouse anococcygeus.

Oxytocin (4 nM)-induced contractions of the male mouse anococcygeus were rapidly and completely lost in EGTA (2 mM)-containing, Ca-free Krebs solution. Contractions were also lost, although more slowly, in Ca-free Krebs solution without EGTA; under such conditions, readdition of Ca did not by itself cause contraction, but readdition of Ca (0.1-2.5 mM) in the presence of 4 nM oxytocin resulted in a rapid contractile response. These Ca-induced responses, in the presence of oxytocin, and those to oxytocin in normal Ca-containing Krebs solution, were unaffected by nitrendipine (0.01-1 microM). Contractions to oxytocin were completely blocked by the calmodulin antagonists trifluoperazine (50 microM) and W-7 (75 microM). It is concluded that oxytocin-induced contraction of the mouse anococcygeus does not require opening of nitrendipine-sensitive Ca channels, and there is no Ca-independent component of the contractile response; the cellular mechanisms linked to the oxytocin receptor in the anococcygeus are therefore different from those in the uterus.

Animals↗
PubMed1988

A negative phase II trial methylene dimethane sulphonate in advanced ovarian cancer (Cancer Research Campaign Phase I/II Trials Committee).

Methylene dimethane sulphonate (MDMS), the first member of the homologous series of dimethane sulphonic acid esters, was administered to 19 patients with advanced epithelial ovarian cancer. All patients had received prior chemotherapy and in addition 3 had received prior radiotherapy. MDMS was given as an i.v. bolus injection at a dose of 125mg m-2 and repeated in a q35 day schedule. Ten patients received only one course, six two courses, two three courses and one four courses. The major toxicity was thrombocytopenia which was cumulative. Serious neutropenia did not occur and no infective episodes requiring i.v. antibiotics were seen. Seven patients experience hair loss and four nausea and vomiting. Sixteen patients were evaluable for response but no objective remissions were seen although three patients had stable disease lasting at least 8 weeks. MDMS is therefore not recommended for further trial in epithelial ovarian carcinoma.

Adult↗
PubMed1988

Adaptations to intermittent drying in germinating Eucalyptus sieberi L. Johnson seeds and young seedlings.

Before Eucalyptus sieberi L. Johnson seeds germinate, the protein reserves in a small group of cells in the collet are mobilized and the cells swell sufficiently to break the seed coat allowing further water uptake. If the seedling is desiccated at this stage, the embryo remains viable and when the seed is rewetted reserves are mobilized in the cells immediately behind those which expanded initially. Mobilization of reserves and subsequent cell elongation occur sequentially along the hypocotyl after successive dry periods until the reserves are exhausted. Early in the sequence, the distal end of the hypocotyl extends and is positively geotropic, whereas at the end of the sequence the proximal end of the hypocotyl extends and is negatively geotropic, raising the cotyledons rapidly. If the radicle is destroyed or unable to elongate, it is replaced by two adventitious roots, one below the petiole of each cotyledon. Indole acetic acid and sucrose can substitute for the cotyledons in the production of adventitious roots.

Journal Article↗
PubMed1988

Agonist profile of ergometrine (ergonovine) on a population of postsynaptic alpha-adrenoceptors.

Ergometrine (0.02-5 microM) produced concentration-related contractions of the mouse anococcygeus muscle, which were unaffected by cocaine (2 microM) or by pretreatment of mice with 6-hydroxydopamine. Contractions were reduced by alpha-adrenoceptor antagonists; the rank order of potency was prazosin greater than phentolamine greater than yohimbine. With phenoxybenzamine as antagonist, the estimated dissociation constant (KD) for ergometrine was 0.41 microM. It is concluded that ergometrine causes direct activation of postsynaptic alpha 1-adrenoceptors, and it is suggested that it acts on the same subtype of the receptor as imidazoline agonists.

Adrenergic alpha-Antagonists↗
PubMed1988

The influence of urotensin II on calcium flux in rat aorta.

The fish neuropeptide urotensin II (UII, 10 nM) caused a 51% increase in uptake of 45Ca by segments of rat aorta; this increase was abolished by the Ca channel blocking drug nitrendipine (200 nM). 45Ca efflux was unchanged in the presence of UII, but was significantly increased following washout of the peptide; again, this increase was not observed in the presence of nitrendipine. The results provide direct evidence that the nitrendipine-sensitive component of the contractile response of rat aorta to UII involves mobilization of extracellular Ca, with subsequent activation of a Ca-induced, Ca-release process intracellularly. The mechanisms responsible for the nitrendipine-resistant component of the contractile response to UII remain to be established.

Animals↗
PubMed1987

Characterization of soluble forms of NCAM.

Neural cell adhesion molecule (NCAM) has been described as a family of membrane glycoproteins. However, soluble NCAM immunoreactivity has long been recognized. We here show that soluble NCAM is composed of two quantitatively major polypeptides of Mr 180,000 and 115,000 and two minor components of Mr 160,000 and 145,000. Soluble NCAM was immunochemically identical to membrane NCAM, was polysialylated and carried the HNK-1 epitope. It only constituted 0.8% of total NCAM in newborn rat brain. Soluble NCAM appeared in neuronal cell culture medium 15-30 min after the start of synthesis preceding accumulation of membrane-associated NCAM on the cell surface. This indicates that soluble NCAM contains a secreted component.

Animals↗
PubMed1987

MR brain scanning in patients with vasculitis: differentiation from multiple sclerosis.

We performed MR (magnetic resonance) brain imaging on 24 patients with a systemic vasculitis. MRI proved to be a sensitive method for detecting brain lesions (clinically silent or manifest) in these patients. The most frequent abnormalities were periventricular lesions seen in 12 cases. Such changes are not specific for vascular disease, and are often seen in multiple sclerosis. However, additional changes were commonly seen which suggested the correct diagnosis.

Adolescent↗