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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 433 records · Page 24Linked to original sources

Alpha 1-adrenoceptor-mediated contraction of rabbit mesenteric artery: a role for intra- and extracellular calcium pools.

The alpha-adrenoceptors that mediate contraction to exogenous and endogenous noradrenaline in rabbit isolated mesenteric artery were investigated. Prazosin (10(-9)-10(-7) M) antagonised contractions to noradrenaline, methoxamine, and, in particular, contractions to neuronal noradrenaline released by field stimulation. Only a high concentration (10(-5) M) of idazoxan was able to markedly antagonise the three contractile stimuli. The effects of idazoxan (at high concentrations) and prazosin were studied upon noradrenaline-evoked contractions attributable to intracellular Ca2+ release using Ca2+ -deplete medium, and, on readministration of Ca2+, upon Ca2+ influx. Both components of the response were inhibited by the two antagonists, but the contraction associated with intracellular Ca2+ release was preferentially inhibited in each case. The results demonstrate that only alpha 1-adrenoceptors are involved in the contraction of this tissue to exogenous and endogenous noradrenaline. This receptor type is linked to both extracellular and intracellular Ca2+ sources, although the latter is more sensitive to inhibition by alpha-adrenoceptor blocking drugs.

Animals↗

Influence of internal sugar levels on apoplasmic retrieval of exogenous sucrose in source leaf tissue.

Sugar levels in Beta vulgaris leaves were increased by heat-girdling the petiole and returning the plant to the controlled-environment chamber for 10 and 34 hours. After 10 hours, sucrose influx into the treated leaves was similar to the controls, although sucrose levels increased from 2.1 to 5.3 micromoles per milligram chlorophyll. However, after a 34-hour treatment, sucrose levels increased from 2.1 to 11.5 micromoles per milligram chlorophyll. In this instance, sucrose influx decreased relative to the untreated controls. Decreasing sugar levels by DCMU treatment resulted in a small stimulation of sucrose influx. A similar DCMU treatment applied to leaves of Allium cepa also resulted in an increase in sucrose influx. However, in A. cepa we could not attribute this increase to a lowering of sugar levels, as the kinetic profiles obtained from control leaves did not vary from each other throughout the day, despite considerable changes in sugar levels. Additionally, it appeared that sucrose uptake in onion may be set at some point and remains invariant throughout the day. Similar studies were also conducted on discs cut from mature leaves of Spinacia oleracea var America. Between 1 and 8 hours after the onset of the photoperiod, the sucrose content of the spinach leaves increased from 2.6 to 9.3 micromoles per milligram chlorophyll. A comparison of the kinetic profiles obtained from leaf discs, taken at these times, indicated that sucrose uptake was not influenced by these changes in internal sugar levels. The relationship between the above findings and ;trans' inhibition of exogenous sucrose uptake is discussed. Although intermediate changes in sugar levels in sugar beet leaves did not appear to affect sucrose influx, autoradiographic studies revealed that these changes dramatically affected the partitioning of exogenously supplied [(14)C]sucrose. Our results indicate that while intermediate changes in internal sugar levels have little effect on sucrose influx across the plasmalemma, they may dramatically affect partitioning between the phloem and the mesophyll vacuole.

Journal Article↗

Influence of mannose on the apoplasmic retrieval systems of source leaves.

Experiments were conducted in which d-mannose was supplied to mature Beta vulgaris L. (sugar beet) leaves, via the transpiration stream, to perturb photosynthetic carbon allocation by sequestering cytosolic Pi. Biochemical and enzymic analyses conducted on this tissue indicated that mannose 6-P was present, that it was only slowly metabolized, and that after a 24-hour pretreatment sugar metabolism was slightly perturbed. However, sucrose retrieval by the mesophyll tissue was greatly impaired in 24-hour mannose-pretreated tissue, a response which was due in part to mannose acting as an osmoticum. Inhibition of glucose, fructose, and arginine uptake into mannose-treated sugar beet leaf discs indicated that mannose may elicit a general perturbation of all membrane transport processes. This conclusion was supported by our finding that sucrose efflux was increased from mannose-treated tissue. Analysis of adenine nucleotide levels showed that whereas these levels declined over the first 3 to 6 hours of the mannose treatment, by 24 hours they had recovered to near control values. Similar experiments conducted on Nicotiana rustica indicated that whereas mannose 6-P was present in mature leaves, it remained at a much lower level than that found in sugar beet. Sucrose uptake into N. rustica was insensitive to mannose pretreatment. However, glucosamine treatment, which is also thought to sequester cytosolic Pi, inhibited sucrose uptake in both N. rustica and B. vulgaris. Further, experiments conducted on N. tabacum L. var Xanthii showed that mannose caused an inhibition of sucrose uptake, indicating that a range of sensitivity to mannose exists between closely related species. These results are discussed in terms of possible mechanisms of inhibition.

Journal Article↗

Anti-spasmogenic and spasmolytic effects of BRL 34915: a comparison with nifedipine and nicorandil.

1 BRL 34915, nifedipine and nicorandil were compared for anti-spasmogenic activity against field stimulation (frequency-response curves), noradrenaline and KCl (concentration-response curves), and for spasmolytic activity against tissues pre-contacted with 3 X 10(-2) and 9 X 10(-2) M KCl, in rabbit isolated mesenteric artery. 2 BRL 34915 was an effective anti-spasmogenic agent (threshold concentration 10(-8) M) against endogenous noradrenaline released by field stimulation, and slightly less effective (threshold concentration 10(-7) M) against exogenous noradrenaline. Anti-spasmogenic activity of BRL 34915 against KCl was limited. BRL 34915 demonstrated spasmolytic activity against contractions to KCl 3 X 10(-2) M (IC50 = 3.7 X 10(-7) M) but not KCl 9 X 10(-2) M. 3 Nicorandil demonstrated anti-spasmogenic activity against all three contractile stimuli although relatively high concentrations (10(-6)-10(-4) M) of the drug were required. Spasmolytic activity was greater against 3 X 10(-2) M KCl contractions (IC50 = 1.0 X 10(-5) M) than against 9 X 10(-2) M KCl contractions (maximum relaxation of 18% at 10(-4) M). 4 Nifedipine (10(-9)-10(-7) M) was a potent inhibitor of contractions over the entire KCl concentration range (1 X 10(-2)-9 X 10(-2) M). Nifedipine was, however, much less effective against contractions to exogenous or endogenous noradrenaline. 5 The results are consistent with the hypotheses that (a) the inhibitory activity of BRL 34915 may involve K+ channel activation, (b) the inhibition by nicorandil involves an additional mechanism(s) and (c) nifedipine is a Ca2+ channel blocker with selectivity for voltage-operated rather than receptor-operated Ca2+ channels.

Animals↗

Translation and membrane insertion of the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus.

The hemagglutinin-neuraminidase (HN) protein of paramyxoviruses is likely in the unusual class of glycoproteins with the amino terminus cytoplasmic and the carboxy terminus lumenal or external to the cell. The properties of the membrane insertion of the HN protein of Newcastle disease virus, a prototype paramyxovirus, were explored in wheat germ extracts containing microsomal membranes. HN protein was inserted into membranes cotranslationally, resulting in a glycosylated protein completely resistant to trypsin and proteinase K digestion. No detectable posttranslation insertion occurred. Insertion required signal recognition particle. Signal recognition particle in the absence of membranes inhibited HN protein synthesis. Comparisons of the trypsin digestion products of the HN protein made in the cell-free system with newly synthesized HN protein from infected cells showed that the cell-free product was in a conformation different from that of the pulse-labeled protein in infected cells. First, trypsin digestion of intact membranes from infected cells reduced the size of the 74,000-dalton HN protein by approximately 1,000 daltons, whereas trypsin digestion of HN protein made in the cell-free system had no effect on the size of the protein. Second, trypsin digestion of Triton X-100-permeabilized membranes isolated from infected cells resulted in a 67,000-dalton trypsin resistant HN protein fragment. A trypsin-resistant core of comparable size was not present in the digestion products of in-vitro-synthesized HN protein. Evidence is presented that the newly synthesized HN protein in infected cels contain intramolecular disulfide bonds not present in the cell-free product.

Animals↗

Mesenteric venous thrombosis and antithrombin III deficiency.

Of the 123 patients with acute mesenteric infarction treated over the past 12 years, 16 (13%) had mesenteric venous thrombosis. Eight of the patients with mesenteric venous thrombosis survived the initial episode; two have since died. The remaining six patients were studied for evidence of haemostatic deficiencies or abnormalities. Antithrombin III deficiency, which is known to be associated with recurrent venous thrombosis, was found in three patients. It is recommended that all patients with mesenteric venous thrombosis should be screened for antithrombin III deficiency as treatment with coumarin anticoagulants may be indicated, providing effective prophylaxis against further thrombotic episodes.

Adult↗

Pharmacokinetics of intravenous trimethoprim-sulfamethoxazole during hemodialysis.

The pharmacokinetics of intravenous trimethoprim-sulfamethoxazole (TMP-SMZ) were studied in patients receiving hemodialysis. 16 stable end-stage renal disease patients received a single ampul of TMP-SMZ (160 mg TMP, 800 mg SMZ) with 250 ml 5% dextrose and water over 45 min just prior to beginning hemodialysis. All patients were dialyzed for 4 h with a 1.0 m2 cuprophane hollow-fiber dialyzer at a blood flow of 200 ml/min. Mean arterial TMP concentration peaked at 1.93 micrograms/ml following infusion and fell to 1.03 micrograms/ml by the end of dialysis (p less than 0.001). Mean arterial SMZ concentration peaked at 41.8 micrograms/ml at the end of the infusion and fell to 16.4 micrograms/ml by the end of dialysis (p less than 0.005). The extraction ratio averaged 19% for TMP and 21% for SMZ. The elimination half-life during dialysis for TMP was 6.0 h and for SMZ was 3.1 h. Dialysis clearance averaged 38 ml/min for TMP and 42 ml/min for SMZ. 44% of the administered TMP and 57% of the administered SMZ were removed during dialysis. Therefore, 50% of the maintenance dose of TMP-SMZ should be supplemented after each dialysis session.

Adult↗

Brain-stem tumors in childhood: a prospective randomized trial of irradiation with and without adjuvant CCNU, VCR, and prednisone. A report of the Childrens Cancer Study Group.

Seventy-four children with a brain-stem tumor diagnosed between 1977 and 1980 were entered into a prospective study in which exploration and assessment for resection were optional, radiation treatment using standard methods was required, and randomization occurred with regard to the use of adjuvant chemotherapy (1-(2-chloroethyl)-1-nitrosourea, vincristine, and prednisone) or no further treatment. The overall 5-year survival rate was 20% and was not improved by the adjuvant chemotherapy program. An increased risk of infection was associated with the adjuvant therapy.

Adolescent↗

Tissue-specific expression of actin genes injected into Xenopus embryos.

We have isolated a complete Xenopus borealis cardiac actin gene, which is normally expressed in the myotomes and heart of the embryo and tadpole. After injection into the zygote, this cloned gene becomes distributed throughout the embryo, but it is expressed almost wholly in the myotomes. The same wide distribution of injected DNA but spatially restricted pattern of expression is found with a fusion between the first two actin gene exons and the last exon of a mouse beta-globin gene. By contrast, a histone-globin fusion gene is expressed fairly uniformly in all regions. We discuss the special advantages of using Xenopus in studies of tissue-specific gene expression from injected, cloned genes in early development.

Actins↗

Insulin receptor processing as a function of erythrocyte age. A kinetic model for down-regulation.

The effects of cell aging on insulin binding and on insulin receptor processing in human erythrocytes were studied. Erythrocytes were found to exponentially lose equal proportions of both high and low affinity receptors as a function of age. The affinities of remaining surface receptors did not change significantly. The maximum extent of insulin receptor down-regulation that could be induced decreased linearly with age over the range studied. Together with dose-response and time course studies, these age-related changes in insulin binding and receptor down-regulation were used to develop a kinetic model in which receptor internalization is a function of surface receptor concentration. The ability of the model to predict the behavior of a heterogeneous population suggests that changes in receptor processing with age may be attributed to changes in the surface receptor concentration.

Dose-Response Relationship, Drug↗

Amylase and gut infarction.

Serum amylase has been determined on admission in 63 (52 per cent) of 122 patients with acute mesenteric infarction. Amylase levels were normal in 34 (54 per cent) and reached greater than twice normal in 15 patients (24 per cent). In 5 patients (3 on admission) amylase levels were in the diagnostic range of acute pancreatitis (greater than 1200 units/l) leading to inappropriate non-operative treatment in 4. Hyperamylasaemia was found in association with all aetiologies of infarction. The magnitude of the hyperamylasaemia appeared to be related to the extent of the bowel infarction, the highest levels occurring when infarction involved the small bowel and colon. The mechanism of hyperamylasaemia in acute mesenteric infarction is discussed.

Amylases↗