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Biomedical subjects

L Wilson

Publications and source records attributed to L Wilson.

At least 343 records · Page 19Linked to original sources
PubMed1984

Tubulin-colchicine complexes differentially poison opposite microtubule ends.

The kinetics of radiolabeled guanosine 5'-triphosphate-tubulin dimer addition to preformed microtubule copolymers, containing large numbers of tubulin-colchicine complexes (TCs), were examined at apparent equilibrium. The results indicated that radiolabeled dimer addition to copolymers occurs predominantly by a "treadmilling" reaction, analogous to that described for unpoisoned microtubules, and that some labeled dimer uptake also occurs by equilibrium exchange. The data further showed that TCs decrease the steady-state treadmilling reaction in a concentration-dependent manner. Since microtubule copolymers exhibited a treadmilling reaction, it was possible to differentially radiolabel opposite copolymer ends with [3H]- and [14C]guanine nucleotides and thus to measure the effects of TCs on dimer loss from opposite copolymer ends upon copolymer dilution. Dimer loss from both copolymer ends was inhibited in a concentration-dependent manner, but dimer loss from copolymer net assembly (A) ends (defined under steady-state conditions) was inhibited to a far greater extent than that from the opposite, net disassembly (D) copolymer ends. TCs therefore exhibited a graded, polar poisoning action, with copolymer A-end association and dissociation rate constants being far more susceptible to TC inhibition than those at the opposite copolymer D ends. The potential significance of this TC effect for regulating microtubule spatial orientation in vivo is discussed.

Animals↗
PubMed1984

Peritoneal fluid prostaglandins and prostanoids in women with endometriosis, chronic pelvic inflammatory disease, and pelvic pain.

Peritoneal fluid obtained at laparoscopy from 49 women was measured for its content of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6-KF), and thromboxane B2 (TxB2) by specific radioimmunoassays. In normal women (n = 10), the concentrations of prostaglandins in peritoneal fluid were (mean +/- SE): PGE2 = 0.79 +/- 0.26, PGF2 alpha = 0.60 +/- 0.18, 6-KF = 0.48 +/- 0.19, and TxB2 = 0.23 +/- 0.09 ng/ml; in women with endometriosis (n = 16): PGE2 = 1.43 +/- 0.72, PGF2 alpha = 1.52 +/- 0.59, 6-KF = 3.32 +/- 0.71, and TxB2 = 1.14 +/- 0.69 ng/ml; in women with chronic pelvic inflammatory disease and/or obstructed tubes (n = 19): PGE2 = 1.94 +/- 1.04, PGF2 alpha = 1.20 +/- 0.61, 6-KF = 1.55 +/- 0.40, and TxB2 = 0.64 +/- 0.24 ng/ml; in women with pelvic pain without any visible pathologic condition (n = 4): PGE2 = 1.11 +/- 0.66, PGF2 alpha = 0.73 +/- 0.55, 6-KF = 1.35 +/- 0.35, and TxB2 = 0.39 +/- 0.17. The mean volumes of peritoneal fluid recovered were 10 to 16 ml and were not significantly different between the groups. Except for a significantly elevated concentration of 6-KF in the peritoneal fluid of women with endometriosis compared to normal women (p = less than 0.02), the prostaglandins measured did not differ significantly between the groups of women studied. The possible significance of elevated 6-KF in the peritoneal fluid of women with endometriosis is discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Investigation of the effects of muscimol on different components of [3H]propyl beta-carboline-3-carboxylate binding to rat hippocampal and cerebellar membranes.

The binding of [3H]propyl beta-carboline-3-carboxylate [( 3H]PCC) to rat hippocampal and cerebellar membranes was investigated together with the displacement by PCC of [3H]flunitrazepam [( 3H]FNM). Results were consistent with the presence of a single recognition site in cerebellum and two sites in hippocampys, but the affinity of neither of the hippocampal sites correlated with that in the cerebellum. Muscimol did not alter the affinity or capacity of any of these sites under the conditions used, indicating that PCC does not show the benzodiazepine-like property of GABAergic modulation, at any of the subpopulations of its binding sites.

Animals↗
PubMed1984

Temporal response of uterine prostaglandins to estradiol treatment in the ovariectomized-pregnant rat.

Previous studies in our laboratory have shown that 24 hours of estradiol treatment significantly enhanced uterine prostaglandin (PG)F, PGE and thromboxane B2 (TxB2) levels but had no effect on 6-Keto-PGF1 alpha (6KF) concentrations in ovariectomized-pregnant rats. One explanation for the lack of an augmentation in 6KF was a temporal difference in response (i.e. 6KF increased and decreased within the 24 hour period). To test this possibility rats were ovariectomized on day 19 of pregnancy and sacrificed 0, 4, 8, 12, 16, 20 and 24 hours after estradiol treatment. Uterine tissue and venous plasma were analyzed for PGs by radioimmunoassay. No significant (p greater than .05) alterations were detected for any of the uterine PGs at 0, 4, 8 and 12 hours. However, at 16 hours PGF, TxB2 and PGE all showed significant (p less than .05) increases (2.4, 3.4 and 2.1 fold, respectively) compared to 12 hours. In contrast, no significant augmentation in 6KF levels (p greater than .05, 1.3 fold) was detected at 16 compared to 12 hours although it was enhanced relative to 0 and 4 hours. In addition, PGF, TxB2 and PGE, but not 6KF, showed further increases 24 hours after estradiol administration. No alterations were found (p greater than .05) for any of the PGs in uterine venous plasma at the time points studied. In summary, uterine PGF, PGE and TxB2 net production appears to be more enhanced by estradiol treatment than 6KF at the time points studied. In addition, there is a slight, but significant, difference in the temporal response characteristics of 6KF compared to the other PGs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Possible role of the opioid peptides in sleep.

The opioid peptide endorphins, enkephalins, and dynorphins--found in brain, pituitary, and gut--are neurohormones involved in the regulation of a number of seemingly diverse biologic activities, including respiration, mood, pain perception, blood pressure, body temperature, and certain visceral responses. When viewed in integrated fashion, however, the spectrum of activities induced by the administration of both the exogenous opiates (e.g. morphine) and the endogenous opioids resembles a natural physiologic state: the sleep state. We propose that the opioid peptides in conjunction with the peptide neurohormone vasopressin are involved in the induction and maintenance of the sleep state. We also propose that the function of sleep is to protect an animal during periods when it is at a selective disadvantage, and we provide evidence to support and integrate both concepts.

Adaptation, Biological↗
PubMed1984

Protection of cells from methotrexate toxicity by 7-hydroxymethotrexate.

Cell growth survival studies have revealed that 7-OH methotrexate is two orders of magnitude less cytotoxic to human melanoma and human acute lymphoblastic leukaemia (ALL) cells in vitro than methotrexate. The influence of 7-OH methotrexate on methotrexate toxicity was investigated by studying cell growth in the presence of methotrexate and its 7-OH metabolite and by studying [3H]-methotrexate movement across the plasma membrane of isolated human cells. Transport was followed for net entry of the drug into drug-free cells, net exit of drug into drug-free medium and for unidirectional exit fluxes with drug and/or metabolite in the extracellular medium (exchange exit). Results indicate that 7-OH methotrexate (10(-6) M) interacts with melanoma cells to reduce the initial cellular uptake rate of [3H]-methotrexate but that no such interaction occurs with ALL cells. Efflux measurements revealed that a stimulatory effect of extracellular methotrexate on [3H]-methotrexate exit was apparent and that extracellular 7-OH methotrexate had a less stimulatory effect. Overall, loss of intracellular drug was greater from melanoma cells than from ALL cells. The results suggest that the drug resistance encountered following high dose therapy may be due to reduced cellular uptake and/or increased efflux of methotrexate from cells, both events being enhanced by 7-OH methotrexate. In addition, there is an apparently endogenous resistance of the melanomas to methotrexate as regards time of exposure to this agent which could also contribute to the lack of clinical response when compared to ALL.

Acute Disease↗
PubMed1984

Colchicine-binding activity distinguishes sea urchin egg and outer doublet tubulins.

The colchicine-binding activity of tubulin has been utilized to distinguish the tubulins from two distinct microtubule systems of the same species, the sea urchin Strongylocentrotus purpuratus. We have analyzed the colchicine-binding affinities of highly purified tubulins from the unfertilized eggs and from the flagellar outer doublet microtubules by van't Hoff analysis, and have found significant differences in the free energy, enthalpy, and entropy changes characterizing the binding of colchicine to the two tubulins. The data indicate that significant chemical differences in the tubulins from the two functionally distinct microtubule systems exist, and that the differences are expressed in the native forms of the tubulins. Our findings are discussed in terms of the possibility that the colchicine-binding site may be an important regulatory site on the tubulin molecule.

Animals↗
PubMed1984

Developmental and biochemical analysis of chick brain tubulin heterogeneity.

Tubulin, isolated from brain tissue of chicks at different stages during late embryonic and early post-hatched development by ion-exchange chromatography and by in vitro microtubule reassembly, was analyzed by high-resolution isoelectric focusing and by two-dimensional polyacrylamide gel electrophoresis. Similar results were obtained with tubulins purified by the two methods. Sixteen isoelectric species of tubulin that differ in apparent net charge under denaturing conditions were detected by isoelectric focusing. By two-dimensional polyacrylamide gel electrophoresis, the chick brain tubulins were resolved into at least seven forms of alpha and 10 forms of beta tubulin. The number and relative proportions of the multiple brain tubulins were modulated during development. Since there are only four alpha tubulin and four beta tubulin genes in chickens, posttranslational modification of the tubulins must play a prominent role in the heterogeneity. Analysis of isotubulin distributions through cycles of microtubule assembly and disassembly indicated that the tubulins differ very little, if at all, in their capacity to assemble into microtubules. Therefore, the chemical differences that distinguish the multiple tubulins have very little structural impact on the protein surface areas involved in microtubule formation. Partial fractionation of the multiple tubulins during ion-exchange chromatography was observed, suggesting that it may be possible to isolate individual native tubulin variants for biochemical studies.

Aging↗
PubMed1984

A comparative trial of a controlled-release formulation of ketoprofen ('Oruvail') and a conventional capsule formulation of ketoprofen ('Orudis') in patients with osteoarthritis of the hip.

An open study was carried out in 46 patients with osteoarthritis of the hip to compare the efficacy and tolerance of treatment with ketoprofen given either as 100 mg capsules twice daily or as 2 capsules of 100 mg ketoprofen in a controlled-release formulation given once daily. The results of subjective and objective assessments before and during 3-months' treatment in the 48 patients who completed the trial showed both treatments produced improvement in all parameters, except for the time taken for inactivity stiffness to develop, and there was no significant difference between treatments in terms of efficacy. The controlled-release preparation, however, was significantly better tolerated than the ordinary capsule form. Minor haematological and biochemical changes during treatment were noted but these were not of clinical importance. Six patients, 2 receiving the controlled-release and 4 receiving the ordinary formulation of ketoprofen, were withdrawn because of lack of efficacy or unacceptable side-effects.

Adult↗
PubMed1984

A moving video window or a mask yoked to eye movements: experiments on letters, words and biological movement with prolonged hemifield stimulation.

We describe the first use of a new technique, which permits prolonged presentation to one or other visual field of complex, realistic, "ecologically valid" stimuli. An infrared eye movement transducer is linked to a visual display such that an electronic mask (of adjustable dimensions) or, alternatively, a "window" can be made to move as consequence of eye movements. The mask can be made to move exactly with the initiating eye movement, or with positive gain, or in the opposite direction (with or without gain), or in both directions simultaneously ("scissoring"). Alternatively, the apparatus can be set to blank the entire display should an eye movement occur with an excursion greater than a preset criterion level. The display itself can be either computer generated or can consist of a pre-recorded video film. We report preliminary findings with this apparatus. When subjects detected a letter target in a three-by-three letter matrix of laterally presented letters, exposure durations from 50 msec to 400 msec showed consistent right visual field (RVF) superiorities. (Nor was there any evidence of left visual-field, LVF, superiorities at very brief exposures as others have claimed.) Equally strong RVF superiorities also appeared when subjects decided whether or not two simultaneously and laterally presented (for 500 msec) words rhymed, the word pairs being phonologically and orthographically similar (DOWN-GOWN), phonologically similar and orthographically distinct (FARE-HAIR), phonologically distinct and orthographically similar (MOWN-DOWN), or both phonologically and orthographically distinct (FORT-GOAT). Finally, Johansson's (1973, 1976) biological movement procedure was adapted for lateral viewing, with unlimited exposure times. However, the predicted LVF superiority did not eventuate, when subjects decided whether moving points of light, attached to the limbs of darkened walkers, were worn by males or females. Further possible applications of this technique are described for normal and clinical subjects.

Eye Movements↗
PubMed1984

Experience with the colony-forming (stem cell) assay of in vitro chemosensitivity in the management of patients with advanced malignant melanoma.

Twenty-two patients with advanced malignant melanoma had tumor nodules biopsied and tumor cell colonies established in vitro in the colony-forming assay in the presence of vindesine. The patients then received iv vindesine at a dose of 3 mg/m2/week for 6 weeks. In four patients, in vitro death of cells exposed to vindesine in vitro correlated with clinical response to therapy. In the remaining 18 patients, lack of both in vitro and clinical response was noted.

Adult↗
PubMed1983

Possible treadmilling in zinc(II)-induced sheet polymers of bovine brain microtubule protein.

We have examined the ability of zinc(II)-induced sheet polymers, formed from thrice-cycled bovine brain microtubule protein prepared in the absence of glycerol, to exchange with tubulin subunits at steady state. By a rapid filtration assay in which labeled GTP was used as a marker for tubulin addition and loss, we found that steady-state sheet polymers, formed in 0.5 mM-ZnCl2, 1 mM-dithiothreitol, and 100 mM-2-(N-morpholino)ethanesulfonic acid (pH 6.75) in the presence of a GTP-regenerating system at 37 degrees C, incorporated the label in a time-dependent manner to a maximum level. The steady-state uptake of label was inhibited by colchicine, podophyllotoxin and vinblastine. In pulse-chase experiments, we observed that label added onto sheet polymers in a short pulse was retained for a period equal to that required by the polymers to become fully labeled in a continuous pulse; thereafter, the label was lost gradually to a baseline level. An average of 82% of the label was retained in the sheet polymers after a "cold" chase of equal duration to the time of the pulse. Sheet polymers assembled from microtubule protein prepared in the presence of glycerol gave similar results. Using a double-labeling procedure to analyze tubulin addition and loss simultaneously, we found that the rates of steady-state addition and loss were similar. Sheet polymers retained their structural integrity throughout these experiments, as determined by electron microscopy. We believe that the data are consistent with a "treadmilling" mechanism of polymerization and depolymerization, analogous to that documented to occur in steady-state microtubules in vitro. Such a mechanism is discussed in the context of recent findings from structural studies, and a model consistent with established structural data is offered.

Animals↗
PubMed1983

On the nonlinear relationship between the initial rates of dilution-induced microtubule disassembly and the initial free subunit concentration.

We have examined the dilution-induced in vitro disassembly kinetics of bovine brain microtubules, initially at steady state, using a wider range of dilutions (2-100-fold) than previously employed. In contrast to earlier results, as well as to the simple nucleation-condensation model for microtubule formation, the initial rate of dimer loss from microtubule ends was not a linear function of the initial concentration of unpolymerized tubulin. Over a 2-20-fold dilution range, plots of the initial rate of dimer loss versus the initial unpolymerized tubulin concentration were approximately linear. However, at greater dilutions, rates of microtubule depolymerization increased nonlinearly. For example, between a 10-fold dilution and a 100-fold dilution, the initial rate of dimer loss for microtubule-associated protein-containing microtubules increased by 300%, rather than a maximum of 11% expected on the basis of a linear rate plot. The nonlinear response was observed for dimer loss from opposite microtubule ends separately and with microtubules containing and lacking associated proteins. Qualitatively similar results were obtained using a wide range of experimental protocols, from which we can reasonably exclude methodological artifact as a basis for the data. We can also reasonably exclude the dissociation of the high molecular weight microtubule-associated proteins 1 and 2 from the microtubules as an explanation for the nonlinearity of the rate plots. The nonlinearity of the rate plots indicates that kinetic constants obtained under nonsteady state conditions of extreme microtubule dilution may not describe the steady state condition accurately.

Animals↗
PubMed1983

Purification, characterization, and assembly properties of tubulin from unfertilized eggs of the sea urchin Strongylocentrotus purpuratus.

Tubulin was purified from unfertilized eggs of the sea urchin Strongylocentrotus purpuratus by chromatography of an egg supernatant fraction on DEAE-Sephacel or DEAE-cellulose followed by cycles of temperature-dependent microtubule assembly and disassembly in vitro. After two assembly cycles, the microtubule protein consisted of the alpha- and beta-tubulins (greater than 98% of the protein) and trace quantities of seven proteins with molecular weights less than 55 000; no associated proteins with molecular weights greater than tubulin were observed. When analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis on urea-polyacrylamide gradient gels, the alpha- and beta-tubulins did not precisely comigrate with their counterparts from bovine brain. Two-dimensional electrophoresis revealed that urchin egg tubulin contained two major alpha-tubulins and a single major beta species. No oligomeric structures were observed in tubulin preparations maintained at 0 degrees C. Purified egg tubulin assembled efficiently into microtubules when warmed to 37 degrees C in a glycerol-free polymerization buffer containing guanosine 5'-triphosphate. The critical concentration for assembly of once- or twice-cycled egg tubulin was 0.12-0.15 mg/mL. Morphologically normal microtubules were observed by electron microscopy, and these microtubules were depolymerized by exposure to low temperature or to podophyllotoxin. Chromatography of a twice-cycled egg tubulin preparation on phosphocellulose did not alter its protein composition and did not affect its subsequent assembly into microtubules. At concentrations above 0.5-0.6 mg/mL, a concentration-dependent "overshoot" in turbidity was observed during the assembly reaction. These results suggest that egg tubulin assembles into microtubules in the absence of the ring-shaped oligomers and microtubule-associated proteins that characterize microtubule protein from vertebrate brain.

Animals↗
PubMed1983

Cardiac arrest: comparison of paramedic and conventional ambulance services.

A prospective study conducted in the Greater Vancouver area compared survival rates in prehospital cardiac arrest managed by an advanced life support (paramedic) service with those in cardiac arrest managed by conventional ambulance service. Management by the paramedic service was associated with higher survival rates for patients found in cardiac arrest but not for patients who suffered the arrest while the ambulance was present. Cardiopulmonary resuscitation by bystanders was associated with a significant increase in survival rates when combined with paramedic services but not when only basic life support services were available.

Allied Health Personnel↗
PubMed1983

Head and body space to left and right, front and rear--II. Visuotactual and kinesthetic studies and left-side underestimation.

We report seven experiments involving unimanual or bimanual tactual or visuotactual judgments with horizontally or vertically disposed rods, performed in left or right hemispace, in the context of Bowers and Heilman's (Neuropsychologia 18, 491-498, 1980) hemispace hypothesis. We were only able to weakly confirm their finding of a left hemispace superiority, though either hand was more accurate when in its own hemispace. However, their observation of a left pseudoneglect phenomenon was supported and extended: we found that the left hand underestimates relative to the right, and that there may be left hemispace underestimation which is lost with 90 degree head turns, when horizontal extents are underestimated in the direction of the head turn.

Cerebral Cortex↗