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Biomedical subjects

L Wilson

Publications and source records attributed to L Wilson.

At least 415 records · Page 23Linked to original sources
PubMed1978

Psoriasis treated with clobetasol propionate and photochemotherapy.

Comparable lesions in 16 patients with chronic plaque psoriasis were treated with clobetasol propionate or placebo ointments for 1 week before beginning photochemotherapy. The greater improvement of the steroid treated lesions was maintained after the ointment was withdrawn and there was a mean period of 31 days before those treated with placebo showed a comparable response to photochemotherapy. By the end of the study 8 patients were completely free of psoriasis, healing being achieved after a mean of 7.2 photochemotherapy treatments on the steroid treated lesions compared with 13.5 where a placebo ointment was used. No patient had any adverse reaction to treatment.

Adult↗
PubMed1978

HLA phenotype frequencies in individuals with cleft lip and/or cleft palate.

The HLA types of 133 patients with cleft lip and/or cleft palate were determined. Caucasian patients with isolated cleft palate showed a possible association with HLA. Ten of 11 male patients had HLA--A2 as compared to one out of eight female patients (P less than 0.005). Caucasian males with cleft lip and cleft palate had a slight increased frequency of HLA--Aw24 (P = 0.07) and Mexican-American males with cleft lip and/or cleft palate showed an increase of antigen HLA-A28 (P = 0.07), though neither were statistically significant. Females with cleft lip and/or cleft palate from either racial group had no differences from the controls. The serum from 90 mothers of patients with cleft lip and/or cleft palate were reacted against their child's lymphocytes. Of these crossmatch tests, 12% were found to be positive. These preliminary results suggest that male patients with isolated cleft palate are worthy of further studies with respect of HLA associations.

Cleft Lip↗
PubMed1977

Structure of the tubulin dimer.

Microtubules are formed from a 110,000-dalton dimeric subunit called tubulin. Two forms of 55,000-dalton monomer, alpha and beta, are found in all microtubule preparations. The dimers could thus theoretically be either heterodimers (alphabeta) or homodimers (alphaalpha and betabeta). This problem was investigated by stigated by chemical cross-linking using several bifunctional reagents, of which one, dimethyl-3,3-(tetrame thylenedioxy) dipropionimidate dihydrochloride (DTDI), was able to make intradimer bonds in tubulin. When soluble chick brain tubulin was cross-linked with DTDI and analyzed by electrophoresis in an acrylamide gel system capable of resolving alphaalpha, alphabeta, and betabeta, 60 to 90% of the cross-linked dimer was alphabeta. If tubulin was incubated at 24 degrees prior to cross-linking with DTDI the total yield of cross-linked dimer increased with time, indicating that tubulin was forming loose aggregates. The relative amounts of cross-linked dimer alphaalpha and betabeta also increase with time, indicating that soluble tubulin is largely alphabeta, and suggesting that cross-linked alphaalpha and betabeta arise from nonspecific aggregation during tubulin purification. The aggregation observed by cross-linking with DTDI was strongly influenced by colchicine and Vinca alkaloids in a pattern similar to the effects of these drugs on tubulin polymerization.

Animals↗
PubMed1976

Properties of tubulin in unfertilized sea urchin eggs. Quantitation and characterization by the colchicine-binding reaction.

The colchicine-binding assay was used to quantitate the tubulin concentration in unfertilized Strongylocentrotus purpuratus eggs and to characterize pharmacological properties of this tubulin. Specificity of colchicine binding to tubulin was demonstrated by apparent first-order decay colchicine-binding activity with stabilization by vinblastine sulfate, time and temperature dependence of the reaction, competitive inhibition by podophyllotoxin, and lack of effect of lumicolchicine. The results demonstrate that the minimum tubulin concentration in the unfertilized egg is 2.71 mg per milliliter or 5.0% of the total soluble cell protein. Binding constants and decay rates were determined at six different temperatures between 8 degrees C and 37 degrees C, and the thermodynamic parameters of the reaction were calculated. delta H0=6.6 kcal/mol, delta S0=46.5 eu, and, at 13 degrees C, delta G=-6.7 kcal/mol. The association constants obtained were similar to those of isolated sea urchin egg vinblastine paracrystals (Bryan, J. 1972. Biochemistry. 11:2611-2616) but approximately 10 times lower than that obtained for purified chick embryo brain tubulin at 37 degrees C (Wilson, L.J.R. Bamburg, S.B. Mizel, L. Grisham, and K. Creswell. 1974. Fed Proc. 33:158-166). Therefore, the lower binding constants for colchicine in tubulin-vinblastine paracrystals are not due to the paracrystalline organization of the tubulin, but are properties of the sea urchin egg tubulin itself.

Animals↗
PubMed1976

The clinical assessment of topical corticosteroid activity.

Glucocorticoid-induced vasoconstriction of human skin has provided a useful guide to topical anti-inflammatory activity. The concentration and base in which a steroid is used influence this activity, and traditional greasy ointments are probably the most effective vehicles. Confirmation of clinical effectiveness should be by double-blind comparison in patients with bilateral skin lesions. Psoriasis provides a more discriminating test of steroidal activity than eczema; the use of occlusive dressings may mask differences between compounds. Short-term trials are informative but in patients with chronic diseases, longer studies should also be done.

Adrenal Cortex Hormones↗
PubMed1976

The effect of clobetasone butyrate and other topical steroids on skin thickness of the domestic pig.

A new glucocorticoid, clobetasone butyrate, has been shown in patients to have good topical anti-inflammatory activity and a minimal effect on hypothalamic-pituitary-adrenal function. Among a group of topically active corticosteroids, compared in a controlled study in the domestic pig, clobetasone butyrate is shown to cause less epidermal thinning than any of the others except only 1% hydrocortisone. This evidence of a lesser atrophogenic effect may indicate further dissociation of unwanted from wanted properties in clobetasone butyrate.

Administration, Topical↗
PubMed1976

The membrane potential of rat diaphragm muscle fibres and the effect of denervation.

1. Resting membrane potentials of rat diaphragm muscles were measured in vitro after previous denervation for 0-10 days. In some experiments denervated muscles were incubated in vitro for 3 hr while in others they were cultured for 15-24 hr to allow adequate exposure to drugs before recording. 2. It was found that resting membrane potentials, within 2-5 mm of the site of nerve section were significantly lower, within 3 hr, than resting membrane potentials measured more than 9 mm away from site of nerve section. This difference could be reduced or abolished by bathing preparations in solutions containing adrenaline (10 muM), noradrenaline (10 muM) or isoprenaline (10 muM) or dibutyryl cyclic AMP (10 muM-0-25 mM in the presence of 2 mM theophylline). Cyclic AMP (0-5 mM) was ineffective. 3. Application of solutions containing dibutyryl cyclic AMP for 3 hr also raised the resting membrane potential of muscles denervated 4-5 days previously. Culture studies showed that this effect was sustained when the time of incubation was 24 hr. 4. Incubating freshly denervated preparations with cycloheximide (22 mug/ml.) or actinomycin D (1 mug/ml.) did not prevent the development of the early (3 hr) fall in resting membrane potential despite a concomitant inhibition of RNA or protein synthesis. Culturing freshly denervated muscles in solutions containing cycloheximide (10 or 25 mug/ml.) which blocked 93% of protein synthesis, did not prevent the expected drop in resting membrane potential after 15 or 24 hr. 5. It was found that exposure to ouabain (1 or 5 mM) produced a rapid (15 min) fall in resting membrane potential in innervated and denervated preparations treated with dibutyryl cyclic AMP but not denervated preparations. After 5 days denervation cyclic AMP levels in muscle were increased by about 40%. 6. It is suggested that upon denervation an electrogenic action of a NA+-pump is blocked and that dibutyryl cyclic AMP and catecholamines are capable of stimulating this pump.

Animals↗
PubMed1975

The mechanism of action of vinblastine. Binding of [acetyl-3H]vinblastine to embryonic chick brain tubulin and tubulin from sea urchin sperm tail outer doublet microtubules.

Tritium-labeled viblastine, specific activity 107 Ci/mol, was prepared by acetylation of desacetylvinblastine with [3H]acetic anhydride, and has been employed in a study of vinblastine binding to tubulin. There are two high affinity vinblastine-binding sites per mole of embryonic chick brain tubulin (KA = 3-5 X 10(5) l./mol). Binding to these sites was rapid, and relatively independent of temperature between 37 and 0degreeC. Vincristin sulfate and desacetylvinblastine sulfate, two other active vinca alkaloid derivatives, competitively inhibited the binding of vinblastine. The inhibition constant for vincristine was 1.7 X 10(-5) M; and for desacetylvinblastine, 2 X 10(-5) M. The vinblastine binding activity of tubulin decayed upon aging, but this property was not studied in detail. Vinblastine did not depolymerize stable sea urchin sperm tail outer doublet microtubules, nor did it bind to these microtubules. However, tubulin solubilized from the B subfiber of the outer doublet microtubules possessed the two high affinity binding sites (KA = 1-3 X 105 l./mol). These data suggest that vinblastine destroys microtubules in cells primarily by inhibition of microtubule polymerization, and does not directly destroy preformed microtubules.

Animals↗