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Biomedical subjects

L Wilson

Publications and source records attributed to L Wilson.

At least 325 records · Page 18Linked to original sources
PubMed1985

Mechanism of microtubule assembly. Changes in polymer structure and organization during assembly of sea urchin egg tubulin.

Assembly of tubulin, purified from eggs of the sea urchin Stronglyocentrotus purpuratus, was examined at physiological (18 degrees C) and nonphysiological (37 degrees C) temperatures. Critical concentrations for assembly were 0.71 mg/ml at 18 degrees C and 0.21 mg/ml at 37 degrees C. At tubulin concentrations above 1.2 mg/ml at 18 degrees C and 0.5 mg/ml at 37 degrees C, a concentration-dependent "overshoot" in turbidity and in small-angle light scattering was observed; turbidity and scattering increased rapidly to a peak, then decreased asymptotically toward a steady-state value. Quantitative sedimentation analysis revealed that the mass of assembled polymer reached and maintained a constant level during overshoot of turbidity. Changes in the wavelength dependence of turbidity were consistent with the initial formation of sheets of tubulin, followed by conversion of the sheets to microtubules, both at 18 and 37 degrees C. Examination by negative-stain electron microscopy showed that sheetlike structures predominated during the early stages of overshoot assembly, while complete microtubules were present at steady state. Furthermore, measurements of average polymer length revealed that the overshoots in turbidity and in light scattering are unlikely to be caused by polymer length redistribution. Qualitative observations of solution birefringence suggested that the polymer became progressively more aligned during assembly. These results suggest that the turbidity/light-scattering overshoots reflect changes in the form or in the organization of the assembling polymer, or both.

Animals↗
PubMed1985

A latent activity dynein-like cytoplasmic magnesium adenosine triphosphatase.

A MgATPase has been isolated and characterized from unfertilized sea urchin eggs which is very similar, but not identical, to latent activity axonemal dynein. The cytoplasmic MgATPase activity sediments at 20 S, slightly slower than 21 S latent activity flagellar dynein. Activity is stimulated by nonionic detergent and is inhibited by sodium orthovanadate but is not as sensitive to vanadate as is 21 S flagellar dynein. The egg 20 S MgATPase is composed, at least in part, of three high molecular weight polypeptides. In addition, two intermediate-sized polypeptides appear to co-sediment with the 20 S MgATPase activity. A novel microtubule-affinity assay reveals that high molecular weight polypeptides 1 and 2 of the egg 20 S MgATPase can bind to reassembled microtubules and can be released from the microtubules with MgATP2-. Further, the apparent specific activity of the egg MgATPase is enriched 15-fold by a single microtubule binding step. The results suggest that the cytoplasmic 20 S MgATPase is a dynein-like microtubule translocator which resides in the unfertilized egg awaiting future incorporation onto microtubules in order to perform work. The egg 20 S enzyme might function in cytoplasmic microtubule-mediated movement or it might be a precursor of embryonic ciliary dynein.

Adenosine Triphosphatases↗
PubMed1985

Effects of alprazolam and diazepam on the daytime sleepiness of non-anxious subjects.

Eighteen non-anxious volunteers underwent sleep recordings and daytime tests of sleepiness, performance, and mood while receiving, either alprazolam 0.5 mg b.i.d. or diazepam 5 mg b.i.d. for 7 consecutive days. Recordings and tests were done before treatment and on the 1st and 7th days of treatment. Nocturnal sleep changes were similar for both groups; there were no statistically significant changes in mood. However, levels of daytime sleepiness differed. Alprazolam subjects showed more daytime sedation than diazepam subjects on treatment day 1, but showed a significant decrease in Day 1-7 daytime sedation. Although diazepam subjects were less sedated at the onset, they showed no tolerance to this effect; thus by treatment day 7, the two groups did not differ in levels of daytime sleepiness. Results suggested that tolerance to alprazolam's sedative effects (which develops during the 1st week of treatment) may be separable from tolerance to its antianxiety effects (which develops after at least 4 weeks). As daytime sedation is common and potentially dangerous with most anxiolytics, selective tolerance to this side effect is highly desirable.

Adult↗
PubMed1985

Hand and hemispace effects in tactual tasks in children.

In Experiment I, 3-and 5-yr-old dextrals matched textures better by either hand when it operated in left hemispace. Girls and 3-yr olds were the more disadvantaged by non-alignment of hand and hemispace. In Experiment II, 8-yr-olds reproduced finger sequences; dextrals demonstrated a right-hand and sinistrals a right-hemispace superiority. In Experiment III, both a left-hand and a left-hemispace superiority appeared when 5-yr-old dextrals reproduced a static configuration of finger spacing. Asymmetries were generally stronger for the side of presentation than for the side of response. Our findings are consistent with the operation of two semi-independent systems, one involving hand-hemisphere connections, and the other mapping of extracorporeal space by the hemispheres.

Age Factors↗
PubMed1985

Bisecting rods and lines: effects of horizontal and vertical posture on left-side underestimation by normal subjects.

In Experiment I normal subjects performed the classical clinical line-bisection task, and demonstrated a left-side underestimation. In Experiment II subjects maintained fixation upon a central position and adjusted a rod passing through this fixation point so that both extremities were judged equal. The left-side underestimation was very much greater under these conditions, but was considerably reduced when retinal and gravitational coordinates were dissociated by making the subjects lie horizontally on one or other side. Subjects then demonstrated greater left-side and top-half underestimation when lying on the left than on the right side. Gravitational coordinates and the apparent locus of events in extrapersonal space are determinants of perceptual asymmetries at least as important as anatomical connectivities.

Adult↗
PubMed1985

Mirror reading in right and left handers: are sinistrals really superior?

While left handers, where they do in fact appear to differ from right handers in cognitive function, have generally been found to be slightly inferior on verbal tasks, there are some reports of a sinistral superiority for nonverbal or spatial abilities. Tankle and Heilman (Brain and Language, 1982, 17, 124-132) report a sinistral superiority in (obligatory) reading of left-right mirror-reversed text. However, in an investigation which included various other forms of geometrical transformation of the written word, we find that strong familial sinistrals are either not different from or even slightly inferior to dextrals in reading most transformations, including left-right mirror reversals.

Adolescent↗
PubMed1985

In vitro production of IgE in humans: kinetic studies and analysis of serum enhancing and inhibitory factors.

By using a sensitive and reliable method for the measurement of IgE produced in vitro by peripheral blood lymphomonocytes, the following observations may be made. Serum obtained from atopic donors shows a significant capacity to enhance the in vitro synthesis of IgE of PBL from atopic as well as of non-atopic donors. On the other hand, serum obtained from non-atopic donors demonstrates a clear-cut inhibitory effect on IgE synthesis of cells from both atopic and non-atopic individuals. The kinetics of the IgE production was studied. As early as 30 min after initiation of culture, PBL of atopic individuals showed the capacity to synthesize large amounts of IgE. The IgE synthesis continued, with variations from case to case, for 7 days. This capacity of the cells is completely inhibited following incubation of the PBL for a short period of time with a protein synthesis inhibitor, cycloheximide. This in vitro procedure represents a valuable tool for the study and identification of the enhancing and suppressor factors of IgE synthesis present in the serum.

Cells, Cultured↗
PubMed1985

Cytotoxicity of etretinate and vindesine.

The effects of an aromatic retinoid, etretinate and a vinca alkaloid, vindesine were investigated by culture of malignant melanoma cells in vitro with these two agents; either separately or in combination. Etretinate inhibited growth of a murine melanoma but only minimal effects were recorded with two human melanomas. Vindesine however, was inhibitory for all of the cell lines and this effect was enhanced in the presence of the retinoid. Entry of 3H labelled vindesine or etretinate into drug free cells was followed in the absence or presence of unlabelled drug. It was found that etretinate enhanced cellular uptake of vindesine in two of the cell lines and this may be responsible for the enhanced toxicity of vindesine in the presence of etretinate. The human melanoma which did not exhibit retinoid stimulated vindesine uptake, appeared to be intrinsically sensitive to the vinca alkaloid. No effect on cellular retinoid uptake by vindesine was recorded in any of the melanomas. The results indicate that the intracellular concentrations combined with the intrinsic sensitivities of each cell line to etretinate and vindesine determines the toxic response.

Animals↗
PubMed1985

Altered divalent ion metabolism in early renal failure: role of 1,25(OH)2D.

The present study evaluates the role of 1,25(OH)2D in the pathogenesis of abnormal mineral metabolism in patients with early renal failure (ERF). This was accomplished by examining the calcemic response to PTH and the handling of an oral phosphate load both before and after 6 weeks of therapy with 1,25(OH)2D. Twelve patients with ERF and six normal volunteers were studied. Patients with ERF as compared with normal subjects have low serum phosphate, low urinary calcium, low serum 1,25(OH)2D, and high plasma PTH and urinary cyclic AMP (cAMP). With EDTA infusion, an impaired calcemic response to PTH is observed in patients with ERF. The phosphate load test shows that these patients have an increased ability to excrete phosphate. After 1,25(OH)2D therapy a significant increase in serum phosphate, urinary calcium, and a decrease in urinary cAMP is observed only in ERF patients. In addition, the impaired calcemic response to PTH improves significantly, the renal handling of phosphate becomes normal, and the low baseline level of 1,25(OH)2D increases to normal. A significant correlation between levels of 1,25(OH)2D and creatinine clearance is observed in both patients and normals. In summary, the present data suggest that a mild deficiency of 1,25(OH)2D is present in ERF patients. The pathophysiological consequence of such a deficiency in patients with ERF may be important.

Aged↗
PubMed1985

Microtubule-associated proteins (MAPs): a monoclonal antibody to MAP 1 decorates microtubules in vitro but stains stress fibers and not microtubules in vivo.

A monoclonal antibody (mAb 7-1.1) was produced against a bovine brain microtubule-associated protein (MAP) preparation that had been separated from tubulin after initial purification by cycles of microtubule assembly and disassembly in vitro. The antibody reacted specifically with two high molecular weight polypeptides of the MAP 1 class, designated MAP 1.1 and MAP 1.2, and also with the surfaces of MAP 1-containing microtubules that had been assembled in vitro. Double immunofluorescence microscopy using mAb 7-1.1 and a well-characterized rabbit anti-tubulin antibody revealed that mAb 7-1.1 stained stress fibers in fixed and permeabilized cultured mammalian cells rather than microtubules. The antibody also stained cell nuclei in a punctate fashion. mAb 7-1.1 is one of a number of monoclonal antibodies that react with presumptive MAP 1 polypeptides. Some of the MAP 1 antibodies have been found to bind specifically to microtubules in fixed and permeabilized cells, while others have been reported to react with nonmicrotubule structures. Our results, together with the results of other investigations, indicate that "MAP 1" may be a family of several high molecular weight polypeptides that adventitiously behave as MAPs by the criterion of in vitro coassembly with tubulin through cycles of polymerization and depolymerization but whose cellular distributions, and perhaps functions, are varied.

Animals↗
PubMed1985

Contributions of the fetoplacental unit to augmented uterine prostaglandin levels periparturition in the rat.

The purpose of the present study was to determine if the acute alterations in uterine prostanoid levels at the end of pregnancy are influenced locally by the fetoplacental unit (FPU). Unilaterally pregnant rats were killed on Days 20 and 21 of pregnancy (delivery = Day 21.5) and uterine tissue was removed and analyzed for prostaglandin (PG) E, PGF, thromboxane B2 (TxB2), and 6-keto-PGF1 alpha (6KF) by radioimmunoassay. A significant (P less than 0.05) main effect of Day (20 vs. 21) and Uterine Horn (nonpregnant vs. pregnant), but no interaction for PGE, PGF, and TxB2 was detected. In contrast, a significant interaction (P less than 0.05) of Day with Uterine Horn was found for uterine 6KF levels. Examination of the simple main effects indicated an enhanced level (P less than 0.05) of 6KF in uterine tissue adjacent compared to opposite the FPU at Days 20 and 21. However, uterine 6KF levels in the nonpregnant, but not pregnant, uterine horn were greater at Day 21 compared to Day 20 of pregnancy. The lack of a significant interaction of the main effects for PGE, PGF, and TxB2 suggests that the increased levels of these PGs between Days 20 and 21 were proportional in the nonpregnant and pregnant uterine horn. Therefore, the factor(s) responsible for the augmentation in these uterine PG levels between Days 20 and 21 is(are) most likely arriving via systemic circulation. In addition, the proportionate increases in uterine PGs imply that the FPU is not conferring upon adjacent uterine tissue any unique ability to respond to systemic factors.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1985

The radiosensitivity of human neuroblastoma cells estimated from regrowth curves of multicellular tumour spheroids.

Multicellular tumour spheroids may provide a suitable in-vitro model for micrometastases in vivo. In this paper, the results are reported of experimental studies on the radiation response of two lines of spheroids derived from human neuroblastoma. Spheroids of approximately 200-250 microM mean diameter were exposed to graded doses of X rays (50-350 cGy) and, following a static or regression phase, regrew at rates which approximated those of unirradiated spheroids. Clonogenic surviving fraction was estimated, at each dose level, by extrapolation of the regrowth curve to zero dose. It is proposed that this procedure is more suitable for regrowth curves of spheroids than in-vivo tumours, because of the absence in vitro of complicating factors which occur only in vivo. By this means, survival curves were deduced and were found (for both cell lines) to be almost exponential in form, with little indication of capacity for accumulation of sublethal damage (multitarget parameters: DQ values: 17 and 25 cGy; Do values: 104 and 81 cGy respectively). These results contribute to the evidence for high radiosensitivity of neuroblastoma cells in vitro and provide a rationale for the use of hyperfractionation in the clinical treatment of neuroblastoma by radiotherapy.

Cell Division↗
PubMed1985

The effect of valproate on blood metabolite concentrations in spontaneously diabetic, ketoacidotic, BB/E Wistar rats.

Valproate is an effective anticonvulsant which is rarely associated with hepatotoxicity. It has profound effects on the intermediary metabolism of isolated rat hepatocytes. In this paper the effect of valproate on blood metabolite concentrations in spontaneously diabetic BB/E rats has been studied. Valproate causes a marked fall in blood ketone body concentrations and a smaller fall in blood glucose concentrations following either oral or intraperitoneal administration. Valproate may have a role in the treatment of patients with "brittle" diabetes.

Animals↗
PubMed1985

Comparison of the effects of vinblastine, vincristine, vindesine, and vinepidine on microtubule dynamics and cell proliferation in vitro.

Vinepidine, a new derivative of vincristine, and three clinically used Catharanthus derivatives, vinblastine, vincristine, and vindesine, were examined for their abilities to inhibit net tubulin addition at the assembly ends of bovine brain microtubules at steady state. Although all four derivatives were generally similar in potency, their relative abilities to inhibit tubulin addition were distinguishable. Vinepidine and vincristine were the most potent derivatives (Ki, 0.079 +/- 0.018 (SD) microM and 0.085 +/- 0.013 microM, respectively), followed by vindesine (Ki, 0.110 +/- 0.007 microM) and vinblastine (Ki, 0.178 +/- 0.025 microM). In contrast to their relative abilities to inhibit microtubule assembly in vitro, vinblastine and its derivative, vindesine, were generally more potent than vincristine and vinepidine in inhibiting cell proliferation in culture. Vinblastine was nine times more potent than the weakest derivative, vinepidine, in B16 melanoma cells. In L-cells, vinblastine completely inhibited growth at 40 nM, whereas vincristine and vindesine caused about 25% inhibition, and vinepidine was inactive. When B16 melanoma cells were treated with drug before being injected into mice, retardation of tumor growth was best achieved with vindesine, one of the weaker of the four derivatives in vitro. The results demonstrate that chemical differences among the Catharanthus derivatives, which affect to small extents the abilities of the derivatives to inhibit microtubule assembly in vitro, result in significant differences in the order and the magnitude of the abilities of the drugs to inhibit cell growth.

Animals↗
PubMed1984

Human T-cell leukemia virus (HTLV-I) antibodies in Africa.

Antibodies specific for human T-cell leukemia-lymphoma virus type I (HTLV-I) were demonstrated in serum samples from various groups of people in South Africa, Uganda, Ghana, Nigeria, Tunisia, and Egypt. The samples had been collected for other purposes and were presumably selected without bias toward clinical conditions associated with HTLV infections. Regional differences in antibody positivity were observed, indicating widely distributed loci of occurrence of HTLV on the African continent in people of both black and white ancestry. Two patients with high titers of antibody to HTLV-I had some signs of adult T-cell leukemia-lymphoma. In several groups a high frequency of false positive serum reactions was indicated when specific confirmation steps were included in the assay. Further characterization of these sera revealed highly elevated immunoglobulin levels, possibly due to polyclonal activation of immunoglobulin synthesis in these subjects. The possibility that related cross-reactive human retroviruses coexist in the same groups was not eliminated.

Adult↗