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Biomedical subjects

L Wilson

Publications and source records attributed to L Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1997

Daily changes in plasma and amniotic fluid prolactin during the last third of pregnancy in the baboon.

Alterations in plasma and amniotic fluid prolactin (PRL) levels have not been previously described in the pregnant baboon. In addition, PRL increases dramatically in response to estrogens and thus might be a good marker for expression of estrogen's biologic action. Therefore, the purpose of this study was to characterize the changes in plasma and amniotic fluid PRL with advancing gestational age and assess whether there was a correlation between plasma estradiol and PRL levels. A tethered pregnant baboon model was utilized for these studies. Blood was collected from five animals every day at 0900-1000 h (AM value) and 1800 h (PM value) from 125 to 135 days of pregnancy until delivery. Amniotic fluid was collected every day in the morning. Samples were analyzed by RIA for PRL, estradiol, and progesterone. PRL did not change with advancing gestational age. However, PRL showed a significant diurnal variation, with the PM values significantly higher (p < 0.05) than the AM values. In contrast to findings for PRL, AM values for estradiol and progesterone were on average higher that PM values (p < 0.05). A significant correlation was observed between the log10 estradiol (AM+PM) and log10 PRL (AM) from the following day (r = 0.52; p < 0.05). Finally, amniotic fluid PRL was present in high concentrations (200-400 ng/ml) but did not vary with gestational age. In conclusion, PRL, estradiol, and progesterone show distinct diurnal variations during the last one-third of pregnancy in the baboon. In addition, plasma PRL is positively correlated with estradiol.

Amniotic Fluid↗
PubMed1997

Agenesis of the corpus callosum in Turner syndrome with ring X.

An 8-year-old girl with Turner syndrome and 45,X/46,X,r(X) mosaicism was found to have agenesis of the corpus callosum and various other characteristics including 'kabuki makeup' facial features and mild learning disability. Only two other cases of Turner syndrome associated with agenesis of the corpus callosum have been reported, both in patients with a 45,X karyotype. In both of those patients the constellation of signs differed from those of the present patient in a number of ways. It remains to be confirmed whether there is a higher incidence of CNS malformation in girls who have Turner syndrome with a ring X than has been reported for girls with Turner syndrome in general.

Agenesis of Corpus Callosum↗
PubMed1997

Inhibition of mitosis and microtubule function through direct tubulin binding by a novel antiproliferative naphthopyran LY290181.

The mechanism of action of a novel antiproliferative compound LY290181 [2-amino-4-(3-pyridyl)-4H-naphtho(1,2-b)pyran-3-carbonitrile] was characterized. LY290181 is a potent inhibitor of cell proliferation, producing 50% inhibition of vascular smooth muscle, endothelial, Chinese hamster ovary, HeLa, and human erythroleukemia cells at concentrations of 8-40 nM. Cell cycle analysis showed that LY290181 caused accumulation of smooth muscle cells at the G2/M phase and induced mitotic arrest in Chinese hamster ovary cells and HeLa cells. At low concentrations (3-30 nM), LY290181 blocked transition of cells from metaphase to anaphase and disrupted mitotic spindle organization. At high concentrations (>/=100 nM), LY290181 produced a concentration-dependent loss of cytoplasmic and spindle microtubules. LY290181 inhibited the polymerization of purified bovine brain microtubule protein into microtubules, and it depolymerized preformed microtubules. Using tubulin-1-anilino-8-naphthalene sulfonate complex fluorescence, we have shown that LY290181 directly interacted with tubulin in a unique manner. These studies show that LY290181 induces cell growth arrest in prometaphase/metaphase, and tubulin appears to be its molecular target.

Animals↗
PubMed1997

Moderate drinking.

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Alcohol Drinking↗
PubMed1997

The quality management jigsaw.

The current scene in Australia, as in a large part of the developed world, in relation to the subject of quality management in health care, is characterized by confusion, blurred objectives, patchy involvement and very high opportunity costs. Much of the confusion is caused by a failure to understand or use correctly the bewildering array of terminology that characterizes what is becoming a new discipline in its own right. A series of simple definitions permits the reader to understand what the author is attempting to say. The paper also provides a conceptual framework for the implementation of quality management in hospitals: a jigsaw of activity which hospitals have some difficulty conceptualizing and without which hospitals will never be able to respond seriously to the challenge of assuring quality.

Australia↗
PubMed1997

A special trip.

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Charities↗
PubMed1996

Differential effects of vinblastine on polymerization and dynamics at opposite microtubule ends.

We have characterized the effects of vinblastine on the growing and shortening dynamics at opposite ends of individual bovine brain microtubules at steady state in vitro by video microscopy. Vinblastine exerted strikingly different effects on the dynamics and polymer mass at the plus and minus ends of microtubules. At concentrations between 0.1 and 0.4 microM, the drug strongly depolymerized microtubules at minus ends, whereas it did not significantly depolymerize microtubules at plus ends. Vinblastine stabilized plus ends by suppressing the rate and extent of growth and shortening, decreasing the catastrophe frequency, and increasing the rescue frequency. In contrast, vinblastine destabilized minus ends by increasing the catastrophe frequency and decreasing the rescue frequency, whereas it had no effect on the rate or extent of growth or shortening. Thus, vinblastine moderately increased the overall dynamicity at minus ends while strongly suppressing dynamicity at plus ends. Both the kinetic destabilization of microtubules at minus ends and the stabilization at plus ends may contribute to the altered function of mitotic spindle microtubules of cells blocked in mitosis by low concentrations of vinblastine.

Animals↗
PubMed1996

Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains.

Src homology 3 (SH3) domains have been shown to mediate selected interactions between signaling molecules and are essential for the activation of a number of receptor-driven pathways. The Wiskott-Aldrich syndrome protein was identified as a protein that associated selectively with the SH3 domains derived from c-Src, p85alpha, phospholipase Cgamma1, and c-Fgr. Significantly reduced association was detected to the N-terminal SH3 domain and the tandem SH3 domains of p47(phox), and no binding was detected to the SH3 domain of n-Src, the C-terminal SH3 domain of p47(phox), or either of the SH3 domains of p67(phox). Three peptides corresponding to potential Wiskott-Aldrich syndrome protein SH3 domain binding motifs were found to inhibit its association with c-Src, Fgr, and phospholipase Cgamma1 SH3 domains, but not the p85alpha SH3 domain. These peptides have the sequences MRRQEPLPPPPPPSRG, TGRSGPLPPPPPGA, and KGRSGPLPPVPLGI and show homology with other SH3 domain binding motifs. It is possible that the intracellular association of Wiskott-Aldrich syndrome protein with other signaling proteins is mediated by its SH3 domain-binding regions, and this may play a role in its putative function as a regulatory molecule in immune cells.

Amino Acid Sequence↗
PubMed1996

Characterization of Grb2-binding proteins in human platelets activated by Fc gamma RIIA cross-linking.

Glutathione-S-transferase (GST)-Grb2 fusion proteins have been used to identify the potential role of Grb2-binding proteins in platelet activation by the platelet low-affinity IgG receptor, Fc gamma RIIA. Two tyrosine phosphoproteins of 38 and 63 kD bind to the SH2 domain of Grb2 following Fc gamma RIIA stimulation of platelets. Both are located in the particulate fraction following platelet activation and are also able to bind to a GST-construct containing the SH2 and SH3 domains of phospholipase C gamma 1. p38 also forms a complex with the tyrosine kinase csk in stimulated cells and is a substrate for the kinase. The SH3 domains of Grb2 form a stable complex with SOS1 and two proteins of 75 kD and 120 kD, which undergo tyrosine phosphorylation in Fc gamma RIIA stimulated cells. The 75-kD protein is recognized by antibodies to SLP-76, which has recently been isolated from T cells and sequenced. Tyrosine phosphorylation of p38 and p63 is also observed in platelets stimulated by the tyrosine kinase-linked receptor agonist collagen and by the G protein-coupled receptor agonist thrombin, although phosphorylation of SLP-76 is only observed in collagen-stimulated platelets. p38 and p63 may provide a docking site for Grb2, thereby linking Grb2 SH3-binding proteins SOS1, SLP-76, and p120 to downstream signalling events.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Prediction of calf mortality by use of tests for passive transfer of colostral immunoglobulin.

OBJECTIVE: To examine the ability of several commonly used tests for evaluation of passive transfer of immunoglobulin to predict mortality in dairy replacement heifers. DESIGN: Prospective observational study. ANIMALS: 246 dairy replacement heifers between 1 and 8 days of age. PROCEDURE: Using serum samples obtained from each calf, total serum protein concentration and results of zinc sulfate turbidity, sodium sulfite turbidity, radial immunodiffusion, and glutaraldehyde coagulation were determined. Calves were monitored for 100 days, and relative risks for death were calculated. Logistic regression models predicting death also were developed. RESULTS: None of the logistic regression models detected a significant association between test results and mortality. The greatest relative risks of mortality were observed in calves with serum protein concentrations < 4.5 g/dl, serum IgG1 concentrations < 500 mg/dl, and sodium sulfite test scores < 1+. CLINICAL IMPLICATIONS: Calves with lower passive transfer values had increased risk of death; however, failure of passive transfer is not an infallible predictor of mortality.

Animals↗
PubMed1996

Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death.

Paclitaxel at low concentrations (10 nM for 20 h) induces approximately 90% mitotic block at the metaphase/anaphase transition in HeLa cells, apparently by suppressing dynamics of spindle microtubules (M. A. Jordan et al., Proc. Natl. Acad. Sci. USA, 90: 9552-9556, 1993). It is not known, however, whether inhibition of mitosis by such low paclitaxel concentrations results in cell death. In the present work, we found that after removal of paclitaxel (10 nM-1 microM), blocked cells did not resume proliferation. Instead, cells exited mitosis abnormally within 24 h. They did not progress through anaphase or cytokinesis but entered an interphase-like state (chromatin decondensed, and an interphase-like microtubule array and nuclear membranes reformed). Many cells (> or = 55%) contained multiple nuclei. Additional DNA synthesis and polyploidy did not occur. DNA degradation into nucleosome-sized fragments characteristic of apoptosis began during drug incubation and increased after drug removal. Cells died within 48-72 h. Incubation with paclitaxel (10 nM for 20 h) resulted in high intracellular drug accumulation (8.3 microM) and little efflux after paclitaxel removal; intracellular retention of paclitaxel may contribute to its efficacy. The results support the hypothesis that the most potent chemotherapeutic mechanism of paclitaxel is kinetic stabilization of spindle microtubule dynamics.

Anaphase↗
PubMed1996

Modulation of CENP-E organization at kinetochores by spindle microtubule attachment.

CENP-E is a protein of the kinesin superfamily that appears as small paired globules at kinetochores of chromosomes in mammalian cells during prometaphase and metaphase of mitosis [Yen et al., 1992: Nature 359:536-539]. In the present study we found that a significant number of chromosomes during early prometaphase in HeLa cells (approximately 30%) were stained with a CENP-E antibody in the form of large C-shaped "collars" that partially encircled the chromosomes. The C-shaped CENP-E collars were present only transiently and were completely replaced by small paired globular forms prior to metaphase. Most chromosomes had persistent CENP-E collars in cells blocked at mitosis with a vinblastine concentration sufficient to prevent all microtubule formation. Attachment of newly formed microtubules to the kinetochores after removal of vinblastine resulted in loss of the collars and replacement with small paired globules. Similarly, a higher proportion of chromosomes isolated from vinblastine-treated cells contained CENP-E collars (73%), and the "capture" (i.e., attachment) of microtubules by the chromosomes resulted in conversion of the collars into small paired globules in vitro. Thus, the CENP-E collars form prior to microtubule attachment and disappear after attachment of the chromosomes to the spindle. The CENP-E collars may facilitate capture of microtubules by chromosomes during prometaphase.

Antibodies↗
PubMed1996

Fasciola hepatica: irradiation-induced alterations in carbohydrate and cathepsin-B protease expression in newly excysted juvenile liver fluke.

Irradiation has been successful in the attenuation of infective stage parasites for use as vaccines against a number of parasites including Fasciola spp. The mechanisms of action of irradiation-attenuated vaccines, however, are not clearly understood. In this study, we examined the effect of 3, 10, and 40 krad of gamma-irradiation on the expression of carbohydrates and cathepsin-B by newly excysted juvenile Fasciola hepatica (NEJ). Following irradiation of metacercariae, the expression of concanavalin A (ConA)-specific sugars was decreased on the surface of NEJ and the expression of wheat germ agglutinin (WGA)-specific sugars was increased in the gut and reduced on the surface of NEJ. Cathepsin proteases are a major component of liver fluke excretory/secretory material (ES) and can cleave host immunoglobulin (Ig). Cathepsin-B protease was localized in nonirradiated NEJ to the gut lumen and to secretory granules within the gut epithelia. Irradiation of fluke with 3, 10, and 40 krad of gamma-rays significantly reduced the tissue expression of cathepsin-B at 8 hr postirradiation in an apparently dose-dependent manner. After a further 24 hr culture tissue expression of cathepsin-B was significantly reduced in 10- and 40-krad-irradiated NEJ. Protease activity of ES samples collected over a 24-hr period from irradiated and nonirradiated NEJ cultured in vitro were tested using a rabbit Ig cleavage assay. The proteolytic activity of ES from 10- and 40-krad-irradiated NEJ was reduced during the initial 6 hr in culture and between 12 and 24 hr when compared to ES from nonirradiated controls. Biosynthetic labeling experiments using [35S]methionine and [35S]cysteine indicated that ES material was actively synthesised during 48 hr in vitro culture. Therefore, from this study, we conclude that gamma-irradiation of NEJ alters expression of cathepsin-B protease and WGA- and ConA-specific sugars which may be detrimental to parasite invasion and contribute to the protective immune responses generated in the host by irradiation-attenuated metacercariae of Fasciola spp.

Animals↗