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Biomedical subjects

L Wilson

Publications and source records attributed to L Wilson.

At least 271 records · Page 15Linked to original sources

Topographical EEG differences between schizophrenic patients and controls during neuropsychological functional activation.

Ten DSM III schizophrenic patients belonging to an Active syndrome were compared with 10 age- and sex-matched normal controls on neuropsychological tests with concurrent monitoring of topographical EEG using a brain imager with a 28-electrode array. In line with predictions, abnormalities in patients were found in tests involving right hemispheric functions. Deficits were found in recognition memory for faces as distinct from a verbal recognition memory task. Right temporo-parietal involvement in the faces task was confirmed by an absence of beta II amplitude reduction in patients compared with controls in the right temporo-parietal region. A similar anomaly occurred in patients in a left- but not right-hand finger-thumb apposition test in left anterior and right posterior regions, and also in a passive visual fixation task where it was located bilaterally in the occipito-parietal region. Functional activation with neuropsychological tests holds promise as one approach to the validation of topographical mapping of brain electrical activity.

Adult↗

A new tocolytic agent: development of an oxytocin antagonist for inhibiting uterine contractions.

A potent oxytocin antagonist has been developed and tested on both the rat and human uterus. In the rat the oxytocin antagonist: (1) inhibited in vitro and in vivo uterine contractions in the nonpregnant animal in response to exogenous oxytocin, (2) inhibited milk letdown, and (3) disrupted the progress of labor. In addition, the oxytocin antagonist inhibited the in vitro contractile response to exogenous oxytocin of human myometrial tissue obtained by cesarean section at term. The results of these studies suggest that the oxytocin antagonist can be used to study the role of oxytocin in labor and has the potential of inhibiting preterm labor in humans.

Animals↗

Spatial and temporal colocalization of the Golgi apparatus and microtubules rich in detyrosinated tubulin.

The integrity and intracellular distribution of the Golgi apparatus appear to depend upon microtubules. We have found that the microtubules rich in detyrosinated tubulin are located preferentially in the vicinity of the Golgi. Cells were double-stained with antibodies specific for either tyrosinated or detyrosinated tubulin and an antibody to prolactin or wheat germ agglutinin (Golgi markers). Microtubules rich in detyrosinated tubulin showed a close codistribution with the Golgi in three different cultured cell lines GH3, BS-C-1, and AtT20. Disruption of microtubules with nocodazole in GH3 cells resulted in fragmentation and dispersal of the Golgi apparatus as reported previously. During recovery of the microtubules and the Golgi complex after removal of the nocodazole, there was a spatial and temporal colocalization of the Golgi apparatus and microtubules rich in detyrosinated tubulin. Our results suggest that a functional relationship may exist between the structure and organization of the Golgi complex and the detyrosination of alpha-tubulin in microtubules.

Animals↗

Lactated Ringer's solution versus 3% albumin for resuscitation of a lethal intestinal ischemic shock in rats.

Previously, we determined that a colloid concentration of about 3% was optimal for resuscitation of lethal ischemic intestinal shock model in rats. Maximal volumes of lactated Ringer's solution (RL) alone only expanded plasma volume (PV) to 80% of preshock level, while increasing volumes of 3% albumin (ALB) in RL linearly expanded PV up to twice the preshock level. This study compares the effect of RL and ALB on survival and PV in 175 rats. The solutions were given in volumes to induce suboptimal PV expansion, requiring 10 and 44 ml/100 g body weight (bwt) of ALB and RL, respectively. ALB (20 ml/100 g bwt) was then given to induce a PV above the preshock level. Shock was induced by exteriorizing the small intestine and occluding the superior mesenteric vessels for 75 min. PV was estimated using Hct. Therefore, infusions were given continuously for 6 h in volumes that maintained a stable Hct. Untreated shocked animals developed hemoconcentration (Hct 58%) corresponding to a PV of 56% of preshock level, with 2% (1/53) of the animals surviving 24 h. The maximum effect of RL (44 ml/100 g bwt) was to expand PV to 80% of preshock level, with a 32% 24-h survival rate. Only 23% as much ALB (10 ml/100 g bwt) was needed to induce similar blood volume expansion with 24-h survival rate of 46%. When the larger volume of ALB (20 ml/100 g bwt) was used, PV expanded to 115% of preshock level, and 24-h survival to 76%, greater than that achieved with either the smaller volume of ALB or RL alone (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Idiopathic dilated cardiomyopathy--an evidence of abnormal lipid accumulation accumulation in myocardium.

A case of idiopathic dilated cardiomyopathy was studied histologically and by quantitative determination of tissue lipid concentration in order to document increased lipid accumulation. Four chambers of the heart were dilated with left ventricular dominance. Microscopically, there was a mixture of primarily fragmented myocytes with sarcoplasmic degeneration and minorly hypertrophic myocytes. There were numerous areas of moth-eaten appearance of myocardium in all of the sections, which corresponded to fatty degeneration, composed of numerous small lipid droplets between decreasing contractile elements. Ultrastructurally, there were widened Z-bands in degenerated myocardium, corresponding to light microscopically enlarged contraction bands. The extent of moth-eaten appearance was more extensive in the left than in the right ventricle, which was also verified by a three-fold increase of triglyceride concentration in the left ventricle compared with age-matched control hearts. The moth-eaten appearance was also observed in the auricles and atria with less immunohistochemical staining intensity for atrial natriuretic polypeptide, demonstrating that this fatty change involves all parts of the myocardium.

Adult↗

Preparation and characterization of mitotic cytoskeletons from embryos of the sea urchin Strongylocentrotus franciscanus.

We present here a preparation protocol and molecular characterization of mitotic cytoskeletons isolated from embryos of the spiny red sea urchin, Strongylocentrotus franciscanus. The mitotic cytoskeletons are produced by detergent lysis of S. franciscanus embryos during cell division and consist of a mitotic apparatus enclosed in a thin shell of cortical filaments. Mitotic cytoskeletons produced in this way are stable for a year at liquid nitrogen temperature. S. franciscanus is of interest because it is commercially available in large quantities and each animal provides prodigious amounts of gametes. Furthermore, embryos from this sea urchin will develop synchronously at high densities and are an excellent source of quantities of cytoskeletal proteins appropriate for biochemical studies.

Animals↗

Development of mouse embryos cryopreserved by an ultra-rapid method of freezing.

High concentrations of cryoprotectant combined with sucrose were utilized in an ultra-rapid freezing protocol for mouse preimplantation embryos. Dimethylsulphoxide (DMSO, 1.5 or 3.5 M) or propanediol (PROH, 1.5 or 3.0 M) combined with 0.25 M sucrose were used as freezing solutions. One-, 2- or 8-cell embryos were placed directly into these solutions at room temperature, loaded into straws and plunged into liquid nitrogen within 2-3 min. The straws were rapidly thawed and the embryos expelled into the solution in which they were frozen for 10 min. The cryoprotectants were then removed by single- or multi-step dilution. Survival and development of the embryos in vitro and in vivo were assessed. DMSO (1.5 M) and both concentrations of PROH were totally inadequate as a cryoprotectant in this freezing protocol. A concentration of 3.5 M DMSO gave high survival and development rates when a multi-step dilution procedure was used, but not with a single-step dilution. One-cell embryos gave 71% survival, 35% in-vitro development and 10% in-vivo viability; 2-cell embryos showed 87% survival, 77% in-vitro development and 66% in-vivo viability; and 8-cell embryos showed 97% survival, 87% in-vitro development and 62% in-vivo viability. The results for the 2- and 8-cell stages compared favourably with non-frozen controls, which had 71% in-vivo viability. This method of cryopreservation is therefore fast and viable.

Animals↗

A pituitary POU domain protein, Pit-1, activates both growth hormone and prolactin promoters transcriptionally.

The anterior pituitary gland provides a model for investigating the molecular basis for the appearance of phenotypically distinct cell types within an organ, a central question in development. The rat prolactin and growth hormone genes are expressed selectively in distinct cell types (lactotrophs and somatotrophs, respectively) of the anterior pituitary gland, reflecting differential mechanisms of gene activation or restriction, as a result of the interactions of multiple factors binding to these genes. We find that when the pituitary-specific 33-kD transcription factor Pit-1, expressed normally in both lactotrophs and somatotrophs, is expressed in either the heterologous HeLa cell line or in bacteria, it binds to and activates transcription from both growth hormone and prolactin promoters in vitro at levels even 10-fold lower than those normally present in pituitary cells. This suggests that a single factor, Pit-1, may be capable of activating the expression of two genes that define different anterior pituitary cell phenotypes. Because a putative lactotroph cell line (235-1) that does not express the growth hormone gene, but only the prolactin gene, appears to contain high levels of functional Pit-1, a mechanism selectively preventing growth hormone gene expression may, in part, account for the lactotroph phenotype.

Animals↗

Binding of vinblastine to stabilized microtubules.

Addition of 2-200 microM vinblastine to microtubules at steady state in vitro causes the microtubules to depolymerize, with the formation of protofilament spirals and other aggregated forms of microtubule protein. The presence of such spirals and protein aggregates, which are difficult to separate from microtubules, has complicated attempts to measure the binding of vinblastine to microtubules. We have found that stabilizing bovine brain microtubules in vitro with dimethyl sulfoxide, taxol, or a combination of dimethyl sulfoxide and taxol prevents or greatly retards the formation of protofilamentous spirals, thus permitting us to measure the binding of vinblastine to intact microtubules. Reciprocal plots of binding data indicate the presence of 1.4-1.7 vinblastine binding sites/mol of tubulin in the microtubule, with a Ka of approximately 3-4 x 10(3) M-1. The Ka value obtained is within 1 order of magnitude of the apparent intrinsic binding constant for the binding of vinblastine to tubulin dimers. The results support the idea that depolymerization of microtubules by intermediate and high concentrations of vinblastine occurs by stoichiometric binding of vinblastine to tubulin along the microtubule surface.

Alkaloids↗

Selective inhibition of cytokinesis in sea urchin embryos by low concentrations of stypoldione, a marine natural product that reacts with sulfhydryl groups.

Stypoldione is a marine natural product that inhibits cells division in marine embryos and in mammalian cell cultures. The mechanism responsible for the ability of the compound to inhibit cell division is not known. The compound was found in early studies to inhibit polymerization of tubulin into microtubules in vitro, which lead to the suggestion that inhibition of microtubule polymerization in cells might be responsible for the ability of the compound to inhibit cell division. More recently, stypoldione was found to react covalently with the sulfhydryl groups of a number of proteins including tubulin and with sulfhydryl groups of peptides and small molecules. Thus, stypoldione could potentially react with a large number of cellular targets. In the present study, we have examined the effects of stypoldione on the organization of microtubules and chromatin in cells, in relation to the ability of the compound to inhibit cell division. We used indirect immunofluorescence light microscopy of fixed and stained sea urchin embryos during the first and second divisions after fertilization, with stains specific for tubulin and DNA. We found that stypoldione exerted qualitatively different effects on cell division and microtubule organization and function at different concentrations. At the lowest effective concentrations, 5-10 microM, stypoldione selectively inhibited cytokinesis. Mitotic division occurred normally, usually with no discernible perturbation of microtubule organization or function, and cells became multinuclear. At somewhat higher concentrations, 20-40 microM, stypoldione blocked embryos before streak stage of the first division and, although microtubules were present, their organization was perturbed and they often formed unusual "spiral aster" arrays. At 80 microM and above, microtubules in blocked cells were largely absent. Thus, stypoldione uncouples cytokinesis from mitosis at the lowest effective concentrations and, although it can disrupt microtubules at relatively higher concentrations, it inhibits cell division at the lowest effective concentrations by a selective action on cytokinesis through a mechanism that does not appear to involve disassembly of microtubules.

Animals↗

Impairments on neuropsychologic tests of temporohippocampal and frontohippocampal functions and word fluency in remitting schizophrenia and affective disorders.

Experimental neuropsychologic tests were administered to acute patients with schizophrenia and affective psychosis and to normal controls. Patients had remitting illnesses. Tests included memory for recurring digit and block spans (left and right temporohippocampal), digit and block spans (lateralized parietal/frontal), spatial and nonspatial conditional associate learning (frontohippocampal), and oral word fluency to letter-designated categories (frontal) and semantic-designated categories (left-sided). In 81% of schizophrenic patients patterned deficits incompatible with generalized losses of function were disclosed. Patterns were heterogeneous and characterized by (1) the frequency and severity of left temporohippocampal impairment; (2) asymmetric frontohippocampal function such that severity of bilateral impairment was associated with poorer nonspatial learning and superior performance with better nonspatial learning; (3) syndrome relationships predicted by the hemisphere imbalance syndrome model pertaining to positive and negative symptoms and the catatonic syndrome; (4) a generalized deficit independent of temporohippocampal functions; and (5) no relationship between performance and computed tomographic signs or medication. Patients with affective disorders had patterned deficits characterized by bilateral impairments that disclosed a preponderance of deficits in spatial learning and memory; depressives demonstrated impairments in digit span.

Affective Disorders, Psychotic↗

MHC class I expression by developmental tumors: teratocarcinoma stem cells are TCA positive.

We have investigated the expression of antigens recognized by several alloantisera and monoclonal antibodies to class I and class I-like MHC gene products on four developmental tumor cell lines derived from teratocarcinoma and choriocarcinoma. The analysis by cytotoxicity, immunoprecipitation, and Northern blotting analysis was also performed following treatment of the cells with gamma interferon. Three of four of the cell lines apparently do not express polymorphic determinants of HLA-A,B,C class I MHC genes. Immunoprecipitation with antibodies to HLA monomorphic determinants or beta 2m showed that some cell lines express distinct novel class I MHC-like molecules; the latter show molecular sizes different from regular HLA molecules and are associated with beta 2m. The Northern blotting showed class I mRNA present in three out of four of the developmental tumor cell lines but at at least tenfold lower levels than in lymphoid cells; it is possible that the RNAs homologous to class I DNA probes include transcripts of non-HLA-A,B,C genes. The cells were serologically typed for one such locus, TCA, which lies telomeric to HLA-A; the choriocarcinomas are negative and the teratocarcinomas are positive. The relationship between the different antigenic molecules and their possible functional significance is discussed in terms of maternofetal interactions, cancer, and transplantation.

Choriocarcinoma↗

Prostaglandin production and contractile response of umbilical arteries in preeclamptic pregnancies with and without intrauterine growth retardation.

Biochemical and biophysical properties of umbilical arteries from normotensive and preeclamptic pregnancies were examined. The production of prostaglandins E and F, 6-keto-PGF1 alpha, and thromboxane B2 by umbilical arteries from normotensive, mildly preeclamptic, and severely preeclamptic pregnancies were measured in incubation media at baseline and after addition of arachidonic acid. The initial baseline values of 6-keto-PGF1 alpha were decreased in the severely preeclamptic patients with intrauterine growth retardation (IUGR) but not in any of the other groups. Addition of arachidonic acid resulted in a significant increase in 6-keto-PGF1 alpha production over initial baseline in all groups except in the severely preeclamptic pregnancies without IUGR. These results suggest a differential defect in the 6-keto-PGF1 alpha metabolic pathway in severely preeclamptic patients with IUGR compared with those without IUGR. The stretch response curve to serotonin was decreased in the severely preeclamptic group with IUGR compared with the control group. The contractile response to individual vasoactive agents (serotonin, prostaglandin F2, norepinephrine, angiotensin II, and arachidonic acid) showed no significant difference between the normotensive and preeclamptic groups.

Angiotensin II↗