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Biomedical subjects

L Wilson

Publications and source records attributed to L Wilson.

At least 199 records · Page 11Linked to original sources
PubMed1994

Anxiety and its determinants in patients undergoing magnetic resonance imaging.

This study assessed anxiety reactions in 40 adults outpatients undergoing MRI. Ninety-five percent of the patients completed the procedure although 37% reported moderate to severe anxiety. It is concluded that (a) anxiety in patients undergoing MRI is a multifaceted phenomenon involving fear of enclosed places (claustrophobia), pain, the unknown, as well as apprehension about what the test might reveal, and (b) the best way to avoid traumatizing the patient is to assess these variables in advance of the procedure. Methods to reduce anxiety can then be tailored to the needs of the patient.

Adolescent↗
PubMed1994

In vivo serotonin release and learned helplessness.

Learned helplessness, a behavioral depression caused by exposure to inescapable stress, is considered to be an animal model of human depressive disorder. Like human depression, learned helplessness has been associated with a defect in serotonergic function, but the nature of this relationship is not entirely clear. We have used in vivo microdialysis brain perfusion to measure serotonin (5-hydroxytryptamine, 5HT) in extracellular space of medial frontal cortex in conscious, freely moving rats. Basal 5HT levels in rats perfused before exposure to tail-shock stress did not themselves correlate with subsequent learned helplessness behavior. However, 5HT release after stress showed a significant increase with helpless behavior. These data support the hypothesis that a cortical serotonergic excess is causally related to the development of learned helplessness.

Animals↗
PubMed1994

Cellular immune recognition of HLA-A*0201 following gene transfer into a human embryonal carcinoma cell line.

Previously, we have established that transcription and cell surface expression of MHC class I and beta 2m genes in undifferentiated Tera-2 stem cells, a teratocarcinoma-derived cell line, was extremely low. In this study, we have transfected an HLA-A*0201-encoding cDNA driven by the CMV-promoter into Tera-2 cells. Prior to IFN gamma treatment, membrane expression of HLA-A*0201 by these Tera-2 transfectants was nearly lacking. Consequently, the HLA-A*0201 Tera-2 transfectants were not recognized by the allo-HLA-A*0201-specific CTL clone 3E7. Following IFN gamma treatment, which resulted in upregulation of HLA-A*0201, Tera-2 cells were lysed by CTL clone 3E7. In contrast, loading of HLA-A*0201 with the influenza-A-matrix peptide 58-66 resulted in partial lysis of Tera-2 cells by the influenza-A-matrix protein-specific CTL clone Q66-9, and nearly complete lysis was observed following IFN gamma treatment. These results suggest that the HLA-A*0201 transgenes in Tera-2 cells can be loaded with peptides and used as targets for peptide-specific CTLs.

Base Sequence↗
PubMed1994

Comparison of binding affinity of oxytocin antagonists to human and rat uterine oxytocin receptors and their correlation to the rat uterine oxytocic bioassay.

One of the primary methods used to screen the development of oxytocin antagonists (OTAs) is the rat oxytocic bioassay. The purpose of this study was to determine whether the rat oxytocic bioassay is a good predictor of binding affinity to human and rat uterine oxytocin receptors (OTr). The binding affinities of five OTAs to human and rat uterine OTr were determined and correlated with pA2 values derived from the rat uterine oxytocic bioassay. Human uterine myometrial tissue was obtained from patients at the time of cesarean section. Rat uterine tissue for the OTr assay was taken at Day 21 of pregnancy. OTr assays were accomplished by isolating uterine cell membranes and performing saturation analysis with cold OTAs and tritium-labeled oxytocin. The association constants (Ka; 10(+8)/M) were calculated by nonlinear curve-fitting techniques. The Ka for the five OTAs (Mpa1-OT, Antag I, L366948, Antag II, and Antag III), as estimated from the human OTr assay, were 0.55, 0.60, 2.27, 1.91, and 47.20, respectively. Ka estimates obtained through use of rat uterine membranes were 0.51, 1.16, 5.89, 2.03, and 24.40, respectively. Correlation of the log10 of the rat oxytocic bioassay results with those of the rat and human OTr assay was 0.94 and 0.98, respectively (p < 0.01). Antag III was approximately 55, 48, and 90 times more potent than Mpa1-OT as determined by the rat bioassay and rat and human uterine OTr assays, respectively. Mpa1-OT is an OTA that is currently undergoing clinical evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Degradation of xenobiotic compounds in situ: capabilities and limits.

Exploiting microorganisms for remediation of waste sites is a promising alternative to groundwater pumping and above ground treatment. The objective of in situ bioremediation is to stimulate the growth of indigenous or introduced microorganisms in regions of subsurface contamination, and thus to provide direct contact between microorganisms and the dissolved and sorbed contaminants for biotransformation. Subsurface microorganisms detected at a former manufactured gas plant site contaminated with coal tars mineralized significant amounts of naphthalene (8-43%) and phenanthrene (3-31%) in sediment-water microcosms incubated for 4 weeks under aerobic conditions. Evidence was obtained for naphthalene mineralization (8-13%) in the absence of oxygen in field samples. These data suggest that biodegradation of these compounds is occurring at the site, and the prospects are good for enhancing this biodegradation. Additional batch studies demonstrated that sorption of naphthalene onto aquifer materials reduced the extent and rate of biodegradation, indicating that desorption rate was controlling the biodegradation performance.

Bacteria, Aerobic↗
PubMed1994

Detection of porcine reproductive and respiratory syndrome virus and efficient differentiation between Canadian and European strains by reverse transcription and PCR amplification.

Two sets of oligonucleotide primers (1008PS-1009PR and 1010PLS-1011PLR) were designed according to the sequence of the nucleocapsid protein (N) gene of Quebec reference strain IAF-exp91 of porcine reproductive and respiratory syndrome virus (PRRSV). The primers were used in reverse transcription and PCR (RT-PCR) experiments for detection of viral genomic RNA either from infected porcine alveolar macrophages (PAM) or tissues from experimentally infected specific-pathogen-free pigs. Considering the high degree of variation detected between the nucleotide sequences of the N genes of IAF-exp91 and Lelystad virus (LV) strains of PRRSV, the primers 1008PS-1009PR were referred to as the specific primers, since they were chosen in such a manner that they could amplify only sequences from IAF-exp91 RNA and not from LV. On the other hand, the primer pair 1010PLS-1011PLR was common to both strains of PRRSV. When analyzed by agarose gel electrophoresis, the products of RT-PCR from each set of primers were resolved as single band of the predicted size, the specificity of amplified products being confirmed by Southern blotting with a specific IAF-exp91 N gene probe. No amplification was observed when RNA was extracted from uninfected PAM or from other porcine viruses. As expected, only the common primer pair was able to amplify RNA from the Quebec reference strain and two European strains (LV and Weybridge). The resulting bands displayed differences in electrophoretic mobilities due to the absence of 37 nucleotides in both European strains, thus allowing their differentiation from the IAF-exp91 strain. Most of the tissue culture-adapted Quebec isolates were detected with both primer pairs. The sensitivity of the enzymatic amplification method for detection of PRRSV from lung tissues was a 50% tissue culture infective dose of 5. RT-PCR was found to be more sensitive than indirect immunofluorescence assay for detection of PRRSV in tissues from experimentally infected pigs and as sensitive as virus isolation in PAM, especially when combined with Southern blotting with the digoxigenin-labeled N probe and chemiluminescence detection.

Abortion, Veterinary↗
PubMed1994

Multicomponent intervention for agitated behavior in a person with Alzheimer's disease.

We evaluated a multicomponent intervention for agitated behavior in a man with probable Alzheimer's disease. Hypotheses about variables controlling his agitated behavior guided intervention design. Based on staff interviews, direct observations, and brief experimental probes, intervention components were chosen to increase rate of reinforcement and decrease aversive aspects of his job. Intervention reduced agitated behavior without disrupting his work rate.

Aged↗
PubMed1994

Reconstruction after malunion and nonunion of intra-articular fractures of the distal humerus. Methods and results in 13 adults.

We reviewed the results of 13 adults of secondary reconstruction of malunited and ununited intraarticular distal humeral fractures. Their average age was 39.7 years, and preoperatively all had pain, loss of motion and functional disability; the average arc of motion was only 43 degrees and the average flexion contracture was 45 degrees. Nine patients had ulnar neuropathy. Elbow reconstruction, at an average of 13.4 months after the original injury, included osteotomy for malunion or debridement for nonunion, realignment with stable fixation and autogenous bone grafts, anterior and posterior capsulectomy and ulnar neurolysis. The elbows were mobilised 24 hours postoperatively. There were no early complications and all nonunions and intra-articular osteotomies healed. After a mean follow-up of 25 months, the average arc of motion was 97 degrees with no progressive radiographic degeneration. Ulnar nerve function improved in all cases and clinical assessment using the Morrey score showed two excellent, eight good and three fair results. Reconstruction of intra-articular malunion and nonunion of the distal humerus in young active adults is technically challenging, but can improve function by restoring the intrinsic anatomy of the elbow.

Adolescent↗
PubMed1994

Interaction of drug metabolites with the class I antiarrhythmic drug receptor on rat cardiac myocytes.

The use of class I antiarrhythmic drugs may be complicated by the presence of active metabolites. A simple technique to predict the clinical activity of these metabolites might help with the clinical use of these drugs. We tested the hypothesis that drug metabolites bind to the class I drug receptor, but that only clinically active metabolites bind appreciably at clinically observed concentrations. Using a radioligand assay, we determined whether 13 class I drug metabolites interacted with a receptor for class I drugs associated with the cardiac sodium channel. The radioligand was [3H]batrachotoxinin A20 benzoate. All 13 metabolites bound to the drug receptor with IC50 values of 2.7 to 375 microns, and a mean Hill number of 1.0 +/- 0.3. All of the seven active metabolites (N-acetylprocainamide, mono-N-dealkyldisopyramide, 5-hydroxypropafenone, N-desisopropylpropafenone, 0-demethylencainide, 3-methoxy-0-demethylencainide and desethylamiodarone) each bound to the receptor at concentrations approaching their clinical concentrations, whereas none of the six inactive metabolites (quinidine-N-oxide, 3-hydroxyquinidine, glycinexylidide, monoethylglycinexylidide, N-demethylencainide and N,0-demethylencainide) did. Using a relationship which correlates drug IC50 values and clinically observed drug concentrations we calculated predicted clinical concentrations if the metabolites were clinically active. A predicted/observed ratio < or = 10 correlates with 100% positive and negative accuracies whether a drug metabolite has clinical activity. Thus a simple radioligand assay predicts whether class I drugs have clinical activity.

Animals↗
PubMed1993

Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations.

Taxol inhibited HeLa cell proliferation by inducing a sustained mitotic block at the metaphase/anaphase boundary. Half-maximal inhibition of cell proliferation occurred at 8 nM taxol, and mitosis was half-maximally blocked at 8 nM taxol. Inhibition of mitosis was associated with formation of an incomplete metaphase plate of chromosomes and an altered arrangement of spindle microtubules that strongly resembled the abnormal organization that occurs with low concentrations of vinblastine and other antimitotic compounds. No increase in microtubule polymer mass occurred below 10 nM taxol. The mass of microtubules increased half-maximally at 80 nM taxol and attained maximal levels (5 times normal) at 330 nM taxol. At submicromolar concentrations, taxol suppressed growing and shortening at the ends of microtubules reassembled in vitro from bovine brain tubulin in a manner that resembled suppression by vinblastine. Taxol was concentrated in HeLa cells several hundredfold to levels that were similar to those which suppressed dynamic instability in vitro. The results indicate that taxol shares a common antiproliferative mechanism with vinblastine. At its lowest effective concentrations, taxol appears to block mitosis by kinetically stabilizing spindle microtubules and not by changing the mass of polymerized microtubules.

Cell Division↗
PubMed1993

Purification and biochemical characterization of tubulin from the budding yeast Saccharomyces cerevisiae.

We describe a method for isolating milligram quantities of assembly-competent tubulin from the budding yeast Saccharomyces cerevisiae. The tubulin is > 95% purified and free of contaminating enzyme activities. As a result, it has been possible to determine the yeast tubulin equilibrium-binding constant for Mg-GTP and the tubulin GTPase activity under nonassembling and assembling conditions. We also determined the critical concentration for yeast tubulin polymerization and found it to be significantly lower than that for bovine brain tubulin under identical conditions. Similarly, the dynamic properties both of individual yeast microtubules and of bulk microtubule suspensions were significantly different from those of bovine brain microtubules free of microtubule-associated proteins. The data suggest that the properties of the yeast tubulin may reflect the particular functional requirements of the yeast cell. With this method, it is now possible to introduce any desired tubulin gene mutation into the budding yeast and correlate the phenotypic effects of the mutation in cells with the effects of the mutation on the biochemical and polymerization properties of the tubulin.

Binding Sites↗
PubMed1993

Calcium ionophore A23187 induces interleukin-8 gene expression and protein secretion in human monocytic cells.

The regulation of the expression of the interleukin-8 (IL-8) gene in human monocytic cell lines has been investigated. Agents such as interleukin-1 (IL-1) or interferon-gamma (IFN gamma) did not induce increased IL-8 expression in THP-1 or U937 cells. Bacterial lipopolysaccharide endotoxin (LPS) or phorbol myristate acetate (PMA) alone induced suboptimal expression as assessed by Northern blotting; however, preincubation of cells with PMA followed by endotoxin induced much higher levels of IL-8 mRNA. Incubation of the cells with the calcium ionophore A23187 resulted in consistent increased IL-8 gene expression comparable to that of cells treated with endotoxin alone. In addition to inducing IL-8 mRNA this calcium ionophore also induced IL-8 protein synthesis as assessed by immunofluorescence and secretion as detected by ELISA. These results indicate that increases in intracellular calcium result in IL-8 gene expression and protein secretion.

Blotting, Northern↗
PubMed1993

The effect of advanced age on the efficacy of radiation therapy for early breast cancer, local prostate cancer and grade III-IV gliomas.

PURPOSE: This study was undertaken to determine the effect of advanced age on radiation therapy outcomes for early breast cancer, local prostate cancer and Grade 3-4 gliomas of the brain. METHODS AND MATERIALS: Radiation therapy outcomes for three malignancies (N = 1,401) were determined for a geriatric cancer population defined as 70 years of age or older and compared to a non-geriatric cancer population defined as less than 70 years of age. The three patient groups studied were: (a) primary breast cancer patients with clinical Stage I or II disease treated with lumpectomy and radiation therapy (N = 994), (b) local prostate cancer patients with Stage A2, B, or C disease treated with radical radiation therapy (N = 294), and (c) patients with Grade 3-4 gliomas of the brain treated with high dose radiation therapy (N = 113). RESULTS: For Stage I and II breast cancer, there was no statistically significant difference in the overall 10-year survival rates (63% vs. 73%), 10-year cause-specific disease-free survival rates (70% vs. 63%), and 10-year local breast recurrence free survival rates (76% vs. 79%) comparing the geriatric cancer population to the non-geriatric cancer population. For local prostate cancer, there was no statistically significant difference in the 10-year survival rates (38% vs. 41%) or in the 10-year cause-specific disease-free survival rates (58% vs. 52%) in the geriatric population compared with the non-geriatric population. On the other hand, the use of high dose radiation therapy for malignant gliomas resulted in statistically significant inferior 1-year (18% vs. 38%) and 2-year (0% vs. 10%) survival rates for the geriatric population versus the non-geriatric population. CONCLUSION: This study strongly supports the use of standard radiation therapy programs for early breast and prostate cancer patients age 70 years or more. However, our study raises questions about the efficacy of radiation therapy in patients over the age of 70 years with Grade 3-4 gliomas.

Age Factors↗
PubMed1993

Systematic substitution of an oxytocin antagonist with D-amino acids: unexpected high antagonistic potency of the D-Cys6-substituted analogue.

We report twelve analogues (1-12) of [Pmp1,D-Trp2,Arg8]oxytocin, PA (parent antagonist), (Pmp = beta,beta-pentamenthylene-beta-mercaptopropionic acid), which is a potent antagonist (pA2 = 7.77) of the uterotonic effect of oxytocin (OT) in rats. The analogues were designed by replacement of each optically active amino acid residue at positions 3-8 in PA with a D-amino acid. Analogues 1-8, featuring D-amino acids in the ring portion, were weaker antagonists than PA or were inactive. Unexpectedly, replacement with D-Cys6 gave analogue 9, pA2 = 8.29, which is more than 3 times as potent as PA, and replacement with D-Pen6 gave analogue 10, pA2 = 7.98, also more potent than PA. Replacement with D-Pro7 and D-Arg8 gave analogues 11 and 12, which are approximately equipotent or somewhat more potent than PA. These data suggest that neither the orientation of the tail sequence with respect to the plane of the ring portion of an antagonist nor the configuration of individual amino acids in the tail sequence may be critical for preservation of antagonism to the uterotonic action of OT. In the antidiuretic assay, analogues 9 and 12 were very weak partial agonists and had estimated pA2 = < 6.3 and < 5.6, respectively. Analogue 9 constitutes an interesting lead for the future design of OT antagonists with different molecular requirements than those featuring L-Cys6 as a substituent.

Amino Acid Sequence↗
PubMed1993

Kinetic stabilization of microtubule dynamic instability in vitro by vinblastine.

The antiproliferative action of vinblastine at low concentrations appears to result from modulation of the polymerization dynamics of spindle microtubules rather than from depolarization of the microtubules [Jordan, M. A., Thrower, D., & Wilson, L. (1991) Cancer Res. 51, 2212-2222; (1992) J. Cell. Sci. 102, 401-416]. In the present study, we used differential interference contrast video microscopy to analyze the effects of vinblastine on the growing and shortening dynamics (dynamic instability) of individual bovine brain microtubules in vitro. With microtubules which were either depleted of microtubule-associated proteins (MAPs) or rich in MAPs, low concentrations of vinblastine (0.2 microM-1 microM) suppressed the growing and shortening rates and increased the percentage of time that the microtubules spent a state of attenuated activity, neither growing nor shortening detectably. Vinblastine also suppressed the duration of microtubule growing and shortening, and increased the duration of the attenuated state, during which the microtubules neither grew nor shortened detectably. Consistent with previous data obtained using radiolabeled nucleotide exchange in microtubule suspensions [Jordan, M. A., & Wilson, L. (1990) Biochemistry 29, 2730-2739], vinblastine suppressed growing and shortening dynamics at the kinetically more rapid plus ends. The results suggest that vinblastine kinetically stabilizes microtubule ends by modulating the gain and loss of the stabilizing GTP or GDP-Pi "cap", which is believed to be responsible for the transitions between the growing and shortening phases. The data support the hypothesis that (1) low concentrations of vinblastine inhibit mitosis by kinetically stabilizing the polymerization dynamics of spindle microtubules and that (2) the dynamics of spindle microtubules are critical for the proper progression of mitosis.

Animals↗
PubMed1993

Pharmacological modulation of c-fos mRNA expression in the HL60 and U937 cell lines.

A variety of drugs known to act via increasing intracellular cAMP are used in the treatment of asthma. In this study we asked whether anti-asthma drugs are capable of altering gene activation. We determined whether phosphodiesterase inhibitors, either alone or in combination with adrenoceptor agonists, were able to alter the abundance of mRNA of the cAMP responsive gene c-fos in the cell-lines HL60 and U937. Incubation of cells with phosphodiesterase inhibitors aminophylline, theophylline or pentoxyphylline all resulted in an increase in c-fos mRNA. Further upregulation of c-fos mRNA abundance was observed when the cells were stimulated with the combination of aminophylline and adrenoceptor agonists with beta 2-agonist activity. These increases in c-fos mRNA were accompanied by increases in intracellular concentration of cAMP. These data suggest that in these in vitro models, combinations of beta 2-adrenoceptor agonists and phosphodiesterase inhibitors can increase intracellular cAMP and affect gene activation.

Adrenergic beta-Agonists↗