Biomedical subjects

L A Taylor

Publications and source records attributed to L A Taylor.

15 recordsLinked to original sources

PubMed1992

Predicting antisense oligonucleotide inhibitory efficacy: a computational approach using histograms and thermodynamic indices.

Antisense oligonucleotides (ASOs) are designed to bind to a specific mRNA and selectively suppress its translation. To facilitate selection of optimal ASO targets, we have developed three thermodynamic indices to evaluate putative structural complexes important in ASO action. These indices are: a secondary structure score (Sscore), which estimates the strength of local mRNA secondary structures at the ASO target site; a duplex score (Dscore), which estimates the delta Gformation for the ASO:mRNA target sequence duplex; and a competition score (Cscore), which is the difference between the Dscore and the Sscore. We also present two histograms to graphically display these indices from different regions of the mRNA. The indices are compared to the inhibition reported in five studies of ASO-mediated suppression of gene expression. The Dscore is the most consistent predictor of ASO efficacy in four of the five studies (r2 from 0.44 to 0.99), while the results of the fifth study could not be predicted by any thermodynamic or physical index. Thus the Dscores and their histogram may prove useful in selection of ASO targets.

Algorithms↗

PubMed1992

Percutaneous translumbar and transhepatic inferior vena caval catheters for prolonged vascular access in children.

Central venous access for children with caval occlusion remains a major challenge to pediatric surgeons. Traditionally, children with superior and inferior vena cava (SVC, IVC) thrombosis have often required a thoracotomy to directly cannulate the azygos system or right atrium (RA). Recently, the possibility of placing tunneled RA catheters (RACs) by a percutaneous translumbar or transhepatic approach has become available. We report our experience of seven children with SVC and IVC obstruction who have received 11 transhepatic and 4 translumbar RACs from 1987 to 1991. All but one child was less than 2.5 years old and all were chronically dependent on parenteral nutrition. All catheters were placed in the angiography suite under general anesthesia using ultrasound guidance and Seldinger technique. This technique was successful in all seven children. Perioperative complications included accidental extubation in one patient and aspiration pneumonia in another. Mechanical complications requiring RAC replacement occurred 5 times in three infants (greater than 2,650 catheter days) and included catheter dislodgement (2) and thrombosis (3). In the patients with catheter thrombosis, the existing tract was successfully wired and the catheter exchanged on three occasions. Thrombolytic therapy was effective in restoring catheter patency on three other occassions. Nine episodes of catheter sepsis occurred in five children. Two late deaths occurred from infection. Of the five remaining children, four are dependent on total parenteral nutrition and have a translumbar or transhepatic catheter in situ and one child has adapted successfully to enteral feedings. Percutaneous translumbar or transhepatic IVC catheters provide excellent alternative routes for prolonged central venous access in those patients whose traditional vascular access sites are no longer available. Complications of the technique itself were minimal and although late catheter complications were not infrequent, they appear to be comparable to the standard approaches reported.

Adolescent↗

PubMed1992

Identification of müllerian inhibiting substance specific binding in human cell lines.

The receptor for Müllerian Inhibiting Substance (MIS), a gonadal glycoprotein hormone, has not been previously identified. Plasma membranes from MIS-sensitive human tumor cell lines (HTB-111, endometrial carcinoma; and A-431, vulvar squamous carcinoma) were detergent extracted and incubated with 125I-labeled MIS anti-idiotypic antibody, or radioiodinated human recombinant MIS (125I rhMIS), with and without unlabeled competitors. 125I anti-idiotypic MIS antibody bound to HTB-111 membrane extracts was displaceable by unlabeled anti-idiotypic antibody, but not by anti-isotypic antibody prior to cross-linking. Specific binding of the anti-idiotypic MIS antibody to endometrial carcinoma cells was verified using fluorescence activated cell analysis and fluoresceinated antibody. Furthermore, unlabeled anti-idiotypic MIS antibody competed for 125I rhMIS binding to A-431 vulvar carcinoma membranes. The labeled anti-idiotypic MIS antibody binding complex could be separated from 32P labeled EGF receptor in the A-431 membranes, indicating that EGF, a natural inhibitor of MIS activity, and MIS itself bind to different receptors. These studies demonstrate a specific, displaceable binder for MIS in the plasmalemmae of two human tumor lines. Purification of this cell surface receptor protein will be greatly aided by using the MIS anti-idiotypic antibody.

Anti-Mullerian Hormone↗

PubMed1992

Consensus among geriatric experts on the components of a complete nursing-home admission assessment.

Standards of practice for nursing-home admissions have not been established, and it is not known if geriatric clinicians agree on the components of an appropriate patient-admission evaluation. This study describes the consensus expressed by experts in clinical geriatrics regarding the most important components of nursing-home admission assessments. Directors of all geriatric-nurse-practitioner and geriatric-medicine fellowship programs (n = 79) were sent a two-round questionnaire asking them to describe and rate the components of a "complete admission assessment for every elderly patient entering a nursing home." Nurse practitioners and physicians ranked medication review, evaluation of urinary incontinence, mental status, vision and bowel status the highest, and gave them equal priority. Routine laboratory tests were not included among the highest-ranked items by either nurses or doctors. An enhanced assessment focusing on the functional consequences of diseases rather than on the traditional "head-to-toe" systems approach emerged as the most appropriate assessment for elderly nursing-home patients.

Aged↗

PubMed1992

Glycoprotein 60 of equine herpesvirus type 1 is a homologue of herpes simplex virus glycoprotein D and plays a major role in penetration of cells.

Monoclonal antibodies (MAbs) specific for equine herpesvirus type 1 (EHV-1) glycoprotein 60 (gp60) and gp 17/18 (F3132 and 5H6 respectively) were found to react with the same protein, which was identified as a homologue of herpes simplex virus type 1 gD. MAb F3132 strongly neutralized virus infectivity and inhibited the penetration of the virus into the cell. The effects on penetration were shared with three other MAbs against this protein (P68, F3116 and F3129), but no effect on virus penetration was found with any other anti-EHV-1 MAb tested. The level of glycosylation of gp60 was analysed using glycanase enzymes and glycosylation inhibitors, and consisted of mainly N-linked carbohydrate. The M(r) of non-N-glycosylated gp60 was 50K.

Animals↗

PubMed1992

Development and evaluation of an enzyme-linked immunosorbent assay for detection of bovine antibodies to epizootic hemorrhagic disease of deer viruses.

An indirect enzyme-linked immunosorbent assay (I.ELISA) is described for detection of bovine serum antibody to epizootic hemorrhagic diseases of deer virus (EHDV). Serum samples, at a dilution of 1:200, were incubated with group-specific EHDV antigens, pre-adsorbed to microtiter plates. Bound antibodies were detected by a murine monoclonal antibody to bovine immunoglobulin (Ig)G1 (heavy-chain specific) conjugated with horseradish peroxidase. The performance of the I.ELISA in detecting antibodies to EHDV in sequential serum samples from calves experimentally infected with serotypes 1,2,3 and 4 was evaluated. The I.ELISA detected EHDV antibodies from 14 days postinfection when seroconversion by the standard agar gel immunodiffusion (AGID) test was also evident. The group-specific antibodies to EHDV increased exponentially during the first two to four weeks postinfection and remained relatively stable for about 12 months in some calves. Unlike observations with the AGID test, no reaction was seen in the I.ELISA between blue-tongue virus (BTV) antigen and sera from calves given a single dose of EHDV. The performance of the I.ELISA and AGID were compared using 3,135 AGID negative bovine field sera from herds in Ontario, Alberta and British Columbia and 130 AGID positive samples collected from cattle in 1987 and 1988 during and after outbreaks of EHD in the Okanagan Valley, British Columbia. The specificity and sensitivity of the assay relative to the AGID test were 99.3% and 91.5% respectively, with an overall agreement of 99.0% between the tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Measurement of arachidonic acid release from human polymorphonuclear neutrophils and platelets: comparison between gas chromatographic and radiometric assays.

a simple gas chromatographic method for the assay of phospholipase A2 (PLA2) has been described in which arachidonic acid released from endogenous phospholipid pools is measured following its extraction and derivatization to pentafluorobenzyl esters. Using this assay, PLA2 activities in control and calcium ionophore-stimulated human neutrophils, as well as in control, thrombin, and calcium ionophore stimulated human platelets, have been measured. These values are compared with those obtained by monitoring the release of radioactivity from [3H]- or [14C]arachidonic acid prelabeled cells. While the radiometric assay measures only the release of exogenously incorporated radioactive arachidonic acid, the gas chromatographic assay measures arachidonic acid released from all the endogenous pools. Thus, the apparent increase in PLA2 activity in stimulated cells measured by the gas chromatographic assay is four- to fivefold higher than that by the radiometric assay. Inclusion of fatty acid free bovine serum albumin in the reaction buffer significantly increases the amount of arachidonic acid that is measured by gas chromatography. The gas chromatographic method has also been successfully utilized for measuring PLA2 activity in cell-free preparations derived from physically disrupted human neutrophils.

Acetophenones↗

PubMed1991

The binding of SCH 39166 and SCH 23390 to 5-HT1C receptors in porcine choroid plexus.

SCH 39166 is a novel benzonaphthazepine, which has been characterized as a potent and selective D1 antagonist. Recently, its D1 selective benzazepine predecessor, SCH 23390, has been shown to bind to 5-HT1C binding sites in the choroid plexus. Therefore, the present studies were undertaken to determine if SCH 39166 has any measurable affinity for 5-HT1C binding sites. Our results indicate that SCH 39166 exhibited poor affinity for the 5-HT1C receptor, with a Ki of 1327 nM. In contrast, SCH 23390 inhibited [3H]-mesulergine binding to 5-HT1C receptors with a Ki of 30 nM. The non-selective 5-HT antagonist, methysergide, inhibited binding with a Ki of 2.4 nM. Finally, studies with the stereoisomers of SCH 39166 and SCH 23390 demonstrated that stereoselectivity at the 5-HT1C site is significantly less than for the D1 site.

Animals↗

PubMed1987