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Biomedical subjects

L A Taylor

Publications and source records attributed to L A Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1994

In vivo hepatic gene therapy: complete albeit transient correction of factor IX deficiency in hemophilia B dogs.

Hemophilia B is a bleeding disorder caused by mutations in the factor IX gene. The disorder is X-linked recessive with a prevalence of about 1 in 30,000 Caucasian males. Factor IX is naturally synthesized in the liver and secreted into blood. Here we report the construction of recombinant adenoviral vectors containing the canine factor IX cDNA that are capable of transducing hepatocytes in mice at high efficiencies in vivo without partial hepatectomy. The recombinant viral vector was used to treat hemophilia B dogs by direct vector infusion into the portal vasculature of deficient animals. Plasma factor IX concentrations in the treated hemophilia B dogs increased from 0 to 300% of the level present in normal dogs, resulting in complete amelioration of the disease as demonstrated by normal blood coagulation and hemostatic measurements. Although plasma factor IX concentration started to decline after a few days, therapeutic levels of factor IX persisted for 1-2 months in the treated animals. The results validate the principle of in vivo hepatic gene delivery to reconstitute the genetic deficiency in a large animal model and suggest that gene therapy is achievable when long-acting vectors are developed.

Adenoviridae↗
PubMed1994

Chronic lung disease is the leading risk factor correlating with the failure (wrap disruption) of antireflux procedures in children.

Recurrent gastroesophageal reflux (GER) after antireflux procedures (ARP) has been correlated with significant neurological impairment (NI). Other major risk factors for recurrent GER have not been extensively characterized. The authors reviewed their experience with ARPs in children to better characterize the risk factors for recurrent GER and identify successful management strategies for these patients. The charts of 281 consecutively treated children who had an ARP at our institution (1985 to 1992) were reviewed. The neurological status of each child was assessed as normal or impaired (cerebral palsy, seizures, mental retardation, spasticity), and other medical diagnoses such as chronic pulmonary disorders (eg, interstitial disease, cystic fibrosis, bronchopulmonary dysplasia, asthma, etc), and congenital malformations and syndromes were identified. The average follow-up period was 3 years (range, 1 to 7.5 years). Patients with symptoms of recurrent GER were evaluated with an upper gastrointestinal study. Patients with a radiologically intact fundoplication and suspected GER were further evaluated with a 24-hour pH probe. Statistical analyses were performed using the Fisher's Exact Test. Of the 281 patients who underwent ARP, 39 had documented recurrent GER (average, 16 months after surgery). Twenty-five (64%) of these children had chronic pulmonary disease (CPD). Thirty-two percent of all children with CPD had recurrent GER after ARP, versus 7% of those without CPD (P < .0001). For children with NI and CPD there was an increased risk (P < .0001) of failure when compared with the risk in the normal subgroup (children without CPD or NI) who underwent ARP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Characterization of the binding of SCH 39166 to the five cloned dopamine receptor subtypes.

Characterization studies were conducted on the five cloned dopamine receptor subtypes (D1-D5) using the novel D1-selective antagonist, SCH 39166, as well as other related benzazepines and dopaminergic agents. The results demonstrate that SCH 39166 exhibits saturable, high-affinity binding to the D1 and D5 receptors, but binds with low affinity to the D2, D3, and D4 receptors. In contrast, the D2 antagonist haloperidol showed low affinity for the "D1-like" receptors and high affinity for the "D2-like" receptors. A series of agonists was also evaluated and the D5 receptor subtype displayed a two-site fit for the endogenous agonist dopamine, as well as for the agonist apomorphine. Differences in agonist binding among the D1-like receptors reflect the importance of the nonconserved amino acid substitutions.

Benzazepines↗
PubMed1993

Intraseptal injection of GABA and benzodiazepine receptor ligands alters high-affinity choline transport in the hippocampus.

Injection of GABA and benzodiazepine (BDZ) agonists and antagonists into the medial septum produced bidirectional alterations in hippocampal high-affinity choline transport (HAChT). Male Sprague-Dawley rats were injected in the medial septum with either drug vehicle, a BDZ agonist, antagonist, or inverse agonist, or with a GABA-A or GABA-B agonist or antagonist and sacrificed 1 h later for assessment of HAChT in hippocampal synaptosomes. The GABA-A agonist muscimol, the GABA-B agonist baclofen, and the BDZ agonist chlordiazepoxide (CDP) produced dose-related decreases in HAChT 1 h following injection into the septum. The muscimol-induced decrease in HAChT was prevented by prior intraseptal injection of the GABA-A antagonist, bicuculline. Intraseptal injection of GABA-A (bicuculline) or GABA-B (2-hydroxysaclofen) antagonists did not alter HAChT, whereas the BDZ antagonist flumazenil (RO15,1788) and the BDZ inverse agonist methyl-beta-carboline-3-carboxylate (beta-CCM) increased this measure up to 30% in a dose-dependent manner. These results demonstrate that cholinergic neurons in the medial septum can be modulated in a bidirectional way through the pharmacological manipulation of GABA-A, GABA-B, and BDZ receptors. The potential functional and therapeutic consequences of these interactions are discussed.

Acetylcholinesterase↗
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↗
PubMed1988

Outbreak of cryptosporidiosis among young children attending a day-care centre in Durban.

During an outbreak of an enteric illness occurring among infants and toddlers in a day-care centre in Durban, Cryptosporidium was detected in 51 (73%) of 70 children. Two (10%) of 20 staff members were also found to have cryptosporidiosis. Symptoms occurred in all but 4 of the Cryptosporidium-positive infants and toddlers and lasted for 1-33 days. Oocyst excretion often persisted after cessation of symptoms and continued for up to 50 days in some children. Transmission is considered to have occurred predominantly by person-to-person spread. Measures to prevent transmission of enteric-type diseases were implemented and coincided with cessation of the outbreak.

Animals↗
PubMed1988

Sodium cholate extraction of rat liver nuclear xenobiotic-metabolizing enzymes.

DNA is the purported target of several carcinogenic and mutagenic agents. Nuclear enzymes which could generate or detoxify reactive metabolites are of major concern. Several such enzymes have been identified within nuclei, but obtaining samples with enriched content or activity is difficult, time-consuming, and uses harsh isolation techniques. Extraction of rat liver nuclear suspensions with cholate-containing buffer results in solubilization of 25-30% of the protein. Linear extraction was obtained for total protein and cytochromes P-450 and b5, NADPH-cytochrome P-450 reductase, NADH-cytochrome b5 reductase, DT-diaphorase, and microsomal-like epoxide hydrolase with specific activities comparable to values reported for isolated nuclear membrane, while the yield was five to ten times greater. Detergent extracts of rat liver nuclei were employed to study the comparative response of microsomal and nuclear enzymes to chemical treatment. While the responses to acute inductive (phenobarbital and 3-methylcholanthrene) and toxic (carbon tetrachloride and dibromochloropropane) treatments were qualitatively similar, an initiation-promotion protocol (diethylnitrosamine with phenobarbital promotion) resulted in divergent responses between the enzymes in the two subcellular fractions. Detergent extracts of nuclei offer an efficient means of recovering xenobiotic-metabolizing enzymes from rat liver nuclei, and have been utilized to demonstrate a differential response of nuclear enzymes during preneoplastic development.

Animals↗
PubMed1988

The effects of blood sugar level changes on cognitive function, affective state, and somatic symptoms.

In an attempt to find out whether decreased blood sugar level is associated with impaired cognitive function, adverse emotional changes, or somatic symptoms, 35 subjects who suspected that they had hypoglycemia were given 5-hr glucose tolerance tests (GTTs). Nine blood samples were taken during the GTT, and the subject's mood, Serial Sevens Test (SST) performance, and somatic symptom reports were recorded on each occasion of sampling. The subjects reported significantly more negative affect and somatic symptoms after glucose nadir than before nadir. SST performance deteriorated at glucose nadir. These effects were more pronounced for subjects with high hypoglycemic index scores than for subjects with low index scores. The impairment in SST performance was greater for subjects who showed rapid decreases in blood sugar than for subjects who showed slow decreases. Dividing subjects by high and low nadirs did not reveal any differences in symptomatology.

Adult↗
PubMed1988

Differential inhibition of indirect immunofluorescence in rat liver sections incubated with antibodies against microsomal cytochromes P-450a, b, and c and epoxide hydrolase.

Rat liver sections were incubated with antibodies (100-1000 micrograms IgG/ml) against microsomal cytochromes P-450a, P-450b, and P-450c, and epoxide hydrolase. Inhibition of indirect immunofluorescence, which progressed with higher concentrations of primary antibody, corresponded with antigen-enriched tissue in frozen liver sections from male and female rats. It was found in liver sections from phenobarbital-treated rats incubated with anti-P-450b and anti-epoxide hydrolase and from 3-methylcholanthrene-treated rats incubated with anti-P-450c. No inhibition was found in sections from untreated rats or rats receiving treatments that did not induce the specific antigen. No inhibition was found in sections incubated with anti-P-450a. Inhibition of immunofluorescence was abolished in frozen sections subjected to dehydration-rehydration protocols known to extract antigens, and was prevented by certain solvents and detergent-wash. Inhibition of immunofluorescence provides a unique method for confirming the antigen-rich regions of the liver lobules specific for microsomal expoxide hydrolase and the cytochrome P-450s.

Animals↗