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Biomedical subjects

G Taylor

Publications and source records attributed to G Taylor.

At least 325 records · Page 18Linked to original sources

Lymphocyte transformation response of calves to respiratory syncytial virus.

Virus-specific cell-mediated immunity, as determined by in vitro lymphocyte transformation (LT), was demonstrated in calves following infection and vaccination with respiratory syncytial virus (RSV). After experimental infection, 4 of 6 gnotobiotic calves and 6 of 21 conventional calves developed a significant LT response to RSV. By means of a whole blood assay, the LT responses of calves were examined after vaccination with an inactivated vaccine, which consisted of glutaraldehyde-fixed bovine nasal mucosa cells persistently infected with a bovine strain of RSV (GC), a live modified bovine strain of RSV (MV), or a live temperature-sensitive mutant of a human strain of RSV (ts-l). Three weeks after vaccination, a virus-specific LT response was detected in 6 of 6 calves given the GC vaccine, 0 of 4 calves given the MV vaccine, and 2 of 4 calves given the ts-l vaccine. The magnitude of the response was greatest in those animals given the GC vaccine. There was no significant correlation between the magnitude of the LT response and levels of serum neutralising antibody. However, the LT response did correlate with serum antibody measured by the single radial haemolysis test 3 weeks after the first vaccination. LT activity to RSV was associated with T and not B lymphocytes. The development of a virus-specific LT response in calves given an inactivated RSV vaccine was not associated with an increase in respiratory disease following challenge with live virus, but rather was related to increased resistance to RSV infection.

Animals↗

Blunt liver trauma at Sunnybrook Medical Centre.

Between 1 June 1976 and 30 June 1985 Sunnybrook Medical Centre Regional Trauma Unit admitted 2,016 patients of whom 220 (11%) sustained liver injury. Of these 220 patients, 211 (96%) sustained blunt liver trauma; 175 of 176 patients who underwent open peritoneal lavage had a true positive lavage. Resuscitation was successful in 212 patients, of whom 209 underwent laparotomy and three were treated nonoperatively: 129 of 209 patients (62%) required only minor surgical treatment; the remaining 80 patients (38%) required major surgical procedures. The overall mortality was 29% (64/220). Eight patients died during resuscitation, one of them of liver hemorrhage. Of the 56 patients who died after admission, the cause of death was head injury in 31, liver hemorrhage in 11 (five intraoperatively) and 14 died of other causes. Overall, liver hemorrhage was the cause of death in 12 of 64 deaths (19%). In other words, 12 of the total of 220 patients (6%) died from liver-related mortality.

Accidents↗

Plasma antipyrine half-life can be determined from urine data.

Antipyrine half-life has been determined from measurements of antipyrine concentrations in spontaneously voided urine specimens in eleven subjects, studied on a total of forty-seven different occasions while receiving no drugs, interferon or ketoconazole. Plasma and saliva half-lives show good intrasubject correlation. Plasma and urine half-lives show good intrasubject correlation provided total urine output is at least 1.1 l day-1. The range of intrasubject correlation coefficients for plasma and urinary half-lives was 0.76 to 0.98, with a median value of 0.85. Saliva and urine half-lives show good intrasubject correlation, with the range of intrasubject correlation coefficients from 0.74 to 0.98, and with a median value of 0.75. There is a small but consistent bias towards shorter urinary half-life estimates; this averaged 0.75 h for the plasma-urine studies and 0.192 h for the saliva-urine studies. There were parallel changes in antipyrine half-life estimated from plasma and urine for one of our subjects who received multiple doses of recombinant beta-interferon and had a 150% increase in antipyrine half-life over the study period.

Adult↗

Immune and histopathological responses in animals vaccinated with recombinant vaccinia viruses that express individual genes of human respiratory syncytial virus.

Previous reports have established that vaccinia virus (VV) recombinants expressing G, F, or N protein of respiratory syncytial (RS) virus protect small animals against intranasal challenge with live RS virus. This work demonstrates that a variety of parameters affect the protection induced by recombinant viruses. The route of vaccination, the subtype of challenge virus, and the species used influenced the antibody titers and extent of protection. During these studies, observations were also made on the subclass of antibody generated, and pulmonary histopathological changes induced by challenge after vaccination were noted. The effect of route of inoculation on host response was examined by vaccinating mice intranasally, intraperitoneally, or by scarification with a recombinant VV expressing the RS virus G glycoprotein. Intranasal vaccination induced 25-fold-higher titers of antibody to RS virus in the lung than the intraperitoneal route did, but both routes resulted in complete suppression of virus replication after intranasal challenge 21 days after vaccination. Scarification was a less effective method of vaccination. The antibody induced by recombinant VV in mice was mostly immunoglobulin G2a (IgG2a) with some IgG2b. No antibody to RS virus was detected in the IgA, IgM, IgG1, or IgG3 subclass irrespective of the vaccination route. The G and F glycoproteins were shown to elicit similar subclasses of antibody. However, animals vaccinated with the G and F vectors differed strikingly in their response to challenge by heterologous virus. Mice or cotton rats vaccinated with recombinant VV carrying the G gene of RS virus were protected against challenge only with homologous subtype A virus. Vaccination with a recombinant VV expressing the F glycoprotein induced protection against both homologous and heterologous subtype B virus challenge. The protection induced in mice was greater than that detected in cotton rats, indicating that the host may also affect immunity. Finally, this report describes histological examination of mouse lungs after vaccination and challenge. Vaccinated mice that were subsequently challenged had significantly greater lung lesion scores than unvaccinated challenged mice. The lesions were primarily peribronchiolar and perivascular infiltrations of polymorphonuclear cells and lymphocytes. Further work will establish whether these pulmonary changes are a desirable immune response to virus invasion or a potential immunopathogenic hazard. The results have important implications for planning a strategy of vaccination against RS virus and emphasize potential dangers that may attend the use of recombinant VV as vaccines.

Administration, Cutaneous↗

Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro.

Pseudomonas aeruginosa culture filtrates varied in their ability to slow human ciliary beat frequency (7-71%). This activity did not correlate with known virulence factors. However, a close correlation (r = 0.97) existed between ciliary slowing and pigment content. In a prolonged culture, the increase in activity correlated (r = 0.94) with pigment accumulation. Gel filtration of lyophilized filtrate yielded a single peak of activity corresponding to the pigment fraction. Pyocyanin extracted from an active strain, and 1-hydroxyphenazine were purified by high performance liquid chromatography, and characterized by ultraviolet absorbance spectra and mass spectrometry. Both slowed cilia in a dose-dependent manner, and were synthesized and shown to be indistinguishable from the biological compounds. Pyocyanin caused gradual onset of slowing and ultimate widespread ciliostasis with epithelial disruption. 1-hydroxyphenazine caused rapid onset of ciliary slowing associated with dyskinesia and ciliostasis. Pyocyanin assayed within filtrates accounted for a significant proportion of the bioactivity present.

Alginates↗

Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells.

Little is known of the role of T-cell mediated immune responses in the clearance and pathogenesis of respiratory syncytial virus (RSV) infection. In this study, we established persistent pulmonary RSV infections in athymic nu/nu BALB/c mice or immunodeficient irradiated BALB/c mice, and examined the patterns of virus clearance following adoptive transfer of splenic memory T cells. Primed T cells transferred between Day 5 and Day 8 of infection will clear lung RSV from both nu/nu mice and irradiated mice within 10 days of transfer. Partially purified Lyt 2+ T cells are more effective than L3T4+-selected T cells. No RSV-specific serum antibody could be detected, suggesting that clearance is by an antibody-independent mechanism. In contrast, delayed (Day 14) transfer of primed L3T4+-selected cells clears lung RSV from nu/nu mice, and this correlates with RSV-specific serum antibody production. Clearance is not seen following Day 14 transfer of total primed T cells or T cells selected for the Lyt 2+ subset.

Animals↗

Modified enzyme immunoassays for tobramycin using reduced sample and reagent volumes.

The accuracy of two modified enzyme immunoassay (EMIT) methods using reduced sample and reagent volumes for determining serum tobramycin concentrations was compared with that of the standard method. The modified EMIT assays used sample and reagent volumes of 25 and 30 microL instead of the standard 50-microL volumes. Solutions of tobramycin sulfate with known concentrations of 1, 2, 4, 8, and 12 mg/L were assayed five times using each of the three methods. Fourteen blood samples containing unknown concentrations of tobramycin were obtained from patients over a four-week period and assayed once by each method. The mean percentage recovery of tobramycin using the standard 50-microL sample-volume method (104.4 +/- 8.8%) was not significantly different from that of the 30-microL (106.6 +/- 9.9%) or the 25-microL (100.4 +/- 11.4%) assay method. There was good correlation between the standard method and the 25-microL (r = 0.993) and the 30-microL (r = 0.988) methods for determining unknown tobramycin concentrations. If the 25- and 30-microL assays were used in place of the standard 50-microL assay, costs would be reduced and the number of assays per kit would increase. The 30-microL and 25-microL sample and reagent volumes used in this study for the tobramycin EMIT assay allow substantial cost savings without a significant loss in accuracy.

Analysis of Variance↗

The role of glutathione conjugate metabolism and cysteine conjugate beta-lyase in the mechanism of S-cysteine conjugate toxicity in LLC-PK1 cells.

A cell line derived from pig kidney, LLC-PK1, was grown in a culture system in which the cells express morphological and biochemical characteristics of the proximal tubule. This model was used to investigate the mechanism of S-cysteine conjugate toxicity and the role of glutathione conjugate metabolism. LLC-PK1 cells have the degradative enzymes of the mercapturate pathway, and S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)-L-glutathione are toxic. S-(1,2-Dichlorovinyl)-L-glutathione is not toxic when the cells are pretreated with AT-125, an inhibitor of gamma-glutamyl transpeptidase. The cells respond to a variety of toxic cysteine conjugates. Cysteine conjugate beta-lyase activity is not detectable by standard assays, but can be measured using radiolabeled S-(1,2-dichlorovinyl)-L-cysteine. Pyruvate stimulates the beta-elimination reaction with S-(1,2-dichlorovinyl)-L-cysteine as substrate 2-3-fold. The data suggest that a side transamination reaction regulates the flux of substrate through the beta-elimination pathway; therefore, cysteine conjugate beta-lyase in LLC-PK1 cells may be regulated by transamination, and measurement of lyase activity in some systems may require the presence of alpha-ketoacids. Aminoxyacetic acid blocks both the metabolism of S-(1,2-dichlorovinyl)-L-cysteine to a reactive species which covalently binds to cellular macromolecules and toxicity. Glutathione inhibits the binding of the sulfur containing cleavage fragment to acid insoluble material in vitro. The data provide direct evidence that S-(1,2-dichlorovinyl)-L-cysteine is metabolized to a reactive species which covalently binds to cellular macromolecules, and the binding is proportional to toxicity.

Acetylcysteine↗

Elevations of intracellular cAMP result in a change in cell shape that resembles dome formation in cultured rat glomerular epithelial cells.

Cultured glomerular epithelial cells form a continuous monolayer of polyhedral-shaped cells. PGE2 (1 microgram/ml) in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (MIX) markedly raises intracellular and medium cyclic AMP (cAMP) levels at 20 min (intracellular: MIX alone, 112 +/- 6.6 pmol cAMP/mg protein, MIX plus PGE2, 2252 +/- 63 pmol cAMP/mg protein; medium: MIX, 20.6 +/- 2.1 pmol cAMP/mg protein; MIX plus PGE2, 117 +/- 3.8 pmol cAMP/mg protein). By 2 h, when cellular and medium cAMP levels were still elevated, the cells underwent a change in shape that was similar to dome formation (15 to 20% of the monolayer changing shape). Derivatives of cAMP [i.e. dibutyryl and 8-(4-chlorophenylthio)-cAMP], when added to the incubation medium also caused shape change in glomerular epithelial cells at 2 h; cAMP itself did not. The formation of domes has been used as a morphological indicator of the vectorial transport of salt and water in other cultured epithelial cells.

1-Methyl-3-isobutylxanthine↗

Pulmonary absorption of carboxyfluorescein in the rat.

The pulmonary absorption of the fluorescent marker 6-carboxyfluorescein (CF) has been characterized. CF was administered intratracheally (i.t.) as a fluid instillate to pentobarbitone-anaesthetized rats at doses of 0.5 and 2 mg kg-1. The absorption was characterized by both model-independent and model-dependent pharmacokinetic analyses of blood concentration data with reference to previous intravenous (i.v.) studies. The mean fraction available (F) of CF was 90 and 112% with a mean absorption time of 107 and 109 min for the lower and higher doses, respectively. The terminal half-life for the i.t. administered CF (73 and 83 min for the 0.5 and 2 mg kg-1 doses, respectively) was significantly longer (P less than 0.001) than after i.v. dosing (18 min). This indicates a slow pulmonary absorption of CF. Blood concentration-time profiles could not be adequately described by models involving a simple first-order absorption process; a model incorporating two simultaneous first-order inputs gave a much better description, its absorption rate constants differing by almost two orders of magnitude.

Absorption↗

Modified latissimus dorsi and teres major transfer for external rotation deficit of the shoulder.

Variable impairment occurs following birth associated brachial plexus injury. Muscle transpositions have evolved in response to patient need for functional reconstruction. Loss of external rotation limits the ability to perform activities with the arm in an overhead position. A modification of the combined latissimus dorsi and teres major transfer is described by means of which increased excursion of the transfer may be achieved.

Birth Injuries↗

Symbolic functioning in anorexia nervosa.

This study examined 20 patients with anorexia nervosa using a projective test with a quantitative scoring system (the SAT9), and an indirect measure of symbolic function (the interoceptive awareness subscale of the EDI). The findings support the clinical observation that patients with anorexia nervosa are often arrested developmentally, and are without the ability to deal adequately with the anxieties created by the process of maturation. The results of this study have significance for the psychotherapy techniques used in the treatment of these patients.

Adult↗