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Biomedical subjects

G Taylor

Publications and source records attributed to G Taylor.

At least 271 records · Page 15Linked to original sources
PubMed1991

Diacylglycerol generation in fluoride-treated neutrophils: involvement of phospholipase D.

Neutrophils exposed to fluoride ion (F-) respond with a delayed and sustained burst of superoxide anion release that is both preceded by and dependent on the influx of Ca2+ from the extracellular medium. The results of this study demonstrate a similarly delayed and sustained generation of 1,2-diglyceride in F(-)-treated neutrophils, over 90% of which was 1,2-diacylglycerol. Diacylglycerol generation was not dependent on the presence of extracellular Ca2+. Conversely, in contrast to results obtained with other agonists, removal of extracellular Ca2+ markedly potentiated synthesis of diacylglycerol in F(-)-treated neutrophils. This effect was accompanied by a corresponding decrease in the recovery of phosphatidic acid. In either the presence or absence of extracellular Ca2+, phosphatidic acid accumulated before diacylglycerol in F(-)-treated cells, suggesting the latter was derived from the former. Consistent with this hypothesis, the phosphatidic acid phosphohydrolase inhibitor, propranolol, suppressed generation of diacylglycerol as it potentiated the accumulation of phosphatidic acid in F(-)-treated neutrophils. This effect was observed both in the presence and absence of extracellular Ca2+. Moreover, high levels of propranolol (160 mumol/L) effected complete inhibition of diacylglycerol generation in F(-)-treated neutrophils with a corresponding increase in phosphatidic acid generation. Phosphatidylethanol accumulated in neutrophils stimulated with F- in the presence of ethanol. The extent of phosphatidylethanol accumulation at all time points after addition of F- corresponded to decreased levels of both phosphatidic acid and diacylglycerol, indicating that phosphatidylethanol was derived from the phospholipase D-catalysed transphosphatidylation reaction. The results indicate that F- activates a Ca(2+)-independent phospholipase D, which appears to be the major, if not sole, catalyst for both phosphatidic acid and diacylglycerol generation in F(-)-treated neutrophils. Ca2+, mobilized as a result of F- stimulation and possibly as a consequence of phospholipase D activation, exerts a profound effect on cellular second messenger levels by modulating the conversion of phosphatidic acid to diacylglycerol.

Calcium↗
PubMed1991

Synthetic peptides corresponding to the F protein of RSV stimulate murine B and T cells but fail to confer protection.

We have previously located a major neutralization site of the fusion protein of respiratory syncytial virus (RSV) in the polypeptide region extending from amino acids Ile221 to Glu232. In this report, 8 peptides corresponding to the six major hydrophilic regions of the F1 subunit were selected to analyse their immunogenic and protective capacities as well as their ability to block the high neutralization activities of 4 monoclonal antibodies (MAbs). Only 5 of the 8 peptides tested induced specific antibodies while all induced an in vitro interleukin-2 response of splenocytes from immunized mice. Peptide 3 (Ile221-Phe237) was able to elicit neutralizing antibodies, confirming our previous hypothesis concerning the location of a neutralization site. However, immunization with the latter did not induce significant reduction of virus in lungs of BALB/c mice upon challenge, probably due to an inadequate level of circulating neutralizing antibodies. Interestingly, peptides 2 (Asn216-Glu232), 3 (Ile221-Phe237), and 5 (Ser275-Ile288) blocked in vitro neutralization by four different F1 specific MAbs. A hypothesis is proposed to explain these results.

Amino Acid Sequence↗
PubMed1991

Effect of Pseudomonas aeruginosa-derived pyocyanin and 1-hydroxyphenazine on pulmonary mucociliary clearance monitored scintigraphically in the baboon model.

The effect of products of the bacterium Pseudomonas aeruginosa on mucociliary lung clearance has been monitored in vivo in the baboon model by scintigraphy. Clearance was found to be inhibited by both 1-hydroxyphenazine and pyocyanin, and a dose-effect was illustrated by the former. This confirms previous in vitro results as well as results from work on guinea-pigs, and holds good prospects for the use of the baboon model under anesthesia in such investigations.

Aerosols↗
PubMed1991

Reshaping a human monoclonal antibody to inhibit human respiratory syncytial virus infection in vivo.

We transferred the complementarity determining regions from a murine monoclonal antibody that neutralizes infection by respiratory syncytial virus (RSV) to a human IgG1 monoclonal antibody. The resulting reshaped human antibody lost affinity for RSV, but an additional alteration to one of the framework regions restored binding affinity and specificity. This second generation reshaped human monoclonal antibody cross-reacted with all clinical isolates of RSV tested and both prevented disease and cured mice even when administered four days after infection. We expect the antibody will prove useful in the management of this major childhood disease.

Amino Acid Sequence↗
PubMed1991

A process for developing a curriculum in ethics and human values.

This article describes the process and results of the deliberations of the group of authors at the 1989 spring meeting of the Northeast Group for Educational Affairs. The participants worked under the premise that someone had given an unlimited amount of money to fund a new medical school. They had to select and define what the educational goals would be and produce a plan to help students reach these goals. There had to be an evaluation process that documented progress toward the stated goals. This paper describes the ethics and human values curriculum, which should be of interest to cancer educators. The knowledge, skills, values, and attitudes are defined and the four-year process of implementing the teaching is described. This curriculum-planning process is applicable to any aspect of cancer education--first defining the outcome, then the evaluation process, and finally, how to get to that outcome.

Curriculum↗
PubMed1991

Comparison of the virulence of wild-type thymidine kinase (tk)-deficient and tk+ phenotypes of vaccinia virus recombinants after intranasal inoculation of mice.

A recombinant vaccinia virus vector was constructed which expressed the major surface glycoprotein G of human respiratory syncytial virus (RSV) and the thymidine kinase (tk) gene of vaccinia virus. The virulence of this tk+ recombinant virus was compared with that of a tk- recombinant and the wild-type (wt) virus after intranasal inoculation of mice. Respiratory infection with wt virus resulted in a lethal infection with widespread dissemination of virus. In contrast, infection with the tk- recombinant was not lethal and the virus had a reduced ability to disseminate to extrapulmonary tissue compared with wt virus. Insertion of the tk gene restored the virulence of the recombinant virus to the level of that of the wt virus. Despite a dramatic reduction in virulence of the tk- recombinant, virus could occasionally be recovered from the brains of mice. The expression of the attachment glycoprotein of RSV appeared to enhance the ability of the tk- recombinant virus to replicate in the lungs when compared with recombinants expressing fusion or nucleoprotein genes. The results confirm that inactivation of the tk gene results in a dramatic reduction of virulence for mice but suggest that there is still a potential danger of infection of the brain following intranasal administration of virus.

Animals↗
PubMed1991

Blunt liver trauma at sunnybrook Medical Centre: a 13 year experience.

Between June 1, 1976 and June 30, 1989 The Regional Trauma Unit at Sunnybrook Medical Centre in Toronto, Ontario, Canada received 3730 patients. Of these 335 (9%) sustained a liver injury, 95% being due to blunt trauma. Open peritoneal lavage was performed on 80% of liver trauma patients (267/335), 99% being true positive. A laparotomy was performed on 97% of patients (324/335). Major surgical treatment was required in 132 patients (41%) and minor treatment in 192 patients (59%). The remaining 11 patients were treated conservatively (n = 3) or died during resuscitation (n = 8). Morbidity directly related to the liver injury was seen in 29 of 249 surviving patients (11%) although overall morbidity was 27% (67/249). Reoperation was required in 6% (14/249) with abscess or hematoma accounting for 11 of 14 operations. The overall mortality rate was 26% (86/335). Eighty two percent of patients (n = 276) had a grade I, II or III liver trauma according to Moore's classification with a mortality of 12% (n = 32). The remaining 18% of patients (n = 59) had a grade IV or V liver trauma with a mortality of 44% (n = 26). Of the 86 deaths, head injury accounted for 48 (56% of deaths); liver hemorrhage for 17 (20%), liver sepsis for 1 (1%) and other causes for 20 deaths (23%). Thus death due to the liver injury itself (hemorrhage and sepsis) occurred in 18 out of 335 patients (5% overall). Head injury accounted for the death of 48 out of 335 patients (14% overall). Over the past 13 years a trend has occurred at our institution whereby we are seeing less liver trauma in our population of multiply injured patients from 12% (1976-1983) down to 7% (1985-1989); with a gradual decline in overall mortality from 32% (1976-1983) to 19% (1985-1989), whereas the percentage of deaths due to head injuries and liver injury have increased.

Cause of Death↗
PubMed1991

Oxamniquine pharmacokinetics in healthy Kenyan African volunteers.

Oxamniquine pharmacokinetics were studied following oral administration of 750, 1000 mg or 1250 mg (equivalent to approximately 15 mg/kg) to five healthy Kenyan African volunteers. Peak plasma concentrations ranging between 1 and 4.3 mg/1 were achieved 1 to 4 h after dosing. The estimated mean elimination half-life (t1/2) was 2.2 h. Despite the limited number of subjects in the study, it is concluded that the pharmacokinetics of oxamniquine in healthy Kenyan Africans do not markedly differ from those in Africans from other regions of the continent where previous studies have been reported.

Administration, Oral↗
PubMed1991

Wound infections in orthopedic surgery: effect of extended surveillance on infection rate.

Substantial evidence now exists that ongoing surveillance of surgical wound infections can contribute to reduced infection rates. What is not yet determined is whether surveillance should be limited to the postoperative hospital stay or should be continued after patient discharge. To determine the number of infections occurring after discharge, the authors contacted a random sample of their patients who did not have wound infections during their hospitalization after orthopedic surgery. This was done 30 days after the procedure. The authors selected 273 patients of 1375 who underwent orthopedic surgery over a 7-month period and were able to contact 199 (73%). At the 30-day follow-up 23 patients (11.6%) had wound infections, as judged by wound discharge and physician prescription of antibiotics in 20 and the patient's description of pus issuing from the wound in 3. During the same period postoperative wound infections were found in only 19 (1.5%) of 1278 patients who were subjected to in-hospital surveillance. The authors conclude that, in patients who undergo orthopedic procedures, the majority of wound infections occur after discharge from the hospital and that infection rates based only on in-hospital surveillance greatly under represent true surgical wound infection rates for orthopedic procedures.

Alberta↗
PubMed1990

The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dry air.

BACKGROUND: The enzyme 5-lipoxygenase catalyzes the metabolism of arachidonic acid to form products that have been implicated in the airway obstruction of asthma. We hypothesized that if products of the 5-lipoxygenase pathway are important in mediating this obstruction, then prevention of their formation should decrease the severity of an induced asthmatic response. METHODS: In a randomized, double-blind, placebo-controlled, crossover study, we examined the effect of A-64077, a 5-lipoxygenase inhibitor, on the bronchoconstriction induced by hyperventilation of cold, dry air in 13 patients with asthma. The completeness of 5-lipoxygenase inhibition was confirmed by examining the profile of eicosanoids produced in whole blood ex vivo after activation with the calcium ionophore A-23187. RESULTS: A-64077 decreased the mean (+/- SEM) ionophore-induced synthesis of leukotriene B4, a 5-lipoxygenase product, by 74 percent (from 265.3 +/- 30.3 to 69.5 +/- 21.5 ng per milliliter, P less than 0.001), but it did not affect the ionophore-induced synthesis of thromboxane B2, a cyclooxygenase metabolite of arachidonic acid (80.0 +/- 17.1 ng per milliliter before A-64077 vs. 75.8 +/- 14.3 ng per milliliter after A-64077). In concert with the selective inhibition of 5-lipoxygenase by A-64077, the amount of cold, dry air (expressed as respiratory heat exchange) required to reduce the forced expiratory volume in one second by 10 percent was increased by 47 percent after A-64077 (3.0 kJ per minute for placebo vs. 4.4 kJ per minute for A-64077, P less than 0.002). Similar results were obtained when minute ventilation was used as an indicator of outcome (27.5 liters per minute for placebo vs. 39.8 liters per minute for A-64077, P less than 0.005). CONCLUSIONS: Selective inhibition of 5-lipoxygenase by A-64077 is associated with a significant amelioration of the asthmatic response to cold, dry air, suggesting that 5-lipoxygenase products are involved in this response. This approach may be useful in the treatment of asthma.

Asthma↗
PubMed1990

X-ray analyses of aspartic proteinases. II. Three-dimensional structure of the hexagonal crystal form of porcine pepsin at 2.3 A resolution.

The molecular structure of the hexagonal crystal form of porcine pepsin (EC 3.4.23.1), an aspartic proteinase from the gastric mucosa, has been determined by molecular replacement using the fungal enzyme, penicillopepsin (EC 3.4.23.6), as the search model. This defined the space group as P6522 and refinement led to an R-factor of 0.190 at 2.3 A resolution. The positions of 2425 non-hydrogen protein atoms in 326 residues have been determined and the model contains 371 water molecules. The structure is bilobal, consisting of two predominantly beta-sheet lobes which, as in other aspartic proteinases, are related by a pseudo 2-fold axis. The strands of the mixed beta-sheets (1N and 1C) of each lobe are related by an intra-lobe topological 2-fold symmetry. Two further beta-sheets, 2N and 2C, are each composed of two topologically related beta-hairpins folded below the 1N and 1C sheets. A further six-stranded sheet (3) spans the two lobes and forms a structure resembling an arch upon which the four other sheets reside. The interface between sheets 1N and 1C forms the catalytic centre consisting of absolutely conserved aspartate residues 32 and 215, which are shielded from solvent by a beta-hairpin loop (75 to 78). The crystal structure of a mammalian aspartic proteinase indicates that interactions with substrate may be more extensive on the prime side of the active site cleft than in the fungal enzymes and involve Tyr189 and the loop 290 to 295, perhaps contributing to the transpeptidase activity of pepsin and the specificity of the renins. Comparison with the high-resolution structure of pepsinogen gives a root-mean-square deviation of 0.9 A and reveals that, in addition to local rearrangement at the active site, there appears to be a rigid group movement of part of the C-terminal lobe of pepsin towards the cleft on activation. A large proportion of the absolutely conserved residues in aspartic proteinases are polar and buried. An examination of the pepsin structure reveals that these side-chains are involved in hydrogen-bond interactions with either the main chain of the protein or other conserved side-chains of the enzyme or propart.

Amino Acid Sequence↗