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K M Taylor

Publications and source records attributed to K M Taylor.

At least 19 recordsLinked to original sources
PubMed1992

Mechanism of magainin 2a induced permeabilization of phospholipid vesicles.

The magainins, peptide antibiotics secreted by the frog Xenopus laevis, have previously been shown to permeabilize phospholipid vesicles. To elucidate the mechanism of permeabilization, we have conducted detailed kinetic studies of magainin 2 amide (mgn2a)-induced release of 6-carboxyfluorescein from vesicles of phosphatidylserine. The results show that dye release occurs in (at least) two stages--an initial rapid phase, with t1/2 approximately 3 s, followed by a much slower phase that approaches zero leakage rate before all the dye is released. Light-scattering studies showed that mgn2a does not cause gross changes in vesicle structure. The peptide was found to rapidly equilibrate between vesicles; this was demonstrated by determining a binding isotherm for the peptide-lipid interaction, and by showing that addition of unloaded vesicles rapidly quenches peptide-induced leakage from loaded vesicles. Transient dye release in the presence of an equilibrating peptide can be explained in two ways: (1) the peptide exists only transiently in an active form; (2) the vesicles are only transiently leaky. Preincubation of mgn2a at assay concentrations in buffer alone or with unloaded vesicles did not inactivate the peptide. Therefore, rapid leakage is probably due to transient destabilization of the vesicle upon addition of mgn2a.

Animals↗
PubMed1992

Regional distribution and regulation of [125I]calcitonin gene-related peptide binding sites in coronary arteries.

Quantitative in vitro autoradiographic techniques were used to localize and characterize 125I-labelled human calcitonin gene-related peptide ([125I]hCGRP) binding sites in sections of bovine left anterior descending coronary artery (LAD). Specific high affinity (Kd 0.4 nM) [125I]hCGRP binding sites were localized to the media of both epicardial and myocardial coronary arteries. Binding site density was greater in distal epicardial and myocardial arteries than in proximal epicardial regions of the LAD. Binding sites exhibited a significantly higher affinity for alpha-hCGRP (Ki 1.1 nM) than for hCGRP-(8-37) (Ki 7.0 nM) and [Cys(ACM)2,7]hCGRP (Ki 27.4 nM). Guanosine-5'-O-(3-thiotriphosphate) inhibited [125I]hCGRP binding in a concentration-dependent manner. Extrinsic denervation of the bovine heart resulted in a depletion of CGRP-like immunoreactive perivascular nerve fibres and an increase in the density of coronary artery [125I]hCGRP binding sites (P = 0.0092). The regional distribution of binding sites in human coronary arteries differed from that observed in bovine and porcine vessels. It is concluded that selective, G protein-coupled, CGRP receptors are present in the media of bovine coronary arteries; there are both regional and species differences in the distribution of CGRP binding sites in coronary arteries and endogenous CGRP may exert a tonic influence on coronary vasomotor tone.

Animals↗
PubMed1992

Granulocyte colony stimulating factor in the management of chronic neutropenia.

OBJECTIVE: To report two cases of chronic neutropenic states successfully treated with granulocyte colony stimulating factor (G-CSF). CLINICAL FEATURES: A 23-year-old man with severe congenital cyclic neutropenia causing lifelong recurrent infections and consequent debilitation presented with intractable infected leg ulcers. A 56-year-old man with acquired idiopathic neutropenia presented with severe perianal infection and sepsis. INTERVENTION AND OUTCOME: Both patients were successfully treated with recombinant G-CSF. CONCLUSION: G-CSF is an agent with major clinical potential for the therapy of primary neutropenic states.

Adult↗
PubMed1992

CGRP-immunoreactive endocrine cell proliferation in normal and hypoxic rat lung studied by immunocytochemical detection of incorporation of 5'-bromodeoxyuridine.

We have tested the suggestion that the reported increase, in hypoxic rats, in the number of lung endocrine cells immunoreactive for the regulatory peptide CGRP is caused by an accumulation of peptide within the cells which renders them more detectable, rather than by a real increase in proliferation. The incorporation of continuously infused 5'-bromodeoxyuridine (BrdU) into nuclei of CGRP-containing cells was studied by immunohistochemistry in the airway and respiratory epithelium of rats kept in a hypoxic (10% O2), normobaric conditions for 7 days and in normoxic, normobaric controls. Some CGRP-immunoreactive cells could also be labelled for BrdU. However, the ratio of the number of cells labelled with both CGRP and BrdU to the number of cells labelled with CGRP alone did not differ significantly between hypoxic and normoxic rats (7.1 +/- 0.7 and 6.1 +/- 1.2, respectively; mean +/- SEM; P = 0.49). These data strongly suggest that CGRP-containing endocrine cells or their precursors do proliferate in adult rat lung, but that the proliferation is not increased significantly in hypoxia.

Animals↗
PubMed1992

Integrating conflicting professional roles: physician participation in randomized clinical trials.

The traditional identification of physicians as either clinician or researcher is challenged by the emergence of randomized clinical trials (RCTs) where research and clinical care are performed simultaneously. A mail survey using a self-administered questionnaire, the Physician Orientation Profile, was conducted of 101 physicians from the Collaborative Ocular Melanoma Study (COMS), a set of trials which compares surgical removal of the eye with radiation in the treatment of medium sized eye cancers. A 95% response rate was obtained; follow-up telephone interviews were conducted with 87% of respondents. Key findings suggest that RCTs challenge traditional definitions of physician's 'core task,' because they participate in a social process that requires them to integrate the formerly disparate and sometimes competing roles of researcher and clinician. Three implications of this integration are discussed: amending the expert reward system, altering customary clinical practice and redefining reference groups for professional interaction.

Adult↗
PubMed1992

Cardiac denervation in the calf using cryoablation: functional evidence and regional tissue catecholamine content.

Twenty-six calves were subjected to a technique of cryoablation in order to establish an animal model of complete cardiac denervation. All 26 survived the procedure, and 20 were alive to be re-evaluated 2-4 weeks later. Mean heart rate in the denervated animals rose from 77 +/- 7.8 beats/min to 102 +/- 16.4 (P less than 0.01). Cryoablation abolished the heart rate responses to electrical stimulation of the vagus nerve and thoracic sympathetic trunk. The reduction in myocardial noradrenaline concentrations averaged 99% in the right atrium, 90% in the left atrium, 85% in the right ventricle and 90% in the left ventricle, when compared with tissue obtained from control animals. Cryoablation is a relatively simple means of accomplishing complete functional cardiac denervation in the calf. On the basis of the observed change in heart rate, the calf model appears to be more comparable with human heart transplant recipients than the dog.

Animals↗
PubMed1992

Capillary plasma elastase alpha 1-proteinase inhibitor in infected and non-infected neonates.

Capillary heel prick plasma elastase alpha 1-proteinase inhibitor (E alpha 1-PI) measured by an immunoassay (using commercially available reagents) was examined as an early indicator of neonatal sepsis. Fifty five infants were studied within 24 hours of birth; 60 (including 10 studied on the first day of life) were examined between two and 30 days after birth. Reference ranges for the neonatal period were developed. Raised E alpha 1-PI concentrations (range 440-2600 micrograms/l) were found at the outset of each of the 24 infectious episodes including five with concomitant neutropenia. On the first day of life, obstetric and neonatal complications were also associated with high concentrations (range 190-2400 micrograms/ml). In infants who survived infection, E alpha 1-PI normalised with antibiotic treatment. It is concluded that capillary heel prick plasma is suitable for E alpha 1-PI testing and raised concentrations provide a sensitive but non-specific index of infection in the first 24 hours after birth. Sequential testing may provide early warning of infectious complications and serve as a guide to the cessation of antibiotic treatment.

Bacterial Infections↗
PubMed1992

The United Kingdom Heart Valve Registry.

The United Kingdom Heart Valve Registry project began in 1986 following discussions between the Department of Health (DOH) and the Society of Cardiothoracic Surgeons of the United Kingdom and Ireland. The intention was to establish a computerized database for valve replacement operations carried out in the UK Health Service cardiac units. This paper describes the experience gained over the first five years of this project. Around 30,000 patients were entered in the registry between 1986 and 1990. All Uk Health Service cardiac surgical units contribute their data, which is processed by the central Registry Office. The accuracy of the mortality data is ensured by tracking the registered patients through the Office of Population Census and Surveys (OPCS). The pattern of valve replacement surgery over the period 1986-90 revealed several interesting trends. Although the number of procedures remained static at around 5,000 valve transplants per year, the number of aortic replacements increased and the number of mitrals decreased. The use of prosthetic valves increased from 54% in 1986 to over 70% in 1990. The mean age of the patients increased from 58.31 years in 1986 to 60.97 years in 1990, with over 22% of the valve replacement operations in 1990 being performed on patients over 70 years of age. The five year survival rate for patients over 70 years at the time of the valve implant is significantly lower than for patients under 70 years (p < 0.005).

Aged↗
PubMed1992

Physician participation in a randomized clinical trial for ocular melanoma.

One substudy of the Collaborative Ocular Melanoma Study (COMS) is a randomized trial examining surgery versus radiation therapy for ocular melanoma. To understand the perspective of the physician investigators, a survey of the 101 COMS physicians from 29 major institutions in the United States and Canada was completed before randomization of the first patient. A 95% response rate was obtained, and follow-up interviews were conducted with 87% of the physicians. The study found that (1) COMS physicians identified significant differences between incentives and disincentives to participate in any trial compared with participating in COMS, (2) COMS physicians could be differentiated and had a stronger clinical rather than research orientation, and (3) COMS physicians exhibited a high intention to recruit an identifiable subset of eligible patients. These data suggest that continued support of individual investigators and a close examination of incentives and disincentives to physician participation would be useful in enhancing accrual in this study. A follow-up of this group is planned throughout the anticipated ten-year duration of patient recruitment of this COMS trial.

Adult↗
PubMed1991

Angioscopic evaluation of intravascular morphology after coronary endarterectomy.

Coronary endarterectomy in diffuse coronary disease is attended by an increased incidence of perioperative myocardial infarction and vein graft occlusion, which have been partially attributed to the presence of occlusive or thrombogenic intraluminal flaps in the main vessel or its smaller branches. To define the nature and incidence of these features we studied 15 endarterectomized right coronary arteries in 15 patients (12 men, 3 women; age, 55 +/- 7 years [mean +/- standard deviation]) undergoing a coronary operation for multivessel disease. After endarterectomy and distal graft anastomosis, angioscopy was performed using a 1.8-mm Olympus angioscope during graft perfusion with crystalloid solution. The endarterectomy cores were 66 +/- 30 mm in length with 11 major bifurcations and two trifurcations providing 30 major endpoints. At 22 of 30 major endpoints the distal end of the core was smooth and tapered. There were 17 minor side-branch endpoints. Angioscopy revealed the presence of wispish intraluminal fronds and medial bruising in all (100%) arteries. Twenty-nine of the 30 intraluminal endpoints could be visualized. Major intraluminal flaps were seen at the eight nontapered endpoints and six of the 21 smooth tapered endpoints that were visualized. Fifteen minor side branches could be identified angioscopically: a flap was seen at only one side-branch origin. The average examination time was 3.2 +/- 1.1 minutes (7.7% +/- 2.7% of cross-clamp time), and examination required 200 to 250 mL of perfusate. This technique enables immediate and accurate postinterventional assessment of intravascular morphology with minimal prolongation of ischemic time and has shown that small side branches are not compromised by endarterectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Bypass↗
PubMed1991

Intraabdominal complications after cardiopulmonary bypass.

Thirty-three intraabdominal complications occurred in 27 patients over a 16-year period in 4,629 patients who underwent cardiopulmonary bypass (0.58% incidence). The mortality was 14.8% for the intraabdominal complication group compared with 3.4% for the control group of patients (p less than 0.01). The most common complication was gastrointestinal hemorrhage (n = 20), of which esophagitis (n = 6) was the most common cause. However, patients with duodenal ulcer (n = 4) had the highest mortality; 2 patients who underwent truncal vagotomy and pyloroplasty subsequently died. Two further patients underwent operation for perforated anterior duodenal ulcers without further morbidity. Cholecystitis developed in 5 patients and acute pancreatitis in 4; all were managed nonoperatively with no mortality. Multisystem organ failure developed in 2 patients, of whom 1 died. There was a significant correlation between intraabdominal complications and prolonged bypass time. The mean bypass time was 96.7 +/- 28.6 minutes for the patients with gastrointestinal complications, compared with 81.7 +/- 48.4 minutes for the whole group (p less than 0.01). No correlation was demonstrated for type of operation undergone or the age of the patient. In the last 5 years, 2,145 patients underwent cardiopulmonary bypass, of whom 562 received pulsatile and 1,583 nonpulsatile flow. The incidence of intraabdominal complications was 0.18% (n = 1) in the pulsatile group compared with 0.63% (n = 10) for the nonpulsatile group (p = 0.14). Intraabdominal complications, although of low incidence, carry a significantly high mortality, and the clinician must be alert in the postoperative period to institute early therapy.

Aged↗
PubMed1991

Development of tumor cell resistance to tumor necrosis factor cytolysis results in reduced fibronectin binding and altered ganglioside expression.

U937A cells are highly susceptible to tumor necrosis factor (TNF) cytolysis. They are also motile and incorporate fibronectin into the extracellular matrix (ECM). This takes the form of a dense fibrillar network in confluent cultures, but in sparse cultures appears as a "snail trail" of insolubilized fibronectin behind the moving cell. In contrast, U937A/R cells selected for resistance to TNF cytolysis are poorly motile and, although they synthesize fibronectin, fail to incorporate it into the ECM. Compared to U937A/R, U937A cells spread more rapidly and extensively on fibronectin-coated plastic and also bound 125I-fibronectin more effectively. Inhibition of U937A spreading on fibronectin required higher doses of GRGDSPK peptide, indicating greater expression on U937A of integrin-type, fibronectin receptors. Gangliosides are non-integrin structures which can bind fibronectin, and there were also qualitative and quantitative differences in ganglioside expression with U937A having two to five times more than U937A/R. Therefore the development of TNF resistance by U937A/R cells is accompanied by a reduced ability to interact with fibronectin, and this probably accounts for the reduced motility and inability to deposit fibronectin in the ECM.

Amino Acid Sequence↗