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Biomedical subjects

L Higgins

Publications and source records attributed to L Higgins.

At least 19 recordsLinked to original sources
PubMed2002

More than zero tolerance? Burnout and tolerance for patient aggression amongst mental health nurses in China and the UK.

OBJECTIVE: The aim of the study was to examine attitudes toward patient aggressive behaviour amongst mental health nurses in China and the UK and the relationship between these attitudes and burnout. The UK government policy of 'zero tolerance' of patient aggression may conflict with practitioner attitudes and could potentially increase the risk of aggression occurring. METHOD: Two surveys of mental health nurses were conducted, one in the People's Republic of China and one in the UK using the Perceptions of Aggression Scale (POAS). The UK sample also completed the Maslach Burnout Inventory (MBI). RESULTS: Some nurses in both groups agreed that patient aggression could sometimes have positive benefits. A sense of personal accomplishment at work (MBI) was significantly associated with a tendency to endorse positive statements about aggression. DISCUSSION: Nurses seem to have a complex set of attitudes toward this issue that do not simply equate with 'zero tolerance'.

Aggression↗
PubMed2001

Reduced outer membrane permeability of Escherichia coli O157:H7: suggested role of modified outer membrane porins and theoretical function in resistance to antimicrobial agents.

Outer membrane permeability of Escherichia coli O157:H7 was determined by an in vivo kinetic model with the periplasmic enzyme alkaline phosphatase [Martinez et al. (1996) Biochemistry 35, 1179-1186]. p-Nitrophenyl phosphate (PNPP) substrate, added to intact bacteria, must diffuse through the outer membrane to reach the enzyme. At low substrate concentration the bacterium was in the perfectly reactive state where all molecules that entered the periplasm were captured and converted to product. Transmembrane diffusion was rate limiting, and the permeability of the outer membrane was determined from kinetic properties. The O157:H7 strain grown at 30 degrees C showed one-sixth the permeability of wild-type E. coli grown at 30 degrees C. Wild-type bacteria grown at >/=37 degrees C show a physiological response with a shift in expression of outer membrane porins that lowered permeability to PNPP by approximately 70%. The O157:H7 strain did not display this temperature-sensitive shift in permeability even though a change in porin expression could be visualized by staining intensity of Omp F and Omp C on acrylamide gels. Altered behavior of the O157:H7 membrane was also indicated by a several thousand-fold lower response to transformation relative to wild-type E. coli. Matrix-assisted laser desorption ionization time of flight mass spectrometry and electrospray ionization mass spectrometry confirmed the expression of the Omp F and Omp C variants that are unique to E. coli O157:H7. This reduced outer membrane permeability can contribute to enhanced resistance of O157:H7 to antimicrobial agents.

Amino Acid Sequence↗
PubMed2001

An assessment of the reaction energetics for cytochrome P450-mediated reactions.

Regioselectivity is used to determine the absolute energetic differences for four different reactions catalyzed by P450. Abstraction of a hydrogen from a benzylic carbon containing a chlorine has a 1.0 kcal/mol lower barrier than abstraction from a simple benzylic carbon, which in turn is 0.4 to 0.9 kcal/mol lower than abstraction from the methyl group of an aromatic ether and 0.1 to 0.6 kcal/mol easier than aromatic hydroxylation. Isotope effects are used to determine if the enzyme-substrate complexes leading to each product, from a given substrate, are in rapid equilibrium. For all enzymes isotopically sensitive branching is observed from the benzylic carbon upon deuterium incorporation at that position to each of the other positions, indicating that each product arises from the same active oxygen species. The energetic differences determined experimentally are accurately reproduced by theoretical hydrogen atom abstractions at both the AM1 semiempirical and DFT levels of theory.

Anisoles↗
PubMed2001

Mass spectrometric analysis of recombinant adenylate cyclase toxin from Bordetella pertussis strain 18323/pHSP9.

The adenylate cyclase toxin-hemolysin (ACT) is a key virulence factor of the whooping cough agent Bordetella pertussis (Bp). The major cytotoxic activity of this 1706-residue protein consists of its capacity to invade a variety of eukaryotic cells directly across their cytoplasmic membrane and to deliver into cells a catalytic adenylate cyclase domain. This causes impairment of immune effector cells and apoptosis of lung macrophages by uncontrolled conversion of ATP to cAMP. The adenylate cyclase toxin-hemolysin acquires biological activity upon post-translational amide-linked palmitoylation of the epsilon-amino group of lysine 983 (K983) by the accessory fatty acyltransferase, CyaC. However, an additional conserved acylation site can be identified in ACT at lysine 860 (K860) and this residue is palmitoylated when recombinant ACT is produced in Escherichia coli (r-Ec-ACT). In this paper we report the double acylation of r-Bp-ACT secreted by a recombinant Bp strain 18323/pHSP9. This strain overproduces ACT from an oligocopy plasmid carrying the entire cya locus of Bordetella pertussis 18323. Palmitoylation of both conserved lysines (K860 and K983) of r-Bp-ACT expressed by this Bp strain was found. In addition, an error in the deduced protein sequence was identified, with Leu being the real residue at position 1001 and not the Val residue given in the published gene sequence. We also discuss these results in comparison with those from recombinant ACT expressed in E. coli strain K12 XL1-Blue. The analytical approach for characterization of the fatty acylation of ACT from strain 18323/pHSP9 consisted of multiple proteolytic digestion procedures (trypsin, Asp-N), microcapillary liquid chromatography/tandem mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Adenylate Cyclase Toxin↗
PubMed2001

Composition and mass of the bacteriophage phi29 prohead and virion.

The protein composition of the Bacillus subtilis bacteriophage phi29 prohead and virion was determined by combustion of gel bands of (3)H-labeled proteins. Copy numbers of individual proteins were calculated relative to the 12 copies of the head-tail connector protein. The mean numbers of copies of the major capsid protein in the prohead and virion were 241 and 218, respectively, approaching the 235 copies determined previously by cryoelectron microscopy. The mean numbers of copies of the dimeric head fiber on the prohead and virion were 24 and 31, respectively, demonstrating partial occupancy of the 55 fiber binding sites. Measured copies of neck and tail proteins in the virion included 11 of the lower collar, 58 of the appendage, and 9 of the tail; if the true copies of these proteins are 12, 60, and 9, respectively, the entire neck and tail of phi29 has quasi-sixfold symmetry. The mass of the fiberless prohead with pRNA was about 14.2 MDa, and the mass of the prohead determined by scanning transmission electron microscopy was consistent with the biochemical data. The mass of the fiberless virion containing the 12.8-MDa DNA genome was about 30.4 MDa. A full complement of dimeric fibers on the prohead or virion would increase the mass of the particle by about 3.2 MDa. The data complement studies relating the structure of phi29 components to dynamic functions in morphogenesis and infection.

Bacillus Phages↗
PubMed2001

Enhancing recall of information from a patient education booklet: a trial using cardiomyopathy patients.

A quasi-experimental trial was conducted to compare the effect on information recall of: (a) the use of adjunct questions (AQ) in printed materials; and (b) a procedure (the 5Rs) for integrating printed patient education materials into face-to-face teaching. A total of 51 patients with severe left ventricular failure (cardiomyopathy) was assigned to one of three groups (n=17). Each group worked with a purpose-prepared booklet, the first in association with the 5Rs procedure; the second group with a version of the booklet containing adjunct questions; and the third with a text only version of the booklet. Recall of information from the booklet was measured using a checklist scored on the basis of responses secured in a standardised interview. Improved recall was associated with both the adjunct questions and the 5Rs procedure, with the latter achieving a substantially superior outcome. The practical implications of these findings are presented and directions for further research indicated.

Analysis of Variance↗
PubMed2000

A tissue specific IL-1 receptor antagonist homolog from the IL-1 cluster lacks IL-1, IL-1ra, IL-18 and IL-18 antagonist activities.

Interleukin (IL)-1-like protein 1 (IL-1L1) is a 155-amino acid protein that shares 27% identity with IL-1beta and 47% with IL-1 receptor antagonist (IL-1ra). A 2.7-kb IL-1L1 mRNA was cloned from human placenta and is detectable in the trophoblastic cell line JEG-3, in macrophages and in endotoxin-stimulated monocytes. Expression of IL-1L1 is much less abundant and less widespread than IL-1ra. We have determined the human and mouse IL-1L1 cDNA sequences and the complete sequence of the human gene, IL1L1. IL1L1 consists of four coding exons, has two alternative non-coding first exons, lies between IL1B and IL1RN, is orientated in the same direction as IL1RN and is separated from it by approximately 53 kb. The predicted IL-1L1 protein lacks both signal sequence and glycosylation signals. A 17-kDa protein was recovered by immunoprecipitation with IL-1L1-specific antibodies from JEG-3. IL-1L1 did not stimulate IL-6 production from primary human fibroblasts or human umbilical vein endothelial cells nor did it block the IL-1alpha or IL-1beta-dependent activation of IL-6 expression. We conclude, contrary to a recent suggestion made by others, that IL-1L1 is not a functional IL-1ra. IL-1L1 also had no detectable agonistic or antagonistic effect on IFN-gamma production in response to IL-18 in KG-1 cells.

Amino Acid Sequence↗
PubMed1999

Critical pathways: application to selected patient outcomes following coronary artery bypass graft.

As health care reform evolves in the United States, many hospitals are implementing strategies to contain the cost of coronary artery bypass graft (CABG) surgery. The purpose of this study was to examine the length of stay in the intensive care unit (ICU) after CABG surgery relative to the number of hours, postoperation, when ambulation occurred, and to examine the overall postoperative length of hospital stay. The study found a significant difference between ICU length of stay and the time when ambulation was initiated (t(150) = -2.68; p = .004). These results suggest that CABG patients with shorter ICU stays begin ambulation sooner, thus potentially reducing the risk of postoperative complications as well as cost. No other significant differences were demonstrated.

Adult↗
PubMed1999

Effect of circumferential plasma-spray porous coating on the rate of femoral osteolysis after total hip arthroplasty.

BACKGROUND: Osteolysis of the femur has been a serious problem associated with some designs of total hip-replacement implants; it frequently leads to failure of the femoral component. We evaluated the effect of a circumferential plasma-spray porous coating on the rate of osteolysis in a study that included two groups of hips, each of which received an implant with the same design except for the extent of the porous coating. Our goal was to determine the possible role of circumferential porous coating in protecting the bone-implant interface from osteolysis. METHODS: A series of consecutive primary total hip replacements performed with insertion of the Mallory-Head implant without cement was divided into two study groups. The first 126 hips (Group 1) were treated with a femoral stem that had a noncircumferential plasma-spray porous titanium coating. The next ninety hips (Group 2) were treated with a circumferentially coated stem of the same design. The average duration of radiographic follow-up was 7.8 years in Group 1 and 7.5 years in Group 2. RESULTS: The average rate of polyethylene wear was similar for the two groups (0.187 millimeter per year in Group 1 and 0.189 millimeter per year in Group 2). The prevalence of osteolysis in Group 1 (40 percent; fifty of 126 hips) was significantly higher than that in Group 2 (10 percent; nine of ninety hips) (p < 0.001). Osteolysis remote from the joint space (distal to zones 1 and 7) was found in 11 percent (fourteen) of the hips in Group 1 but in none of those in Group 2 (p = 0.0004). The average total area of osteolysis in Group 1 (5.0 square centimeters) was significantly larger than that in Group 2 (2.9 square centimeters) (p < 0.05). CONCLUSIONS: A circumferential plasma-spray titanium porous coating on the femoral component of a total hip-replacement prosthesis inserted without cement appears to provide an effective barrier preventing wear debris from gaining access to the endosteal surface of the femur and the greater trochanter. This finding supports the hypothesis of the so-called effective joint space, which predicts that wear debris from the joint bearing can migrate, driven by intracapsular pressures, to all areas to which joint fluid has access and thus can result in osteolysis. The reduction of the prevalence of osteolysis and the elimination of osteolysis from the zones remote from the joint space by the use of a circumferential plasma-spray porous coating indicates that the femur was effectively sealed off from the joint space. We believe that the durability and longevity of the femoral component should be enhanced by the use of such a coating.

Coated Materials, Biocompatible↗
PubMed1998

Design of a novel P450: a functional bacterial-human cytochrome P450 chimera.

We report the construction of a functional chimera from approximately 50% bacterial (cytosolic) cytochrome P450cam and 50% mammalian (membrane-bound) cytochrome P450 2C9. The chimeric protein shows a reduced CO-difference spectrum absorption at 446 nm, and circular dichroism spectra indicate that the protein is globular. The protein is soluble and catalyzes the oxidation of 4-chlorotoluene using molecular oxygen and reducing equivalents from bacterial putidaredoxin and putidaredoxin reductase. This chimera provides a novel method for addressing structure-function issues and may prove useful in the design of oxidants for benign and stereospecific synthesis, as well as catalysts for bioremediation of polluted areas. Furthermore, these results provide the first evidence that bacterial P450 enzymes and mammalian P450 enzymes are likely to share a common tertiary structure.

Bacterial Proteins↗
PubMed1998

Evaluation of cytochrome P450 mechanism and kinetics using kinetic deuterium isotope effects.

In this paper two hypotheses are tested: (i) the active oxygen species is similar in energetics for all cytochrome P450 (CYP) enzymes and (ii) linear free-energy relationships can be used to evaluate the mechanism of the reaction of these enzymes. A series of intramolecular isotope effects were determined and compared for CYPs 1A2, 2B1, 2C9, 2E1, and P450cam. The results indicate that the isotope effects are very similar for each of these isoforms of P450 and that the first hypothesis is likely to be true. Attempts to establish a linear free-energy relationship were only moderately successful: log Vmax = 0.11sigma+p + 1.73; r2 = 0.588. It was determined, through the use of intermolecular isotope effects, that the rates of hydrogen atom abstraction are masked. Thus, the second hypothesis is found to be false. This is likely to be a general result for CYP reactions, and linear free-energy relationships can only be used to determine the mechanism under very special circumstances. In all cases, the rate-limiting step should be evaluated with isotope effect experiments before any mechanistic conclusions can be drawn. If the intermolecular isotope effects are found to be masked, no mechanistic conclusion can be drawn from the linear free-energy relationship study.

Binding, Competitive↗
PubMed1998

The treatment of symptomatic os acromiale.

During a four-year period, fourteen individuals (fifteen shoulders) who had been seen at the shoulder service of our institution because of pain in the shoulder had a radiographic finding of an os acromiale. On clinical examination, the pain appeared to be due to an unstable os acromiale because the patients had point tenderness over the acromion and pain on forward elevation of the shoulder. The diagnosis of an os acromiale was confirmed on radiographs, magnetic resonance images, or a bone scan. Eight patients had an associated tear of the rotator cuff. The os acromiale was located in the pre-acromion in one shoulder, the meso-acromion in eleven shoulders, and the meta-acromion in three shoulders. At the operation, the anterior aspect of the acromion was found to be unstable in all shoulders. Eleven patients (twelve shoulders) had open reduction of the os acromiale and insertion of an autogenous iliac-crest bone graft. Of those patients, four (five shoulders) had open reduction and internal fixation with a tension-band procedure with use of pins and wires. Only one of those shoulders had a solid osseous union, and the other four shoulders had a non-union that was due to a disruption of the fixation. The remaining seven patients (seven shoulders) had open reduction and internal fixation with use of cannulated screws and a tension-band construct; a solid osseous union was achieved in all but one of them. One patient had excision of the pre-acromion, which relieved the pain. Two patients who had had failed open reduction and internal fixation had excision of a grossly unstable os acromiale in the meso-acromion; both patients had pain and weakness after this procedure. Of the twelve shoulders that had open reduction and bone-grafting, seven had union of the os acromiale; the average time to radiographic and clinical union was nine weeks (range, seven to twenty weeks). We concluded that, although it is rare, symptomatic unstable os acromiale does occur and can be effectively treated with use of autogenous bone-grafting and internal fixation with a rigid tension-band construct and cannulated screws.

Acromion↗
PubMed1996

Vitamin A status in acute exacerbations of cystic fibrosis.

Vitamin A is an essential nutrient for epithelial cell maintenance and repair, and it is known that infectious stresses may depress plasma vitamin A concentrations. Patients with cystic fibrosis are at risk for vitamin A deficiency because of fat malabsorption as well as for the inflammatory stresses of pulmonary exacerbations of their underlying disease. We therefore hypothesized that acute pulmonary exacerbations of CF would depress plasma retinol concentrations, and that these concentrations would return to baseline values when clinical symptoms improved. We prospectively studied 35 CF patients (mean age: 24.2 y) consecutively admitted with pulmonary exacerbations. Plasma retinol, vitamin E, retinol binding protein (RBP), and C-reactive protein (CRP) concentrations were measured on hospital admission and discharge. Dietary intake was measured by using a semiquantitative food-frequency questionnaire. Regression analysis was used to identify significant clinical and laboratory correlates of retinol concentrations. On admission, mean (+/- SD) concentrations of plasma retinol were 1.14 +/- 0.5 mumol/L compared with 1.70 +/- 0.6 mumol/L on discharge (P = 0.0001). Of 35 subjects, 8 (22.9%) had plasma retinol concentrations considered to be in the deficient range (< 0.70 mumol/L). Concurrently, mean concentrations of plasma RBP increased during hospital admission (from 1.46 to 2.24 mumol/L, P = 0.003), and the mean CRP concentration declined (from 25.7 to 9.8 mg/L, P = 0.002). Significant positive correlations were found between plasma retinol concentrations at admission and age, weight, body mass index, triceps-skinfold-thickness percentile, midupper arm circumference percentile, plasma vitamin E, and RBP concentration, thus suggesting that better-nourished patients had more optimal vitamin A status. At admission, plasma retinol concentrations were negatively correlated with maximum body temperature and CRP concentrations, which indicated that the body's acute-phase response was associated with the depression in retinol concentrations. We conclude that plasma retinol concentrations are depressed in acute pulmonary exacerbations of cystic fibrosis, and that concentrations considered to be in the deficient range are common. Vitamin A metabolism during acute inflammatory stress deserves further study.

Acute Disease↗
PubMed1995

Designing safer chemicals: predicting the rates of metabolism of halogenated alkanes.

A computational model is presented that can be used as a tool in the design of safer chemicals. This model predicts the rate of hydrogen-atom abstraction by cytochrome P450 enzymes. Excellent correlations between biotransformation rates and the calculated activation energies (delta Hact) of the cytochrome P450-mediated hydrogen-atom abstractions were obtained for the in vitro biotransformation of six halogenated alkanes (1-fluoro-1,1,2,2-tetrachloroethane, 1,1-difluoro-1,2,2-trichloroethane, 1,1,1-trifluro-2,2-dichloroethane, 1,1,1,2-tetrafluoro-2-chloroethane, 1,1,1,2,2,-pentafluoroethane, and 2-bromo-2-chloro-1,1,1-trifluoroethane) with both rat and human enzyme preparations: In(rate, rat liver microsomes) = 44.99 - 1.79(delta Hact), r2 = 0.86; In(rate, human CYP2E1) = 46.99 - 1.77(delta Hact), r2 = 0.97 (rates are in nmol of product per min per nmol of cytochrome P450 and energies are in kcal/mol). Correlations were also obtained for five inhalation anesthetics (enflurane, sevoflurane, desflurane, methoxyflurane, and isoflurane) for both in vivo and in vitro metabolism by humans: In[F(-)]peak plasma = 42.87 - 1.57(delta Hact), r2 = 0.86. To our knowledge, these are the first in vivo human metabolic rates to be quantitatively predicted. Furthermore, this is one of the first examples where computational predictions and in vivo and in vitro data have been shown to agree in any species. The model presented herein provides an archetype for the methodology that may be used in the future design of safer chemicals, particularly hydrochlorofluorocarbons and inhalation anesthetics.

Animals↗
PubMed1995

The effect of adjunct questions on older adults' recall of information from a patient education booklet.

The effect of adjunct questions on the amount of information retained from the reading of a patient education booklet was investigated experimentally. Ninety older adults (mean age 77 years) were assigned randomly to a treatment, treatment control or non-treatment control group, 30 in each. The treatment condition was established by having subjects spend 30 min with a booklet about post-operative eye care. The booklet included four sets of review questions. The treatment control group spent the same period with a booklet which was identical apart from the questions. Knowledge of eye care was measured using a checklist scored on the basis of responses secured in a standardised interview. Although the two treatment groups decisively outperformed the control group on the measure, no effect attributable to the adjunct questions was detected. Factors which might account for this outcome are discussed. Directions for further research and implications for practice are indicated.

Aged↗