A rapidly enlarging neck mass.
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Adolescent↗
Biomedical subjects
A Paterson
Publications and source records attributed to A Paterson.
Purification and characterization of sn-1-stearoyl-2-arachidonoylglycerol kinase from pig testes.
1-Stearoyl-2-arachidonoylglycerol (SAG) kinase was identified in the particulate fraction of pig testes. This activity was enriched by hydroxyapatite and blue dye chromatography. The enzyme was selective for polyunsaturated diradylglycerol species and activity was not modulated by other diradylglycerol species or sphingomyelin metabolites. Further purification resulted in the isolation of 55 and 50 kDa proteins that corresponded with SAG kinase activity. These results support the view that the phosphorylation of polyunsaturated diradylglycerol is regulated by structural determinants in the molecule.
Animals↗
Dependence of the activity of phospholipase C beta on surface pressure and surface composition in phospholipid monolayers and its implications for their regulation.
We have examined the influence of surface pressure and phospholipid composition on hydrolysis of phosphatidylinositol (4,5)-bisphosphate (PIP2) by phospholipase C beta 1 (PLC beta 1) and PLC beta 2 in mixed composition phospholipid monolayers. Increasing the monolayer surface pressure from 15 to 36 mN/m reduced the rate at which PIP2 was hydrolyzed by PLC beta 1 and PLC beta 2 by 4-6-fold, although PLC beta 1 was more active than PLC beta 2, even at high surface pressure. Reduced enzyme activity was accompanied by an increase in reaction induction times, suggesting that increasing surface pressure reduced the penetration rate of the enzymes into the monolayer. Quantitation of interfacial enzyme concentration using 35S-labeled PLC beta 1 confirmed that less enzyme was associated with the monolayer at higher pressures. The relationship between PLC activity and substrate concentration was examined at a single surface pressure of 30 mN/m. This relationship was not hyperbolic, and increases in the mole percentage (mol %) of PIP2 in the monolayer resulted in an upwardly-curving increase in PLC activity. Thus, PLC beta 1 activity increased 7-fold and PLC beta 2 activity increased 4-fold when the mol % of PIP2 in the monolayer increased from 17.9% to 29%, increasing further thereafter. Paradoxically, increasing the mol % of PIP2 from 0 to 60% was accompanied by a 3-fold decrease in interfacial enzyme concentrations. Taken together, these data show that the catalytic activity of PLC beta involves some element of penetration of lipid interfaces, and suggest that the organization of the substrate facilitates PLC activity, giving credence to the substrate theory of interfacial activation of phospholipases. We present a hypothesis suggesting that PIP2 molecules coalesce into enriched lateral domains which favor PLC beta activity.
Enzyme Activation↗
Comparative biotransformation of pentachlorophenol in soils by solid substrate cultures of Lentinula edodes.
Sterilised and non-sterilised soils contaminated with pentachlorophenol (PCP) were inoculated with solid substrate cultures of Lentinula edodes LE2 ("shiitake" mushroom) to simulate monoculture bioremediation treatments and treatments in which the fungus competes with natural microflora. With monocultures of L. edodes, rates of PCP depletion were rapid for the initial 4 weeks and, although thereafter the rate decreased, 99% biotransformation was obtained in 10 weeks. In mixed culture, PCP biotransformation by L. edodes was markedly slower and only 42% of the PCP was depleted after 10 weeks. Maximal rates of PCP transformation, biomass (ergosterol) accumulation and oxidative enzymes (phenol oxidase and manganese-peroxidase) production were observed after 2 weeks of incubation. In monocultures, phenol oxidase activity was 195.5 U g-1 and Mn-peroxidase 138.4 U g-1. In mixed cultures, fungal enzyme activities were markedly lower: 70.33 U g-1 for phenol oxidase and 85.0 g-1 for Mn-peroxidase. Analyses of soil metabolites after 10 weeks revealed that monocultures of L. edodes had eliminated both PCP and pentachloroanisole. Pentachloroanisole, however, was detected in soils with the mixed microflora. Both dechlorination and mineralisation of the xenobiotic compound were effected by L. edodes LE2.
Anisoles↗
Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer.
A pilot phase II study examined the feasibility of 75 mg/m2 of docetaxel (Taxotere) in combination with 50 mg/m2 of doxorubicin and 500 mg/m2 of cyclophosphamide (Cytoxan, Neosar) in the first-line treatment of metastatic breast cancer. This study was designed to evaluate the efficacy and toxicity of the docetaxel/doxorubicin/cyclophosphamide combination both alone and as induction before high-dose chemotherapy, supplemented by autologous peripheral blood stem-cell transplantation. Patients were divided into three groups: one group received 8 courses of docetaxel/doxorubicin/cyclophosphamide; the second received 4 to 6 courses of the same combination with cell sampling, followed by high-dose chemotherapy with autologous peripheral blood stem-cell transplantation; and the third group's regimen was identical to that of the second, with additional granulocyte-colony stimulating factor (G-CSF, filgrastim [Neupogen]). Of 28 patients (149 courses) evaluable for toxicity and response, the overall response rate was 82%, with 5 (18%) complete responses and 18 (64%) partial responses. The most frequent hematologic toxicity was neutropenia; grade 4 neutropenia occurred in 86% of patients, with febrile neutropenia in 9 patients (18%). There was no incidence of infection, possibly because of the administration of oral ciprofloxacin (Cipro) from days 5 to 15 of each cycle. Nonhematologic adverse events were not severe; there was no significant cardiotoxicity. Future randomized trials of docetaxel/doxorubicin/cyclophosphamide as first-line adjuvant therapy of high-risk patients and as induction chemotherapy are in development.
Adult↗
Drug interactions with the nonsedating antihistamines.
The nonsedating antihistamines are frequently prescribed agents. Well-documented drug-drug interactions with two of these agents, terfenadine and astemizole, may result in serious adverse effects, including death, when they are prescribed along with macrolide antibiotics and/or the antifungal agents itraconazole or ketoconazole. Fexofenadine and loratadine appear to be the least likely nonsedating antihistamines to interact with other medications and to result in a life-threatening interaction. This article reviews the known drug-drug interactions involving nonsedating antihistamines and provides a basis from which the clinician can predict potential interactions.
Cytochrome P-450 Enzyme System↗
Purification and G protein subunit regulation of a phospholipase C-beta from Xenopus laevis oocytes.
Xenopus oocytes exhibit both pertussis toxin-sensitive and -insensitive inositol lipid signaling responses to G protein-coupled receptor activation. The G protein subunits Galphai, Galphao, Galphaq, Galphas, and Gbetagamma all have been proposed to function as activators of phospholipase C in oocytes. Ma et al. (Ma, H.-W., Blitzer, R. D., Healy, E. C., Premont, R. T., Landau, E. M., and Iyengar, R. J. Biol. Chem. 268, 19915-19918) cloned a Xenopus phospholipase C (PLC-betaX) that exhibits homology to the PLC-beta class of isoenzymes. Although this enzyme was proposed to function as a signaling protein in the pertussis toxin-sensitive inositol lipid signaling pathway of oocytes, its regulation by G protein subunits has not been directly assessed. As such we have utilized baculovirus-promoted overexpression of PLC-betaX in Sf9 insect cells and have purified a recombinant 150-kDa isoenzyme. PLC-betaX catalyzes hydrolysis of phosphatidylinositol(4,5)bisphosphate and phosphatidylinositol(4)monophosphate, and reaction velocity is dependent on Ca2+. Recombinant PLC-betaX was activated by both Galphaq and Gbetagamma. PLC-betaX exhibited a higher apparent affinity for Galphaq than Gbetagamma, and Galphaq was more efficacious than Gbetagamma at lower concentrations of PLC-betaX. Relative to other PLC-beta isoenzymes, PLC-betaX was less sensitive to stimulation by Galphaq than PLC-beta1 but similar to PLC-beta2 and PLC-betaT. PLC-betaX was more sensitive to stimulation by Gbetagamma than PLC-beta1 but less sensitive than PLC-beta2 and PLC-betaT. In contrast PLC-betaX was not activated by the pertussis toxin substrate G proteins Galphai1, Galphai2, Galphai3, or Galphao. These results are consistent with the idea that PLC-betaX is regulated by alpha-subunits of the Gq family and by Gbetagamma and do not support the idea that alpha-subunits of pertussis toxin-sensitive G proteins are directly involved in regulation of this protein.
Animals↗
Molecular cloning, expression and regulatory activity of G alpha 11- and beta gamma-subunit-stimulated phospholipase C-beta from avian erythrocytes.
A turkey erythrocyte phospholipase C (PLC) has been instrumental in delineating the role of G-proteins in receptor-regulated inositol lipid signalling. This isoenzyme is uniquely regulated both by alpha-subunits of the Gq family and by G-protein beta gamma-subunits. A 4819 bp cDNA encoding this PLC has been cloned from a turkey erythrocyte cDNA library. The open reading frame of this cDNA encodes a 1211-amino-acid protein (calculated molecular mass 139050 Da) that contains amino acid sequences of 16 peptides sequenced from the turkey erythrocyte PLC. The predicted sequence of the turkey PLC shows considerable similarity with the sequences of previously cloned members of the PLC-beta family, with the highest identity (71%) shared with PLC-beta 2 and lesser identities observed with PLC-beta 1 (49%), PLC-beta 3 (46%) and PLC-beta 4 (37%). The largest differences in sequence between the turkey PLC-beta and other PLC-beta isoenzymes occur in the C-terminal domain and in the region between the X- and Y-domains. The turkey isoenzyme and PLC-beta 2, which differ in their regulation by G-protein alpha-subunits, are only 44% similar across the approx. 400 amino acid residues of the C-terminal domain that has been implicated in alpha q activation of these proteins. Recombinant turkey PLC-beta was purified to homogeneity following expression from a recombinant baculovirus in Sf9 insect cells. The immunoreactivity and mobility on SDS/PAGE of the recombinant enzyme were the same as observed with native turkey erythrocyte PLC-beta. Moreover, the catalytic activities of the recombinant enzyme were indistinguishable from those of native turkey erythrocyte PLC-beta in assays carried out in the presence of cholate and Ca2+, or in assays of activity after reconstitution with G alpha 11 or G-protein beta gamma-subunits. The turkey PLC-beta was more sensitive to activation by G alpha 11 than was PLC-beta 2, and was more sensitive to activation by beta gamma-subunits than either PLC-beta 2 or PLC-beta 1.
Amino Acid Sequence↗
Time-dependent inhibition of phospholipase C beta-catalysed phosphoinositide hydrolysis: a comparison of different assays.
The properties of three different beta-isoforms of phospholipase C (PLC) were analysed using substrate lipids dispersed in phospholipid vesicles, phospholipid-detergent mixed micelles and phospholipid monolayers spread at an air-water interface. Phosphatidylinositol 4,5-bisphosphate hydrolysis went virtually to completion in monolayers, but inositol trisphosphate production was curtailed prematurely in vesicular and micellar assays. Assays were linear for less than 2 min with vesicles; the linear portion could be significantly extended in micelles by increasing the ratio of micelles to enzyme molecules. However, onset of a second lower rate of substrate hydrolysis always occurred when < or = 10% of PtdIns(4,5)P(2) had been utilized. This was not due to enzyme inactivation in the micellar interface, determined by addition of fresh substrate or fresh enzyme after the slow phase of activity had started, nor was it due to overt product inhibition of PLC or apparent entrapment of PLC at the micelle surface. These results are similar to those seen in assays using bacterial PLC and we suggest that the biphasic kinetics may be due to product-dependent changes in the presentation of substrate lipic to PLC in lamellar assays, leading to reduced activity.
Animals↗
Influence of environmental parameters on pentachlorophenol biotransformation in soil by Lentinula edodes and Phanerochaete chrysosporium.
The influences of temperature, soil moisture potential and initial pH on the biotransformation of pentachlorophenol (PCP) by the lignicolous fungi Lentinula edodes and Phanerochaete chrysosporium were examined. At 10 degrees C, L. edodes was more effective in degrading PCP (P < 0.05) than P. chrysosporium. At 15 degrees C similar results were obtained for the two fungi. The highest levels of degradation occurred for both fungi at 25 degrees C. With P. chrysosporium, the extent of PCP elimination was directly related to soil moisture content and optimal at approximately 47%. With L. edodes, in contrast, the process was inversely related to moisture content and maximal at 26%. The initial soil pH also had a marked influence, and pH 4.0 was optimal for both fungi.
Agaricales↗
Maxillofacial injuries in multiply injured patients.
Experience in team management of multiply injured patients with maxillofacial injuries is reported. During 1992, out of 169 patients transferred to the Royal London Hospital, UK by the Helicopter Emergency medical Service 38 (22.4%) had injuries to the maxillofacial region, 17 of whom were scored on the Abbreviated Injury Scale (AIS) as having sustained facial AIS > 2. The median Injury Severity Score (ISS) was 22, while the ISS was 17.7 for survivors and 34.5 for those who died (chi 2 = 7.3, 0.05 < P > 0.02). Facial AIS (median 4) and facial AIS contribution to ISS were found to be poor indicators of severity of injury. Revised Trauma Score (RTS) and percentage probability of survival (Ps%) were found to be useful discriminators of severity of overall injuries. RTS compared between survivors and those who died was 0.05 < P > 0.02 (chi 2), while Ps% was 0.01 < P > 0.001 (chi 2). It was concluded that the severity of maxillofacial injuries, and hence their contribution to total injury assessments, tended to be underscored. We propose that refined facial injury assessment methods be tested.
Abbreviated Injury Scale↗
Maxillofacial injuries in the multiply injured.
A survey of patients with maxillofacial injuries (MFI) was carried out in a triaged cohort of multiply injured patients (n = 802) evacuated from accident scenes by the helicopter emergency medical service (HEMS). Despite intubation at accident scenes, some patients required further airway protection on arrival at hospital. One hundred and ninety-six patients (24.5%) had MFI and 90 (11.2%) were classified as severe with ISS of facial region > 2 or more severe (ISS up to 16, median 4). The latter group were commonly found to be associated with other severe injuries (median ISS of 36) leading to death in 41 patients (5.1% of the total). Out of the 196 multiply injured patients with MFI, 57 (29%) had diagnostic peritoneal lavage for suspected haemorrhage, 27 (14%) subsequently underwent laparotomy. Six (3%) had thoracotomies and 29 (15%) had chest drains inserted. Seventeen (9%) had emergency craniotomies and 14 (7%) required intracranial pressure monitoring. Orthopaedic injuries were most commonly associated with MFI and 91 patients (46%) underwent surgical interventions. The purpose of the present study was primarily to establish a database for MFI patients with multiple injuries. The longer term objective being to gain evidence for early definitive management of these complicated cases rather than the more traditional expectant policies. In our view delayed management of MFI can rarely correct all the consequent facial deformities.
Adolescent↗
Weak pinning of interfaces.
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Journal Article↗
Kinetic analysis of phospholipase C beta isoforms using phospholipid-detergent mixed micelles. Evidence for interfacial catalysis involving distinct micelle binding and catalytic steps.
Phosphatidylinositol 4,5-bisphosphate (PtdIns (4,5)-P2) hydrolysis by three different beta-isoforms of phospholipase C (PLC) was examined to investigate the catalytic action of these extracellular signal-regulated enzymes. Depletion of phospholipase C from solution by incubation with sucrose-loaded vesicles of differing compositions followed by ultracentrifugation demonstrated stable attachment of PLC to the vesicles from which an equilibrium association constant of PLC with PtdIns (4,5)P2 could be determined. A mixed micellar system was established to assay PLC activity using dodecyl maltoside, which behaved as an essentially inert diluent of PtdIns (4,5)P2 with respect to PLC beta activity. Kinetic analyses were performed to test whether PLC beta activity was dependent on both bulk PtdIns (4,5)P2 concentration and surface concentration in the micelles as has been shown for other lipid metabolising enzymes. Each of the PLC beta isoforms behaved similarly in these analyses, which indicated the involvement of at least two binding events. Interfacial Michaelis constants were calculated to be between 0.1-0.2 mol fraction for all three enzymes, and Ks (the equilibrium dissociation constant of PLC for lipid) ranged between 100-200 microM. The apparent multiple interfacial binding events did not appear to result from lipid-induced PLC beta oligomerization implying that PLC beta monomers possess more than one lipid-binding site. Surface dilution of PLC-catalyzed PtdIns (4,5)P2 hydrolysis was assessed in the presence of increasing concentrations of various nonsubstrate phospholipids, which profoundly reduced PLC activity, suggesting that these lipids may inhibit enzyme action. The data indicate that G protein-regulated isoforms of PLC operate with separate lipid binding and catalytic steps and imply that under physiological conditions, PLC beta isoforms operate under first-order conditions. These findings may have implications for the mechanisms of regulation of PLC beta s by G protein subunits.
Animals↗
Childhood antecedents of schizophrenia.
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Adoption↗
An update on the careers of dentists undertaking a medical qualification.
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Adult↗