bluuebunny/crossref_metadata_2025_split huggingface dataset:
PDI Improves Secretion of Redox‐Inactive β‐Glucosidase
Authors: Powers Sara Lawrence , Robinson Anne Skaja 
Published: February 2007

AbstractAlthough manipulation of the endoplasmic reticulum (ER) folding environment in the yeast Saccharomyces cerevisiae has been shown to increase the secretory productivity of recombinant proteins, the cellular interactions and processes of native enzymes and chaperones such as protein disulfide isomerase (PDI) are still unclear. Previously, we reported that overexpression of the ER chaperone PDI enabled up to a 3‐fold increase in secretion levels of the Pyrococcus furiosus β‐glucosidase in the yeast S. cerevisiae. This result was surprising since β‐glucosidase contains only one cysteine per monomer and no disulfide bonds. Two possible mechanisms were proposed: PDI either forms a transient disulfide bond with the lone cysteine residue of the nascent β‐glucosidase during the folding and assembly process or acts as a chaperone to aid in proper folding. To discern between the two mechanisms, the single cysteine residue was mutated to serine, and the secretion of the two protein variants was determined. The serine mutant still showed increased secretion in vivo when PDI levels were elevated. When the folding bottleneck is removed by increasing expression temperatures to 37 °C rather than 30 °C, PDI no longer has an improvement on secretion. These results suggest that, unexpectedly, PDI acts in a chaperone‐like capacity or possibly cooperates with the cellapos;s folding or degradation mechanisms regardless of whether the protein is redox‐active.
Variable Stoichiometry during the Laccase‐Catalyzed Oxidation of Aqueous Phenol
Authors: Kurniawati Selvia , Nicell James A. 
Published: February 2007

AbstractThe oxidation of aqueous phenol through the catalytic action of laccase from Trametes versicolor was studied over a wide range of phenol concentrations and enzyme activities. The stoichiometric ratio, which is defined as the molar ratio of phenol transformed to oxygen consumed in the catalytic reaction, was found to increase with phenol concentration in the reaction mixture from a theoretical lower limit of 1 and to approach a theoretical upper limit of 4. A logistic equation was proposed to relate reaction stoichiometry to substrate concentration and was successfully used to relate these parameters over a range of phenol concentrations extending from approximately 0.15 to 8 mM. This expression was incorporated into two kinetic models in order to account for variations in reaction stoichiometry during the reaction and to extend the range over which the models may be accurately applied. The new models demonstrated an improved ability to predict concentrations of phenol and oxygen over time in a closed batch reaction system.
Surface phospholipids in gastric injury and protection when a selective cyclooxygenase‐2 inhibitor (Coxib) is used in combination with aspirin
Authors: Lichtenberger L M , Romero J J , Dial E J 
Published: February 2007

Background and purpose:Clinical studies demonstrate that aspirin consumption reverses the gastrointestinal (GI) benefits of coxibs, by an undefined mechanism.Experimental approach:Rodent models were employed to investigate the effects of combinations of celecoxib and aspirin on gastric ulcerogenesis, bleeding, surface hydrophobicity (by contact angle analysis) and ulcer healing. We also evaluated the effects of phosphatidylcholine (PC)‐associated aspirin in these rodent models and confirmed its cyclooxygenase (COX)‐inhibitory activity by measuring mucosal prostaglandin E2 (PGE2) concentration.Key results:We present evidence that aspirin's ability to induce gastric injury and bleeding in rats, was exacerbated in the presence of a coxib and was dependent on its ability to reduce gastric surface hydrophobicity. In contrast, co‐administration of phosphatidylcholine (PC)‐associated aspirin and celecoxib induced little or no gastric injury/bleeding and maintained the stomach's hydrophobic properties. Interestingly, aspirin and aspirin/PC equally inhibited gastric mucosal PGE2 concentration. Aspirin in combination with a coxib retarded the healing of experimentally induced gastric ulcers, whereas healing rates of rats treated with celecoxib in combination with aspirin/PC were comparable to controls.Conclusions and implications:Aspirin's gastric toxicity in combination with a coxib can be dissociated from its ability to inhibit COX‐1 and appears to be dependent, in part, on its ability to attenuate the stomach's surface hydrophobic barrier. This adverse drug interaction between aspirin and coxibs, which impacts the treatment of osteoarthritic and cardiac patients requiring cardiovascular prophylaxis, can be circumvented by the administration of phosphatidylcholine (PC)‐associated aspirin, to maintain the stomach's hydrophobic properties.British Journal of Pharmacology (2007) 150, 913–919. doi:10.1038/sj.bjp.0707176
Ectopic activity in the rat pulmonary vein can arise from simultaneous activation of α1‐ and β1‐adrenoceptors
Authors: Maupoil V , Bronquard C , Freslon J‐L , Cosnay P , Findlay I 
Published: February 2007

Background and purpose:Atrial fibrillation (AF) is the most common electrical cardiac disorder in clinical practice. The major trigger for AF is focal ectopic activity of unknown origin in sleeves of cardiac muscle that extend into the pulmonary veins. We examined the role of noradrenaline in the genesis of ectopic activity in the pulmonary vein.Experimental approach:Mechanical activity of strips of pulmonary vein isolated from male Wistar rats was recorded via an isometric tension meter. Twitch contractions of cardiac myocytes were evoked by electrical field stimulation in a tissue bath through which flowed Krebs‐Heinseleit solution warmed to 36‐37°C and gassed with 95% O2 5% CO2.Key results:The superfusion of noradrenaline induced ectopic contractions in 71 of 76 different isolated pulmonary veins. Ectopic contractions in the pulmonary vein were not associated with electrically evoked twitch contractions. The effect of noradrenaline on the pulmonary vein could be replicated by the simultaneous, but not separate, application of the α adrenoceptor agonist phenylephrine and the β adrenoceptor agonist isoprenaline. The use of selective agonists and antagonists for adrenoceptor subtypes showed that ectopic activity in the pulmonary vein arose from the simultaneous stimulation of α1 and β1 adrenoceptors. The application of noradrenaline to isolated strips of left atrium did not induce ectopic contractions (n=10).Conclusions:These findings suggest an origin for ectopic activity in the pulmonary vein that requires activation of both α and β adrenoceptors. They also open new perspectives towards our understanding of the triggering of AF.British Journal of Pharmacology (2007) 150, 899–905. doi:10.1038/sj.bjp.0707177
SOME RESPIRATORY DISTURBANCES DURING GENERAL ANÆSTHESIA
Authors: NOSWORTHY MICHAEL D. 
Published: February 2007

Summary1. Keeping the airway clear is very largely dependent on the avoidance of reflex response.2. The various factors which influence the bronchial lumen are considered.3. The depressant qualities of modern anæsthetic methods make the different levels of anæsthesia less easily distinguishable.4. Marked central depression may be injurious and is not necessarily accompanied by adequate reflex suppression.5. Examples and the results of reflex respiratory activity during anæsthesia are given.
MUSCLE RELAXANTS IN CLINICAL PRACTICE
Authors: EDWARDS PHYLLIS M. 
Published: February 2007

SummaryThe ideal muscle relaxant is defined. The pharmacological action of the dextro‐tubocurarine and allied compounds is described. The pharmacological action of myanesin is mentioned. Diagnostic techniques with curarisation are enumerated.Therapeutic uses of curarisation are detailed.The possibilities of further employment of muscle relaxant drugs are discussed.
Hyperglycemia is not associated with mortality in bacterial meningitis
Authors: Powers William J. 
Published: February 2007

AbstractAn association between hyperglycemia and mortality from cerebral ischemia has been reported in both animals and man. Recently, a similar observation has been made in animals with bacterial meningitis. The present study of 83 patients with bacterial meningitis showed no association between initial serum glucose concentration and subsequent mortality. Therefore, no therapeutic recommendations regarding optimal blood glucose levels in patients with meningitis can be made at this time.
Lafora disease: Liver histopathology in presymptomatic children
Authors: Baumann Robert J. , Kocoshis Samuel A. , Wilson Dianne 
Published: February 2007

AbstractLafora disease is an inborn error of carbohydrate metabolism with storage of a polyglucosan in various tissues including brain and liver. Recently, distinctive histopathological changes in liver have been emphasized, and the diagnosis has been confirmed by the relatively simple procedure of percutaneous liver biopsy. We utilized this technique to study three asymptomatic preadolescent children from one family in which older siblings had symptomatic Lafora disease confirmed by brain or liver biopsy. Liver biopsies from the asymptomatic children showed altered hepatocytes identical to those seen in symptomatic subjects, although the cells were considerably less numerous. All three children subsequently became symptomatic. Distinctive liver changes can antedate the onset of symptoms in Lafora disease.
Gastro‐oesophageal reflux during elective laparoscopy
Authors: ROBERTS C. J. , GOODMAN N. W. 
Published: February 2007

SummaryAn oesophageal pH electrode was used to record gastro‐oesophageal reflux in 73 women who had elective laparoscopy for various gynaecological procedures. No refluxes were recorded during the 63 procedures from which results could be analysed; the upper 95% confidence limit from this observation is 3 in 63 (4.8%). Two of the excluded women refluxed during episodes of hiccough that occurred shortly after induction of anaesthesia. Tracheal intubation may be required during laparoscopy, although the need to protect against the possibility of aspiration of gastric contents may not be a valid reason unless, with the same logic, it is suggested that all patients who hiccough should be intubated.
Predictability of difficult laryngoscopy in patients with long‐term diabetes mellitus
Authors: REISSELL E. , ORKO R. , MAUNUKSELA E‐L. , LINDGREN L. 
Published: February 2007

SummaryThe laryngoscopic conditions of 62 diabetic patients who underwent renal transplantation or vitrectomy were studied. Anaesthesia was induced with fentanyl and a sleep dose of thiopentone. Conditions for direct laryngoscopy after 0.1 mg/kg vecuronium were scored from 0 to 3 (easy‐very difficult). All patients gave their palm prints after operation which were scored: 0, phalangeal areas completely visible; 1, phalangeal areas partly visible; 2, phalangeal areas hardly visible; 3, only fingertips printed. The incidence of difficult laryngoscopy was 31%. The higher the scores in the palm test, the more difficult was the laryngoscopy. The correlation coefficient between these two factors was r = 0.6 (p < 0.001). Our study shows that joint rigidity possibly caused by tissue glycosylation may also involve laryngeal and cervical areas resulting in a strenuous laryngoscopy. A defective palm print is a warning sign for difficult laryngoscopy.
Antireflux valves in patient‐controlled analgesia
Authors: KLUGER M. T. , OWEN H. 
Published: February 2007

SummaryAntireflux valves are widely used in conjunction with patient‐controlled analgesia devices. It is important to appreciate the limitations and dangers of these systems. They can achieve a potential ‘stored volume’ if occluded and they may, as part of the administration set, retard fluid administration. Seven antireflux systems currently available were tested in conjunction with three patient‐controlled analgesia pumps. The systems’ volume, time to occlusion alarm and flow rates were measured. Results showed that the sets with low stored volumes were less efficient as administration sets. A potentially dangerous bolus could result after release of occlusion if sets with large stored volumes were used in conjunction with pumps that utilised concentrated solutions of opioid. This study has identified the ideal antireflux valve system.
Use of the oesophageal detector device in children under one year of age
Authors: HAYNES S. R. , MORTON N. S. 
Published: February 2007

SummaryThe efficacy of a modified oesophageal detector device was evaluated in a single‐blind study of 20 healthy infants. It was found to be unreliable as a method to discriminate oesophageal from tracheal intubation in this age group.
Patient‐controlled analgesia in children
Authors: Lawrie S. C. , Forbes D. W. , Akhtar T. M. , Morton N. S. 
Published: February 2007

SummaryWe report our experience in introducing patient‐controlled analgesia at the Royal Hospital for Sick Children, Glasgow. Twenty‐five children used the technique after orthopaedic or general surgery using the Graseby system. The pump was loaded with 1 mg/kg morphine sulphate in 50 ml. A bolus dose of 0.02 mg/kg (1 ml) and a lockout interval of 10 minutes were the initial settings. The dose used, pain and sedation scores, respiratory rate and arterial oxygen saturation were recorded. Ages ranged from 5–15 years (mean 9.6) and the method was used for a mean of 48 hours after operation. Morphine requirements averaged 26 (μg/kg)/hour (SD 10.6). Pain control was good and sedation minimal. Adverse effects were few and minor. Education of patients, parents and nurses is essential for its success and safety. The technique is an effective and safe means of providing good quality analgesia in school age children.
KIR2DL1 allelic diversity: four new alleles characterized in a bone marrow transplant population and three families
Authors: Hou L. H. , Steiner N. K. , Chen M. , Belle I. , Ng J. , Hurley C. K. 
Published: February 2007

AbstractSequencing of PCR amplified genomic DNA including most of the coding region was used to identify killer cell immunoglobulin‐like receptor 2DL1 alleles from three families and 77 bone marrow transplant patients and donors. Alleles 2DL1*00302 and *002 were frequently observed in addition to two other known alleles and four new alleles, 2DL1*00402, 2DL1*007, 2DL1*008, and 2DL1*009.
Collaborative studies to establish the first World Health Organization International Standard for detection of human antibody against human platelet antigen‐3a
Authors: Berry J. , Allen D. , Porcelijn L. , De Haas M. , Kekomaki R. , Kaplan C. , Ouwehand W. H. , Metcalfe P. 
Published: February 2007

Background and Objectives  The platelet‐specific antibody anti‐human platelet antigen‐3a (anti‐HPA‐3a) is involved in neonatal alloimmune thrombocytopenia, post‐transfusion purpura, and platelet refractoriness. However, HPA‐3a antibodies are often difficult to detect, probably because the antigen is labile. This report describes the production of a freeze‐dried preparation of pooled human plasma, coded 03/190, containing IgG antibodies against the HPA‐3a. The material is intended for use as a minimum sensitivity reagent in glycoprotein‐specific assays currently used for anti‐HPA‐3a detection. Laboratories can use it to assess the sensitivity of their ‘in‐house’ assays for anti‐HPA‐3a and to calibrate local controls for routine use in each batch of tests.Materials and Methods  Plasma containing anti‐HPA‐3a was obtained from a mother of two babies both born with severe thrombocytopenia, and following dilution it was freeze dried in glass ampoules.Results  Two collaborative studies demonstrated that the candidate material contained anti‐HPA‐3a and human leucocyte antigen (HLA) class I antibodies, but no other HPA antibodies that might confuse the detection of the anti‐HPA‐3a. The minimum dilution that should give a positive result was determined to be 1 : 8 by two further international collaborative studies involving a total of 49 laboratories in 23 countries.Conclusion  The material also contains HLA antibodies and is suitable for use only in techniques that are glycoprotein specific (i.e. monoclonal antibody immobilization of platelet antigens and enzyme‐linked immunosorbent assay) where only HPA antibodies will be detected. This standard will allow laboratories to measure their sensitivity of detection of anti‐HPA‐3a and will also allow those laboratories with relatively insensitive techniques to monitor their performance as they improve their methodology.
Why we will need to learn new skills to control cancer
Authors: Brown M. P. , Buckley M. F. , Rudzki Z. , Olver I. N. 
Published: February 2007

AbstractAs a society and as specialists involved in the diagnosis and management of cancer, we must begin to find new cost‐effective ways to provide equitable access to the innovative, effective and expensive drugs that may begin to make cancer a chronic rather than rapidly lethal disease. Drugs such as trastuzumab and gefitinib are safer ‘targeted therapies’ that only attract government subsidies after the pathologist identifies the target present in a minor subset of patients. Nonetheless, funding for pathological identification of these targets remains a challenge. To illustrate, gefitinib may produce ‘Lazarus’ responses and prolonged survival among patients with epidermal growth factor receptor mutation‐positive non‐small‐cell lung cancer. Many such examples will enter the clinical domain in the coming years. As we enter this era of personalized medicine, we argue that the use of expensive targeted therapies should be limited to pathologically proven indications because truly effective drugs are best applied to those individuals who would most benefit. It follows that medical oncologists should be trained properly to use targeted therapies. Then a new generation of oncologists would be empowered to participate in the iterative cycles of research between bench and bedside that are necessary for optimal use of biotherapies and their integration into multimodality cancer treatment programmes. We propose that cancer pathology be made available as a training option in the postgraduate education of medical oncologists. Oncologists and pathologists may jointly administer and mutually accredit the training module, which may also contribute towards the award of a higher degree.
Ca2+ influx through both L‐ and N‐type Ca2+ channels increases c‐fos expression by electrical stimulation of sympathetic neurons
Authors: Zhao Rubing , Liu Liwang , Rittenhouse Ann R. 
Published: February 2007

AbstractDuring direct membrane depolarization, Ca2+ influx primarily through L‐type Ca2+ (L‐) channels initiates activity‐dependent gene transcription. This is surprising given that in most neurons a minority of the total Ca2+ current arises from L‐channel activity. However, many studies have stimulated Ca2+ influx with unphysiological stimuli such as chronic membrane depolarization using high K+ medium. Few studies have tested whether other Ca2+ channels stimulate gene transcription in adult neurons as a consequence of direct electrical stimulation. Therefore, we evaluated the role of L‐ and N‐type Ca2+ (N‐) channel activity in regulating mRNA levels of c‐fos, an activity‐dependent transcription factor, in adult rat superior cervical ganglion (SCG) neurons as the majority of Ca2+ channels are N‐type, while only a minority are L‐type. Changes in c‐fos mRNA levels were measured using semi‐quantitative and single‐cell RT‐PCR. Phosphorylation of CREB (pCREB) and changes in c‐Fos levels were visualized in dissociated cells by immunocytochemistry. Increases in pCREB, c‐fos mRNA and c‐Fos protein with either K+ or electrical depolarization required Ca2+ influx. These results support previous findings that elevated c‐fos levels result from pCREB stimulating c‐fos transcription. Elevation of pCREB, c‐fos and c‐Fos with K+ depolarization depended on L‐channel activity. By contrast, antagonizing either channel at 10‐Hz stimulation minimized these increases despite unequal numbers of the two channel types. Transition to exclusive L‐channel involvement occurred with increasing frequency of stimulation (from 10 to 20 to 50 Hz). Our results demonstrate that N‐ and L‐channel participation in regulating c‐fos expression is encoded in the pattern of electrical stimulation.
A numerical study of red–green colour opponent properties in the primate retina
Authors: Momiji Hiroshi , Hankins Mark W. , Bharath Anil A. , Kennard Christopher 
Published: February 2007

AbstractIt remains an important question whether neural function is mediated entirely by its tailored circuitry. A persistent debate in retinal colour vision is whether the centre and the surround of a ganglion cell receptive field receive dominant inputs either from L or M cones in an antagonistic manner (the selective wiring model) or mixed inputs (the mixed wiring model). Despite many anatomical, physiological and psychophysical experiments, a decisive conclusion has not been reached. An in‐depth examination of what the pure mixed wiring mechanisms predicts is therefore important. These two models make different predictions both for the fovea and for the peripheral retina. Recently, a dynamic cellular model of the primate fovea was developed [Momiji et al. (2006) Vis. Res., 46, 365–381]. Unlike earlier models, it explicitly incorporates spatial non‐uniformities, such as the random arrangement of L and M cones. Here, a related model is developed for the peripheral retina by incorporating anatomically reasonable degrees of convergence between cones, bipolar cells and ganglion cells. These two models, in which selective wiring mechanisms are absent, are applied to describe both foveal and peripheral colour vision. In numerical simulations, peripheral ganglion cells are less colour sensitive than foveal counterparts, but none‐the‐less display comparative sensitivities. Furthermore, peripheral colour sensitivity increases with temporal frequency, relative to foveal sensitivity. These results are congruent with recent physiological experiments.
PKCε induces astrocyte stellation by modulating multiple cytoskeletal proteins and interacting with Rho A signalling pathways: implications for neuroinflammation
Authors: Burgos Miguel , Calvo Soledad , Molina Francisca , Vaquero Cecilia F. , Samarel Allen , Llopis Juan , Tranque Pedro 
Published: February 2007

AbstractDespite the importance of stellation to maintain astrocyte functionality, the intracellular signals controlling morphology in these cells are poorly characterized. Our goal was to examine the implication of protein kinase C epsilon (PKCε) in astrocyte stellation. We found that the morphological transformation of astrocytes induced by exposure to the pro‐inflammatory agent lipopolysaccharide is enhanced by adenoviral expression of wild‐type PKCε, and that activation of PKCε is sufficient to trigger a dramatic stellation. Such an effect is mediated by the rearrangement of microtubules and filaments of glial fibrillary acidic protein, disorganization of stress fibres, and formation of new actin filaments within growing cellular processes. Furthermore, PKCε regulates actin‐interacting elements such as non‐muscle myosin and proteins of the ezrin/radixin/moesin family. We also observed that at least part of the actions of PKCε depend on its catalytic activity. Finally, stellation by PKCε could be blocked by the expression of a constitutively active form of Rho A implicated in the stability of the flat astrocytic morphology. In summary, PKCε stands out as a key intracellular regulator of morphological plasticity in astrocytes, affecting a large range of cytoskeletal elements and inactivating Rho A‐dependent pathways. These morphological effects of PKCε may play essential roles during the course of neuroinflammation.