An unusual cause of abdominal pain.
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Abdominal Pain↗
Biomedical subjects
J Lund
Publications and source records attributed to J Lund.
Improved early risk stratification and diagnosis of myocardial infarction, using a novel troponin I assay concept.
BACKGROUND: We evaluated the clinical performance of a novel cardiac troponin I (cTnI) assay specifically designed to improve the very early risk stratification in acute coronary syndromes. SUBJECTS AND METHODS: Serum and plasma samples (taken 0, 6-12 h and 24 h after admission) from 531 patients with suspected acute coronary syndrome were studied using a novel investigational cTnI assay, reference cTnI assay and myoglobin. The lowest cTnI concentration giving a total assay imprecision of 10% was used as the positive myocardial infarction (MI) cut-off value. RESULTS: At the time of admission, the investigational assay was positive in 27.9% of the patients, the reference cTnI assay was positive in only 17.5% (P < 0.001) and myoglobin in 24.1% (P = 0.067). Receiver operating characteristic (ROC) curve analysis for the detection of myocardial injury on admission gave area-under-curve (AUC) values of 0.937, 0.775 and 0.762, respectively (P < 0.001). Of those MI patients who presented within 3 h of symptom onset, 50.0% were identified by the investigational assay at the time of presentation, compared with 44.2% by myoglobin (P = 0.791) but only 11.5% by the reference assay (P < 0.001). CONCLUSIONS: The novel cTnI assay considerably improves the performance of cTnI as an early rule-in biomarker for MI.
Aged↗
Caudal bupivacaine supplemented with caudal or intravenous clonidine in children undergoing hypospadias repair: a double-blind study.
BACKGROUND: Clonidine is used increasingly in paediatric anaesthetic practice to prolong the duration of action of caudal block with a local anaesthetic agent. Which route of administration of clonidine is the most beneficial remains unknown. We compared the effects of caudal and i.v. clonidine on postoperative analgesia produced by caudal bupivacaine after hypospadias repair. METHODS: Forty-six children (ASA I or II) aged 24-104 months received standardized premedication with midazolam, a general anaesthetic and a caudal block with bupivacaine 0.25%, 0.5 ml kg(-1). The children were randomized in a double-blind fashion to two groups: the i.v. group received clonidine 2 micro g kg(-1) i.v. and simultaneously the same volume of saline caudally. The caudal group received clonidine 2 micro g kg(-1) caudally and a similar volume of saline i.v. After surgery, all children received acetaminophen 20 mg kg(-1) rectally or orally 6-hourly and were given a patient-controlled or nurse-controlled analgesia (PCA/NCA) pump with i.v. morphine (bolus of 25 micro g kg(-1) and an 8-min lockout period with no background infusion). Monitoring of scores for pain, sedation, motor block, and postoperative nausea and vomiting was performed by nurses blinded to the study allocations. Time to first activation of the PCA/NCA pump and 0-24 h and 24-48 h morphine consumption were also recorded. RESULTS: Forty-four children completed the study. Age, weight and duration of anaesthesia and surgery were similar in the two groups. The median (range) time to first activation of the PCA/NCA pump was similar in the two groups: 425 (150-1440) min in the i.v. group and 450 (130-1440) min in the caudal group. The number of children not requiring postoperative morphine was four and seven respectively. Morphine consumption during 0-24 h and 24-48 h was similar between groups. CONCLUSIONS: The analgesic effect of clonidine 2 micro g kg(-1) as an adjunct to caudal block with bupivacaine 0.25%, 0.5 ml kg(-1) is similar whether administered i.v. or caudally.
Adrenergic alpha-Agonists↗
Relationship between peripheral airway dysfunction, airway obstruction, and neutrophilic inflammation in COPD.
BACKGROUND: Considerable research has been conducted into the nature of airway inflammation in chronic obstructive pulmonary disease (COPD) but the relationship between proximal airways inflammation and both dynamic collapse of the peripheral airways and HRCT determined emphysema severity remains unknown. A number of research tools have been combined to study smokers with a range of COPD severities classified according to the GOLD criteria. METHODS: Sixty five subjects (11 healthy smokers, 44 smokers with stage 0-IV COPD, and 10 healthy non-smokers) were assessed using lung function testing and HRCT scanning to quantify emphysema and peripheral airway dysfunction and sputum induction to measure airway inflammation. RESULTS: Expiratory HRCT measurements and the expiratory/inspiratory mean lung density ratio (both indicators of peripheral airway dysfunction) correlated more closely in smokers with the severity of airflow obstruction (r = -0.64, p<0.001) than did inspiratory HRCT measurements (which reflect emphysema severity; r = -0.45, p<0.01). Raised sputum neutrophil counts also correlated strongly in smokers with HRCT indicators of peripheral airway dysfunction (r = 0.55, p<0.001) but did not correlate with HRCT indicators of the severity of emphysema. CONCLUSIONS: This study suggests that peripheral airway dysfunction, assessed by expiratory HRCT measurements, is a determinant of COPD severity. Airway neutrophilia, a central feature of COPD, is closely associated with the severity of peripheral airway dysfunction in COPD but is not related to the overall severity of emphysema as measured by HRCT.
Airway Obstruction↗
Coronary arterial sling operation.
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Coronary Angiography↗
Role of oligosaccharide residues of IgG1-Fc in Fc gamma RIIb binding.
Engagement of Fc gamma receptors (Fc gamma Rs) with the Fc region of IgG elicits immune responses by leukocytes. The recent crystal structure of Fc gamma RIII in complex with IgG-Fc has provided details of molecular interactions between these components (Sondermann, P., Huber, R., Oosthuizen, V., and Jacob, U. (2000) Nature 406, 267-273). One of the most intriguing issues is that glycosylation of IgG-Fc is essential for the recognition by Fc gamma Rs although the carbohydrate moieties are on the periphery of the Fc gamma RIII-Fc interface. To better understand the role of Fc glycosylation in Fc gamma R binding we prepared homogeneous glycoforms of IgG-Fc (Cri) and investigated the interactions with a soluble form of Fc gamma RIIb (sFc gamma RIIb). A 1:1 complex stoichiometry was observed in solution at 30 degrees C (K(d), 0.94 microm; Delta G, -8.4 kcal mol(-1); Delta H, -6.5 kcal mol(-1); T Delta S, 1.9 kcal mol(-1); Delta C(p), -160 cal mol(-1) K(-1)). Removal of terminal galactose residues did not alter the thermodynamic parameters significantly. Outer-arm GlcNAc residues contributed significantly to thermal stability of the C(H)2 domains but only slightly to sFc gamma RIIb binding. Truncation of 1,3- and 1,6-arm mannose residues generates a linear trisaccharide core structure and resulted in a significantly decreased affinity, a less exothermic Delta H, and a more negative Delta C(p) for sFc gamma RIIb binding, which may result from a conformational change coupled to complex formation. Deglycosylation of the C(H)2 domains abrogated sFc gamma RIIb binding and resulted in the lowest thermal stability accompanied with noncooperative unfolding. These results suggest that truncation of the oligosaccharides of IgG-Fc causes disorder and a closed disposition of the two C(H)2 domains, impairing sFc gamma RIIb binding.
Antigens, CD↗
A gene expression map for Caenorhabditis elegans.
We have assembled data from Caenorhabditis elegans DNA microarray experiments involving many growth conditions, developmental stages, and varieties of mutants. Co-regulated genes were grouped together and visualized in a three-dimensional expression map that displays correlations of gene expression profiles as distances in two dimensions and gene density in the third dimension. The gene expression map can be used as a gene discovery tool to identify genes that are co-regulated with known sets of genes (such as heat shock, growth control genes, germ line genes, and so forth) or to uncover previously unknown genetic functions (such as genomic instability in males and sperm caused by specific transposons).
Algorithms↗
Sialylation of human IgG-Fc carbohydrate by transfected rat alpha2,6-sialyltransferase.
A recombinant IgG3 antibody with Phe-243 replaced by Ala (FA243) was expressed in a CHO-K1 parental cell line. The resulting IgG-Fc-linked carbohydrate was significantly alpha2,3-sialylated (53% of glycans), as indicated by normal- and reverse-phase HPLC analyses. Following transfection of a rat alpha2,6-sialyltransferase gene into this parental cell line, IgG-Fc-linked glycans were sialylated (60% of glycans) such that the ratio of alpha2,6- to alpha2,3-linked sialic acid was 0.9:1.0. By comparison, the wild-type IgG3 (F243) is minimally sialylated (2-3% alpha2,3-linked), thus suggesting that sialylation is controlled primarily by the protein structure local to the carbohydrate and that the two sialyltransferases compete to sialylate the nascent oligosaccharide. The additional alpha2,6-sialylation affected the function of the recombinant antibody. FA243 IgG3 having both alpha2,6 and alpha2,3-sialylation restored recognition to wild-type IgG3 levels for human FcgammaRI, FcgammaRII, and target cell lysis by complement. We discuss how sialylation linkage could modulate IgG function.
Animals↗
Acetylation of steroidogenic factor 1 protein regulates its transcriptional activity and recruits the coactivator GCN5.
Steroidogenic factor-1 (SF-1) is an orphan nuclear receptor that plays an essential role in the development of the hypothalamic-pituitary-gonadal axis in both sexes. SF-1 belongs to the hormone nuclear receptor superfamily and possesses an N-terminal DNA binding domain and a C-terminal ligand binding domain. Activation function domain 2 is located C-terminal of the ligand binding domain of SF-1 and is important for the transactivation of target genes. Coactivators with histone acetyltransferase activity such as cAMP response element-binding protein-binding protein and steroid receptor coactivator 1 interact and increase SF-1-mediated transcriptional activity. In this study we demonstrate that SF-1 is acetylated in vivo. Histone acetyltransferase GCN5 acetylates SF-1 in vitro. Moreover, we found that SF-1 recruited a novel coactivator GCN5, which can be a newly identified coactivator for SF-1. Acetylation of SF-1 stimulates its transcriptional activity. Inhibition of deacetylation by trichostatin A, a histone deacetylase inhibitor, increased SF-1-mediated transactivation and stabilized and induced the nuclear export of the SF-1 protein.
Acetylation↗
A two-receptor pathway for catabolism of Clara cell secretory protein in the kidney.
Clara cell secretory protein (CCSP) is a transport protein for lipophilic substances in bronchio-alveolar fluid, plasma, and uterine secretion. It acts as a carrier for steroid hormones and polychlorinated biphenyl metabolites. Previously, the existence of receptors for uptake of CCSP.ligand complexes into the renal proximal tubules had been suggested. Using surface plasmon resonance analysis, we demonstrate that CCSP binds to cubilin, a peripheral membrane protein on the surface of proximal tubular cells. Binding to cubilin results in uptake and lysosomal degradation of CCSP in cultured cells. Surprisingly, internalization of CCSP is blocked not only by cubilin antagonists but also by antibodies directed against megalin, an endocytic receptor that does not bind CCSP but associates with cubilin. Consistent with a role of both receptors in renal uptake of CCSP in vivo, patients deficient for cubilin or mice lacking megalin exhibit a defect in tubular uptake of the protein and excrete CCSP into the urine. These findings identify a cellular pathway consisting of a CCSP-binding protein (cubilin) and an endocytic coreceptor (megalin) responsible for tissue-specific uptake of CCSP and associated ligands.
Animals↗
Butyrate increases production of human chimeric IgG in CHO-K1 cells whilst maintaining function and glycoform profile.
The influence of sodium butyrate on the production and glycosylation of recombinant mouse/human chimeric antibody by transfected CHO-K1 cells was investigated. We selected cells expressing 'wild-type' antibody with a human IgG3 heavy chain and a mutant of this molecule in which Phe 243 is replaced by Ala. These proteins have previously been shown to exhibit very different glycoform profiles with the mutant IgG being comprised of glycoforms having a high galactose and sialic acid content. Cell culture with 0-5 mM butyrate was shown to effect a 2-4-fold increase in antibody production whilst the induction of apoptosis was observed in a dose-dependent manner. The optimal butyrate concentration was observed to be 2 mM. The glycoform profile of each antibody produced in the presence of butyrate was analyzed by HPAEC-PAD and shown to be unchanged, relative to that produced in the absence of butyrate. Biological activity was evaluated by the ability of the antibodies to trigger superoxide generation, through Fc gamma RI, and shown to be independent of production in the presence or absence of butyrate. A similar increase in production was observed for a high antibody-producing cell line when expanded in a hollow fibre bioreactor under low-serum conditions (1%). These results demonstrated that butyrate is of value for increasing the productivity of CHO-K1 for recombinant IgG and does not compromise either glycosylation or biological activity.
Animals↗
The molecular specificity of IgG-Fc interactions with Fc gamma receptors.
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Binding Sites↗
Permanent impairments, disabilities and disability pensions related to accidents in Norway.
The purpose of this study was to estimate the burden of accidents in terms of new disability pensioners related to accidental injuries in Norway and to use this information to supplement the picture of the epidemiology of accidents in Norway. The basis of the study was 7,241 new disability pensioners due to accidents in the Disability Register of the National Insurance Administration in Norway for 1992-1997. Included in the analyses are some data from health surveys in USA and Norway. The rate of disability pensioners (16-66 years old) due to accidents increased 4% annually during 1992-1997, and in the age group 16-44 years 8% annually. The increase is found in all types of accidents, except for home and the group other accidents, where the rate is constant. 45% had been injured in traffic accidents, 33% in occupational accidents, 16% in leisure accidents, 4% in home accidents and 2% in other accidents. The rates of disability pensionings due to occupational accidents are three to four times higher among 'blue collar' workers than among 'white collar' workers. While disability pensioning rate in the age group 16-66 years due to accidents has increased 4% annually, the accident mortality for the age group 15-64 years has decreased 3% annually. The relationship between disability pensioning and mortality in the age group 15-64 years is found to be approximately 2:1 for all accidents. For occupational accidents the relationship is 5:1, for traffic accidents 2.5:1, for leisure and other accidents 1:1 and for home accidents 1:2.7. The complete epidemiologic picture due to accidents in Norway per 100,000 of population seems to be: medically treated, 10,000; hospitalised, 1,200; permanently impaired, 800 (of whom probably 50% are treated as out-patients); disabled (restricted activity), 400; fatalities, 40; and disability pensioned in the age group 16-66 years, 50. Medically treated and hospitalised patients due to accidents seem to show a slightly decreasing rate, fatalities a higher decreasing rate. This supplement to the epidemiological picture of rates and trends of impairments, disability and disability pensionings (the more serious consequences of accidents), points to the need to focus on the current trends for accident prevention.
Accident Prevention↗
Compulsory averaging of crowded orientation signals in human vision.
A shape can be more difficult to identify when other shapes are near it. For example, when several grating patches are viewed parafoveally, observers are unable to report the orientation of the central patch. This phenomenon, known as 'crowding,' has historically been confused with lateral masking, in which one stimulus attenuates signals generated by another stimulus. Here we show that despite their inability to report the orientation of an individual patch, observers can reliably estimate the average orientation, demonstrating that the local orientation signals are combined rather than lost. Our results imply that crowding is distinct from ordinary masking, and is perhaps related to texture perception. Under crowded conditions, the orientation signals in primary visual cortex are pooled before they reach consciousness.
Algorithms↗
Altered lung gene expression in CCSP-null mice suggests immunoregulatory roles for Clara cells.
Clara cell secretory protein (CCSP) is one of the most abundant proteins present in airway lining fluid of mammals. In an effort to elucidate the function of CCSP, we established CCSP-null [CCSP(-/-)] mice and demonstrated altered sensitivity to various environmental agents including oxidant pollutants and microorganisms. Although CCSP deficiency itself may be central to the observed changes in environmental susceptibility, altered lung gene expression associated with CCSP deficiency may contribute to the observed phenotype. To determine whether CCSP deficiency results in altered lung gene expression, high-density cDNA microarrays were used to profile gene expression in the total lung RNA of wild-type and CCSP(-/-) mice. Genes that were differentially expressed between wild-type and CCSP(-/-) mice included a previously non-annotated expressed sequence tag (EST W82219) and immunoglobulin A (IgA), both of which were elevated with CCSP deficiency. mRNA expression of EST W82219 and IgA was localized in the lungs of wild-type and CCSP(-/-) mice to airway Clara cells and peribronchial lymphoid tissues, respectively. We conclude that CCSP deficiency is associated with 1) altered gene expression in Clara cells of the conducting airway epithelium and 2) alterations to peribronchial B lymphocytes. These findings identify new roles for Clara cells and their secretions in airway homeostasis.
Animals↗
Postprandial hormone and metabolic responses amongst shift workers in Antarctica.
The circadian rhythms of many night-shift workers are maladapted to their imposed behavioural schedule, and this factor may be implicated in the increased occurrence of cardiovascular disease (CVD) reported in shift workers. One way in which CVD risk could be mediated is through inappropriate hormonal and metabolic responses to meals. This study investigated the responses to standard meals at different circadian times in a group of night-shift workers on a British Antarctic Survey station at Halley Bay (75 degrees S) in Antarctica. Twelve healthy subjects (ten men and two women) were recruited. Their postprandial hormone and metabolic responses to an identical mixed test meal of 3330 kJ were measured on three occasions: (i) during daytime on a normal working day, (ii) during night-time at the beginning of a period of night-shift work, and (iii) during the daytime on return from night working to daytime working. Venous blood was taken for 9 h after the meal for the measurement of glucose, insulin, triacylglycerol (TAG) and non-esterified fatty acids. Urine was collected 4-hourly (longer during sleep) on each test day for assessment of the circadian phase via 6-sulphatoxymelatonin (aMT6s) assay. During normal daytime working, aMT6s acrophase was delayed (7.7+/-1.0 h (s.e.m.)) compared with that previously found in temperate zones in a comparable age-group. During the night shift a further delay was evident (11.8+/-1.9 h) and subjects' acrophases remained delayed 2 days after return to daytime working (12.4+/-1.8 h). Integrated postprandial glucose, insulin and TAG responses were significantly elevated during the night shift compared with normal daytime working. Two days after their return to daytime working, subjects' postprandial glucose and insulin responses had returned to pre-shift levels; however, integrated TAG levels remained significantly elevated. These results are very similar to those previously found in simulated night-shift conditions; it is the first time such changes have been reported in real shift workers in field conditions. They provide evidence that the abnormal metabolic responses to meals taken at night during unadapted night shifts are due, at least in part, to a relative insulin resistance, which could contribute to the documented cardiovascular morbidity associated with shift work. When applied to the 20% of the UK workforce currently employed on shift work, these findings have major significance from an occupational health perspective.
Adult↗
Endovascular management of a bleeding mandibular arteriovenous malformation by transfemoral venous embolization with NBCA.
A 13-year-old boy presented with an arteriovenous malformation (AVM) involving the left mandible that bled after intraoral biopsy. The AVM was treated on an emergency basis by primary intravenous delivery of n-butyl cyanoacrylate after transfemoral catheterization, resulting in complete anatomic and clinical cure.
Adolescent↗
[Language as a tool. "Physician's words"].
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Communication↗