Prevalence and diagnosis of cobalamin deficiency in older people.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
T Nilsson
Publications and source records attributed to T Nilsson.
Primate homologues of rat TGN38: primary structure, expression and functional implications.
cDNAs encoding the human and macaque homologues of rat TGN38 have been cloned and sequenced. The proteins have a highly conserved N terminus (comprising the signal peptide) and C terminus (comprising part of the lumenal domain, the membrane spanning region and cytoplasmic tail) but vary in the other part of the lumenal domain, which contains the repeat region. Whereas rat TGN38 contains 6 tandem repeats of an 8mer, both primate proteins possess 14 tandem repeats of a 14mer sequence. The human protein, like rat TGN38, is localised primarily to the TGN but is present on the cell surface and returns via endosomes. This behaviour is consistent with conservation of the membrane spanning region and the cytoplasmic tail, which contain the retention and retrieval signals, respectively, for localisation in the TGN. The unexpected differences in the lumenal domain can best be rationalised by the fact that both types of repeat domains have most of the properties of mucins. We suggest that TGN38 homologues are mucin-like molecules that regulate membrane traffic to and from the TGN.
Amino Acid Sequence↗
The role of the membrane-spanning domain and stalk region of N-acetylglucosaminyltransferase I in retention, kin recognition and structural maintenance of the Golgi apparatus in HeLa cells.
Using a series of chimeric and truncated N-acetylglucosaminyltransferase I (NAGT I) molecules we have shown that part of the lumenal stalk region is both necessary and sufficient for kin recognition of mannosidase II and retention in the Golgi stack. The membrane-spanning domain was not required for retention, but replacing part or all of this domain with leucine residues did have a dramatic effect on Golgi morphology. In stable cell lines, stacked cisternae were replaced by tubulo-vesicular clusters containing the mutated NAGT I. The loss of stacked cisternae was proportional to the number of leucines used to replace the membrane-spanning domain.
Amino Acid Sequence↗
Characterization of neuropeptide Y receptors mediating contraction, potentiation and inhibition of relaxation.
In addition to its direct vasoconstrictive effect, neuropeptide Y (NPY) potentiates noradrenaline-(NA) induced contraction and inhibits acetylcholine-(ACh) induced relaxation: The aim of the present study was to elucidate the NPY receptor subtypes responsible for mediating these three responses. NPY, peptide YY (PYY) and pro34NPY (a NPY Y1 receptor agonist) induced equipotent and equally strong concentration-dependent contractions of guinea pig basilar arteries. NPY13-36 (a NPY Y2 receptor agonist), however, caused only weak contraction with significantly lower potency. The NPY-induced contraction was significantly inhibited by the selective NPY Y1 receptor antagonist BIBP3226 (1 microM). NPY, PYY and pro34NPY but not NPY13-36 significantly potentiated the NA-induced contraction in guinea pig mesenteric arteries. The potentiation was significantly inhibited by BIBP3226 (1 microM). In precontracted guinea pig basilar arteries, ACh induced a concentration-dependent relaxation which was significantly inhibited by NPY, PYY and NPY13-36 but not by pro34NPY. BIBP3226 had no significant effect on the NPY-induced inhibition of the relaxation. These results suggests that the NPY Y1 receptors mediate the direct contraction and the potentiation of the NA-induced contraction but not the inhibition of the ACh-induced relaxation. This effect seems to be mediated by another NPY receptor subtype, presumably by the Y2 receptor, as judged from the agonist potency order.
Acetylcholine↗
Vibrotactile perception thresholds as determined by two different devices in a working population.
OBJECTIVES: The purpose of this study was to investigate whether two devices for measuring vibrotactile perception thresholds produced similar results on an individual basis and to compare the thresholds in the presence or absence of sensorineural hand symptoms and vibration exposure. METHODS: Vibrotactile perception thresholds were measured with a vibrameter and a tactilometer in 178 men. The tactilometer uses seven discrete frequencies from 8 to 500 Hz, and the vibrameter uses one frequency (100 Hz). Agreement was assessed from the correlations and from a comparison of subjects who had thresholds above the upper quartile of each device as to the presence of sensorineural hand symptoms and occupational vibration exposure. RESULTS: The correlation between the vibrameter and the tactilometer (125 Hz) was 0.59. The agreement between the vibrameter and the tactilometer (63 Hz), when the upper quartile was used as a limit, had a sensitivity of 0.56 and a specificity of 0.85. The sensitivity and specificity for the agreement with symptoms were 0.44 and 0.79, respectively, for the tactilometer and 0.40 and 0.78, respectively, for the vibrameter. The indices combined from the different frequencies of the tactilometer did not improve the agreement. CONCLUSIONS: Some of the discrepancy between the measurement of the vibrameter and tactilometer can be explained by differences in the equipment, the measurement procedures, and the examiner, combined with high inter-and intraindividual variability. Neither of the two devices was superior when the results were compared as to the occurrence of hand symptoms and vibration exposure. As evaluated in this study vibrotactile perception threshold has a restricted value for screening and diagnostic purposes on an individual basis.
Adult↗
Comparison of different methods for vibration measurements on hand-held vibrating tools.
Vibration measurements have been done on hand-held tools in a group of 48 platers by evaluating the individual vibration acceleration and absorption of vibration energy. The measurement of acceleration has been done frequency-weighted and frequency-unweighted in accordance with ISO 5349 and NIOSH (USA) recommendations for hand-arm vibration standards, respectively. The acceleration and the energy absorption have been measured simultaneously in the three orthogonal directions, the latter by using a specially designed adapter. The exposure time has been determined by both subjective rating and objective measurements. Individual energy-equivalent accelerations and vibration dosages have been calculated from these data. The outcome shows that the type of tool was critical to vibration load when the different measures for determining vibration levels were used. Of the methods used, the evaluation specified by ISO 5349 makes most consideration of low frequencies of vibration (< 50 Hz), absorption of vibration energy middle frequencies (50-200 Hz) and NIOSH of high frequencies (> 200 Hz). The results show a poor correlation between the three methods used. Close agreement between mean subjective rating and objective measurement of the average exposure time was found. Further studies of the relation between results presented here and generated disturbance will be conducted, which may clarify any exposure-response relationship.
Acceleration↗
[Pain rehabilitation is a pedagogic task. Chronic pain dealt with in a model for behavior-therapy].
Explore the source record for details and available documents.
Behavior Therapy↗
Study of the Unstable Nucleus 10Li in Stripping Reactions of the Radioactive Projectiles 11Be and 11Li.
Explore the source record for details and available documents.
Journal Article↗
Redrawing compartmental boundaries in the exocytic pathway.
Compartments can be defined both morphologically as well as biochemically. The former relies on a direct visualisation of membrane boundaries and the latter by the characterisation of enzymatic functions taking place within the compartment. The combination of morphology and biochemistry has led to the identification of several compartments within the exocytic pathway, each assumed to carry out independent functions in a logical succession [Palade, G. (1975) Science 189, 347-358]. However, recent findings show that resident enzymes are confined to not one but at least two adjacent compartments suggesting that morphological and biochemical definitions do not coincide. We will here discuss these findings and propose a model to explain how compartments are organised and maintained along the exocytic pathway.
Biological Transport↗
Oxygen reaction and proton uptake in helix VIII mutants of cytochrome bo3.
The oxygen reaction of wild-type and helix VIII mutants of cytochrome bo3 from Escherichia coli, and the associated proton uptake during this reaction, has been studied using flash photolysis of the CO complex of the reduced protein after rapid mixing with oxygen. We have focused on mutations in the transmembrane helix VIII where protonatable residues have been exchanged, and mainly on the inactive mutants (i.e., T352A, T359A, and K362L, -M, and -Q). The kinetics for electron transfer during oxidation for the mutants are similar to the wild-type; two rate constants of 3.2 x 10(4) and 3.4 x 10(3) s-1 (at 1 mM oxygen) are detected. Proton uptake is observed for wild-type as well as for the mutant enzymes, but the mutations within helix VIII have affected the rate of proton uptake; it is significantly accelerated in the mutants. These results show that none of the protonatable residues in helix VIII are required in the reaction between the fully reduced cytochrome bo3 and oxygen. We have also studied electron redistribution after photolysis of CO from the mixed-valence compound; we found three kinetic components for wild-type and the mutants T352A and T359A, but for K362M only the first and third components are observed, with amplitudes that are lower than those for the corresponding components in the wild-type enzyme, suggesting that the characteristics of internal electron transfer in the K362M mutant are different from those of the wild-type enzyme.
Carbon Monoxide↗
Effects of caffeine on cytoplasmic free Ca2+ concentration in pancreatic beta-cells are mediated by interaction with ATP-sensitive K+ channels and L-type voltage-gated Ca2+ channels but not the ryanodine receptor.
In the pancreatic beta-cell, an increase in the cytoplasmic free Ca2+ concentration ([Ca2+]i) by caffeine is believed to indicate mobilization of Ca2+ from intracellular stores, through activation of a ryanodine receptor-like channel. It is not known whether other mechanisms, as well, underlie caffeine-induced changes in [Ca2+]i. We studied the effects of caffeine on [Ca2+]i by using dual-wavelength excitation microfluorimetry in fura-2-loaded beta-cells. In the presence of a non-stimulatory concentration of glucose, caffeine (10-50 mM) consistently increased [Ca2+]i. The effect was completely blocked by omission of extracellular Ca2+ and by blockers of the L-type voltage-gated Ca2+ channel, such as D-600 or nifedipine. Depletion of agonist-sensitive intracellular Ca2+ pools by thapsigargin did not inhibit the stimulatory effect of caffeine on [Ca2+]i. Moreover, this effect of caffeine was not due to an increase in cyclic AMP, since forskolin and 3-isobutyl-1-methylxanthine (IBMX) failed to raise [Ca2+]i in unstimulated beta-cells. In beta-cells, glucose and sulphonylureas increase [Ca2+]i by causing closure of ATP-sensitive K+ channels (KATP channels). Caffeine also caused inhibition of KATP channel activity, as measured in excised inside-out patches. Accordingly, caffeine (> 10 mM) induced insulin release from beta-cells in the presence of a non-stimulatory concentration of glucose (3 mM). Hence, membrane depolarization and opening of voltage-gated L-type Ca2+ channels were the underlying mechanisms whereby the xanthine drug increased [Ca2+]i and induced insulin release. Paradoxically, in glucose-stimulated beta-cells, caffeine (> 10 mM) lowered [Ca2+]i. This effect was due to the fact that caffeine reduced depolarization-induced whole-cell Ca2+ current through the L-type voltage-gated Ca2+ channel in a dose-dependent manner. Lower concentrations of caffeine (2.5-5.0 mM), when added after glucose-stimulated increase in [Ca2+]i, induced fast oscillations in [Ca2+]i. The latter effect was likely to be attributable to the cyclic AMP-elevating action of caffeine, leading to phosphorylation of voltage-gated Ca2+ channels. Hence, in beta-cells, caffeine-induced changes in [Ca2+]i are not due to any interaction with intracellular Ca2+ pools. In these cells, a direct interference with KATP channel- and L-type voltage-gated Ca(2+)-channel activity is the underlying mechanism by which caffeine increases or decreases [Ca2+]i.
Adenosine Triphosphate↗
Inositol 1,2,3-trisphosphate and inositol 1,2- and/or 2,3-bisphosphate are normal constituents of mammalian cells.
1. An inositol trisphosphate (InsP3) distinct from Ins(1,4,5)P3 and Ins(1,3,4)P3, which we previously observed in myeloid and lymphoid cells [French, Bunce, Stephens, Lord, McConnell, Brown, Creba and Michell (1991) Proc R. Soc. London B 245, 193-201; Bunce, French, Allen, Mountford, Moore, Greaves, Michell and Brown (1993) Biochem. J. 289, 667-673], is present in WRK1 rat mammary tumour cells and pancreatic endocrine beta-cells. 2. It has been identified as Ins(1,2,3)P3 by a combination of oxidation to ribitol, a structurally diagnostic polyol, and ammoniacal hydrolysis to identified inositol monophosphates. 3. Ins(1,2,3)P3 concentration in HL60 cells changed little during stimulation by ATP or fMetLeuPhe or during neutrophilic or monocytic differentiation, and Ins(1,2,3)P3 was unresponsive to vasopressin in WRK1 cells. 4. Ins(1,2,3)P3 was usually more abundant than Ins(1,4,5)P3, often being present at concentrations between approximately 1 microM and approximately 10 microM. 5. HL60, WRK-1 and lymphoid cells also contain Ins(1,2)P2 or Ins(2,3)P2, or a mixture of these two enantiomers, as a major InsP2 species. 6. Ins(1,2,3)P3 and Ins(1,2)P2/Ins(2,3)P2 are readily detected in cells labelled for long periods, but not in acutely labelled cells. This behaviour resembles that of InsP6, the most abundant cellular inositol polyphosphate that includes the 1,2,3-trisphosphate motif, which also achieves isotopic equilibrium with inositol only slowly. 7. Ins(1,2,3)P3 is the major InsP3 that accumulates during metabolism of InsP6 by WRK-1 cell homogenates. 8. Possible metabolic relationships between Ins(1,2,3)P3, Ins(1,2)P2/Ins(2,3)P2 and other inositol polyphosphates in cells, and a possible role for Ins(1,2,3)P3 in cellular iron handling, are considered.
Animals↗
Characterization of a cis-Golgi matrix protein, GM130.
Antisera raised to a detergent- and salt-resistant matrix fraction from rat liver Golgi stacks were used to screen an expression library from rat liver cDNA. A full-length clone was obtained encoding a protein of 130 kD (termed GM130), the COOH-terminal domain of which was highly homologous to a Golgi human auto-antigen, golgin-95 (Fritzler et al., 1993). Biochemical data showed that GM130 is a peripheral cytoplasmic protein that is tightly bound to Golgi membranes and part of a larger oligomeric complex. Predictions from the protein sequence suggest that GM130 is an extended rod-like protein with coiled-coil domains. Immunofluorescence microscopy showed partial overlap with medial- and trans-Golgi markers but almost complete overlap with the cis-Golgi network (CGN) marker, syntaxin5. Immunoelectron microscopy confirmed this location showing that most of the GM130 was located in the CGN and in one or two cisternae on the cis-side of the Golgi stack. GM130 was not re-distributed to the ER in the presence of brefeldin A but maintained its overlap with syntaxin5 and a partial overlap with the ER-Golgi intermediate compartment marker, p53. Together these results suggest that GM130 is part of a cis-Golgi matrix and has a role in maintaining cis-Golgi structure.
Amino Acid Sequence↗
PU box-binding transcription factors and a POU domain protein cooperate in the Epstein-Barr virus (EBV) nuclear antigen 2-induced transactivation of the EBV latent membrane protein 1 promoter.
Expression of the Epstein-Barr virus (EBV) latent membrane protein (LMP1) is regulated by virus- and host cell-specific factors. The EBV nuclear antigen 2 (EBNA2) has been shown to transactivate a number of viral and cellular gene promoters including the promoter for the LMP1 gene. EBNA2 is targeted to at least some of these promoters by interacting with a cellular DNA binding protein, RBP-J kappa. In the present report we confirm and extend our previous observation that the LMP1 promoter can be activated by EBNA2 in the absence of the RBP-J kappa-binding sequence in the LMP1 promoter regulatory region (LRS). We show that two distinct LRS regions, -106 to +40 and -176 to -136, contribute to EBNA2 responsiveness. Site-directed mutagenesis analysis of the upstream -176/-136 EBNA2 responsive element revealed that two critical cis-acting elements are required for full promoter function. These same elements analysed by electrophoretic mobility shift assays define two binding sites recognized by nuclear factors derived from B cells. An octamer-like sequence (-147 to -139) contained overlapping binding sites for an unidentified transcriptional repressor on the one hand and a factor(s) belonging to the POU domain family but distinct from Oct-1 and Oct-2 on the other. An adjacent purine tract (-171 to -155) held a PU.1 binding site, which was also recognized by a related factor. The results suggest that the POU domain protein and either of two PU box-binding factors bind simultaneously to LRS, creating a ternary complex that might be in part responsible for mediating the transactivation of the LMP1 promoter by EBNA2. There were no qualitative differences between EBV-negative and EBV-positive cells with regard to transcription factor binding to the octamer-like sequence and the PU.1 recognition site, as revealed by electrophoretic mobility shift assays.
Antigens, Viral↗
Mapping the distribution of Golgi enzymes involved in the construction of complex oligosaccharides.
The distribution of beta 1,2 N-acetylglucosaminyltransferase I (NAGT I), alpha 1,3-1,6 mannosidase II (Mann II), beta 1,4 galactosyltransferase (GalT), alpha 2,6 sialyltransferase (SialylT) was determined by immuno-labelling of cryo-sections from HeLa cell lines. Antibody labelling in the HeLa cell line was made possible by stable expression of epitope-tagged forms of these proteins or forms from species to which specific antibodies were available. NAGT I and Mann II had the same distribution occupying the medial and trans cisternae of the stack. GalT and SialylT also had the same distribution but they occupied the trans cisterna and the trans-Golgi network (TGN). These results generalise our earlier observations on the overlapping distribution of Golgi enzymes and show that each of the trans compartments of the Golgi apparatus in HeLa cells contains unique mixtures of those Golgi enzymes involved in the construction of complex, N-linked oligosaccharides.
Animals↗
Oral anticoagulant treatment in a medical care district--a descriptive study.
OBJECTIVE: To describe how oral anticoagulant therapy is performed in a defined catchment area in order to improve the quality of care. DESIGN: Two study periods of 8 weeks were compared with reference to monitoring sites, i.e. hospital departments and primary health care centres. SETTING: The health care district of Umeå in northern Sweden, with 125,300 inhabitants. PARTICIPANTS: Patients on oral anticoagulant therapy at the department of Internal Medicine, Umeå University Hospital, in 1987 (n = 243) were compared with all patients treated in 1990 at health centres (n = 175) and at the department of Internal Medicine (n = 290) in the Umeå district. MAIN OUTCOME MEASURES: The prevalence of treatment failures and complications was calculated per patient year, as well as the relative frequencies of patients within treatment recommendations. RESULTS: 80-83% of the patients were within treatment recommendations. Treatment failures were 3.6% of hospital patients, and 2.6% of primary care patients. Corresponding figures for bleeding complications were 8.9% and 5.1%, respectively. The differences are partly explained by differences in the studied groups, e.g. age, indications for treatment, and concomitant diseases.
Administration, Oral↗
Vibrotactile perception sensitivity and its relation to hand-arm vibration exposure.
Vibrotactile perception thresholds (VPT) at seven test frequencies (8-500 Hz) have been measured and evaluated among 170 male employees at a heavy engineering production workshop, 125 of them were at present, or in the past, exposed to hand-arm vibration. All participants were examined by a physician and none had symptoms of diseases or were exposed to other factors known to cause sensory neuropathies. VPTs [for the three lowest (8-32 Hz; non-Pacinian), for the four highest (63-500 Hz; Pacinian) and for all test frequencies together] and a sensitivity index (SI) has been individually graded in four (normal, slightly deteriorated, deteriorated and seriously deteriorated) and two (normal, abnormal) stages, respectively, and put in relation to individual exposure of vibration. The results do not show any clear relationship on an individual basis between vibration exposure and degraded vibrotactile perception. On a group basis, however, there is a clear tendency towards detoriorated VPTs when the study group is divided in exposure categories. The detorioration is most pronounced in the frequency range mediated by Pacinian corpuscles. In this range an approximately four-fold increase of relative risk for elevated VPT for those in the highest exposure category was observed compared to the non-exposed group. Corresponding relative risk estimate for SI is about 6. Therefore, the results suggest an existence of an exposure-response relationship.
Adult↗
Assessment of heat pain perception in relation to vibration exposure.
The effect of vibration on thin unmyelinated sensory fibers was studied by perception threshold measurement of heat pain. The investigation was a cross-sectional study of 98 vibration-exposed and 53 non-vibration-exposed workers. Pain perception was determined by using the "Marstock" method. The perception threshold of contact heat induced pain was assessed by the method of limits. Quantified personal energy-equivalent vibration exposure was assessed for all subjects on a group basis. The cumulated lifetime equivalent frequency-weighted vibration exposure was estimated based on measurements according to ISO 5349. The mean heat perception threshold was 46.2 degrees C (SD 2.6 degrees C) for the right hand and 46.0 degrees C (SD 2.7 degrees C) for the left. The results showed no mean difference (left = 0.1 degree C, right = 0.6 degree C) in heat pain perception between vibration-exposed and non-exposed subjects. There was a high correlation between the right and left hand measurements (r = 0.81). The risk (rate ratio) for impairment was 1.02 (95% CI 0.81-1.30) for the right hand and 1.00 (95% CI 0.79-1.26) for the left. The results of the study did not indicate any impairment as assessed by an increased perception threshold for heat pain. The lack of an increased heat pain threshold among the vibration-exposed workers in our study cannot exclude a possible lesional somatosensory influence from the exposure, as the lesional effect may also be a lowering of the threshold. The multiple and unrelated percepts of thermal sensations imply that it is not legitimate to draw conclusions about the total status of the small calibre afferents when testing only the heat pain perception.
Adult↗