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Biomedical subjects

T Nilsson

Publications and source records attributed to T Nilsson.

At least 109 records · Page 6Linked to original sources
PubMed1997

An isoform of the Golgi t-SNARE, syntaxin 5, with an endoplasmic reticulum retrieval signal.

The early Golgi t-SNARE (target-membrane-associated soluble-N-ethylmaleimide-sensitive factor attachment protein receptor) syntaxin 5 is thought to specify the docking site for both COPI and COPII coated vesicles originating from the endoplasmic reticulum (ER) and COPI vesicles on the retrograde pathway. We now show that there are two forms of syntaxin 5 that appear to be generated from the same mRNA by alternative initiation of translation. The short form (35 kDa) corresponds to the published sequence. The long form (42 kDa) has an N-terminal cytoplasmic extension containing a predicted type II ER retrieval signal. When grafted onto a reporter molecule, this signal localized the construct to the ER. Biochemical fractionation and immunofluorescence microscopy showed that there was less of the long form in the Golgi apparatus and more in peripheral punctate structures, some of which colocalized with markers of the intermediate compartment. The predicted absence of the long form in budding yeast points to a function unique to higher organisms.

Alternative Splicing↗
PubMed1997

Presence of contractile endothelin-A and dilatory endothelin-B receptors in human cerebral arteries.

OBJECTIVE: The aim of the present study was to elucidate the endothelin receptor subtypes responsible for the endothelin-induced vasomotor responses of human cerebral arteries. METHODS: Human cerebral arteries with endothelium were mounted in in vitro tissue baths, and the vascular responses to endothelin-1 (ET-1) and sarafotoxin 6c (a selective ETB agonist) were studied in the presence or absence of endothelin blockers, bosentan (Ro 47-0203), a novel nonpeptide ETA and ETB receptor antagonist, and FR139317, a selective ETA receptor antagonist. The presence of messenger ribonucleic acid encoding the human ETA and ETB receptors in human cerebral arteries with intact endothelium and in segments denuded of endothelium was studied by the use of reverse transcriptase-polymerase chain reaction. RESULTS: ET-1 induced concentration-dependent contraction of human cerebral arteries; the pEC50 value was 9.4 +/- 0.2. The vasoconstriction was significantly antagonized both by bosentan and by FR139317. The pA2 values were 7.2 +/- 0.4 and 7.4 +/- 0.4, respectively. Sarafotoxin 6c failed to cause contraction of human cerebral arteries. In precontracted vessels, however, sarafotoxin 6c induced dilatation that was significantly inhibited by bosentan (10 mumol/L), resulting in a pA2 value of 6.0 +/- 0.2. Furthermore, messenger ribonucleic acid encoding the human ETA and ETB receptors was detected in human cerebral arteries both with and without endothelium. CONCLUSION: The ET-1-induced vasoconstriction of human cerebral arteries is primarily mediated by the ETA receptor, whereas the sarafotoxin 6c-induced vasodilatation seems to be mediated via the ETB receptor.

Cerebral Arteries↗
PubMed1997

Observer agreement and accuracy for lung scintigraphy: a comparison with pulmonary angiography.

This study investigated whether the moderate observer agreement rate for lung scintigraphy, when using the PIOPED criteria, reflects significant variations in accuracy. In a prospective study, 170 patients were investigated with lung scintigraphy and pulmonary angiography. The lung scintigrams were read according to the PIOPED criteria by three skilled observers from different hospitals who had no experience of consensus interpretation. The scintigrams were reinterpreted 6 months later. The inter-observer agreement rates were moderate and fair, with kappa values of 0.49 (0.44-0.54) for the first reading and 0.36 (0.31-0.41) for the second reading. The intra-observer agreement rates were good and moderate, with kappa values of 0.62 (0.51-0.73), 0.52 (0.42-0.62) and 0.54 (0.44-0.64). There were no significant differences between the observers in the areas under the ROC curves. However, one observer showed a significant difference between his first and second reading (P = 0.02). All three observers showed good accuracy. Although there were substantial variations in the inter- and intra-observer agreement rates, this was only reflected to a minor degree in the accuracy.

Angiography↗
PubMed1997

Effects of dihydroergotamine and sumatriptan on isolated human cerebral and peripheral arteries and veins.

BACKGROUND: Pharmacological cerebral vasoconstriction has recently been suggested as treatment for patients with increased intracranial pressure (ICP) after severe traumatic brain lesions. Hypothetically, a moderate constriction of precapillary resistance vessels might be advantageous since it decreases intracapillary blood pressure, and a contraction of cerebral veins might effectively reduce intracranial blood volume and ICP. This report examines the in vitro effects of two vasoconstrictors, dihydroergotamine (DHE) and sumatriptan, which may be considered for treatment of increased ICP. METHODS: The reactivity of isolated small human cerebral subcutaneous and omental arteries and veins were studied during exposure to different concentrations of DHE and sumatriptan. RESULTS: Both sumatriptan and DHE induced concentration-dependent contractions in human cerebral arteries and veins and 50% of maximum contractions were obtained at significantly lower concentrations of DHE than of sumatriptan. The maximum contraction of cerebral arteries was significantly higher with sumatriptan than with DHE. Both drugs caused contractions of subcutaneous arteries at concentrations of 10(-7)-10(-6)M, which is within the therapeutic concentration range of sumatriptan, while no effect was obtained in omental vessels. CONCLUSIONS: Both DHE and sumatriptan cause contraction of isolated human cortical arteries and veins at very low concentrations. The differences observed between the two drugs may be explained by the fact that DHE is an alpha-adrenergic as well as a 5-HT agonist while sumatriptan acts specifically on 5-HT receptors. The study supports the hypothesis underlying the use of DHE for the treatment of increased ICP in patients with severe traumatic brain lesions.

Cerebral Arteries↗
PubMed1997

Human Rer1 is localized to the Golgi apparatus and complements the deletion of the homologous Rer1 protein of Saccharomyces cerevisiae.

Sec12p is a type II membrane glycoprotein in the endoplasmic reticulum (ER) of Saccharomyces cerevisiae which is essential for transport vesicle budding. It is the guanine nucleotide exchange factor for the small GTP-binding protein Sar1p which is a constituent of COP II ER to Golgi vesicles. We report the sequence and localization of the human homologue to yeast Rer1p, which has recently been identified genetically as an essential component for retention of Sec12p in the ER. Reverse polymerase chain reaction was used to obtain cDNAs from HeLa cells. They code for a protein of 196 amino acids, corresponding to a molecular mass of 23 kDa. The translated sequence is 44% identical and 65% similar to yeast Rer1 protein. The four putative transmembrane domains are predicted to form a W-topology with both N- and C-terminus facing the cytosol. The functional activity of myc-tagged human Rer1 was demonstrated by the complementation of the RER1 deletion in S. cerevisiae. Mislocalization of the Sec12-reporter protein was reduced similar to the results obtained with yeast Rer1p. Human Rer1 protein was expressed in HeLa cells and the subcellular distribution analyzed by double immunofluorescence and immunoelectron microscopy of thawed cryosections. The tagged protein was localized to the Golgi apparatus and peripheral elements of the ER-Golgi interface. High overexpression leads to relocation of human Rer1 to ER-like structures together with KDEL-receptor and affects the structural organization of the Golgi apparatus. Under conditions of brefeldin A treatment, human Rer1 distributes together with recycling Golgi proteins.

Adaptor Proteins, Vesicular Transport↗
PubMed1997

Job Strain in Shift and Daytime Workers.

Cross-sectional questionnaire data were used to compare the levels of job strain in shift and daytime workers. Job strain was measured according to Karasek's Demands/Discretion model. Four occupational groups were included: drivers, industrial workers, policemen/watchmen, and cooks. The study subjects were a random sample of 508 daytime workers and 418 shift workers. Job demand did not differentiate between shift and daytime workers, comparing groups broken down by gender and by occupation. The daytime workers reported higher levels of job strain than the shift workers, and women experienced a higher level of job strain than did men. Multiple linear regression analysis showed that only occupational group and gender predicted job strain level. Shiftwork was not significantly associated with job strain in the regression model.

Journal Article↗
PubMed1996

[Incisional hernia. A study of morbidity, mortality and bed utilization in a Danish county].

Four hundred and four patients operated for ventral hernia during a five year period were reviewed with special emphasis on morbidity, mortality and number of days in hospital. The patients were divided into 357 patients who had been operated for ventral hernia only once (A) and 47 patients who had been operated more than once for ventral hernia (B). There were no significant differences between the two groups regarding to ages or preoperative condition. The postoperative complications were 21% in group A and 12% in group B, although this was not statistically significant. Of those who suffered a complication after the operation, 76% had a competing illness prior to the operation. The overall mortality was 0.5%. The patients were hospitalized for a total of 4846 days. In view of the results of this material and of the high recurrence rate demonstrated in the literature, a restrictive attitude towards operations for ventral hernia is recommended.

Adolescent↗
PubMed1996

Neuropeptide Y potentiates noradrenaline-induced contraction through the neuropeptide Y Y1 receptor.

To elucidate which neuropeptide Y receptor subtype is responsible for the neuropeptide Y-induced potentiation of the noradrenaline-evoked contraction in human omental arteries we used antisense oligodeoxynucleotide (Antisense), the new selective neuropeptide Y Y1 receptor antagonist, BIBP3226 {(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl) methyl]-D-arginine-amide} and the reverse transcriptase-polymerase chain reaction (RT-PCR). Neuropeptide Y significantly potentiated the noradrenaline-induced contraction in non-incubated vessels (pEC50 6.4 +/- 0.2 vs. 5.9 +/- 0.2) and in vessels incubated with 1 microM Sense oligodeoxynucleotide (Sense) (pEC50 6.0 +/- 0.1 vs. 5.6 +/- 0.2). In vessels incubated with 1 microM Antisense the potentiating effect of neuropeptide Y was completely abolished. BIBP3226 (1 microM) inhibited the neuropeptide Y-induced potentiation in human omental arteries (pEC50 5.8 +/- 0.3 vs. 6.4 +/- 0.2). Finally, messenger RNA for the neuropeptide Y Y1 receptor was detected using RT-PCR. On the basis of our results we conclude that the neuropeptide Y-induced potentiation of the noradrenaline-induced contraction is mediated by the neuropeptide Y Y1 receptor.

Adrenergic alpha-Agonists↗
PubMed1996

Kinetics of electron and proton transfer during the reaction of wild type and helix VI mutants of cytochrome bo3 with oxygen.

Site-directed mutagenesis was used to investigate the mechanism of electron and proton transfer in the ubiquinol oxidase, cytochrome bo3, from Escherichia coli. The reaction between the fully reduced form of the enzyme and dioxygen was studied using the flow--flash method. After rapid mixing of CO-bound enzyme with an O2-containing solution, CO was photodissociated, and the subsequent electron- and proton-transfer reactions were measured spectrophotometrically, the latter using a pH-indicator dye. In the wild-type, pure bo3 enzyme, without bound quinones, we observed a single kinetic phase with a rate constant of about 2.4 x 10(4) s-1, associated with formation of the ferry1 oxygen intermediate, followed by proton uptake from solution with a rate constant of about 1.2 x 10(4) s-1. Enzyme in which heme o instead of heme b was incorporated into the low-spin site displayed a slower ferry1 formation with a rate constant of about 3.6 x 10(3) s-1. Upon replacement of the acidic residue glutamate 286 in helix VI of subunit I with a nonprotonatable residue, electron transfer was slightly accelerated, and proton uptake was impaired. Mutations of other residues in the vicinity of E286 also resulted in a dramatic decrease of proton uptake, suggesting that the environment of this residue is important for efficient proton transfer. In the closely related cytochrome aa3 from P. denitrificans, the corresponding residue (E278) has been suggested to be part of a proton-transfer pathway [Iwata, S., Ostermeier, C., Ludwig, B., & Michel, H. (1995) Nature 376, 660-669]. The results are discussed in terms of a model for electron-proton coupling during dioxygen reduction.

Carbon Monoxide↗
PubMed1996

Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca2+ in glucose-stimulated pancreatic beta-cells.

Closure of ATP-sensitive K+ (K(ATP)) channels is part of the stimulus-secretion coupling mechanism in the pancreatic beta-cell, leading to membrane depolarization and influx of Ca2+ through voltage-sensitive L-type Ca2+ channels. The elevated ATP/ADP ratio seen in the presence of high levels of glucose has been postulated to mediate the glucose-induced closure of the K(ATP) channels and rise in cytoplasmic free Ca2+ concentration ([Ca2+]i), or alternatively to be a consequence of activation of mitochondrial dehydrogenases by the increase in [Ca2+]i. To distinguish between these two possibilities, the time course of the change in the ATP/ADP ratio was determined in comparison with that of [Ca2+]i. We here show that a severalfold rise in the ATP/ADP ratio occurs rapidly on stimulation of suspensions of mouse pancreatic beta-cells with glucose. The change in the ATP/ADP ratio is an early event that begins within 20-40 s and precedes the rise in [Ca2+]i. The temporal relationship indicates that the adenine nucleotide changes cannot be a consequence of the [Ca2+]i changes and may indeed be the connecting link between glucose metabolism and [Ca2+]i changes. When the cells were sequentially treated with high glucose concentration, clonidine and finally high extracellular Ca2+ concentration to induce synchronized oscillations in [Ca2+]i in the cell suspension, corresponding oscillations in the ATP/ADP ratio were observed. Glucose 6-phosphate levels oscillated out of phase with the ATP/ADP ratio. These results support the hypothesis that the Ca2+ oscillations previously observed in glucose-stimulated single islets or beta-cells may reflect oscillations in the ATP/ADP ratio that accompany oscillatory glycolysis.

Adenosine Diphosphate↗
PubMed1996

Presence of neuropeptide Y Y1 receptor mediating vasoconstriction in human cerebral arteries.

The neuropeptide Y-induced vasoconstriction of human cerebral arteries is mediated by the neuropeptide Y Y1 receptor. We conclude this on the basis of our results from: (1) in vitro studies on neuropeptide Y agonists. Neuropeptide Y and pro34NPY caused potent and long-lasting contractions of human cerebral arteries, while NPY 13-36 had no contractile effect at all on the vessels tested; (2) in vitro studies using the selective Y1 receptor antagonist BIBP3226 which in increasing concentrations (10(-9)-10(-6)M) caused a parallel shift to the right of the neuropeptide Y concentration-response curve without change of the maximum contractile response (pA2 value 8.38 +/- 0.10); and (3) with reverse transcriptase-polymerase chain reaction (RT-PCR) we detected specific mRNA for a neuropeptide Y Y1 receptor in human pial and human middle cerebral arteries using three forward primers and one reverse primer.

Arginine↗
PubMed1996

Classification of species in the genus Penicillium by Curie point pyrolysis/mass spectrometry followed by multivariate analysis and artificial neural networks.

Curie point pyrolysis/mass spectrometry of Penicillium species was performed with 530 degrees C Curie point foils. The mass spectra were submitted to principal component analysis, canonical variates analysis and hierarchical cluster analysis, producing a final dendrogram by the use of average linkage clustering. By this approach a successful classification of the species Penicillium italicum, P. expansum and P. digitatum originating from fruits was obtained. Isolates of the same species grouped together in the dendrogram, while the different species were distinguished. Also when grown on two different agar media, replicates of the same species grouped together. Likewise, a satisfactory classification was achieved by multivariate analysis of the data for various isolates of the cheese-associated fungi Aspergillus versicolor, P. discolor, P. roqueforti, P. solitum, P. verrucosum, P. commune and P. palitans. However, some difficulties appeared in distinguishing the closely related species P. commune and P. palitans. Such difficulties became greater on including more isolates and limiting the analysis to five of the species. The use of back-propagation artificial neural networks, in contrast, resulted in a correct classification in all cases. Thus, it is concluded that Curie point pyrolysis/mass spectrometry is useful in chemotaxonomic studies of the closely related species in the genus Penicillium.

Cheese↗
PubMed1996

A flash-photolysis study of the reactions of a caa3-type cytochrome oxidase with dioxygen and carbon monoxide.

The time course of absorbance changes following flash photolysis of the fully-reduced carboxycytochrome oxidase from Bacillus PS3 in the presence of O2 has been followed at 445, 550, 605, and 830 nm, and the results have been compared with the corresponding changes in bovine cytochrome oxidase. The PS3 enzyme has a covalently bound cytochrome c subunit and the fully-reduced species therefore accommodates five electrons instead of four as in the bovine enzyme. In the bovine enzyme, following CO dissociation, four phases were observed with time constants of about 10 microseconds, 30 microseconds, 100 microseconds, and I ms at 445 nm. The initial, 10-microsecond absorbance change at 445 nm is similar in the two enzymes. The subsequent phases involving heme a and CuA are not seen in the PS3 enzyme at 445 nm, because these redox centers are re-reduced by the covalently bound cytochrome c, as indicated by absorbance changes at 550 nm. A reaction scheme consistent with the experimental observations is presented. In addition, internal electron-transfer reactions in the absence of O2 were studied following flash-induced CO dissociation from the mixed-valence enzyme. Comparisons of the CO recombination rates in the mixed-valence and fully-reduced oxidases indicate that more electrons were transferred from heme a3 to a in PS3 oxidase compared to the bovine enzyme.

Animals↗
PubMed1996

A computerized induction analysis of possible co-variations among different elements in human tooth enamel.

In recent decades software tools in the area of artificial intelligence have rapidly developed for use in personal computers. Interactive rule induction utilizing mathematical algorithms has become a powerful tool in data analysis and in making rules and patterns explicit. Data from a Secondary Ion Mass Spectrometry (SIMS) elemental analysis of human dental enamel were used to elucidate co-variations between certain elements. A co-variation analysis was performed employing a computerized induction analysis program, as well as a neural network program. Both analyses, confirming each other, revealed co-variations between certain elements in dental enamel in addition to exclusion of data of no importance for chosen outcomes. The results are presented in hierarchic diagrams, in which the importance for every specific element is given by its position and level in the diagram (decision tree). From the results it became evident that elements such as chlorine and sodium expressed a high co-variation level. Similarly fluorine and potassium co-varied, as well as magnesium and the trace element strontium. It was demonstrated that data from an elemental analysis could be processed by an induction analysis to reveal co-variations between certain elements in tooth enamel. The biological significance of these data is not fully understood, and further analyses in the field are needed.

Algorithms↗
PubMed1996

Contractile effects of neuropeptide Y in human subcutaneous resistance arteries are mediated by Y1 receptors.

The aim of our study was to determine the neuropeptide Y (NPY) receptor subtype responsible for the NPY-induced contraction of human subcutaneous (s.c.) resistance arteries. To elucidate this, we used (a) in vitro studies of NPY agonists: NPY, peptide YY (PYY), and Pro34NPY induced equally strong and equipotent concentration-dependent contractions of human s.c. resistance arteries, whereas NPY13-36 and NPY18-36 had no contractile effects; (b) in vitro studies using the NPY Y1-receptor antagonist, BIBP3226, which in nanomolar concentrations inhibited the contractile effect of NPY, causing a rightward shift of the concentration-response curve. pEC50 for NPY alone, 8.41 +/- 0.21; NPY + BIBP3226, 10 nM, 7.79 +/- 0.21; NPY + BIBP3226, 100 nM, 7.18 +/- 0.18; NPY + BIBP3226, 1 microM, 6.32 +/- 0.05 (n = 5-8). Schild-plot analysis indicated competitive antagonism: pA2 = 8.53 +/- 0.22 and slope = 0.99 +/- 0.14; (c) with reverse transcriptase-polymerase chain reaction (RT-PCR), we detected messenger RNA (mRNA) encoding the human NPY Y1 receptor and a splice variant of the receptor in human s.c. resistance arteries. On the basis of the agonists' potency order, the antagonistic effect of BIBP3226 on the NPY-induced contraction, and the presence of mRNA encoding the NPY Y1 receptor, we conclude that the NPY-induced contraction of human s.c. resistance arteries is mediated by NPY Y1 receptors.

Arginine↗
PubMed1996

B cell-specific activation of the Epstein-Barr virus-encoded C promoter compared with the wide-range activation of the W promoter.

We have studied the activity of reporter plasmids, carrying the Epstein-Barr virus (EBV) nuclear antigen (EBNA) promoters Wp and Cp, in a group of somatic cell hybrids obtained by fusing EBV-positive lymphoblastoid cell lines or group II/III Burkitt's lymphoma cell lines with non-B cell lines. In B/non-B cell hybrids of this type, B cell markers are extinguished as a rule, in parallel with the inactivation of Cp or Wp and down-regulation of EBNA-2-6 expression. A Wp-carrying reporter construct was active in non-B cell lines. Only cells with a B cell phenotype could support the activity of Cp-carrying plasmids. EBNA-2 transactivated Cp only in B cells. Our data suggest that while Wp can be used for EBNA transcription in B and non-B cells, Cp activity is restricted to B cells. The inability of EBNA-2 to transactivate Cp in non-B cells indicates that other factors present in B cells might be involved in Cp transactivation.

Antigens, Viral↗
PubMed1996

Sumatriptan-induced cerebral vasoconstriction as treatment of experimental intracranial hypertension.

BACKGROUND: Increased intracranial pressure (ICP) is a major cause of mortality in severe head injuries and pharmacologically induced cerebral vasoconstriction has been suggested as a possible treatment. In the present study a porcine model of increased ICP was utilized to study the changes in cerebral haemodynamics and energy metabolism induced by a selective 5-hydroxytryptamine1 agonist (sumatriptan). METHODS: ICP was raised by inflation of two balloons covering both parieto-occipital regions extradurally. The animals were randomized into four groups receiving sumatriptan. 0.01 mg.kg-1 (A), 0.03 mg.kg-1 (B), 0.1 mg.kg-1 (C), and 0.5 mg.kg-1 (D) intravenously over 10 min. Measurements of cerebral blood flow (CBF), arterio-venous oxygen content difference (CavO2), and jugular venous pH (vpH) were performed 5, 20, 40, 60, and 75 min after start of the infusion. ICP, mean arterial pressure, and EEG were recorded continuously. Direct effects of sumatriptan were also compared in cortical arteries and veins in vitro. RESULTS: Significant decreases in ICP were obtained in groups A, B, and C while group D exhibited a progressive increase in ICP. Significant reductions in CBF, increase in CavO2, and slowing of EEG were observed in groups B, C, and D. Sumatriptan caused moderate constriction of the arteries and a more pronounced dilatation of veins in vitro. CONCLUSION: The results indicate that a low dose of sumatriptan has the potential to reduce a raised ICP. High doses of sumatriptan cause a further increase of ICP possibly by dilatation of intracerebral veins.

Animals↗