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T Nilsson

Publications and source records attributed to T Nilsson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Cytosolic ATPases, p97 and NSF, are sufficient to mediate rapid membrane fusion.

Much recent work has focussed on the role of membrane-bound components in fusion. We show here that p97 and NSF are sufficient to mediate rapid membrane fusion. Fractionation of cytosol revealed that p97 and its co-factor, p47, constitutes the major fusion activity. This was confirmed by depleting p97 from the cytosol, which resulted in an 80% decrease in fusion. Using purified protein, p97 or NSF was found to be sufficient to mediate rapid fusion in an ATP-dependent manner. A regulatory role was observed for their corresponding co-factors, p47 and alpha-SNAP. When present at a molar ratio half of that of the ATPase, both co-factors increased fusion activity significantly. Intriguingly, at this ratio the ATPase activity of the complex measured in solution was at its lowest, suggesting that the co-factor stabilizes the ATP state. The fusion event involved mixing of both leaflets of the opposing membranes and contents of liposomes. We conclude from these data that p97, NSF and perhaps other related ATPases catalyse rapid and complete fusion between lipid bilayers on opposing membranes. This highlights a new role for p97 and NSF and prompts a re-evaluation of current fusion models.

Adenosine Triphosphatases↗
PubMed1999

Predictive aspects of the abduction external rotation test among male industrial and office workers.

BACKGROUND: Nerve compression of the brachial plexus can be provoked by the Abduction External Rotation (AER) test where the arms are held in a "hands-up" position. METHODS: The AER test was conducted among 137 male industrial and office workers at baseline and after 5 years follow-up, together with a medical examination/history and exposure analysis. Nerve conduction measurements in the wrist regions were also made. RESULTS: The cumulated incidence of neurological signs during the AER test, was estimated to be 2/100 person-years. Factors related to work-conditions, constitution, disease, and neck trauma were associated with AER signs. Subjects with AER signs exhibited a slowing of the nerve conduction velocities in the wrist region. The AER test predicted future neck and upper extremity symptoms and signs of nerve compression. CONCLUSIONS: The results of this study gave support to the "double or multiple crush" theory of nerve compression. Prevention, evaluation, and management of neck and upper extremity nerve compression diseases should, therefore, attend to all probable locations of such compression, even when a specific location is in focus. The AER test can be a supplementary tool in such work, both in epidemiological and occupational health settings.

Adult↗
PubMed1999

Exposure-response relationship between hand-arm vibration and vibrotactile perception sensitivity.

BACKGROUND: The objectives of the study were to examine whether occupational use of vibrating hand-held tools was associated with an impaired vibrotactile perception, whether any exposure-response relationship exists, and whether the different populations of mechano-receptive afferent units are equally affected. METHODS: Vibrotactile perception thresholds have been measured at seven frequencies (8-500 Hz) and evaluated among 125 vibration-exposed and 45 non-exposed male employees in a heavy engineering production workshop. Vibration exposure measurements were assessed on tools in accordance with ISO 5349. Vibrotactile perception thresholds have been individually graded in stages and placed in relation to individual vibration exposure. RESULTS: The outcome did not reveal a clear relationship between vibration exposure and reduced vibrotactile sensitivity on an individual basis. There was a clear tendency on a group basis towards elevated thresholds when the study population was divided into three exposure categories. A fourfold increase in relative risk of reduced vibrotactile sensitivity for test frequencies above 40 Hz was observed between the highest exposure category compared to the non-exposed. CONCLUSIONS: It was concluded that reduced tactile sensitivity is related to the degree of vibration exposure but it is not at present possible to delineate an exposure-response relationship.

Adult↗
PubMed1999

Personality and the prediction of weight loss and relapse in the treatment of obesity.

OBJECTIVE: This prospective study examined whether stable personality traits, as measured by the Karolinska Scales of Personality (KSP), predicted initial weight loss or long-term maintenance in obesity patients. METHOD: The KSP was administered to 102 obese patients prior to entering an 8-week weight loss program. Patients were weighed again at the end of treatment and at 3- and 12-month follow-up. RESULTS: The KSP did not predict initial weight loss after the 8-week program. Several of the KSP scales (Muscle Tension, Monotony Avoidance, Suspicion, and Guilt) had weak associations with 12-month relapse status. Weight gain at the 3-month follow-up was the strongest predictor of 12-month relapse status (O.R. = 0.46; 95% C.I. = 0.32, 0.66). DISCUSSION: Personality traits, as measured by the KSP, do not appear to be important predictors of initial weight loss or 12-month relapse status. Personality assessment may not substantially contribute to predicting treatment outcome in obesity research.

Adult↗
PubMed1999

Validity of pulmonary cine arteriography for the diagnosis of pulmonary embolism.

The aim of this study was to assess the interobserver variations in diagnosis of pulmonary embolism (PE) with cine technique and to compare the diagnostic accuracy of pulmonary arteriograms to final-outcome diagnosis. One hundred and seventy patients with clinical suspicion of acute PE were examined with ECG, laboratory tests, chest X-ray, pulmonary scintigraphy and selective pulmonary cine arteriography. The follow-up time was 6 months. Fifty-one arteriograms were interpreted as positive for PE. Two pulmonary emboli were missed when compared with the diagnosis as stated by the final-outcome committee. No arteriograms were considered as not of diagnostic quality. Mean interobserver agreement in lobar vessels was 100%, in segmental vessels 93% and in subsegmental vessels 63%. The mean interobserver agreement was 89%. Pulmonary cine arteriography produces high diagnostic accuracy and few inconclusive results in patients with suspected PE.

Angiography↗
PubMed1999

A new experimental model for partial ureteric obstruction in sheep.

This study aimed to develop a new experimental model of partial ureteric obstruction in sheep. Graded obstruction of the ureter using various sized catheters (Fr 3-8) for variable durations up to 6 weeks was performed in 19 sheep. The kidneys were studied by radionuclide diuretic renography for up to 21 weeks and had histopathological examination at the end of the experiment. Catheters of Fr 3 or Fr 5 should be used to block the ureter for a minimum of three weeks to produce sufficient functional and pathological changes to be studied. The advantages and disadvantages of this model are discussed.

Animals↗
PubMed1999

Evidence for a COP-I-independent transport route from the Golgi complex to the endoplasmic reticulum.

The cytosolic coat-protein complex COP-I interacts with cytoplasmic 'retrieval' signals present in membrane proteins that cycle between the endoplasmic reticulum (ER) and the Golgi complex, and is required for both anterograde and retrograde transport in the secretory pathway. Here we study the role of COP-I in Golgi-to-ER transport of several distinct marker molecules. Microinjection of anti-COP-I antibodies inhibits retrieval of the lectin-like molecule ERGIC-53 and of the KDEL receptor from the Golgi to the ER. Transport to the ER of protein toxins, which contain a sequence that is recognized by the KDEL receptor, is also inhibited. In contrast, microinjection of anti-COP-I antibodies or expression of a GTP-restricted Arf-1 mutant does not interfere with Golgi-to-ER transport of Shiga toxin/Shiga-like toxin-1 or with the apparent recycling to the ER of Golgi-resident glycosylation enzymes. Overexpression of a GDP-restricted mutant of Rab6 blocks transport to the ER of Shiga toxin/Shiga-like toxin-1 and glycosylation enzymes, but not of ERGIC-53, the KDEL receptor or KDEL-containing toxins. These data indicate the existence of at least two distinct pathways for Golgi-to-ER transport, one COP-I dependent and the other COP-I independent. The COP-I-independent pathway is specifically regulated by Rab6 and is used by Golgi glycosylation enzymes and Shiga toxin/Shiga-like toxin-1.

ADP-Ribosylation Factor 1↗
PubMed1999

Contractile 5-HT1B receptors in human cerebral arteries: pharmacological characterization and localization with immunocytochemistry.

1 The cerebrovascular receptor(s) that mediates 5-hydroxytryptamine (5-HT)-induced vasoconstriction in human cerebral arteries (HCA)has proven difficult to characterize, yet these are essential in migraine. We have examined 5-HT receptor subtype distribution in cerebral blood vessels by immunocytochemistry with antibodies selective for human 5-HT1B and human 5-HT1D receptors and also studied the contractile effects of a range of 5-HT receptor agonists and antagonists in HCA. 2 Immunocytochemistry of cerebral arteries showed dense 5-HT1B receptor immunoreactivity (but no 5-HT1D receptor immunoreactivity) within the smooth muscle wall of the HCA. The endothelial cell layer was well preserved and weak 5-HT1B receptor immunoreactivity was present. 3 Pharmacological experiments on HCA with intact endothelium showed that 5-carboxamidotryptamine was significantly more potent than alpha-methyl-5-HT, 2-methyl-5-HT and 5-HT in causing vasoconstriction. The 5-HT1B/1D receptor agonists naratriptan, sumatriptan, zolmitriptan and 181C91 (N-desmethyl zolmitriptan), all induced equally strong contractions and with similar potency as 5-HT. The maximum contractile response was significantly less for avitriptan and dihydroergotamine. There was a significant correlation between vasoconstrictor potency and 5-HT1B- and 5-HT1D-receptor affinity, but not with 5-HT1A-, 5-ht1F or 5-HT2- receptor affinity. 4 The 5-HT1B/1D-receptor antagonist GR 55562 (10-7 - 10-6 M) inhibited the contractile responses to sumatriptan and 5-CT in a competitive manner with a pKB value for GR 55562 of 7.4. Furthermore, ketanserin (10-7 M), prazosin (10-7 M), and sulpiride (10-7 M) were devoid of significant antagonistic activity of 5-HT-induced contraction in the HCA. 5 The results are compatible with the hypothesis that the 5-HT1B receptors play a major role in 5-HT-induced vasoconstriction in HCA.

Binding, Competitive↗
PubMed1999

Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat.

It was examined to what extent congestive heart failure (CHF) in rats, induced by ligation of the left coronary artery, affects the vascular responses to the vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide (CGRP), and substance P (SP). After induction of CHF status, the basilar, mesenteric and renal arteries and the iliac vein were studied in vitro. Dilatory responses were determined in relation to pre-contraction by the thromboxane mimetic U46619. Sham-operated animals (Sham) served as controls. U46619 induced stronger contraction in CHF basilar and renal arteries compared with the corresponding segments in Sham. ACh induced concentration-dependent dilations in all vessels examined with no difference of maximum relaxation or potency between CHF and Sham. SP induced weak dilations in all arteries examined while the response was markedly attenuated in CHF iliac veins compared with Sham (Emax% 12.2 +/- 3.4 vs. 32.3 +/- 4.8, P = 0.01). The CGRP induced dilation in the CHF basilar artery was weaker (Emax% 18.6 +/- 6.5 vs. 66.9 +/- 5.0, P < 0.001) and less potent (pEC50: 8.2 +/- 0.2 vs. 9.0 +/- 0.2, P = 0.01) compared with Sham. Further, CGRP was less potent in the renal artery of CHF rats compared with Sham (pEC50: 8.1 +/- 0.2 vs. 9.5 +/- 0.3, P < 0.01). In the CHF iliac vein, CGRP was more potent compared with Sham (pEC50: 9.7 +/- 0.4 vs. 8.3 +/- 0.4, P < 0.05). It can be concluded CHF is accompanied by alterations in the vascular response to the dilatory substances studied. The changes differ between vascular beds and between the different substances.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Localization and recycling of gp27 (hp24gamma3): complex formation with other p24 family members.

We report here the characterization of gp27 (hp24gamma3), a glycoprotein of the p24 family of small and abundant transmembrane proteins of the secretory pathway. Immunoelectron and confocal scanning microscopy show that at steady state, gp27 localizes to the cis side of the Golgi apparatus. In addition, some gp27 was detected in COPI- and COPII-coated structures throughout the cytoplasm. This indicated cycling that was confirmed in three ways. First, 15 degrees C temperature treatment resulted in accumulation of gp27 in pre-Golgi structures colocalizing with anterograde cargo. Second, treatment with brefeldin A caused gp27 to relocate into peripheral structures positive for both KDEL receptor and COPII. Third, microinjection of a dominant negative mutant of Sar1p trapped gp27 in the endoplasmic reticulum (ER) by blocking ER export. Together, this shows that gp27 cycles extensively in the early secretory pathway. Immunoprecipitation and coexpression studies further revealed that a significant fraction of gp27 existed in a hetero-oligomeric complex. Three members of the p24 family, GMP25 (hp24alpha2), p24 (hp24beta1), and p23 (hp24delta1), coprecipitated in what appeared to be stochiometric amounts. This heterocomplex was specific. Immunoprecipitation of p26 (hp24gamma4) failed to coprecipitate GMP25, p24, or p23. Also, very little p26 was found coprecipitating with gp27. A functional requirement for complex formation was suggested at the level of ER export. Transiently expressed gp27 failed to leave the ER unless other p24 family proteins were coexpressed. Comparison of attached oligosaccharides showed that gp27 and GMP25 recycled differentially. Only a very minor portion of GMP25 displayed complex oligosaccharides. In contrast, all of gp27 showed modifications by medial and trans enzymes at steady state. We conclude from these data that a portion of gp27 exists as hetero-oligomeric complexes with GMP25, p24, and p23 and that these complexes are in dynamic equilibrium with individual p24 proteins to allow for differential recycling and distributions.

Amino Acid Sequence↗
PubMed1999

Genotoxic exposures of potroom workers.

OBJECTIVES: Potroom workers in aluminum reduction plants have increased risks for bladder and lung cancer due to exposure from polycyclic aromatic hydrocarbons (PAH). In this study correlations between measures of the external, internal, and biological effective dose have been studied for PAH. METHODS: Venous blood samples were obtained from 98 male potroom workers and 55 unexposed male blue-collar workers, for the analysis of aromatic adducts to DNA (deoxyribonucleic acid) in lymphocytes, using the 32P-postlabeling technique. 1-Hydroxypyrene in urine was analyzed with high-pressure liquid chromatography. Personal sampling of both particulate and gas phase PAH was performed during a full workday for the potroom workers and for 5 referents. Individual PAH congeners were determined with liquid chromatographic-mass spectrometric and gas chromatographic-mass spectrometric techniques. RESULTS: The respiratory-zone airborne level of the sum of 22 particulate (median 13.2 micro/m3) and the 7 gas phase PAH-congeners (median 16.3 microg/m3) among the potroom workers was a hundred times higher than among the referents. The urinary concentration of 1-hydroxypyrene before work was 30 times higher for the potroom workers (median 3.43 micromol/mol creatinine) than for the referents. Most airborne PAH congeners correlated with the excretion of 1-hydroxypyrene in urine. The frequency of aromatic DNA adducts did not, however, differ between the potroom workers and the referents, and no correlation was found for 1-hydroxypyrene in urine. CONCLUSIONS: Despite an obvious occupational exposure to PAH, no increase in aromatic DNA adducts in lymphocytes was found among the potroom workers.

Adult↗
PubMed1999

Patient education for adults with chronic eczema.

Seven patients with severe eczema participated in an individual education project. The aim of the education program was to maintain and improve health by providing knowledge in self-care treatment. Patients were provided with new knowledge of their disease and received sufficient information to enable them to apply self-care of their eczema.

Adult↗
PubMed1998

Recycling of golgi-resident glycosyltransferases through the ER reveals a novel pathway and provides an explanation for nocodazole-induced Golgi scattering.

During microtubule depolymerization, the central, juxtanuclear Golgi apparatus scatters to multiple peripheral sites. We have tested here whether such scattering is due to a fragmentation process and subsequent outward tracking of Golgi units or if peripheral Golgi elements reform through a novel recycling pathway. To mark the Golgi in HeLa cells, we stably expressed the Golgi stack enzyme N-acetylgalactosaminyltransferase-2 (GalNAc-T2) fused to the green fluorescent protein (GFP) or to an 11-amino acid epitope, VSV-G (VSV), and the trans/TGN enzyme beta1,4-galactosyltransferase (GalT) fused to GFP. After nocodazole addition, time-lapse microscopy of GalNAc-T2-GFP and GalT-GFP revealed that scattered Golgi elements appeared abruptly and that no Golgi fragments tracked outward from the compact, juxtanuclear Golgi complex. Once formed, the scattered structures were relatively stable in fluorescence intensity for tens of minutes. During the entire process of dispersal, immunogold labeling for GalNAc-T2-VSV and GalT showed that these were continuously concentrated over stacked Golgi cisternae and tubulovesicular Golgi structures similar to untreated cells, suggesting that polarized Golgi stacks reform rapidly at scattered sites. In fluorescence recovery after photobleaching over a narrow (FRAP) or wide area (FRAP-W) experiments, peripheral Golgi stacks continuously exchanged resident proteins with each other through what appeared to be an ER intermediate. That Golgi enzymes cycle through the ER was confirmed by microinjecting the dominant-negative mutant of Sar1 (Sar1pdn) blocking ER export. Sar1pdn was either microinjected into untreated or nocodazole-treated cells in the presence of protein synthesis inhibitors. In both cases, this caused a gradual accumulation of GalNAc-T2-VSV in the ER. Few to no peripheral Golgi elements were seen in the nocodazole-treated cells microinjected with Sar1pdn. In conclusion, we have shown that Golgi-resident glycosylation enzymes recycle through the ER and that this novel pathway is the likely explanation for the nocodazole-induced Golgi scattering observed in interphase cells.

Endoplasmic Reticulum↗
PubMed1998

Altered neuropeptide Y Y1 responses in mesenteric arteries in rats with congestive heart failure.

The aim of the present study was to elucidate if the potentiating effect of neuropeptide Y on various vasoactive agents in vitro is (1) altered in mesenteric arteries from rats with congestive heart failure and (2) mediated by the neuropeptide Y Y1 receptor. The direct vascular effects of neuropeptide Y and its modulating effects on the contractions induced by endothelin-1-, noradrenaline-, 5-hydroxytryptamine (5-HT)-, U46619-(9,11-dideoxy-11alpha, 9alpha-epoxymethano-prostaglandin F2alpha) and ATP, and acetylcholine-induced dilatations were studied in the presence and absence of the neuropeptide Y Y1 antagonist, BIBP3226 (BIBP3226¿(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl ]-D-arginine-amide¿). Neuropeptide Y, per se, had no vasoactive effect in the arteries. The potency of endothelin-1 was significantly decreased in congestive heart failure rats. Neuropeptide Y and neuropeptide Y-(13-36) potentiated the endothelin-1-induced contraction in congestive heart failure mesenteric arteries. In 20% of the congestive heart failure rats, sarafotoxin 6c induced a contraction of 31+/-4%. Neuropeptide Y also potentiated U46619- and noradrenaline-induced contractions but not 5-HT-induced contractions in congestive heart failure arteries. In sham-operated animals neuropeptide Y potentiated noradrenaline- and 5-HT-induced contractions. These potentiations were inhibited by BIBP3226. Acetylcholine induced an equipotent relaxation in both groups which was unaffected by neuropeptide Y. In conclusion, neuropeptide Y responses are altered in congestive heart failure rats. The potentiating effect differs between vasoactive substances. Neuropeptide Y Y1 and non-neuropeptide Y1 receptors are involved.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Structural requirements for O-glycosylation of the mouse hepatitis virus membrane protein.

The mouse hepatitis virus (MHV) membrane (M) protein contains only O-linked oligosaccharides. We have used this protein as a model to study the structural requirements for O-glycosylation. We show that MHV M is modified by the addition of a single oligosaccharide side chain at the cluster of 4 hydroxylamino acids present at its extreme amino terminus and identified Thr at position 5 as the functional acceptor site. The hydroxylamino acid cluster, which is quite conserved among O-glycosylated coronavirus M proteins, is not in itself sufficient for O-glycosylation. Downstream amino acids are required to introduce a functional O-glycosylation site into a foreign protein. In a mutagenic analysis O-glycosylation was found to be sensitive to some particular changes but no unique sequence motif for O-glycosylation could be identified. Expression of mutant M proteins in cells revealed that substitution of any 1 residue was tolerated, conceivably due to the occurrence of multiple UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferases (GalNAc transferases). Indeed, MHV M served as a substrate for GalNac-T1, -T2, and -T3, as was demonstrated using an in situ glycosylation assay based on the co-expression of endoplasmic reticulum-retained forms of the GalNAc transferases with endoplasmic reticulum-resident MHV M mutants. The GalNAc transferases were found to have largely overlapping, but distinct substrate specificities. The requirement for a threonine as acceptor rather than a serine residue and the requirement for a proline residue three positions downstream of the acceptor site were found to be distinctive features.

Acetylgalactosamine↗
PubMed1998

Protein sorting in the Golgi complex.

Even after one hundred years, the Golgi apparatus remains a major challenge in the field of Cell Biology. This is particularly true in terms of transport and of protein sorting. For example, the question how cargo proteins are transported through this organelle is still a matter of debate. Emphasis has been put on the role of anterograde and retrograde transport vesicles. These have been proposed to carry cargo from cisterna to cisterna and to recycle components needed for further rounds of transport. Alternatively, anterograde movement of cargo takes place in cisternal membranes rather than transport vesicles. These membranes assemble and mature in a cis to trans direction. In this case, retrograde transport vesicles need to recycle all components of the Golgi apparatus and this demands a highly dynamic and efficient sorting machinery. Here we will discuss possible mechanisms for protein sorting in the context of cisternal maturation and propose that a common mechanism is sufficient to explain both transport of cargo and sorting of resident proteins.

Carrier Proteins↗
PubMed1998

gp25L/emp24/p24 protein family members of the cis-Golgi network bind both COP I and II coatomer.

Abstract. Five mammalian members of the gp25L/ emp24/p24 family have been identified as major constituents of the cis-Golgi network of rat liver and HeLa cells. Two of these were also found in membranes of higher density (corresponding to the ER), and this correlated with their ability to bind COP I in vitro. This binding was mediated by a K(X)KXX-like retrieval motif present in the cytoplasmic domain of these two members. A second motif, double phenylalanine (FF), present in the cytoplasmic domain of all five members, was shown to participate in the binding of Sec23 (COP II). This motif is part of a larger one, similar to the F/YXXXXF/Y strong endocytosis and putative AP2 binding motif. In vivo mutational analysis confirmed the roles of both motifs so that when COP I binding was expected to be impaired, cell surface expression was observed, whereas mutation of the Sec23 binding motif resulted in a redistribution to the ER. Surprisingly, upon expression of mutated members, steady-state distribution of unmutated ones shifted as well, presumably as a consequence of their observed oligomeric properties.

Amino Acid Sequence↗