| 1. |
- Nilsson, Ida, et al.
(författare)
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The efficacy of P6 acupressure with sea-band in reducing postoperative nausea and vomiting in patients undergoing craniotomy : a randomized, double-blinded, placebo-controlled study
- 2015
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Ingår i: Journal of Neurosurgical Anesthesiology. - 0898-4921 .- 1537-1921. ; 27:1, s. 42-50
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postoperative nausea and vomiting (PONV) is a multifactorial problem after general anesthesia. Despite antiemetic prophylaxis and improved anesthetic techniques, PONV still occurs frequently after craniotomies. P6 stimulation is described as an alternative method for preventing PONV. The primary aim of this study was to determine whether P6 acupressure with Sea-Band could reduce postoperative nausea after elective craniotomy. Secondary aims were to investigate whether the frequency of vomiting and the need for antiemetics could be reduced.Methods: In this randomized, double-blinded, placebo-controlled study, patients were randomized into either a P6 acupressure group (n = 43) or a sham group (n = 52). Bands were applied unilaterally at the end of surgery, and all patients were administered prophylactic ondansetron. Postoperative nausea was evaluated with a Numerical Rating Scale, 0 to10, and the frequency of vomiting was recorded for 48 hours.Results: We found no significant effect from P6 acupressure with Sea-Band on postoperative nausea or vomiting in patients undergoing craniotomy. Nor was there any difference in the need for rescue antiemetics. Altogether, 67% experienced PONV, and this was especially an issue at >24 hours in patients recovering from infratentorial surgery compared with supratentorial surgery (55% vs. 26%; P = 0.014).Conclusions: Unilateral P6 acupressure with Sea-Band applied at the end of surgery together with prophylactic ondansetron did not significantly reduce PONV or the need for rescue antiemetics in patients undergoing craniotomy. Our study confirmed that PONV is a common issue after craniotomy, especially after infratentorial surgery.
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| 2. |
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| 3. |
- Au, Catherine E, et al.
(författare)
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Organellar proteomics to create the cell map.
- 2007
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Ingår i: Current opinion in cell biology. - : Elsevier BV. - 0955-0674. ; 19:4, s. 376-85
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Tidskriftsartikel (refereegranskat)abstract
- The elucidation of a complete, accurate, and permanent representation of the proteome of the mammalian cell may be achievable piecemeal by an organellar based approach. The small volume of organelles assures high protein concentrations. Providing isolated organelles are homogenous, this assures reliable protein characterization within the sensitivity and dynamic range limits of current mass spec based analysis. The stochastic aspect of peptide selection by tandem mass spectrometry for sequence determination by fragmentation is dealt with by multiple biological replicates as well as by prior protein separation on 1-D gels. Applications of this methodology to isolated synaptic vesicles, clathrin coated vesicles, endosomes, phagosomes, endoplasmic reticulum, and Golgi apparatus, as well as Golgi-derived COPI vesicles, have led to mechanistic insight into the identity and function of these organelles.
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| 4. |
- Axelsson, Magnus A. B., et al.
(författare)
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Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins.
- 2001
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 11:8, s. 633-44
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Tidskriftsartikel (refereegranskat)abstract
- Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. This resulted in relocalization of the three studied glycosyltransferases, N-acetylgalactosaminyltransferase 2, beta1,2 N-acetylglucosaminyltransferase I, and beta1,4 galactosyltransferase 1, normally localized to the Golgi stack, the medial/trans-Golgi and the trans-Golgi/TGN, respectively. Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. The general morphology of the endoplasmic reticulum and Golgi apparatus was retained as judged from immunofluorescence and electron microscopy studies. When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. However, no decrease in the number of oligosaccharide chains was indicated. Together, the results suggest that pH is a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus and that altered pH may cause alterations in glycosylation possibly due to a relocalization of glycosyltransferases.
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| 5. |
- Bell, Alexander W, et al.
(författare)
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The protein microscope: incorporating mass spectrometry into cell biology.
- 2007
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Ingår i: Nature methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 4:10, s. 783-4
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Tidskriftsartikel (refereegranskat)abstract
- Mass spectrometry has come into its own as an extremely powerful tool for the study of whole proteomes. So why are not more cell biologists embracing it with open arms?
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| 6. |
- Boström, Pontus, 1982, et al.
(författare)
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SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity.
- 2007
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Ingår i: Nature cell biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 9:11, s. 1286-93
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Tidskriftsartikel (refereegranskat)abstract
- The accumulation of cytosolic lipid droplets in muscle and liver cells has been linked to the development of insulin resistance and type 2 diabetes. Such droplets are formed as small structures that increase in size through fusion, a process that is dependent on intact microtubules and the motor protein dynein. Approximately 15% of all droplets are involved in fusion processes at a given time. Here, we show that lipid droplets are associated with proteins involved in fusion processes in the cell: NSF (N-ethylmaleimide-sensitive-factor), alpha-SNAP (soluble NSF attachment protein) and the SNAREs (SNAP receptors), SNAP23 (synaptosomal-associated protein of 23 kDa), syntaxin-5 and VAMP4 (vesicle-associated membrane protein 4). Knockdown of the genes for SNAP23, syntaxin-5 or VAMP4, or microinjection of a dominant-negative mutant of alpha-SNAP, decreases the rate of fusion and the size of the lipid droplets. Thus, the SNARE system seems to have an important role in lipid droplet fusion. We also show that oleic acid treatment decreases the insulin sensitivity of heart muscle cells, and this sensitivity is completely restored by transfection with SNAP23. Thus, SNAP23 might be a link between insulin sensitivity and the inflow of fatty acids to the cell.
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| 7. |
- Fagman, Henrik, 1975, et al.
(författare)
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Nuclear accumulation of full-length and truncated adenomatous polyposis coli protein in tumor cells depends on proliferation.
- 2003
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 22:38, s. 6013-22
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Tidskriftsartikel (refereegranskat)abstract
- The adenomatous polyposis coli (APC) tumor suppressor is a nucleocytoplasmic protein. The nuclear accumulation of APC was recently found to vary depending on cell density, suggesting that putative APC function(s) in the nucleus is controlled by the establishment of cell contacts. We report here that the density-dependent redistribution of APC between nucleus and cytoplasm prevails in 6/6 thyroid and colorectal carcinoma cell lines. Moreover, mutated APC lacking known nuclear localization sequences had the similar distribution pattern as the full-length protein. APC invariably accumulated in the nuclei of Ki-67 expressing cells, but was largely cytoplasmic when cell cycle exit was induced by serum starvation or at high cell density. APC colocalized with beta-catenin in the nucleus only in one cell line (SW480). Also, APC maintained a predominantly nuclear position in early confluent states when cytoplasmic beta-catenin was recruited to newly formed adherens-like junctions. The results indicate that nuclear targeting of APC is driven by cell cycle entry rather than altered cell-cell contact. The ability of C-terminally truncated APC to accumulate in the nucleus suggests that nuclear import signals other than NLS1(APC) and NLS2(APC) are functionally important. Residual function(s) of N-terminal APC fragments in tumor cells carrying APC mutations might be beneficial to tumor growth and survival.
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| 8. |
- Gilchrist, Annalyn, et al.
(författare)
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Quantitative proteomics analysis of the secretory pathway.
- 2006
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 127:6, s. 1265-81
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Tidskriftsartikel (refereegranskat)abstract
- We report more than 1400 proteins of the secretory-pathway proteome and provide spatial information on the relative presence of each protein in the rough and smooth ER Golgi cisternae and Golgi-derived COPI vesicles. The data support a role for COPI vesicles in recycling and cisternal maturation, showing that Golgi-resident proteins are present at a higher concentration than secretory cargo. Of the 1400 proteins, 345 were identified as previously uncharacterized. Of these, 230 had their subcellular location deduced by proteomics. This study provides a comprehensive catalog of the ER and Golgi proteomes with insight into their identity and function.
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| 9. |
- Grabenbauer, Markus, et al.
(författare)
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Correlative microscopy and electron tomography of GFP through photooxidation.
- 2005
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Ingår i: Nature methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 2:11, s. 857-62
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a simple correlative photooxidation method that allows for the direct ultrastructural visualization of the green fluorescent protein (GFP) upon illumination. The method, termed GRAB for GFP recognition after bleaching, uses oxygen radicals generated during the GFP bleaching process to photooxidize 3,3'-diaminobenzidine (DAB) into an electron-dense precipitate that can be visualized by routine electron microscopy and electron tomography. The amount of DAB product produced by the GRAB method appears to be linear with the initial fluorescence, and the resulting images are of sufficient quality to reveal detailed spatial information. This is exemplified by the observed intra-Golgi stack and intracisternal distribution of a human Golgi resident glycosylation enzyme, N-acetylgalactosaminyltransferase-2 fused either to enhanced GFP or CFP.
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| 10. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency : a prospective randomised trial of a novel hydrocortisone dual-release formulation
- 2012
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 97:2, s. 473-481
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Tidskriftsartikel (refereegranskat)abstract
- Context: Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile.Objective: The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets.Design and Setting: We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers.Patients: The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM).Intervention: The same daily dose of hydrocortisone was administered as OD dual-release or TID.Main Outcome Measure: We evaluated cortisol pharmacokinetics.Results: Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004).Conclusion: The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.
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| 11. |
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| 12. |
- Kartberg, Fredrik, 1978, et al.
(författare)
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Commuting between Golgi cisternae--mind the GAP!
- 2005
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Ingår i: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002. ; 1744:3, s. 351-63
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Forskningsöversikt (refereegranskat)abstract
- Intracellular transport has remained central to cell biology now for more than 40 years. Despite this, we still lack an overall mechanistic framework that describes transport in different parts of the cell. In the secretory pathway, basic questions, such as how biosynthetic cargo traverses the pathway, are still debated. Historically, emphasis was first put on interpreting function from morphology at the ultrastructural level revealing membrane structures such as the transitional ER, vesicular carriers, vesicular tubular clusters, Golgi cisternae, Golgi stacks and the Golgi ribbon. This emphasis on morphology later switched to biochemistry and yeast genetics yielding many of the key molecular players and their associated functions that we know today. More recently, microscopy studies of living cells incorporating biophysics and system analysis has proven useful and is often used to readdress earlier findings, sometimes with surprising outcomes.
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| 13. |
- Lidell, Martin, 1970, et al.
(författare)
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The Adipocyte-Expressed Forkhead Transcription Factor Foxc2 Regulates Metabolism Through Altered Mitochondrial Function
- 2011
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Ingår i: Diabetes. - 0012-1797. ; 60:2, s. 427-435
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Previous findings demonstrate that enhanced expression of the forkhead transcription factor Foxc2 in adipose tissue leads to a lean and insulin-sensitive phenotype. These findings prompted us to further investigate the role of Foxc2 in the regulation of genes of fundamental importance for metabolism and mitochondrial function. RESEARCH DESIGN AND METHODS: The effects of Foxc2 on expression of genes involved in mitochondriogenesis and mitochondrial function were assessed by quantitative real-time PCR. The potential of a direct transcriptional regulation of regulated genes was tested in promoter assays, and mitochondrial morphology was investigated by electron microscopy. Mitochondrial function was tested by measuring oxygen consumption and extracellular acidification rates as well as palmitate oxidation. RESULTS: Enhanced expression of FOXC2 in adipocytes or in cells with no endogenous Foxc2 expression induces mitochondriogenesis and an elongated mitochondrial morphology. Together with increased aerobic metabolic capacity, increased palmitate oxidation, and upregulation of genes encoding respiratory complexes and of brown fat-related genes, Foxc2 also specifically induces mitochondrial fusion genes in adipocytes. Among tested forkhead genes, Foxc2 is unique in its ability to trans-activate the nuclear-encoded mitochondrial transcription factor A (mtTFA/Tfam) gene--a master regulator of mitochondrial biogenesis. In human adipose tissue the expression levels of mtTFA/Tfam and of fusion genes also correlate with that of Foxc2. CONCLUSIONS: We previously showed that a high-calorie diet and insulin induce Foxc2 in adipocytes; the current findings identify a previously unknown role for Foxc2 as an important metabo-regulator of mitochondrial morphology and metabolism.
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| 14. |
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| 15. |
- Simpson, Jeremy C, et al.
(författare)
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Biogenesis of tubular ER-to-Golgi transport intermediates.
- 2006
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Ingår i: Molecular biology of the cell. - 1059-1524. ; 17:2, s. 723-37
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Tidskriftsartikel (refereegranskat)abstract
- Tubular transport intermediates (TTIs) have been described as one class of transport carriers in endoplasmic reticulum (ER)-to-Golgi transport. In contrast to vesicle budding and fusion, little is known about the molecular regulation of TTI synthesis, transport and fusion with target membranes. Here we have used in vivo imaging of various kinds of GFP-tagged proteins to start to address these questions. We demonstrate that under steady-state conditions TTIs represent approximately 20% of all moving transport carriers. They increase in number and length when more transport cargo becomes available at the donor membrane, which we induced by either temperature-related transport blocks or increased expression of the respective GFP-tagged transport markers. The formation and motility of TTIs is strongly dependent on the presence of intact microtubules. Microinjection of GTPgammaS increases the frequency of TTI synthesis and the length of these carriers. When Rab proteins are removed from membranes by microinjection of recombinant Rab-GDI, the synthesis of TTIs is completely blocked. Microinjection of the cytoplasmic tails of the p23 and p24 membrane proteins also abolishes formation of p24-containing TTIs. Our data suggest that TTIs are ER-to-Golgi transport intermediates that form preferentially when transport-competent cargo exists in excess at the donor membrane. We propose a model where the interaction of the cytoplasmic tails of membrane proteins with microtubules are key determinants for TTI synthesis and may also serve as a so far unappreciated model for aspects of transport carrier formation.
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| 16. |
- Weiss, Matthias, et al.
(författare)
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Anomalous subdiffusion is a measure for cytoplasmic crowding in living cells.
- 2004
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Ingår i: Biophysical journal. - : Elsevier BV. - 0006-3495. ; 87:5, s. 3518-24
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Tidskriftsartikel (refereegranskat)abstract
- Macromolecular crowding dramatically affects cellular processes such as protein folding and assembly, regulation of metabolic pathways, and condensation of DNA. Despite increased attention, we still lack a definition for how crowded a heterogeneous environment is at the molecular scale and how this manifests in basic physical phenomena like diffusion. Here, we show by means of fluorescence correlation spectroscopy and computer simulations that crowding manifests itself through the emergence of anomalous subdiffusion of cytoplasmic macromolecules. In other words, the mean square displacement of a protein will grow less than linear in time and the degree of this anomality depends on the size and conformation of the traced particle and on the total protein concentration of the solution. We therefore propose that the anomality of the diffusion can be used as a quantifiable measure for the crowdedness of the cytoplasm at the molecular scale.
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| 17. |
- Weiss, Matthias, et al.
(författare)
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In a mirror dimly: tracing the movements of molecules in living cells.
- 2004
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Ingår i: Trends in cell biology. - : Elsevier BV. - 0962-8924. ; 14:5, s. 267-73
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Forskningsöversikt (refereegranskat)abstract
- The random movement of molecules (diffusion) is fundamental to most cellular processes, including enzymatic reactions, signalling, protein-protein interaction, as well as domain and pattern formation. Despite playing a central role, diffusion is, to a large extent, under-appreciated in the cell biology community. One reason for this is that diffusion is rather challenging to study in living cells. This article is intended to explain, at least in part, how we can go about studying diffusion of molecules in living cells, why it is important and how it provides us with important clues about biological systems. As the title 'In a mirror dimly' suggests, we do this by monitoring faint light emitted by fluorescent probes or proteins using advanced optics (e.g. mirrors) and electronics. The data are then fitted and interpreted with mathematical and physical models, providing a glimpse into the world of molecules.
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| 18. |
- Young, Joanne, et al.
(författare)
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Regulation of microtubule-dependent recycling at the trans-Golgi network by Rab6A and Rab6A'.
- 2005
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Ingår i: Molecular biology of the cell. - 1059-1524. ; 16:1, s. 162-77
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Tidskriftsartikel (refereegranskat)abstract
- The small GTPase rab6A but not the isoform rab6A' has previously been identified as a regulator of the COPI-independent recycling route that carries Golgi-resident proteins and certain toxins from the Golgi to the endoplasmic reticulum (ER). The isoform rab6A' has been implicated in Golgi-to-endosomal recycling. Because rab6A but not A', binds rabkinesin6, this motor protein is proposed to mediate COPI-independent recycling. We show here that both rab6A and rab6A' GTP-restricted mutants promote, with similar efficiency, a microtubule-dependent recycling of Golgi resident glycosylation enzymes upon overexpression. Moreover, we used small interfering RNA mediated down-regulation of rab6A and A' expression and found that reduced levels of rab6 perturbs organization of the Golgi apparatus and delays Golgi-to-ER recycling. Rab6-directed Golgi-to-ER recycling seems to require functional dynactin, as overexpression of p50/dynamitin, or a C-terminal fragment of Bicaudal-D, both known to interact with dynactin inhibit recycling. We further present evidence that rab6-mediated recycling seems to be initiated from the trans-Golgi network. Together, this suggests that a recycling pathway operates at the level of the trans-Golgi linking directly to the ER. This pathway would be the preferred route for both toxins and resident Golgi proteins.
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