| 1. |
- Almroth, Gabriel, 1953-, et al.
(författare)
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Detection and prevention of hepatitis C in dialysis patients and renal transplant recipients : A long-term follow up (1989–January 1997)
- 2002
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 251:2, s. 119-128
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Tidskriftsartikel (refereegranskat)abstract
- Background. Hepatitis C is frequent problem in dialysis wards.Design. A long time (1989–97) follow up of hepatitis C virus (HCV) infection in a Swedish nephrology unit was performed with anti-HCV screening, confirmatory antibody tests, viral RNA detection and molecular characterization. Case histories were reviewed with focus, onset of infection, liver morbidity and mortality.Results. In October 1991, 10% (19 of 184) of the patients in the unit (haemodialysis-, peritoneal dialysis and transplanted patients) were verified or suspected HCV carriers, whilst the number at the end of 1996 was 8% (13 of 157). Most patients were infected before 1991 but only in one case from a known HCV-infected blood donor. No new HCV infections associated with haemodialysis occurred during the study period. A total of 13 of 24 viremic patients had HCV genotype 2b, a pattern suggesting nosocomial transmission. This was further supported by phylogenetic analysis of HCV viral isolates in seven. HCV viremia was also common in patients with an incomplete anti-HCV antibody pattern as 8 of the 12 indeterminant sera were HCV-RNA positive.Conclusions. Awareness, prevention, identification of infected patients and donor testing limited transmission. Indeterminant recombinant immunoblot assays (RIBA)-results should be regarded with caution as a result of the relative immunodeficiency in uremic patients. Our data indicate nosocomial transmission in several patients.
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| 2. |
- Adamsson Eryd, Samuel, et al.
(författare)
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Blood pressure and complications in individuals with type 2 diabetes and no previous cardiovascular disease: national population based cohort study
- 2016
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 354
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To compare the risk associated with systolic blood pressure that meets current recommendations (that is, below 140 mm Hg) with the risk associated with lower levels in patients who have type 2 diabetes and no previous cardiovascular disease. Population based cohort study with nationwide clinical registries, 2006-12. The mean follow-up was 5.0 years. 187 106 patients registered in the Swedish national diabetes register who had had type 2 diabetes for at least a year, age 75 or younger, and with no previous cardiovascular or other major disease. Clinical events were obtained from the hospital discharge and death registers with respect to acute myocardial infarction, stroke, a composite of acute myocardial infarction and stroke (cardiovascular disease), coronary heart disease, heart failure, and total mortality. Hazard ratios were estimated for different levels of baseline systolic blood pressure with clinical characteristics and drug prescription data as covariates. The group with the lowest systolic blood pressure (110-119 mm Hg) had a significantly lower risk of non-fatal acute myocardial infarction (adjusted hazard ratio 0.76, 95% confidence interval 0.64 to 0.91; P=0.003), total acute myocardial infarction (0.85, 0.72 to 0.99; P=0.04), non-fatal cardiovascular disease (0.82, 0.72 to 0.93; P=0.002), total cardiovascular disease (0.88, 0.79 to 0.99; P=0.04), and non-fatal coronary heart disease (0.88, 0.78 to 0.99; P=0.03) compared with the reference group (130-139 mm Hg). There was no indication of a J shaped relation between systolic blood pressure and the endpoints, with the exception of heart failure and total mortality. Lower systolic blood pressure than currently recommended is associated with significantly lower risk of cardiovascular events in patients with type 2 diabetes. The association between low blood pressure and increased mortality could be due to concomitant disease rather than antihypertensive treatment.
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| 3. |
- Adamsson Eryd, Samuel, et al.
(författare)
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Risk of future microvascular and macrovascular disease in people with Type 1 diabetes of very long duration : A national study with 10-year follow-up
- 2017
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071. ; 34:3, s. 411-418
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To describe factors associated with prevalence or absence of microvascular and macrovascular complications in people with Type 1 diabetes of very long duration and to investigate the risk factors associated with the incidence of such complications. Methods: We included individuals with Type 1 diabetes who had been entered in the Swedish National Diabetes Register between 2002 and 2004 (n = 18 450). First, risk factor distribution in people with diabetes duration of ≥ 50 years was compared between people with and without complications. Second, the incidence of complications during a 10-year follow-up period was studied in all individuals who had no complications at baseline. Results: Among people with a diabetes duration of ≥ 50 years (n = 1023), 453 (44%) had macrovascular disease, 534 (52%) had microvascular disease and 319 (31%) did not have either of the diagnoses. Factors that differed significantly between people with and without macrovascular disease were gender, age, HbA1c, BMI, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, albuminuria, antihypertensive medication and lipid-lowering medication. The same factors differed significantly between people with and without microvascular disease, with the exception of gender and HDL cholesterol. During the follow-up period, 6.1% of the study cohort were diagnosed with macrovascular disease and 19.6% with microvascular disease. Incidence of macrovascular disease was significantly associated with HbA1c levels. Hazard ratios decreased with longer diabetes duration. Conclusions: People with Type 1 diabetes who have survived ≥ 50 years without complications are significantly younger, and have significantly lower HbA1c levels, BMI and triglyceride levels than survivors with complications. HbA1c level is a predictor of macrovascular disease, independently of diabetes duration.
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| 4. |
- Adolfsson, Per, 1967-, et al.
(författare)
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Changes in β2-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas
- 2000
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Ingår i: Molecular human reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 6:9, s. 835-842
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of α2- and β2-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the α2/β2-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in β2-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be ~50% lower, whereas the phosphodiesterase activity was significantly increased (by ~100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through β2-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.
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| 5. |
- Aifa, Sami, 1967-, et al.
(författare)
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Electrostatic interactions of peptides flanking the tyrosine kinase domain in the epidermal growth factor receptor provides a model for intracellular dimerization and autophosphorylation
- 2006
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Ingår i: Proteins. - : Wiley. - 0887-3585 .- 1097-0134. ; 62:4, s. 1036-1043
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism by which ligand-activated EGFR induces autophosphorylation via dimerization is not fully understood. Structural studies have revealed an extracellular loop mediated receptor dimerization. We have previously presented experimental data showing the involvement of a positive 13 amino acid peptide (R645-R657, P13+) from the intracellular juxtamembrane domain (JM) of EGFR important for intracellular dimerization and autophosphorylation. A model was presented that suggest that P13+ interacts with a negative peptide (D979-E991, P13-) positioned distal to the tyrosine kinase domain in the opposite EGFR monomer. The present work shows additional data strengthening this model. In fact, by analyzing protein sequences of 21 annotated ErbB proteins from 9 vertebrate genomes, we reveal the high conservation of peptides P13+ and P13- with regard to their sequence as well as their position relative to the tyrosine kinase (TK) domain. Moreover in silico structure modeling of these ErbB intracellular domains supports a general electrostatic P13+/P13- interaction, implying that the C-terminal of one receptor monomer is facing the TK domain of the other monomer in the receptor dimer and vice versa. This model provides new insights into the molecular mechanism of ErbB receptor activation and suggests a new strategy to pharmacologically interfering with ErbB receptor activity. © 2005 Wiley-Liss, Inc.
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| 6. |
- Aifa, Sami, et al.
(författare)
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Interactions between the juxtamembrane domain of the EGFR and calmodulin measured by surface plasmon resonance
- 2002
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Ingår i: Cellular Signalling. - 0898-6568 .- 1873-3913. ; 14:12, s. 1005-1013
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Tidskriftsartikel (refereegranskat)abstract
- One early response to epidermal growth factor receptor (EGFR) activation is an increase in intracellular calcium. We have used surface plasmon resonance (SPR) to study real-time interactions between the intracellular juxtamembrane (JM) region of EGFR and calmodulin. The EGFR-JM (Met644-Phe688) was expressed as a GST fusion protein and immobilised on a sensor chip surface. Calmodulin specifically interacts with EGFR-JM in a calcium-dependent manner with a high on and high off rate. Chemical modification of EGFR-JM by using arginine-selective phenylglyoxal or deletion of the basic segment Arg645-Arg657 inhibits the interaction. Phosphorylation of EGFR-JM by protein kinase C (PKC) or glutamate substitution of Thr654 inhibits the interaction, suggesting that PKC phosphorylation electrostatically interferes with calmodulin binding to basic arginine residues. Calmodulin binding was also inhibited by suramin. Our results suggest that EGFR-JM is essential for epidermal growth factor (EGF)-mediated calcium-calmodulin signalling and for signal integration between other signalling pathways.
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| 7. |
- Anderson, Tony, 1973-, et al.
(författare)
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Frog melanophores cultured on fluorescent microbeads : Biomimic-based biosensing
- 2005
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Ingår i: Biosensors & bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 21:1, s. 111-120
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Tidskriftsartikel (refereegranskat)abstract
- Melanophores are pigmented cells in lower vertebrates capable of quick color changes and thereby suitable as whole cell biosensors. In the frog dermis skin layer, the large and dark pigmented melanophore surrounds a core of other pigmented cells. Upon hormonal stimulation the black-brown pigment organelles will redistribute within the melanophore, and thereby cover or uncover the core, making complex color changes possible in the dermis. Previously, melanophores have only been cultured on flat surfaces. Here we mimic the three dimensional biological geometry in the frog dermis by culturing melanophores on fluorescent plastic microbeads. To demonstrate biosensing we use the hormones melatonin and α-melanocyte stimulating hormone (α-MSH) as lightening or darkening stimuli, respectively. Cellular responses were successfully demonstrated on single cell level by fluorescence microscopy, and in cell suspension by a fluorescence microplate reader and a previously demonstrated computer screen photo-assisted technique. The demonstrated principle is the first step towards "single well/multiple read-out" biosensor arrays based on suspensions of different selective-responding melanophores, each cultured on microbeads with distinctive spectral characteristics. By applying small amount of a clinical sample, or a candidate substance in early drug screening, to a single well containing combinations of melanophores on beads, multiple parameter read-outs will be possible. © 2004 Elsevier B.V. All rights reserved.
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| 8. |
- Andersson, Tony, 1973-, et al.
(författare)
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Phosphoinositide 3-kinase is involved in Xenopus and Labrus melanophore aggregation
- 2003
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Ingår i: Cellular Signalling. - 0898-6568 .- 1873-3913. ; 15:12, s. 1119-1127
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Tidskriftsartikel (refereegranskat)abstract
- Melanophores are pigmented cells capable of quick colour changes through coordinated transport of their intracellular pigment granules. We demonstrate the involvement of phosphoinositide 3-kinase (PI3-K) in Xenopus and Labrus aggregation by the use of the PI3-K inhibitor, LY-294002. In Xenopus, wortmannin-insensitive PI3-K was found to be essential for the aggregation, mitogen-activated protein kinase (MAPK) activation and tyrosine phosphorylation of a 280-kDa protein, and for the maintenance of low cyclic adenosine 3':5'-monophosphate (cAMP) during the aggregated state. Pre-aggregated cells disperse completely to LY-294002 at 50-100 muM, involving a transient elevation in cAMP due to adenylate cyclase (AC) stimulation or to inhibition of cyclic nucleotide phosphodiesterase (PDE). The inactive analogue LY-303511 did not induce dispersion at the same concentrations. PDE4 and/or PDE2 was found to be involved in melanosome aggregation. The similar kinetics of LY-294002 and various PDE inhibitors indicates that the elevation of cAMP might be due to inhibition of PDE. In Labrus melanophores, LY-294002 had a less dramatic effect, probably due to less dependence on PDE in regulation of cAMP levels. In Xenopus aggregation, we suggest that melatonin stimulation of the Mel1c receptor via G(betagamma) activates PI3-K that, directly or indirectly via MAPK, activates PDE. (C) 2003 Elsevier Inc. All rights reserved.
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| 9. |
- Andersson, Tony, 1973-, et al.
(författare)
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Regulation of melanosome movement by MAP kinase
- 2003
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Ingår i: Pigment Cell Research. - : Wiley. - 0893-5785 .- 1600-0749. ; 16:3, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Our objectives were to further characterize the signaling pathways in melatonin-induced aggregation in Xenopus melanophores, specifically to investigate a possible role of mitogen-activated protein kinase (MAPK). By Western blotting we found that melatonin activates MAPK, which precedes melanosome aggregation measured in a microplate reader. Activation of MAPK, tyrosine phosphorylation of a previously described 280-kDa protein, and melanosome aggregation are sensitive to PD98059, a selective inhibitor of MAPK kinase. The MAPK activation is also decreased by the adenylate cyclase stimulant forskolin. In summary, we found that MAPK is activated during melatonin-induced melanosome aggregation. Activation was decreased by an inhibitor of MAPK kinase, and by forskolin. In addition to inhibition of cyclic adenosine 3′,5′-monophosphate (cAMP), reduction in protein kinase A activity (PKA), and activation of protein phosphatase 2A, we suggest that melatonin receptors activate the MAPK cascade and tyrosine phosphorylation of the 280-kDa protein. Although the cAMP/PKA signaling pathway is the most prominent, our data suggest that simultaneous activation of the MAPK cascade is of importance to obtain a completely aggregated state. This new regulatory mechanism of organelle transport by the MAPK cascade might be important in other eukaryotic cells.
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| 10. |
- Avliakulov, NK, et al.
(författare)
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Suramin blocks nucleotide triphosphate binding to ribosomal protein L3 from Trypanoplasma borreli
- 2000
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 267:6, s. 1723-1731
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Tidskriftsartikel (refereegranskat)abstract
- Ribosomal protein L3 (L3) has been demonstrated to participate in formation of the peptidyltransferase center and is essential for its catalytic activity. In the present study we show that L3 is able to bind nucleotide triphosphates with high and specific affinity in vitro. L3 was serendipitously identified by screening of a genomic phage library from a primitive kinetoplastid flagellate Trypanoplasma borreli with the ATPase domain of the topoisomerase II gene as a probe. The cloned gene was overexpressed and purified as a his-tag fusion protein in E. coli. Radioligand binding experiments, using [?-35S]ATP, showed that L3 is able to bind ATP but also GTP and UTP with similar high affinity (IC50 50-100 nM), while it has no ATPase activity. Furthermore, we showed that L3 has more than 500-fold higher affinity for nucleotide triphosphates compared to the corresponding nucleotide monophosphates and diphosphates. Molecular genetic and biochemical analyses allowed us to localize the NTP binding domain of L3 to the N-terminal 296 residues. Suramin, a polysulfonated naphthylamine derivative of urea, known for its chemotherapeutic effects completely inhibited the binding of [?-35S]ATP at subclinical levels. Results obtained with surface plasmon resonance technology showed that suramin both forms weak multimolecular complexes with L3 and bind strongly to L3 in nearly stoichiometric amounts.
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