| 761. |
- Galant, Natalie J., et al.
(författare)
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Substoichiometric inhibition of transthyretin misfolding by immune-targeting sparsely populated misfolding intermediates : a potential diagnostic and therapeutic for TTR amyloidoses
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Wild-type and mutant transthyretin (TTR) can misfold and deposit in the heart, peripheral nerves, and other sites causing amyloid disease. Pharmacological chaperones, Tafamidis (R) and diflunisal, inhibit TTR misfolding by stabilizing native tetrameric TTR; however, their minimal effective concentration is in the micromolar range. By immune-targeting sparsely populated TTR misfolding intermediates (i.e. monomers), we achieved fibril inhibition at substoichiometric concentrations. We developed an antibody (misTTR) that targets TTR residues 89-97, an epitope buried in the tetramer but exposed in the monomer. Nanomolar misTTR inhibits fibrillogenesis of misfolded TTR under micromolar concentrations. Pan-specific TTR antibodies do not possess such fibril inhibiting properties. We show that selective targeting of misfolding intermediates is an alternative to native state stabilization and requires substoichiometric concentrations. MisTTR or its derivative may have both diagnostic and therapeutic potential.
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| 762. |
- Gantelius, Stefan, et al.
(författare)
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Higher Expression of Myosin Heavy Chain IIx in Wrist Flexors in Cerebral Palsy
- 2012
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Ingår i: Clinical Orthopaedics and Related Research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-921X .- 1528-1132. ; 470:5, s. 1272-1277
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Children with cerebral palsy (CP) use their paretic arm less than normal but have a relative overactivity of wrist flexors, causing an impairing flexed position of the wrist. Voluntary use of a muscle downregulates myosin heavy chain (MyHC) IIx, but it is unclear whether the relative overactivity of wrist flexors and extensors in children with CP affects MyHC expression compared to normal subjects. QUESTIONS/PURPOSES: We therefore asked whether MyHC expression composition differs in wrist flexors compared to extensors in children with CP and in controls and whether it is related to clinical findings. METHODS: We took muscle biopsies from wrist flexors and extensors during hand surgery in children with CP (n = 9) and during open reduction of forearm fractures in control children (n = 5). The expression of the MyHC I, IIa, and IIx isoforms were determined on silver-stained 6% SDS-PAGE. RESULTS: CP flexors showed a higher proportion of MyHC IIx (40%) than control flexors (16%) and CP extensors (20%). MyHC IIa isoform proportion was lower in CP flexors (27%) than in control flexors (46%) and in CP extensors (45%). MyHC I expression was lower in CP (36%) than in controls (46%) for wrist extensors only. CONCLUSIONS: Both the brain injury in CP and the different demands on flexors and extensors affect the expression of MyHCs. The higher amount of MyHC IIx in CP could be caused by a decreased voluntary use of the hemiplegic arm. CLINICAL RELEVANCE: More information on the structural difference between flexors and extensors in normal and spastic muscle could improve the understanding of strain of wrist extensors and possibly the development of flexion contractures in CP.
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| 763. |
- Garwicz, Daniel, et al.
(författare)
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Farmakogenetisk analys kan avslöja risk för statinbiverkningar : [Pharmacogenetic analysis can predict adverse effects of statins]
- 2013
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 110:19-20, s. 951-952
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Tidskriftsartikel (refereegranskat)abstract
- Mer än var tionde vuxen i Sverige behandlas med statiner. Muskelsvaghet, -trötthet och -värk är kända biverkningar. I sällsynta fall ses rabdomyolys, som kan leda till akut njursvikt och någon gång dödsfall. Statiners kemiska egenskaper och serumkoncentration påverkar risken för allvarliga biverkningar. Serumkoncentrationen beror på dos och på patientens förmåga att omsätta läkemedlet.Akademiska sjukhuset har som första svenska sjukhus infört analys av en genetisk variant (SLCO1B1*5) som kan förutsäga ökad risk för sällsynta, allvarliga muskelbiverkningar vid statinbehandling.
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| 764. |
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| 765. |
- Gellerstedt, Martin, 1966-
(författare)
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Tolkning av mätvärden
- 2021. - 1
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Ingår i: Medicinsk informatik. - Stockholm : Liber. - 9789147134083 ; , s. 178-191
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 766. |
- Gerdle, Björn, et al.
(författare)
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Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content
- 2024
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Ingår i: FRONTIERS IN PAIN RESEARCH. - : FRONTIERS MEDIA SA. - 2673-561X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This explorative study analyses interrelationships between peripheral compounds in saliva, plasma, and muscles together with body composition variables in healthy subjects and in fibromyalgia patients (FM). There is a need to better understand the extent cytokines and chemokines are associated with body composition and which cytokines and chemokines differentiate FM from healthy controls.Methods Here, 32 female FM patients and 30 age-matched female healthy controls underwent a clinical examination that included blood sample, saliva samples, and pain threshold tests. In addition, the subjects completed a health questionnaire. From these blood and saliva samples, a panel of 68 mainly cytokines and chemokines were determined. Microdialysis of trapezius and erector spinae muscles, phosphorus-31 magnetic resonance spectroscopy of erector spinae muscle, and whole-body magnetic resonance imaging for determination of body composition (BC)-i.e., muscle volume, fat content and infiltration-were also performed.Results After standardizing BC measurements to remove the confounding effect of Body Mass Index, fat infiltration and content are generally increased, and fat-free muscle volume is decreased in FM. Mainly saliva proteins differentiated FM from controls. When including all investigated compounds and BC variables, fat infiltration and content variables were most important, followed by muscle compounds and cytokines and chemokines from saliva and plasma. Various plasma proteins correlated positively with pain intensity in FM and negatively with pain thresholds in all subjects taken together. A mix of increased plasma cytokines and chemokines correlated with an index covering fat infiltration and content in different tissues. When muscle compounds were included in the analysis, several of these were identified as the most important regressors, although many plasma and saliva proteins remained significant.Discussion Peripheral factors were important for group differentiation between FM and controls. In saliva (but not plasma), cytokines and chemokines were significantly associated with group membership as saliva compounds were increased in FM. The importance of peripheral factors for group differentiation increased when muscle compounds and body composition variables were also included. Plasma proteins were important for pain intensity and sensitivity. Cytokines and chemokines mainly from plasma were also significantly and positively associated with a fat infiltration and content index.Conclusion Our findings of associations between cytokines and chemokines and fat infiltration and content in different tissues confirm that inflammation and immune factors are secreted from adipose tissue. FM is clearly characterized by complex interactions between peripheral tissues and the peripheral and central nervous systems, including nociceptive, immune, and neuroendocrine processes.
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| 767. |
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| 768. |
- Gisslander, Karl, et al.
(författare)
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The Role of Sural Nerve Biopsy in the Diagnosis of Vasculitis
- 2022
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 49:9, s. 1031-1036
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The diagnostic yield of sural nerve biopsy (SNB) in vasculitis is uncertain. Our aim was to document relevant characteristics of patients undergoing SNB in the investigation of vasculitis; determine the diagnostic yield; relate positive biopsy findings to patient demographic, laboratory, and clinical variables; and to calculate the rate of surgical complications. Methods. Patients with suspected vasculitis that underwent SNB as part of diagnostic evaluation at academic medical centers in Sweden and the United Kingdom were identified by searching local pathology databases and clinic registers. A structured review of medical case records and pathology reports was conducted. Histological findings were categorized as definite, probable, or no vasculitis in accordance with the 2015 Brighton Collaboration reinterpretation and update of the Peripheral Nerve Society guidelines for vasculitic neuropathy. Definite and probable findings were considered positive for vasculitis. Results. Ninety-one patients that underwent SNB were identified (45% female). Forty (44%) patients showed histological evidence of vasculitis: 14 definite and 26 probable. A concomitant muscle biopsy conducted in 10 patients did not contribute to the diagnostic yield. Positive antineutrophil cytoplasmic antibody test, organ involvement other than the nervous system, and a longer biopsy sample were associated with a positive biopsy. The reported surgical complication rate was 15%. Conclusion. SNB of sufficient length is a useful procedure to confirm a diagnosis of vasculitis.
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| 769. |
- Giwercman, Aleksander, et al.
(författare)
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Novel protein markers of androgen activity in humans : proteomic study of plasma from young chemically castrated men
- 2022
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Ingår i: eLife. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reliable biomarkers of androgen activity in humans are lacking. The aim of this study was, therefore, to identify new protein markers of biological androgen activity and test their predictive value in relation to low vs normal testosterone values and some androgen deficiency linked pathologies. Methods: Blood samples from 30 healthy GnRH antagonist treated males were collected at three time points: (1) before GnRH antagonist administration; (2) 3 weeks later, just before testosterone undecanoate injection, and (3) after additional 2 weeks. Subsequently, they were analyzed by mass spectrometry to identify potential protein biomarkers of testosterone activity. Levels of proteins most significantly associated with testosterone fluctuations were further tested in a cohort of 75 hypo- and eugonadal males suffering from infertility. Associations between levels of those markers and cardiometabolic parameters, bone mineral density as well as androgen receptor (AR) CAG repeat lengths, were explored. Results: Using receiver operating characteristic analysis, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6), and fructose-bisphosphate aldolase (ALDOB), as well as a Multi Marker Algorithm, based on levels of 4HPPD and IGFBP6, were shown to be best predictors of low (<8 nmol/l) vs normal (>12 nmol/l) testosterone. They were also more strongly associated with metabolic syndrome and diabetes than testosterone levels. Levels of ALDOB and 4HPPD also showed association with AR CAG repeat lengths. Conclusions: We identified potential new protein biomarkers of testosterone action. Further investigations to elucidate their clinical potential are warranted. Funding: The work was supported by ReproUnion2.0 (grant no. 20201846), which is funded by the Interreg V EU program.
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| 770. |
- Gomila, Margarita, et al.
(författare)
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Genotypic and phenotypic applications for the differentiation and species-level identification of achromobacter for clinical diagnoses.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- The Achromobacter is a genus in the family Alcaligenaceae, comprising fifteen species isolated from different sources, including clinical samples. The ability to detect and correctly identify Achromobacter species, particularly A. xylosoxidans, and differentiate them from other phenotypically similar and genotypically related Gram-negative, aerobic, non-fermenting species is important for patients with cystic fibrosis (CF), as well as for nosocomial and other opportunistic infections. Traditional phenotypic profile-based analyses have been demonstrated to be inadequate for reliable identifications of isolates of Achromobacter species and genotypic-based assays, relying upon comparative 16S rRNA gene sequence analyses are not able to insure definitive identifications of Achromobacter species, due to the inherently conserved nature of the gene. The uses of alternative methodologies to enable high-resolution differentiation between the species in the genus are needed. A comparative multi-locus sequence analysis (MLSA) of four selected 'house-keeping' genes (atpD, gyrB, recA, and rpoB) assessed the individual gene sequences for their potential in developing a reliable, rapid and cost-effective diagnostic protocol for Achromobacter species identifications. The analysis of the type strains of the species of the genus and 46 strains of Achromobacter species showed congruence between the cluster analyses derived from the individual genes. The MLSA gene sequences exhibited different levels of resolution in delineating the validly published Achromobacter species and elucidated strains that represent new genotypes and probable new species of the genus. Our results also suggested that the recently described A. spritinus is a later heterotypic synonym of A. marplatensis. Strains were analyzed, using whole-cell Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight mass spectrometry (MALDI-TOF MS), as an alternative phenotypic profile-based method with the potential to support the identifications determined by the genotypic DNA sequence-based MLSA. The MALDI-TOF MS data showed good accordance in strain groupings and identifications by the MLSA data.
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