| 1. |
- Björkqvist, Maria, et al.
(författare)
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Somatostatin, misoprostol and galanin inhibit gastrin- and PACAP-stimulated secretion of histamine and pancreastatin from ECL cells by blocking specific Ca(2+) channels.
- 2005
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 130:1-2, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- The oxyntic mucosa is rich in ECL cells. They secrete histamine and chromogranin A-derived peptides, such as pancreastatin, in response to gastrin and pituitary adenylate cyclase-activating peptide (PACAP). Secretion is initiated by Ca2+ entry. While gastrin stimulates secretion by opening L-type and N-type Ca2+ channels, PACAP stimulates secretion by activating L-type and receptor-operated Ca2+ channels. Somatostatin, galanin and prostaglandin E2 (PGE2) inhibit gastrin- and PACAP-stimulated secretion from the ECL cells. In the present study, somatostatin and the PGE2 congener misoprostol inhibited gastrin- and PACAP-stimulated secretion 100%, while galanin inhibited at most 60–65%. Bay K 8644, a specific activator of L-type Ca2+ channels, stimulated ECL-cell secretion, an effect that was inhibited equally effectively by somatostatin, misoprostol and galanin (75–80% inhibition). Pretreatment with pertussis toxin, that inactivates inhibitory G-proteins, prevented all three agents from inhibiting stimulated secretion (regardless of the stimulus). Pretreatment with nifedipine (10 μM), an L-type Ca2+ channel blocker, reduced PACAP-evoked pancreastatin secretion by 50–60%, gastrin-evoked secretion by not, vert, similar 80% and abolished the response to Bay K 8644. The nifedipine-resistant response to PACAP was abolished by somatostatin and misoprostol but not by galanin. Gastrin and PACAP raised the intracellular Ca2+ concentration in a biphasic manner, believed to reflect mobilization of internal Ca2+ followed by Ca2+ entry. Somatostatin and misoprostol blocked Ca2+ entry (and histamine and pancreastatin secretion) but not mobilization of internal Ca2+. The present observations on isolated ECL cells suggest that Ca2+ entry rather than mobilization of internal Ca2+ triggers exocytosis, that gastrin and PACAP activate different (but over-lapping) Ca2+ channels, that somatostatin, misoprostol and galanin interact with inhibitory G-proteins to block Ca2+ entry via L-type Ca2+ channels, and that somatostatin and misoprostol (but not galanin) in addition block N-type and/or receptor-operated Ca2+ channels.
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| 2. |
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| 3. |
- Duarte, Ana I., et al.
(författare)
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Dual Therapy with Liraglutide and Ghrelin Promotes Brain and Peripheral Energy Metabolism in the R6/2 Mouse Model of Huntington's Disease
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal loss alongside altered energy metabolism, are key features of Huntington's disease (HD) pathology. The orexigenic gut-peptide hormone ghrelin is known to stimulate appetite and affect whole body energy metabolism. Liraglutide is an efficient anti-type 2 diabetes incretin drug, with neuroprotective effects alongside anorectic properties. Combining liraglutide with the orexigenic peptide ghrelin may potentially promote brain/cognitive function in HD. The R6/2 mouse model of HD exhibits progressive central pathology, weight loss, deranged glucose metabolism, skeletal muscle atrophy and altered body composition. In this study, we targeted energy metabolism in R6/2 mice using a co-administration of liraglutide and ghrelin. We investigated their effect on brain cortical hormone-mediated intracellular signalling pathways, metabolic and apoptotic markers, and the impact on motor function in HD. We here demonstrate that liraglutide, alone or together with ghrelin (subcutaneous daily injections of 150 μg/kg (ghrelin) and 0.2 mg/kg (liraglutide), for 2 weeks), normalized glucose homeostatic features in the R6/2 mouse, without substantially affecting body weight or body composition. Liraglutide alone decreased brain cortical active GLP-1 and IGF-1 levels in R6/2 mice, alongside higher ADP levels. Liraglutide plus ghrelin decreased brain insulin, lactate, AMP and cholesterol levels in R6/2 mice. Taken together, our findings encourage further studies targeting energy metabolism in HD.
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| 4. |
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| 5. |
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| 6. |
- Reynolds, Regina Hertfelder, et al.
(författare)
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Perturbations in the p53/miR-34a/SIRT1 pathway in the R6/2 Huntington's disease model
- 2018
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431. ; 88, s. 118-129
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Tidskriftsartikel (refereegranskat)abstract
- The three factors, p53, the microRNA-34 family and Sirtuin 1 (SIRT1), interact in a positive feedback loop involved in cell cycle progression, cellular senescence and apoptosis. Each factor in this triad has roles in metabolic regulation, maintenance of mitochondrial function, and regulation of brain-derived neurotrophic factor (BDNF). Thus, this regulatory network holds potential importance for the pathophysiology of Huntington's disease (HD), an inherited neurodegenerative disorder in which both mitochondrial dysfunction and impaired neurotrophic signalling are observed. We investigated expression of the three members of this regulatory triad in the R6/2 HD mouse model. Compared to wild-type littermates, we found decreased levels of miR-34a-5p, increased SIRT1 mRNA and protein levels, and increased levels of p53 protein in brain tissue from R6/2 mice. The upregulation of SIRT1 did not appear to lead to an increased activity of the enzyme, as based on measures of p53 acetylation. In other words, the observed changes did not reflect the known interactions between these factors, indicating a general perturbation of the p53, miR-34a and SIRT1 pathway in HD. This is the first study investigating the entire triad during disease progression in an HD model. Given the importance of these three factors alone and within the triad, our results indicate that outside factors are regulating – or dysregulating – this pathway in HD.
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| 7. |
- Allbrand, Marianne, 1958-, et al.
(författare)
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Placental gene expression of inflammatory markers and growth factors : a case control study of obese and normal weight women
- 2015
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Ingår i: Journal of Perinatal Medicine. - : Walter de Gruyter. - 0300-5577 .- 1619-3997. ; 43:2, s. 159-164
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To survey the placental gene expression of inflammatory markers and growth factors in non-smoking obese women with an uncomplicated pregnancy without associated morbidity and delivery at term compared with normal weight women.Methods: Placental tissue samples from 32 obese women (body mass index, BMI >= 35.0 kg/m(2)) were compared with samples from 94 normal weight women (BMI 18.5-25.0 kg/m(2)) matched for age (+/- 1 year), gestational age (+/- 3 days), parity and mode of delivery. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to analyse toll receptor-2 and -4, interleukin-6 and -8, tumour necrosis factor-alpha, leptin, adiponectin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor.Results: There was no significant difference in gene expression in placental tissue samples from obese and normal weight women.Conclusion: We found no difference in the occurrence of inflammatory marker and growth factor mRNA levels in placental tissue samples from a large group of obese women without associated morbidity and with healthy infants compared to a closely matched control group of healthy normal weight women. Compared with the previous studies, this anomalous finding may be explained by the absence of associated morbidity in the obese women in our study.
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| 8. |
- Bacos, Karl, et al.
(författare)
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Islet beta-cell area and hormone expression are unaltered in Huntington's disease.
- 2008
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Ingår i: Histochemistry and Cell Biology. - : Springer Science and Business Media LLC. - 1432-119X .- 0948-6143. ; 129, s. 623-629
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegenerative disorders are often associated with metabolic alterations. This has received little attention, but might be clinically important because it can contribute to symptoms and influence the course of the disease. Patients with Huntington's disease (HD) exhibit increased incidence of diabetes mellitus (DM). This is replicated in mouse models of HD, e.g., the R6/2 mouse, in which DM is primarily caused by a deficiency of beta-cells with impaired insulin secretion. Pancreatic tissue from HD patients has previously not been studied and, thus, the pathogenesis of DM in HD is unclear. To address this issue, we examined pancreatic tissue sections from HD patients at different disease stages. We found that the pattern of insulin immunostaining, levels of insulin transcripts and islet beta-cell area were similar in HD patients and controls. Further, there was no sign of amyloid deposition in islets from HD patients. Thus, our data show that pancreatic islets in HD patients appear histologically normal. Functional studies of HD patients with respect to insulin secretion and islet function are required to elucidate the pathogenesis of DM in HD. This may lead to a better understanding of HD and provide novel therapeutic targets for symptomatic treatment in HD.
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| 9. |
- Bjerneby Häll, Maria
(författare)
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Allt har förändrats och allt är sig likt : En longitudinell studie av argument för grundskolans matematikundervisning
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med avhandlingen är att beskriva och analysera argument för matematik i grundskolan och att förstå varför och hur de officiella argumenten förändras, från de argument som återfinns i styrdokument till de argument som förs fram av undervisande matematiklärare. En utgångspunkt är att skolmatematikens villkor och verklighet kan beskrivas genom analys av officiella argument och av lärarstudenters och lärares personliga argument för matematik i grundskolan. Specifika forskningsfrågor i anslutning till syftet är:- Vilka argument för lärarstudenten fram inför yrkesdebuten?- Vilka argument för läraren fram under sina första år i yrket?- Vilka beskrivningar av skolmatematikens villkor ger lärarna?En longitudinell studie har genomförts där en grupp lärarstudenter följts genom utbildningen och under de första åren i yrket. Resultatet visar att lärarstudenter under utbildningen utvecklar en syn på matematik och matematikundervisning som stämmer väl med läroplanen och kursplanen i matematik enligt Lpo 94. De nyblivna lärarna med undervisning i matematik och NO-ämnen upplever i början av yrkeskarriären skilda villkor på olika skolor. Gemensamt för de lärare som undervisar i senare delen av grundskolan är upplevelser av krav på att ”hinna med kursen” inför det nationella provet i årskurs 9. Lärarnas mål med matematikundervisningen i grundskolan blir därför att förbereda eleverna för det nationella provet. En faktor som påverkar är kravet på att elever skall ha betyget godkänd för att vara behöriga till gymnasieskolans nationella program. De nyblivna lärarna upplever en konflikt mellan olika officiella argument för matematik i grundskolan. Faktorer som påverkar lärarnas och matematikämnets villkor och verklighet i grundskolan är bl.a. skolornas organisation i arbetslag och lärarnas kombination av undervisningsämnen.
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| 10. |
- Björkqvist, Maria, et al.
(författare)
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A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.
- 2008
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205, s. 1869-1877
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD. Interleukin 6 levels were increased in HD gene carriers with a mean of 16 years before the predicted onset of clinical symptoms. To our knowledge, this is the earliest plasma abnormality identified in HD. Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a cell-autonomous immune activation. A similar pattern was seen in macrophages and microglia from HD mouse models, and the cerebrospinal fluid and striatum of HD patients exhibited abnormal immune activation, suggesting that immune dysfunction plays a role in brain pathology. Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD.
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| 11. |
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| 12. |
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| 13. |
- Björkqvist, Maria, 1959-
(författare)
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Coagulase-negative staphylococci septicaemia in newborns : aspects on host-bacterial interactions with special regard to neutrophil and endothelial response
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Newborn infants, especially those born preterm, are immunologically immature and prone to invasive infections. As a result of the increasing survival of very preterm (VPT < 31 weeks gestational age) newborns, nosocomial septicaemia has become a major concern the neonatal intensive care, and coagulase-negative staphylococci (CoNS) are nowadays the most frequently isolated pathogens in neonatal blood cultures. Further insight into host-bacterial interactions is required for the development of preventive strategies against CoNS septicaemia in VPT newborns.Aim of the study: To investigate host-bacterial interactions in neonatal CoNS septicaemia with special regard to the neutrophil and endothelial response and to bacterial virulence factors.Methods and results: Neonatal blood isolates of CoNS collected at Örebro University Hospital, Örebro, Sweden during the years 1983-1997 were characterised clinically and according to species and to phenotypic and genotypic patterns. Biochemial fingerprinting was found useful as a screening tool for selection of phenotypically related strains, but for further discrimination within a phenotypic cluster, genetic fingerprinting by pulsed field gel electrophoresis (PFGE) was required.The isolates of S. epidermidis collected during the later part of the study period (1990-1997, n = 50) were further investigated. A hypervirulent clone of bacteria was identified, representing 7 of the 12 sepsis isolates in that cohort. These 12 isolates of S. epidermidis induced significantly higher endothelial release of neutrophil chemoattractants from human umbilical vein endothelial cell (HUVEC) cultures than did the isolates regarded as skin contaminants (n = 38). There were no differences between the sepsis and contaminant groups in the prevalence of genes for biofilm production, methicillin resistance or fibrinogen-binding protein.The neutrophil oxidative burst occuring after stimulation by different bacterial strains was investigated by a flow cytometric method applied to a whole blood model. The oxidative activity in unstimulated neutrophils was similar in term (n = 10) and preterm (n = 10) newborns. However, the term newborns showed a significantly higher capacity to up-regulate the oxidative burst after bacterial stimulation. Significant differences in oxidative responses to different bacterial strains were observed, but these differences could not be related exclusively to species or invasive capacity.A neutrophil granule protein, human neutrophil lipocalin (HNL), was evaluated as an early marker of neonatal septicaemia in newborns with clinical signs of infection. The serum level of HNL was significantly higher in the infected group of neonates (n = 25) than in the group with non-proven infection (n = 62). In healthy term controls the HNL level was similar at age 3 days to that at birth and close to the level reported in healthy adults.Conclusions: The increased up-regulation of endothelial inflammatory mediators induced by sepsis isolates of S. epidermidis represents an important step in the pathogenesis of neonatal CoNS septicaemia. HNL might be useful as a marker of neutrophil activity also in VPT newborns. The laboratory assays used in the present study can be further developed for future investigations of the pathogenesis and host-bacterial interactions in neonatal CoNS septicaemia.
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| 14. |
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| 15. |
- Björkqvist, Maria, 1959-, et al.
(författare)
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Colonization pattern of coagulase-negative staphylococci in preterm neonates and the relation to bacteremia
- 2010
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer. - 0934-9723 .- 1435-4373. ; 29:9, s. 1085-1093
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Tidskriftsartikel (refereegranskat)abstract
- Coagulase-negative staphylococci (CoNS) are the major cause of sepsis in extreme preterm (EPT) newborns, but data on the CoNS colonization in EPT newborns prior to invasive infection are limited. Our aim was to describe the early establishment of the CoNS microflora in EPT newborns and to compare the colonization pattern in neonates with and without positive CoNS blood cultures. From a cohort of 46 EPT neonates, newborns with positive CoNS blood culture were identified (n = 10) and compared with matched controls. Samples for bacterial cultures were obtained repetitively from nares, perineum, and umbilicus. All CoNS isolates were characterized using the PhenePlate system for biochemical fingerprinting. Persistent CoNS strains were found on day 2-3 after delivery in 7/20 newborns, and there was a tendency for earlier colonization in nares than in the perineum or umbilicus. The CoNS blood strains were prevalent in superficial sites prior to positive blood culture (11/14 blood strains), but no single invasive pathway was identified. Most CoNS blood strains (9/14) persisted on superficial sites after antibiotic treatment. We hypothesize that the invasive pathways in neonatal CoNS sepsis are complex and that the colonization of mucosal membranes and umbilical catheters might be of equal importance.
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| 16. |
- Björkqvist, Maria, et al.
(författare)
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Defective neutrophil oxidative burst in preterm newborns on exposure to coagulase-negative staphylococci
- 2004
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 55:6, s. 966-971
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Tidskriftsartikel (refereegranskat)abstract
- The neutrophil oxidative burst is a product of the regulated assembly of the multicomponent oxidase enzyme. Our aim was to compare the oxidative burst in term (n = 10) and preterm newborns <31 wk gestational age (n = 10) after stimulation with coagulase-negative staphylococci in vitro. Strains of Streptococcus epidermidis with different invasive and slime-producing properties, one strain of S. haemolyticus, and one strain of group B-streptococcus were investigated. A whole-blood flow cytometric assay using the oxidation of hydroethidine to ethidium bromide was used. The oxidative activity in unstimulated neutrophil granulocytes [polymorphonuclear leukocytes (PMNLs)] was similar in term and preterm newborns, but the preterm newborns showed a significantly lower capacity to up-regulate the oxidative burst intensity after bacterial stimulation (p = 0.004). In the term but not in the preterm group, the oxidative burst intensity after bacterial stimulation correlated with the baseline oxidative burst intensity. After bacterial stimulation, there was a trend toward a greater percentage of activated neutrophils in the term group than in the preterm group, but the difference was less pronounced than that in oxidative burst intensity. Significant differences in oxidative burst response to different bacterial strains were observed (p < 0.001), but the differences could not be correlated exclusively to invasive capacity or slime-producing properties. It is concluded that the baseline oxidative activity is similar in term and preterm PMNLs but that preterm PMNLs have a decreased capacity to increase the oxidative burst in response to bacterial stimulation.
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| 17. |
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| 18. |
- Björkqvist, Maria, et al.
(författare)
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Evaluation of a previously suggested plasma biomarker panel to identify Alzheimer's disease.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need for biomarkers in plasma to identify Alzheimer's disease (AD). It has previously been shown that a signature of 18 plasma proteins can identify AD during pre-dementia and dementia stages (Ray et al, Nature Medicine, 2007). We quantified the same 18 proteins in plasma from 174 controls, 142 patients with AD, and 88 patients with other dementias. Only three of these proteins (EGF, PDG-BB and MIP-1δ) differed significantly in plasma between controls and AD. The 18 proteins could classify patients with AD from controls with low diagnostic precision (area under the ROC curve was 63%). Moreover, they could not distinguish AD from other dementias. In conclusion, independent validation of results is important in explorative biomarker studies.
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| 19. |
- Björkqvist, Maria, et al.
(författare)
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Harnessing immune alterations in neurodegenerative diseases.
- 2009
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273. ; 64:1, s. 21-24
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Tidskriftsartikel (refereegranskat)abstract
- Immune dysfunction, a well-established feature of neuroinflammatory disease, is increasingly recognized in neurodegenerative conditions. Its role is emerging as an early and active participant in neuropathology. Inflammation could be modified, with disease-slowing effects, by targeted interventions; it is also readily detectable and could serve as a source of valuable biomarkers.
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| 20. |
- Björkqvist, Maria, et al.
(författare)
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Human neutrophil lipocalin : normal levels and use as a marker for invasive infection in the newborn
- 2004
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 93:4, s. 534-539
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate human neutrophil lipocalin (HNL) as a marker of neonatal invasive infection and determine the normal serum levels of HNL in newborns. METHODS: HNL is released from neutrophil granulocytes and is regarded as a specific marker of neutrophil activity. In 81 newborns < or = 28 d of age with signs of infection on a total of 87 occasions, HNL and C-reactive protein (CRP) were measured at inclusion and on the three following days. As controls, term healthy newborns were recruited at birth (cord blood, n = 45) and at ages 3-5 d (n = 46). Serum HNL was measured by a radioimmunoassay. RESULTS: 25/87 episodes were classified as infection and 62 as non-proven infection. HNLmax was significantly higher in the infected group (mean 587.6 microg/l) than in the non-proven infected group (mean 217.7 microg/, p < 0.001). HNL peaked at inclusion, 1 d earlier than CRP. In the healthy controls. HNL was the same at 3-5 d of age as at birth (mean 82.4-81.7 microg/l) and similar to normal adult levels. CONCLUSIONS: The release of HNL is not increased in healthy newborns at birth, but neonatal neutrophils rapidly release HNL upon microbial stimulation in vivo. HNL might be useful as an early marker of neonatal infection.
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| 21. |
- Björkqvist, Maria
(författare)
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Immunomodulation - a disease-modifying avenue for treatment of Huntington's disease?
- 2016
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Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 137:5, s. 670-672
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Tidskriftsartikel (refereegranskat)abstract
- This Editorial highlights a study published in the current issue of Journal of Neurochemistry by Dobson et al. (), investigating whether the immunomodulatory agent, laquinimod exerts an immunomodulatory effect on isolated Huntington´s disease monocytes. In Huntington´s disease (HD) a central immune activation is mirrored in the periphery by a low-grade immune response and monocytes isolated from HD gene carriers have been shown pathologically hyperreactive in response to stimulation. This hyperreactive immune system has become recognized as an important feature of HD pathogenesis and the employment of a strategy to affect this hyperreactivity could be a potential disease-modifying avenue in HD. Read the highlighted article 'Laquinimod dampens hyperactive cytokine production in Huntington's disease patient myeloid cells' on doi: 10.1111/jnc.13553.
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| 22. |
- Björkqvist, Maria, et al.
(författare)
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Increased endothelial activation in neonatal sepsis isolates of Staphylococcus epidermidis, but no differences in biofilm producing properties between sepsis and contaminant isolates
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Staphylococcus epidermidis is the predominating etiological agent in neonatal septicemia today, but specific specific factors associated with S. epidermidis are incompletely described. We compared neonatal blood isolates of S. epidermidis representing sepsis (n = 12) or skin contaminants (n = 38) regarding endothelial activation, and the prevalence of genes encoding for biofilm production (icaAB and D), fibrinogen-binding protein (fbe) and methicillin resistance (mecA).Endothelial cells cultured from human umbilical veins (HUVEC) were challenged by the different isolates of S. epidermidis. Endothelial release of adhesion molecules and interleukin-8 (IL-8) was investigated by an ELISA. Endothelial cell death was determined by light microscopy. The different genes were detected by PCR, and phenotypic biofilm production was investigated by Trypan blue staining. The sepsis isolates of S. epidermidis induced significantly higher endothelial release of intracellular adhesion molecule 1 (ICAM-1, p = 0.0021), endothelial selectin (E-selectin, p = 0.002), and IL-8 (p = 0.010) compared to the contaminants. Vaseular cell adhesion molecules 1 (VCAM-1) was not released. The sepsis-isolates were more cytotoxic than the contaminants; Nine out of 12 sepsis strains induced ≥ 50% cytotoxicity to HUVEC, compared to 15/38 contaminant strains (p = 0.047). The prevalence of the ica-operon, biofilm-production, fbe-, or mecA genes did not discriminate between sepsis and contaminant isolates. It is concluded that sepsis isolates of S. epidermidis induced higher endothelial release of chemotactic inflammatory mediators compared to contaminant isolates, but that the production of biofilm might be less important in neonatal infections eaused by S. epidermidis.
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| 23. |
- Björkqvist, Maria
(författare)
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Inflammation Biomarkers in Huntington’s Disease
- 2023
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Ingår i: Contemporary Clinical Neuroscience. - 2627-5341 .- 2627-535X. ; Part F1569, s. 277-304
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Bokkapitel (refereegranskat)abstract
- Neurodegenerative diseases share many features, such as inflammation. Accumulating evidence support the role of neuroinflammation in the pathogenesis and treatment of neurodegenerative diseases, and inflammatory markers are suggested important tools to identify disease risk, diagnose disease, monitor disease progression or treatment response, as well as predict clinical outcomes. In Huntington’s disease (HD) inflammatory processes, both centrally and peripherally, are suggested to contribute to pathology, and modulating the immune system may be a potential therapeutic strategy. Neuroinflammation has been shown to be an important factor and microglial activation can be detected before onset of clinical features. Central inflammatory processes are mirrored peripherally, and a peripheral low-grade immune response has been demonstrated in premanifest HD. Both direct and in-direct effects of mutant huntingtin within inflammatory cells have been demonstrated. As circulating markers of inflammation has been shown to mirror brain inflammatory changes in HD, this has raised the possibility that these markers could be useful as markers of disease features. This chapter aims to summarize current knowledge on biofluid immune markers and discuss how these markers may assist in understanding of HD pathology and aid in detection of new therapeutic targets.
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| 24. |
- Björkqvist, Maria, et al.
(författare)
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Phenotypic and genotypic characterisation of blood isolates of coagulase-negative staphylococci in the newborn
- 2002
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 110:4, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- Coagulase-negative staphylococci (CNS) are the leading cause of late-onset sepsis in newborns (>72 h of age). Our aim was to determine whether phenotypic and/or genotypic differences existed between blood isolates of CNS regarded as inducers of sepsis or as contaminants. Ninety-seven bloodisolates of CNS recovered from newborns at the neonatal intensive care unit, Örebro, Sweden in 1983–1997 were analysed. Twenty-nine of them (30%) were classified as sepsis isolates and 68 (70%) as contaminants. The most prevalent species was Staphylococcus epidermidis (n=59). Staphylococcus haemolyticus (n=16) was most often isolated from newborns with the lowest gestational age and birth weight. Biochemical typing using the Phene Plate system (PhP) and genotyping using pulsed-field gel electrophoresis (PFGE) showed that the S. epidermidis isolates regarded as inducers of sepsis (n=16) were more homogeneous than isolates considered contaminants (n=37). One main genotypic group, representing seven (44%) isolates, was identified among the sepsis isolates. Phenotypically the S. epidermidis sepsis isolates comprised three major clusters. In contrast, among the S. epidermidis contaminants, eight genotypic groups and two phenotypic clusters were identified. The dominating genotypic group among the sepsis isolates of S. epidermidis may represent strains with higher invasive capacity.
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| 25. |
- Björkqvist, Maria, et al.
(författare)
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Progressive alterations in the hypothalamic-pituitary-adrenal axis in the R6/2 transgenic mouse model of Huntington's disease
- 2006
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 15:10, s. 1713-1721
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is characterized by a triad of motor, psychiatric and cognitive symptoms. Although many of these symptoms are likely to be related to central nervous system pathology, others may be due to changes in peripheral tissues. The R6/2 mouse, a transgenic model of HD expressing exon 1 of the human HD gene, develops progressive alterations in the hypothalamic-pituitary-adrenal axis, reminiscent of a Cushing-like syndrome. We observed muscular atrophy, reduced bone mineral density, abdominal fat accumulation and insulin resistance in the mice. All these changes could be consequences of increased glucocorticoid levels. Indeed, hypertrophy of the adrenal cortex and a progressive increase in serum and urine corticosterone levels were found in R6/2 mice. In addition, the intermediate pituitary lobe was markedly enlarged and circulating adreno-corticotrophic hormone (ACTH) increased. Under normal conditions dopamine represses the ACTH expression. In the R6/2 mice, however, the expression of pituitary dopamine D2 receptors was reduced by half, possibly explaining the increase in ACTH. Urinary samples from 82 HD patients and 68 control subjects were analysed for cortisol: in accord with the observations in the R6/2 mice, urinary cortisol increased in parallel with disease progression. This progressive increase in cortisol may contribute to the clinical symptoms, such as muscular wasting, mood changes and some of the cognitive deficits that occur in HD.
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