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Sökning: WFRF:(Holmqvist Bo)

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1.
  • Ahlstedt, Jonas, et al. (författare)
  • Biodistribution and pharmacokinetics of recombinant α1-microglobulin and its potential use in radioprotection of kidneys.
  • 2015
  • Ingår i: American journal of nuclear medicine and molecular imaging. - 2160-8407. ; 5:4, s. 333-347
  • Tidskriftsartikel (refereegranskat)abstract
    • Peptide-receptor radionuclide therapy (PRRT) is a systemically administrated molecular targeted radiation therapy for treatment of neuroendocrine tumors. Fifteen years of clinical use show that renal toxicity, due to glomerular filtration of the peptides followed by local generation of highly reactive free radicals, is the main side-effect that limits the maximum activity that can be administrated for efficient therapy. α1-microglobulin (A1M) is an endogenous radical scavenger shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. An important feature of A1M is that, following distribution to the blood, it is equilibrated to the extravascular compartments and filtrated in the kidneys. Aiming at developing renal protection against toxic side-effects of PRRT, we have characterized the pharmacokinetics and biodistribution of intravenously (i.v.) injected (125)I- and non-labelled recombinant human A1M and the (111)In- and fluorescence-labelled somatostatin analogue octreotide. Both molecules were predominantly localized to the kidneys, displaying a prevailing distribution in the cortex. A maximum of 76% of the injected A1M and 46% of the injected octreotide were present per gram kidney tissue at 10 to 20 minutes, respectively, after i.v. injection. Immunohistochemistry and fluorescence microscopy revealed a dominating co-existence of the two substances in proximal tubules, with a cellular co-localization in the epithelial cells. Importantly, analysis of kidney extracts displayed an intact, full-length A1M at least up to 60 minutes post-injection (p.i.). In summary, the results show a highly similar pharmacokinetics and biodistribution of A1M and octreotide, thus enabling the use of A1M to protect the kidneys tissue during PRRT.
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2.
  • Feridani, Amir, et al. (författare)
  • Combined flow cytometry and confocal laser scanning microscopy for evaluation of BR96 antibody cancer cell targeting and internalization.
  • 2007
  • Ingår i: Cytometry Part A. - : Wiley. - 1552-4930 .- 1552-4922. ; 71A:6, s. 361-370
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Monoclonal antibodies (mAb) are important tools in the management of tumor disease, and the discovery of antibodies with both specific cancer cell targeting and capacity to enter the cells by internalization are critical to improve the therapeutic efficacy. Method: Antibody cancer cell targeting and internalization properties of fluoroscein-conjugated mAb made against Lewis Y (BR96) were evaluated quantitatively and qualitatively by means of flow cytometry (FCM) and confocal laser scanning microscopy (CLSM), respectively, on cells from a rat tumor cell line (BN7005-H1D2). Results: The study demonstrated a specific binding of BR96 to LewisY (LeY) located in the cell membrane and as BR96/LeY immunocomplexes (BR96/LeY) internalized into the cytoplasm. BR96/LeY was internalized into about 15% of the cells, usually distributed throughout the cytoplasm, but also located close to the nuclei. Cytotoxic effects by BR96 were indicated, and CLSM visualized subpopulations containing cells with bound or internalized BR96/LeY that possessed morphologically pyknotic nuclei and disrupted DNA. Conclusion: The spatial-temporal pattern by BR96 cell targeting and internalization processes of BR96/LeY into the cancer cells expressing LeY was demonstrated by FCM and CLSM. Used together, the FCM and CLSM techniques provide a valuable tool for preclinical analyses of antibody targeting and their capacities as carriers of cytotoxic conjugates for the use in cancer therapy.
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3.
  • Kristiansson, Amanda, et al. (författare)
  • Protection of Kidney Function with Human Antioxidation Protein α 1 -Microglobulin in a Mouse 177 Lu-DOTATATE Radiation Therapy Model
  • 2019
  • Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 30:14, s. 1746-1759
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Peptide receptor radionuclide therapy (PRRT) is in clinical use today to treat metastatic neuroendocrine tumors. Infused, radiolabeled, somatostatin analog peptides target tumors that are killed by irradiation damage. The peptides, however, are also retained in kidneys due to glomerular filtration, and the administered doses must be limited to avoid kidney damage. The human radical scavenger and antioxidant, α 1 -microglobulin (A1M), has previously been shown to protect bystander tissue against irradiation damage and has pharmacokinetic and biodistribution properties similar to somatostatin analogs. In this study, we have investigated if A1M can be used as a renal protective agent in PRRT. Results: We describe nephroprotective effects of human recombinant A1M on the short- and long-term renal damage observed following lutetium 177 ( 177 Lu)-DOTATATE (150 MBq) exposure in BALB/c mice. After 1, 4, and 8 days (short term), 177 Lu-DOTATATE injections resulted in increased formation of DNA double-strand breaks in the renal cortex, upregulated expression of apoptosis and stress response-related genes, and proteinuria (albumin in urine), all of which were significantly suppressed by coadministration of A1M (7 mg/kg). After 6, 12, and 24 weeks (long term), 177 Lu-DOTATATE injections resulted in increased animal death, kidney lesions, glomerular loss, upregulation of stress genes, proteinuria, and plasma markers of reduced kidney function, all of which were suppressed by coadministration of A1M. Innovation and Conclusion: This study demonstrates that A1M effectively inhibits radiation-induced renal damage. The findings suggest that A1M may be used as a radioprotector during clinical PRRT, potentially facilitating improved tumor control and enabling more patients to receive treatment. © Amanda Kristiansson et al. 2018; Published by Mary Ann Liebert, Inc.
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4.
  • Odenlund, Malin, et al. (författare)
  • Polyamine synthesis inhibition induces S phase cell cycle arrest in vascular smooth muscle cells.
  • 2009
  • Ingår i: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 36, s. 273-282
  • Tidskriftsartikel (refereegranskat)abstract
    • Polyamines are important for cell growth and proliferation and they are formed from arginine and ornithine via arginase and ornithine decarboxylase (ODC). Arginine may alternatively be metabolised to NO via NO synthase. Here we study if vascular smooth muscle cell proliferation can be reversed by polyamine synthesis inhibitors and investigate their mechanism of action. Cell proliferation was assessed in cultured vascular smooth muscle A7r5 cells and in endothelium-denuded rat arterial rings by measuring [(3)H]-thymidine incorporation and by cell counting. Cell cycle phase distribution was determined by flow cytometry and polyamines by HPLC. Protein expression was determined by Western blotting. The ODC inhibitor DFMO (1-10 mM) reduced polyamine concentration and attenuated proliferation in A7r5 cells and rat tail artery. DFMO accumulated cells in S phase of the cell cycle and reduced cyclin A expression. DFMO had no effect on cell viability and apoptosis as assessed by fluorescence microscopy. Polyamine concentration and cellular proliferation were not affected by the arginase inhibitor NOHA (100-200 muM) and the NO synthase inhibitor L: -NAME (100 muM). Lack of effect of NOHA was reflected by absence of arginase expression. Polyamine synthesis inhibition attenuates vascular smooth muscle cell proliferation by reducing DNA synthesis and accumulation of cells in S phase, and may be a useful approach to prevent vascular smooth muscle cell proliferation in cardiovascular diseases.
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5.
  • Romantsik, Olga, et al. (författare)
  • The heme and radical scavenger α1-microglobulin (A1M) confers early protection of the immature brain following preterm intraventricular hemorrhage
  • 2019
  • Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Germinal matrix intraventricular hemorrhage (GM-IVH) is associated with cerebro-cerebellar damage in very preterm infants, leading to neurodevelopmental impairment. Penetration, from the intraventricular space, of extravasated red blood cells and extracellular hemoglobin (Hb), to the periventricular parenchyma and the cerebellum has been shown to be causal in the development of brain injury following GM-IVH. Furthermore, the damage has been described to be associated with the cytotoxic nature of extracellular Hb-metabolites. To date, there is no therapy available to prevent infants from developing either hydrocephalus or serious neurological disability. Mechanisms previously described to cause brain damage following GM-IVH, i.e., oxidative stress and Hb-metabolite toxicity, suggest that the free radical and heme scavenger α1-microglobulin (A1M) may constitute a potential neuroprotective intervention. Methods: Using a preterm rabbit pup model of IVH, where IVH was induced shortly after birth in pups delivered by cesarean section at E29 (3 days prior to term), we investigated the brain distribution of recombinant A1M (rA1M) following intracerebroventricular (i.c.v.) administration at 24 h post-IVH induction. Further, short-term functional protection of i.c.v.-administered human A1M (hA1M) following IVH in the preterm rabbit pup model was evaluated. Results: Following i.c.v. administration, rA1M was distributed in periventricular white matter regions, throughout the fore- and midbrain and extending to the cerebellum. The regional distribution of rA1M was accompanied by a high co-existence of positive staining for extracellular Hb. Administration of i.c.v.-injected hA1M was associated with decreased structural tissue and mitochondrial damage and with reduced mRNA expression for proinflammatory and inflammatory signaling-related genes induced by IVH in periventricular brain tissue. Conclusions: The results of this study indicate that rA1M/hA1M is a potential candidate for neuroprotective treatment following preterm IVH.
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6.
  • Stenvall, Anna, et al. (författare)
  • Quantitative γ-H2AX immunofluorescence method for DNA double-strand break analysis in testis and liver after intravenous administration of 111InCl3
  • 2020
  • Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: It is well known that a severe cell injury after exposure to ionizing radiation is the induction of DNA double-strand breaks (DSBs). After exposure, an early response to DSBs is the phosphorylation of the histone H2AX molecule regions adjacent to the DSBs, referred to as γ-H2AX foci. The γ-H2AX assay after external exposure is a good tool for investigating the link between the absorbed dose and biological effect. However, less is known about DNA DSBs and γ-H2AX foci within the tissue microarchitecture after internal irradiation from radiopharmaceuticals. Therefore, in this study, we aimed to develop and validate a quantitative ex vivo model using γ-H2AX immunofluorescence staining and confocal laser scanning microscopy (CLSM) to investigate its applicability in nuclear medicine dosimetry research. Liver and testis were selected as the organs to study after intravenous administration of 111InCl3. Results: In this study, we developed and validated a method that combines ex vivo γ-H2AX foci labeling of tissue sections with in vivo systemically irradiated mouse testis and liver tissues. The method includes CLSM imaging for intracellular cell-specific γ-H2AX foci detection and quantification and absorbed dose calculations. After exposure to ionizing radiation from 111InCl3, both hepatocytes and non-hepatocytes within the liver showed an absorbed dose-dependent elevation of γ-H2AX foci, whereas no such correlation was seen for the testis tissue. Conclusion: It is possible to detect and quantify the radiation-induced γ-H2AX foci within the tissues of organs at risk after internal irradiation. We conclude that our method developed is an appropriate tool to study dose–response relationships in animal organs and human tissue biopsies after internal exposure to radiation.
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7.
  • Agyemang, Alex Adusei, et al. (författare)
  • Cell-free oxidized hemoglobin drives reactive oxygen species production and pro-inflammation in an immature primary rat mixed glial cell culture
  • 2021
  • Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Germinal matrix intraventricular hemorrhage (GM-IVH) is associated with deposition of redox active cell-free hemoglobin (Hb), derived from hemorrhagic cerebrospinal fluid (CSF), in the cerebrum and cerebellum. In a recent study, using a preterm rabbit pup model of IVH, intraventricularly administered haptoglobin (Hp), a cell-free Hb scavenger, partially reversed the damaging effects observed following IVH. Together, this suggests that cell-free Hb is central in the pathophysiology of the injury to the immature brain following GM-IVH. An increased understanding of the causal pathways and metabolites involved in eliciting the damaging response following hemorrhage is essential for the continued development and implementation of neuroprotective treatments of GM-IVH in preterm infant.METHODS: We exposed immature primary rat mixed glial cells to hemorrhagic CSF obtained from preterm human infants with IVH (containing a mixture of Hb-metabolites) or to a range of pure Hb-metabolites, incl. oxidized Hb (mainly metHb with iron in Fe3+), oxyHb (mainly Fe2+), or low equivalents of heme, with or without co-administration with human Hp (a mixture of isotype 2-2/2-1). Following exposure, cellular response, reactive oxygen species (ROS) generation, secretion and expression of pro-inflammatory cytokines and oxidative markers were evaluated.RESULTS: Exposure of the glial cells to hemorrhagic CSF as well as oxidized Hb, but not oxyHb, resulted in a significantly increased rate of ROS production that positively correlated with the rate of production of pro-inflammatory and oxidative markers. Congruently, exposure to oxidized Hb caused a disintegration of the polygonal cytoskeletal structure of the glial cells in addition to upregulation of F-actin proteins in microglial cells. Co-administration of Hp partially reversed the damaging response of hemorrhagic CSF and oxidized Hb.CONCLUSION: Exposure of mixed glial cells to oxidized Hb initiates a pro-inflammatory and oxidative response with cytoskeletal disintegration. Early administration of Hp, aiming to minimize the spontaneous autoxidation of cell-free oxyHb and liberation of heme, may provide a therapeutic benefit in preterm infant with GM-IVH.
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8.
  • Allas rätt till bostad : Marknadens begränsningar och samhällets ansvar
  • 2022
  • Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
    • Alla behöver någonstans att bo. Bostaden är så central för vår välfärd att vi ser den som en mänsklig rättighet. Bostadsfrågan skär in i flera olika politikområden och kan diskuteras från vitt skilda utgångspunkter. Var – och hur – vi bor påverkar i hög grad vårt handlingsutrymme och våra framtidsutsikter. De ojämlika förutsättningarna på bostadsmarknaden är en av de tydligaste klassmarkörerna i dagens Sverige.I antologin "Allas rätt till bostad" analyserar 28 bostads- och urbanforskare från olika akademiska discipliner svensk bostadspolitik, dess förutsättningar, historiska utveckling och konkreta resultat. En socialt medveten bostadspolitik behöver inte minst förhålla sig till den växande ojämlikheten i det svenska samhället. Men den bostadspolitik som har förts, med privatiseringar och vinstkrav även på offentligt ägda bolag, har tvärtom fått klyftorna att växa. Hyresrätten är till exempel idag klart missgynnad jämfört med bostadsägandet. Antologins texter diskuterar också – bland mycket annat – den betydelse bostadsbidraget, besittningsskyddet, byggindustrin och barnkonventionen kan ha i ett vidare bostadspolitiskt perspektiv.Bostadspolitiken är en ödesfråga för många människor och för ett demokratiskt samhälle. Antologin visar att  det krävs mer debatt och politisk fantasi och större rättvisa i bostadsfrågan än vi ser i dag.
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9.
  • Azadi, Seifollah, et al. (författare)
  • Thyroid-beta2 and the retinoid RAR-alpha, RXR-gamma and ROR-beta2 receptor mRNAs; expression profiles in mouse retina, retinal explants and neocortex.
  • 2002
  • Ingår i: NeuroReport. - 1473-558X. ; 13:6, s. 745-750
  • Tidskriftsartikel (refereegranskat)abstract
    • In neonatal retinal explants cultured long-term green cones are missing. Recently it was reported that thyroid hormone beta2 receptors (TR-beta2) are essential for these green cones to differentiate. Therefore transcript level of these receptors was investigated in our mouse retinal explants. However, thyroid receptors function as heterodimers with retinoid receptors (RR); so the fate of selected RRs was similarly analyzed using semi-quantitative RT-PCR. Loss of TR-beta2 and RR (RXR-gamma and ROR-beta2) mRNAs was observed after culturing the neonatal retina for 12 days. This indicates that these proteins are involved in determination of green cone identity. In addition, levels of the selected RR transcripts are differentially affected by short- or long-term culture. In the latter case an attached retinal pigment epithelium seems to play a protective role. Furthermore, divergent diurnal peaks of RR mRNAs are present in young as well as aged mouse retina and neocortex. This data might be relevant in the context of human ageing disorders.
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10.
  • Bengtsson, Bo, 1947-, et al. (författare)
  • Allas rätt till bostad : introduktion
  • 2022
  • Ingår i: Allas rätt till bostad. - Göteborg : Daidalos. - 9789171736604 ; , s. 11-22
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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11.
  • Christiansen, Line I., et al. (författare)
  • Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation in Preterm Pigs
  • 2023
  • Ingår i: eNeuro. - 2373-2822. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurode-velopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investi-gated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25 mg/kg/d recombinant human IGF-1/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was measured using in vivo labeling with [2H5] phenylalanine. We showed that the IGF-1 receptor was widely distributed in the brain and largely coexisted with immature neurons. Region-spe-cific quantification of IHC labeling showed that IGF-1 treatment promoted neuronal differentiation, increased subcorti-cal myelination, and attenuated synaptogenesis in a region-dependent and time-dependent manner. The expression levels of genes involved in neuronal and oligodendrocyte maturation, and angiogenic and transport functions were al-tered, reflecting enhanced brain maturation in response to IGF-1 treatment. Cerebellar protein synthesis was increased by 19% at day 5 and 14% at day 9 after IGF-1 treatment. Treatment had no effect on Iba1+ microglia or regional brain weights and did not affect motor development or the expression of genes related to IGF-1 signaling. In conclusion, the data show that supplemental IGF-1 promotes brain maturation in newborn preterm pigs. The results provide further support for IGF-1 supplementation therapy in the early postnatal period in preterm infants.
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12.
  • Eaton, Jennifer L., et al. (författare)
  • Ontogeny of vasotocin-expressing cells in zebrafish: Selective requirement for the transcriptional regulators orthopedia and single-minded 1 in the preoptic area
  • 2008
  • Ingår i: Developmental Dynamics. - : Wiley. - 1097-0177 .- 1058-8388. ; 237:4, s. 995-1005
  • Tidskriftsartikel (refereegranskat)abstract
    • The neurohypophysial peptide arginine vasotocin, and its mammalian ortholog arginine vasopressin, influence a wide range of physiological and behavioral responses, including aspects of sexual and social behaviors, osmoregulation, stress response, metabolism, blood pressure, and circadian rhythms. Here, we demonstrate that, in zebrafish (Danio rerio), the vasotocin precursor gene arginine vasotocin-neurophysin (avt) is expressed in two domains in the developing embryo: the dorsal preoptic area and the ventral hypothalamus. In the dorsal preoptic area, avt-expressing cells are intermingled with isotocin-neurophysin (ist) -expressing cells, and these neurons project to the neurohypophysis (posterior pituitary). In the dorsal preoptic area, the transcriptional regulators orthopedia b (otpb) and simple-minded 1 (siml) are required for expression of both avt and ist. In contrast, olp and siml are not required for avt expression in the ventral hypothalamus. Thus, the development of these two avt expression domains is influenced by separate gene regulatory networks.
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13.
  • Ebbesson, Lars, et al. (författare)
  • Neural circuits and their structural and chemical reorganization in the light-brain-pituitary axis during parr-smolt transformation in salmon
  • 2003
  • Ingår i: Aquaculture. - 0044-8486. ; 222:1-4, s. 59-70
  • Tidskriftsartikel (refereegranskat)abstract
    • Salmonid parr-smolt transformation (smoltification) is a transitional stage between freshwater and seawater life when the salmon imprint on their natal stream, change from a territorial feeding behavior to downstream migration, increase their hypoosmoregulatory competence, and change body shape and coloration. Photoperiod is recognized as the most potent initiator and regulator of the smoltification processes. Environmental light signals giving information about photoperiod are conveyed through a light-brain-pituitary axis that encompasses the neural pathways between photoreceptor organs, the brain and the pituitary, and the diurnal rhythm in melatonin secretion by the photosensory pineal organ. In addition, changes in photoperiod may elicit changes in this axis. Employing retinal neural tract tracing and growth associated protein-43 (GAP-43) immunocytochemistry, we provide here new evidence of a structural reorganization in the light-brain-pituitary axis during smoltification. Retinal tract tracing revealed that projections in smolts expand into new territories of the ipsilateral nucleus preopticus parvocellularis pars anterior (PPa) and additional fibers invade deeper into the contralateral PPa and the nucleus preopticus magnocellularis (PM). At this time, GAP-43-immunoreactive cells appear transiently in specific cell groups throughout the brain, but mainly in the olfactory bulb, telencephalon, and hypothalamus. These structural changes in the light-brain-pituitary axis and hypophysiotropic systems are followed by sequential surges of brain neurotransmitters and receptors, and occur prior to the major surges of circulating thyroid hormone and growth hormone levels that are central to smoltification-related processes. Our data point to a specific period of structural reorganization in certain brain circuits, and we hypothesize that these are involved in triggering the subsequent behavioral, endocrine, and physiological changes associated with smoltification. (C) 2003 Published by Elsevier Science B.V.
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14.
  • Ebbesson, LE, et al. (författare)
  • Nitric oxide synthase in the gill of Atlantic salmon: colocalization with and inhibition of Na+,K+-ATPase
  • 2005
  • Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 208:6, s. 1011-1017
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the relationship between nitric oxide (NO) and Na+,K+-ATPase (NKA) in the gill of anadromous Atlantic salmon. Cells containing NO-producing enzymes were revealed by means of nitric oxide synthase (NOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochernistry, which can be used as an indicator of NOS activity, i.e. NO production. Antibodies against the two constitutive NOS isoforms, neuronal and endothelial NOS, both produced immunoreactivity restricted to large cells at the base and along the secondary lamellae. NADPHd-positive cells showed a corresponding distribution. Antibodies against the inducible NOS isoform only labeled small cells located deep in the filament. Using in situ hybridization and NKA immunoreactivity, cells expressing Na+,K+-ATPase alpha-subunit mRNA were found to have a similar distribution to the NOS cells. Double labeling for NOS immunoreactivity and NKA cc-subunit mRNA revealed cellular colocalization of NKA alpha-subunit mRNA and nNOS protein in putative chloride cells at the base of the lamellae and interlamellar space. Along the lamellae, some NOS- or NKA-immunoreactive cells possessed a relatively lower expression of NKA a-subunit mRNA in smolts. A clear increase in NADPHd staining in the gill was demonstrated from parr to smolt. The regulatory role of NO on gill NKA activity was studied in vitro using sodium nitroprusside (SNP; 1 mmol l(-1)) and PAPA-NONOate (NOC-15; 0.5 mmol l(-1)) as NO donors. Both SNP and NOC-15 inhibited gill NKA activity by 30% when compared to controls. The study shows that NO systems are abundant in the gill of Atlantic salmon, that NO may be produced preferentially by a constitutive NOS isoform, and suggests that NO influence on gill functions is mediated via intracellular, possibly both auto/paracrine, inhibition of Na+,K+-ATPase activity in chloride cells. Furthermore, the increase in NADPHd in the gill during smoltification suggests a regulatory role of NO in the attenuation of the smoltification-related increase in Na+,K+-ATPase activity prior to entering seawater.
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15.
  • Ebbesson, Lars O. E., et al. (författare)
  • Exposure to continuous light disrupts retinal innervation of the preoptic nucleus during parr-smolt transformation in Atlantic salmon
  • 2007
  • Ingår i: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 273:2-3, s. 345-349
  • Konferensbidrag (refereegranskat)abstract
    • High quality salmon smolts are essential for aquaculture, enhancement programs and wild populations. However, intensification of aquaculture smolt production and changes in natural habitats can cause sub-optimal environmental conditions, which may result in poor smolt quality. The salmon brain, as the integrator of environmental information, plays a focal role in relaying this information through the light-brain-pituitary axis, which includes retinal and pineal innervation of the hypothalamus. Here we investigated the effect of rearing juvenile Atlantic salmon, Salmo salar, under constant light (LL) on optic nerve fiber growth into the hypothalamus. This was compared with the normal increased fiber growth in fish reared under a simulated-natural photoperiod (LDN). Parr were sampled from the LDN group in February and from the LDN and LL groups in May (peak smolt status for the LDN group). Retinohypothalamic projections to the preoptic area were traced using 1, 1'-dioctadecyl-3,3, 3,3-tetramethylindocarbocyanine perchlorate (DiI) and confocal laser scanning microscopy. Data showed that parr exposed to LL did not develop the same extensive retinal innervation to the preoptic nucleus (NPO) observed in control salmon smolts raised under LDN. Since the cells in NPO are central pituitary regulatory neurones, the increased retinohypothalamic innervation during normal smoltification may be responsible for the increased endocrine response to photoperiod information. The deprivation of photoperiod information, during continuous light exposure, may inhibit the natural developmental program to proceed during the parr-smolt transformation. (C) 2007 Elsevier B.V. All rights reserved.
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16.
  • Ekström, Claes, et al. (författare)
  • Evaluation of recombinant human IGF-1/IGFBP-3 on intraventricular hemorrhage prevention and survival in the preterm rabbit pup model
  • 2023
  • Ingår i: Scientific Reports. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates processes of vascular maturation. The pathogenesis of intraventricular hemorrhage (IVH) relates to the fragility of the immature capillaries in the germinal matrix, and its inability to resist fluctuations in cerebral blood flow. In this work, using different experimental setups, we aimed to (i) establish an optimal time-point for glycerol-induction of IVH in relation to time-point of recombinant human (rh) IGF-1/rhIGFBP-3 administration, and (ii) to evaluate the effects of a physiologic replacement dose of rhIGF-1/rhIGFBP-3 on prevention of IVH and survival in the preterm rabbit pup. The presence of IVH was evaluated using high-frequency ultrasound and post-mortem examinations. In the first part of the study, the highest incidence of IVH (> 60%), occurred when glycerol was administered at the earliest timepoint, e.g., 6h after birth. At later time-points (18 and 24h) the incidence decreased substantially. In the second part of the study, the incidence of IVH and mortality rate following rhIGF-1/rhIGFBP-3 administration was not statistically different compared to vehicle treated animals. To evaluate the importance of maintaining intrauterine serum levels of IGF-1 following preterm birth, as reported in human interventional studies, additional studies are needed to further characterize and establish the potential of rhIGF-1/rhIGFBP-3 in reducing the prevalence of IVH and improving survival in the preterm rabbit pup.
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17.
  • Ekström, Claes, et al. (författare)
  • THE INSULIN-LIKE GROWTH FACTOR 1 (IGF-1) SYSTEM IN THE PRETERM RABBIT PUP : A CHARACTERIZATION OF THE IGF-1 MRNA EXPRESSION IN LIVER, IGF-1 PROTEIN LEVELS IN SERUM AND BRAIN DISTRIBUTION OF IGF-1 RECEPTORS
  • 2019
  • Konferensbidrag (refereegranskat)abstract
    • IGF-1 is an essential regulator of fetal growth and brain development. Preterm birth in the human is followed by a rapid decrease in serum levels of IGF-1 and decreased levels of IGF-1 have been associated with development of severemorbidity. A recent clinical trial indicated that supplementation with IGF-1 prevented development of severe intraventricular hemorrhage (IVH) in extremely preterm infants. In order to better understand possible mechanisms involved in IGF-1-induced IVH prevention, we evaluated important aspects of the endogenous IGF-1 system; IGF-I mRNA expression in the liver and associated serum protein levels and brain IGF-1 receptor (IGFR) distribution in the preterm rabbit.Rabbit pups were delivered by cesarean section at E29 (preterm) or by vaginal delivery (term = E32), housed in a controlled environment and fed twice daily with bovine colostrum via a gastric tube. Serum concentrations of IGF-1protein and liver expression of IGF-1 mRNA were determined at 0, 2, 6, 12, 24, 48 and 72 h of age in preterm pups. Paraffin brain sections from perfusion fixed untreated animals (preterm pups at 20 h and term pups at 5-7 h and 96 h) were prepared for immunohistochemistry against IGF1R, by labeling with primary antibodies against IGF1R, and processed for chromogen visualization and density/quantitation analysis with confocal microscopy. Mean (SD) serum concentrations of IGF-1 decreased from 166 (33) ng/ml at birth (E29) to 28 (9) ng/ml at day 3 (P0). Hepatic expression of IGF-1 mRNA did not vary over time. The IGF1R was widely distributed in multiple brain regions in both preterm and term pups (Fig). The most abundant density of IGF1R was observed in the choroid plexus, the subfornical organ, the meninges, major fiber tracts, the cortex and sub-ependymal germinal zones. The IGF1R, was mainly localized on outer cell membranes, on cell bodies and along nerve fibers. Quantitative analysis of IGF1R immunoreactivity showed similar IGF1R densities in preterm and term pups of corresponding ages. IGF1R density decreased with increasing postnatal age in term pups.In line with what is observed in the preterm human infant, serum protein levels of IGF-1 in the preterm rabbit pup decrease rapidly following birth. The IGF1R is widely expressed in the brain following birth, with high expressions in regions and structures relevant for vessel rupture in IVH. The preterm rabbit thus presents a well-suited model for characterization and evaluation of mechanisms involved in IGF-1 induced prevention of IVH.
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18.
  • Ekström, Ulf, et al. (författare)
  • Internalization of cystatin C in human cell lines.
  • 2008
  • Ingår i: The FEBS Journal. - : Wiley. - 1742-464X. ; Aug 9, s. 4571-4582
  • Tidskriftsartikel (refereegranskat)abstract
    • Altered protease activity is considered important for tumour invasion and metastasis, processes in which the cysteine proteases cathepsin B and L are involved. Their natural inhibitor cystatin C is a secreted protein, suggesting that it functions to control extracellular protease activity. Because cystatins added to cell cultures can inhibit polio, herpes simplex and coronavirus replication, which are intracellular processes, the internalization and intracellular regulation of cysteine proteases by cystatin C should be considered. The extension, mechanism and biological importance of this hypothetical process are unknown. We investigated whether internalization of cystatin C occurs in a set of human cell lines. Demonstrated by flow cytometry and confocal microscopy, A-431, MCF-7, MDA-MB-453, MDA-MB-468 and Capan-1 cells internalized fluorophore-conjugated cystatin C when exposed to physiological concentrations (1 mum). During cystatin C incubation, intracellular cystatin C increased after 5 min and accumulated for at least 6 h, reaching four to six times the baseline level. Western blotting showed that the internalized inhibitor was not degraded. It was functionally intact and extracts of cells exposed to cystatin C showed a higher capacity to inhibit papain and cathepsin B than control cells (decrease in enzyme activity of 34% and 37%, respectively). The uptake of labelled cystatin C was inhibited by unlabelled inhibitor, suggesting a specific pathway for the internalization. We conclude that the cysteine protease inhibitor cystatin C is internalized in significant quantities in various cancer cell lines. This is a potentially important physiological phenomenon not previously described for this group of inhibitors.
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19.
  • Forsell, Johan, et al. (författare)
  • Molecular identification and developmental expression of UV and green opsin mRNAs in the pineal organ of the Atlantic halibut.
  • 2002
  • Ingår i: Developmental Brain Research. - 0165-3806. ; 136:1, s. 51-62
  • Tidskriftsartikel (refereegranskat)abstract
    • The pineal organ is the only differentiated photoreceptor organ present in embryos and early larvae of the Atlantic halibut (Hippoglossus hippoglossus). We investigated the molecular identity of opsins in the pineal organ, and their expression during different life stages. Using RT-PCR we identified two 681-bp gene sequences, named HPO1 and HPO4, in cDNA from adult pineal and whole embryos. The predicted amino acid sequences showed highest identity to the transmembrane regions of teleostean RH2 green cone opsins (HPO1, 72-91%) and SWS-1 UV cone opsins (HPO4, 71-83%). In situ hybridization revealed expression of HPO1 and HPO4 mRNA transcripts in photoreceptors in the pineal organ of embryos, larvae and adults. HPO1 and HPO4 mRNA transcripts were also expressed in the larval retina. Our study provides molecular evidence for short and middle wavelength light sensitive photoreceptors in the pineal organ of Atlantic halibut throughout life, and suggests that pineal photoreception may play an important role during embryonic and larval life stages, especially at the time when the retina does not possesses corresponding photoreceptor capacity.
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20.
  • Forsell, Johan, et al. (författare)
  • Role of the pineal organ in the photoregulated hatching of the Atlantic halibut
  • 1997
  • Ingår i: International Journal of Developmental Biology. - 0214-6282. ; 41:4, s. 591-595
  • Tidskriftsartikel (refereegranskat)abstract
    • The timing of hatching in the Atlantic halibut (Hippoglossus hippoglossus) has been suggested to be regulated by environmental light conditions. However, the photosensory organ that perceives the triggering light has not been identified. In the present study, we investigated the morphogenesis of the pineal organ and the neurochemical differentiation of photoreceptors in the pineal organ and the retina of the Atlantic halibut during embryonic development. Immunocytochemical techniques were used for detection of integral protein components of the phototransduction process: opsins, arrestin (S-antigen) and α-transducin. We also studied the expression of serotonin (5-HT), a precursor of the neurohormone melatonin known to be synthesized by pineal photoreceptors. In the pineal anlage, opsin immunoreactive (ir) cells appear at 11 days post-fertilization (pf), arrestin, α-transducin and serotonin ir cells appear at 14 days pf; hatching took place 15 days pf. The retina contained no immunoreactive cells in embryos or in newly hatched larva. During this period, the pineal anlage is morphologically discernible only as a wedge-shaped region in the diencephalic roof, where elongated cells are aligned with their long axes converging toward a centrally located presumptive pineal lumen. The results show that the pineal photoreceptors contain serotonin and molecules involved in the phototransduction cascade before hatching. We suggest that the pineal organ has the capacity to perceive and mediate photic information before hatching in halibut embryos, and may thereby influence the timing of hatching.
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21.
  • Hedberg, Bo, et al. (författare)
  • Learning in imaginary organizations
  • 2001
  • Ingår i: Handbook of organizational learning and knowledge. - Oxford : Oxford University Press. - 0198295839 - 0198295820 ; , s. 733-752
  • Bokkapitel (refereegranskat)
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22.
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23.
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24.
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25.
  • Holmqvist, Bo I., et al. (författare)
  • Galanin‐like immunoreactivity in the brain of teleosts : Distribution and relation to substance P, vasotocin, and isotocin in the atlantic salmon (Salmo salar)
  • 1991
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967. ; 306:3, s. 361-381
  • Tidskriftsartikel (refereegranskat)abstract
    • The presence of galanin‐like substances and their relation to substance P‐, vasotocin‐, and isotocin‐immunoreactive neurons and fibers in the brain of teleosts was investigated with immunohistochemical methods. Two specific antisera against synthetic porcine galanin (GAL) revealed cell bodies and fibers in the brain of four different teleost species (Salmo salar, Carassius carassius, Gasterosteus aculeatus, and Anguilla anguilla). In all four species the main location of galanin immunoreactivity was in the hypothalamo‐pituitary region. A detailed study of the distribution of galanin immunoreactivity in S. salar showed that galanin immunoreactive (GALir) perikarya were present in the nucleus preopticus periventricularis, an area that may be compared to the supraoptic nucleus in mammals, and in the nucleus lateralis tuberis, a nucleus involved in pituitary control in fishes that may be compared with the arcuate nucleus in mammals, GALir perikarya were found also in the nucleus recessus lateralis and in the nucleus recessus posterior. Numerous GALir fibers were present in the telencephalon and diencephalon, whereas only small numbers of fibers were found in the brainstem. In contrast to the situation in mammals, no GALir perikarya were observed in the brainstem areas corresponding to the noradrenergic locus coeruleus and serotonergic raphe nuclei in S. salar. We did not find any coexistence of GALir substances with arginine vasotocin or isotocin in neurosecretory neurons, as has been shown for galanin with the mammalian counterparts vasopressin and oxytocin. Also, the galanin‐like substance(s) and their structurally closest related peptide family, the tachykinins, belong to separate neuronal systems in teleosts. The presence of GALir neurons in brain areas known to be involved in pituitary control, and a massive GALir innervation of the pituitary, strongly indicate a role for galanin‐like substances in pituitary control also in teleosts. Furthermore, the presence of extrahypothalamic GALir fibers suggests involvement of galanin‐like substances in other brain functions in teleosts. In conclusion, there are general similarities between teleosts and mammals concerning the distribution of galanin‐like substances. However, there seem to be substantial differences in their distribution relative to functionally related peptides within the hypothalamo‐pituitary system. Whereas galanin appears to be colocalized and released together with vasopressin and oxytocin in mammals, in teleosts the homologous substances are contained within different sets of neurons that innervate the same target, the pituitary.
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26.
  • Holmqvist, Bo I., et al. (författare)
  • Hypophysiotrophic systems in the brain of the Atlantic salmon. Neuronal innervation of the pituitary and the origin of pituitary dopamine and nonapeptides identified by means of combined carbocyanine tract tracing and immunocytochemistry
  • 1995
  • Ingår i: Journal of Chemical Neuroanatomy. - 0891-0618. ; 8:2, s. 125-145
  • Tidskriftsartikel (refereegranskat)abstract
    • The neuroanatomical organization of neurons projecting to the pituitary and the origin of pituitary dopamine and nonapeptides were investigated in the brain of the Atlantic salmon (Salmo salar). Carbocyanine tract tracing in combination with tyrosine hydroxylase, arginine vasotocin and isotocin immunocytochemistry for double labelling revealed a previously unknown organization of hypophysiotrophic cell groups and their extrahypothalamic projections, and provide the first direct identification in a teleost fish of the origin of the dopaminergic and nonapeptidergic innervation of the pituitary. The present data include identification of (1) hypophysiotrophic neurons in the ventral telencephalon and in the periventricular preoptic nucleus, (2) large (magnocellular) vasotocinergic hypophysiotrophic neurons in the most rostral extension of the preoptic area, (3) a distinct neuronal group located in a supraoptic/suprachiasmatic position in the anterior periventricular nucleus, that seems to be the major source of dopaminergic innervation of the pituitary, (4) the nonapeptidergic hypophysiotrophic neurons in the preoptic nucleus, (5) hypophysiotrophic neurons in the ventral and posterior hypothalamus of which some are of liquor-contacting type, (6) projections from hypophysiotrophic and non-hypophysiotrophic neurons in the preoptic nucleus to extrahypothalamic areas such as thalamic and periventricular pretectal nuclei, and (7) subdivisions within the preoptic nucleus that exhibit different combinations of hypophysiotrophic and extrahypothalamic efferent connections. Together with previous studies of retinohypothalamic projections and neurochemical organization of hypothalamic/preoptic areas, the present data suggest that the preoptic nucleus and the anterior periventricular nucleus in teleosts possess functional subdivisions with features that resemble those of the paraventricular, supraoptic and suprachiasmatic nuclei of other vertebrates. In the Atlantic salmon, specific dopaminergic and nonapeptidergic neuronal subdivisions are proposed to play a role for photoperiod control of endocrine activity.
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27.
  • Holmqvist, Bo I., et al. (författare)
  • Nitric oxide synthase in the brain of a teleost
  • 1994
  • Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 171:1-2, s. 205-208
  • Tidskriftsartikel (refereegranskat)abstract
    • The presence and distribution of the nitric oxide (NO) converting enzyme, NO synthase (NOS), was investigated in the brain of a teleost, the Atlantic salmon. Both NOS immunoreactive and NADPH diaphorase positive, non-neuronal and neuronal cell bodies, fibers and putative nerve terminals were identified throughout the brain. Even so, the staining was not identical in all regions. NO, synthesized by NOS-like enzymes, may play an important role in a diversity of cellular mechanisms in the brain of the salmon, including in neural systems related to olfactory, visual, hypophysiotrophic, viscero-sensoric and motor functions.
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28.
  • Holmqvist, Bo, et al. (författare)
  • Subcellular localization of neuronal nitric oxide synthase in the brain of a teleost; an immunoelectron and confocal microscopical study
  • 1997
  • Ingår i: Brain Research. - 0006-8993. ; 745:1-2, s. 67-82
  • Tidskriftsartikel (refereegranskat)abstract
    • The subcellular localization of neuronal nitric oxide (NO) synthase (NOS)-immunoreactive (NOSir) elements in the brain of the Atlantic salmon was investigated by means of electron microscopy and confocal laser scanning microscopy. NOSir structures are present only in neuronal elements. In neuronal processes, strong NOS immunoreactivity was mainly localized within synaptic vesicles or seen as a dense accumulation associated with the plasma membrane of dendrites and at terminal formations. NOSir precipitate was also associated with microtubuli and mitochondrial outer membranes. The highest accumulation of NOS immunoreactivity was found in dendrites located in close apposition to immunonegative myelinated or unmyelinated neural processes. Several NOSir and unmyelinated immunonegative profiles formed synaptic specializations. Immunonegative neurons in contact with NOSir processes always contained round clear synaptic vesicles. In neuronal somata, strong NOS immunoreactivity was localized in the cristae of some large mitochondria, whereas vacuoles and the endoplasmic reticulum showed a relatively weak staining. Confocal microscopic analysis of NOS immunofluorescence showed a corresponding subcellular localization of NOS in different brain regions, but also indicated the presence of NOS axosomatic terminals. Our data show that specific neurons contain a neuronal NOS-like molecule which to a high degree is stored in vesicles and is accumulated at various sites along the neuronal processes or at specific synaptic terminal formations. Thus, NO may be formed and exert its actions at various sites along the processes of NOS-synthesizing neurons. The present study provides evidence at the ultrastructural level that NO may play a messenger role in neural circuits involved in visual and hypophysiotrophic brain functions.
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29.
  • Holmqvist, Bo, et al. (författare)
  • The early ontogeny of neuronal nitric oxide synthase systems in the zebrafish.
  • 2004
  • Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 207:Pt 6, s. 923-935
  • Tidskriftsartikel (refereegranskat)abstract
    • To examine a putative role for neuronal nitric oxide synthase (nNOS) in early vertebrate development we investigated nNOS mRNA expression and cGMP production during development of the zebrafish Danio rerio. The nNOS mRNA expression in the central nervous system (CNS) and periphery showed a distinct spatio-temporal pattern in developing zebrafish embryo and young larvae. nNOS mRNA expression was first detected at 19 h postfertilisation (h.p.f.), in a bilateral subpopulation of the embryonic ventrorostral cell cluster in the forebrain. The number of nNOS mRNA-expressing cells in the brain slowly increased, also appearing in the ventrocaudal cell cluster from about 26 h.p.f., and in the dorsorostral and hindbrain cell cluster and in the medulla at 30 h.p.f. A major increase in nNOS mRNA expression started at about 40 h.p.f., and by 55 h.p.f. the expression constituted cell populations in differentiated central nuclei and in association with the proliferation zones of the brain, and in the medulla and retina. In parts of the skin, nNOS mRNA expression started at 20 h.p.f. and ended at 55 h.p.f. Between 40 and 55 h.p.f., nNOS mRNA expression started in peripheral organs, forming distinct populations after hatching within or in the vicinity of the presumptive swim bladder, enteric ganglia, and along the alimentary tract and nephritic ducts. Expression of nNOS mRNA correlated with the neuronal differentiation pattern and with the timing and degree of cGMP production. These studies indicate spatio-temporal actions by NO during embryogenesis in the formation of the central and peripheral nervous system, with possible involvement in processes such as neurogenesis, organogenesis and early physiology.
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30.
  • Holmqvist, Claes, et al. (författare)
  • A flexible approach for modelling flow in multi-component blade formers
  • 2006
  • Ingår i: Nordic Pulp & Paper Research Journal. - 0283-2631 .- 2000-0669. ; 21:1, s. 73-81
  • Tidskriftsartikel (refereegranskat)abstract
    • The internal structure of the fibre network constituting a paper is to a dominating extent determined in the forming zone of the paper machine. In this article we present a method for modelling the pressure distributions in blade forming sections, which is commonly considered to be a key quantity of the process. The ambition is to obtain a tool by which the interaction between the different components of blade sections can be studied. It is achieved by defining modules out of which arbitrary sections can be constructed. The modules are solved independently and matched to each other iteratively Keeping the interface between the modules simple provides great flexibility in the modelling. By virtue of a slenderness assumption, the equations governing each module can be reduced to one-dimensional form, hence limiting the computational work and permitting systems of many components to be studied. Dimensionless numbers defining the problem are identified, and the magnitude of the nonlinear effects are estimated. Simulations are presented that illustrate the potential of the method.
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31.
  • Hurley, Sinead M., et al. (författare)
  • The dynamics of platelet activation during the progression of streptococcal sepsis
  • 2016
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Platelets contribute to inflammation however, the role of platelet activation during the pathophysiological response to invasive bacterial infection and sepsis is not clear. Herein, we have investigated platelet activation in a mouse model of invasive Streptococcus pyogenes infection at 5,12, and 18 hours post infection and correlated this to parameters of infection. The platelet population in ex-vivo blood samples showed no increased integrin activation or surface presentation of CD62P, however platelet-neutrophil complex formation and plasma levels of CD62P were increased during bacterial dissemination and the progression of sepsis, indicating that platelet activation had occurred in vivo. Platelet-neutrophil complex formation was the most discriminatory marker of platelet activation. Platelet-neutrophil complexes were increased above baseline levels during early sepsis but decreased to significantly lower levels than baseline during late sepsis. The removal of these complexes from the circulation coincided with a significant increase in organ damage and the accumulation of platelets in the liver sinusoids, suggesting that platelet activation in the circulation precedes accumulation of platelets in damaged organs. The results demonstrate that monitoring platelet activation using complementary methods may provide prognostic information during the pathogenesis of invasive S. pyogenes infection.
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32.
  • Isfoss, Björn, et al. (författare)
  • Distribution of aldehyde dehydrogenase 1-positive stem cells in benign mammary tissue from women with and without breast cancer.
  • 2012
  • Ingår i: Histopathology. - : Wiley. - 0309-0167. ; 60:4, s. 617-633
  • Tidskriftsartikel (refereegranskat)abstract
    • Isfoss B L, Holmqvist B, Alm P & Olsson H (2012) Histopathology Distribution of aldehyde dehydrogenase 1-positive stem cells in benign mammary tissue from women with and without breast cancer Aims: Aldehyde dehydrogenase 1 (ALDH1) in female breast tissue has been linked to stem cells, but little is known about the benign cellular organization in situ. We investigated the distribution of ALDH1-immunoreactive (ALDH1+) cells in histomorphologically benign breast tissue from 28 women with or without breast cancer. Methods and results: ALDH1+ cells were detected in benign tissue of women aged 20-72 years, located most commonly at the luminal and intermediate ductular levels and in the stroma. ALDH1+ cell populations and Ki67+ cell populations were present in separate ductules, both cell types rarely showing epithelial differentiation. ALDH1+ cells were non-reactive to Ki67 and oestrogen receptor. Stromal round/oval ALDH1+ non-leukocyte cells in both age groups expressed contractile protein. There was a lower concentration of luminal and intermediate ductular ALDH1+ cells in postmenopausal women than in premenopausal women, and in cancer patients than in non-cancer patients, and a higher concentration in women receiving exogenous hormones. Conclusions: This study provides further evidence for the stem cell character of ALDH1+ cells, here in benign breast tissue of cancer and non-cancer patients throughout non-lactating adult life, and contributes evidence of benign stromal ALDH1+ cells. The distribution of ductular ALDH1+ stem cells appears to be influenced by hormonal status.
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33.
  • Isfoss, Björn Logi, et al. (författare)
  • Stellate cells and mesenchymal stem cells in benign mammary stroma are associated with risk factors for breast cancer - an observational study
  • 2018
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: It is not known whether stromal cells in benign breast tissue can mediate risk of breast cancer. We recently described aldehyde dehydrogenase 1 A1 (ALDH1) positive (+) cells in morphologically normal breast stroma of premenopausal women, and the data indicated that their distribution is associated with clinical risk factors for breast cancer. The aim of the present study was to define the identities of these cells using histologic and immunohistologic methods, and to investigate associations between those cells and hormonal and genetic risk factors in pre- and postmenopausal women. Methods: Stroma of morphologically normal tissue was analyzed in samples from 101 well-characterized women whose breasts had been operated. Morphology and immunolabeling were applied to determine cell identities based on the putative stem cell markers ALDH1 and stage-specific embryonic antigen-3 (SSEA3), and immunophenotypes indicating mast cells or stellate cells. The results were compared with the patients' risk factors using regression analysis (two-tailed). Results: ALDH1+ round/oval cells were associated with low parity in BRCA1/2 carriers (p=0.022), while in non-BRCA1/2-carriers they were negatively associated with nulliparity (p=0.057). In premenopausal women ALDH1+ round/oval cells were associated with family history (p=0.058). SSEA3+ round/oval cells were morphologically and immunohistologically consistent with multilineage stress-enduring (Muse) cells, and these cells were independently associated with the breast cancer risk factors low parity (p=0.015), family history (p=0.021), and hormone use after menopause (p=0.032). ALDH1+ spindle-shaped/polygonal cells were immunohistologically consistent with stellate cells, and were negatively associated with family history of breast cancer (p=0.001). Conclusion: This study identified novel stromal cell types in benign breast tissue that have a potential for stratifying women for breast cancer risk.
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34.
  • Isfoss, Björn Logi, et al. (författare)
  • The absence of aldehyde dehydrogenase 1 A1-positive cells in benign mammary stroma is associated with risk factors for breast cancer
  • 2016
  • Ingår i: Breast Cancer: Targets and Therapy. - 1179-1314. ; 8, s. 117-124
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, aldehyde dehydrogenase 1 (ALDH1)-expressing cells in stroma of histologically normal breast tissue from premenopausal women were investigated in situ regarding cellular morphology, cell distribution, and relation to the additional stem cell markers, CD44 (+) and CD24 (-). These results were correlated with hormonal and genetic risk factors for breast cancer. Triple immunofluorescence labeling was performed on tissues from premenopausal women with a family history of breast cancer, and breast reduction specimens from premenopausal women with no family history of breast cancer were used as a control group. The majority of ALDH1-immunoreactive cells in stroma were spindle-shaped or polygonal, and such cells that were CD44- and CD24- were absent in the breast stroma of a significantly larger number of nulliparous than parous women. A less common morphological type of ALDH1-positive cells in stroma was round or oval in shape, and such cells that were CD44+ and CD24- were absent in a significant number of women with a family history of breast cancer. The CD44+/CD24- immunophenotype is consistent with stem cells, and the round/oval morphology suggests mesenchymal cells. This study demonstrates that there are two morphologically distinct types of ALDH1-positive cells in histologically benign mammary stroma, and the absence of these cells is correlated with clinical risk factors for breast cancer in premenopausal women.
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35.
  • Isfoss, Björn L, et al. (författare)
  • Women with familial risk for breast cancer have an increased frequency of aldehyde dehydrogenase expressing cells in breast ductules
  • 2013
  • Ingår i: BMC Clinical Pathology. - : Springer Science and Business Media LLC. - 1472-6890. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Knowledge is limited regarding the association between stem cells in histologically benign breast tissue and risk factors for breast cancer, and hence we addressed this issue in the present study. Recently, we assessed the histology of benign breast tissue from cancer and non-cancer patients for cells positive for the putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH), and the findings indicated an association between expression of ALDH and the hormonal factors menopause and hormone therapy. The current investigation examined possible associations between various known clinical and genetic risk factors for breast cancer and cellular expression of ALDH in ductules in benign human breast tissue.METHODS: The study included breast surgery patients that were BRCA1/2 mutation carriers without breast cancer (n = 23), had BRCA1/2 (n = 28) or sporadic (n = 21) breast cancer, or required non-cancer-related mammoplasty (n = 34). The distribution and frequency of ALDH-immunolabelled cells were correlated to patient subgroups with different risk factors, using mammoplasty patients as a control group. Statistical analyses comprised linear and logistic regression, Spearman's rank test, Pearson's test, and Fisher's exact test. In two-tailed tests, p < 0.05 was considered significant.RESULTS: A strong association was found between family history of breast cancer and a high frequency of ALDH+ cells (p = 0.001) at all ductular levels in all groups, regardless of BRCA status, age, parity, or occurrence of cancer. In pre-menopausal non-BRCA cancer patients, the frequency of ALDH+ cells increased with age (p < 0.01) but decreased with increasing parity (p < 0.03). High frequencies of ALDH+ cells were found in the non-basal ductular levels in BRCA1 mutation carriers (p = 0.03), but in the basal ductular level in BRCA2 cancer patients (p = 0.02). Among post-menopausal patients, only on-going hormone replacement therapy was correlated with a high number of ALDH+ cells (p < 0.03).CONCLUSION: In histologically normal breast tissue, we found a positive association between the frequency of ductular ALDH+ cells and several breast cancer risk factors, particularly family history of this disease, which supports previous evidence that ALDH plays a role in breast cancer.
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36.
  • Jankovskaja, Skaidre, et al. (författare)
  • Visualisation of H2O2 penetration through skin indicates importance to develop pathway-specific epidermal sensing
  • 2020
  • Ingår i: Microchimica Acta. - : Springer. - 0026-3672 .- 1436-5073. ; 187:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated amounts of reactive oxygen species (ROS) including hydrogen peroxide (H2O2) are observed in the epidermis in different skin disorders. Thus, epidermal sensing of H2O2 should be useful to monitor the progression of skin pathologies. We have evaluated epidermal sensing of H2O2 in vitro, by visualising H2O2 permeation through the skin. Skin membranes were mounted in Franz cells, and a suspension of Prussian white microparticles was deposited on the stratum corneum face of the skin. Upon H2O2 permeation, Prussian white was oxidised to Prussian blue, resulting in a pattern of blue dots. Comparison of skin surface images with the dot patterns revealed that about 74% of the blue dots were associated with hair shafts. The degree of the Prussian white to Prussian blue conversion strongly correlated with the reciprocal resistance of the skin membranes. Together, the results demonstrate that hair follicles are the major pathways of H2O2 transdermal penetration. The study recommends that the development of H2O2 monitoring on skin should aim for pathway-specific epidermal sensing, allowing micrometre resolution to detect and quantify this ROS biomarker at hair follicles. Graphical abstract
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37.
  • Krochak, Paul J., et al. (författare)
  • Headbox induced sheet variability
  • 2017
  • Ingår i: PaperCon 2017. ; , s. 673-680
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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38.
  • Laskar, Pia, 1956- (författare)
  • Ett bidrag till heterosexualitetens historia : Kön, sexualitet och njutningsnormer i sexhandböcker 1800 - 1920
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis examines and analyses Swedish sex manuals written for the most part by doctors between 1800 and 1920. The study focuses on constructions of gender, sexuality and norms for pleasure, and investigates how these processes change over time. A fundamental question raised in the study concerns the descriptions of sexual union between the binary opposed genders and how these descriptions are subsequently connected to medical and scientific ideas during the relevant period. By specifying and drawing attention to these issues, the study makes a contribution to the history of heterosexuality. Special attention is given to sex manuals written by women and published at the turn of the century in 1900.The construction of norms in the sex manuals becomes evident, partly through descriptions of desirable, moderate, sexual behaviour with reference to health, reason, cultural progress and the maximisation of sexual pleasure, and partly through the presentation of deterrents and counter images referring to abnormal, primitive and degenerate genders and sexualities. The construction of a European, middle class gender and sexuality ideal is made apparent in that the norms are also linked to the working class, domestic minorities and other “races”. I call the positive normatisation of heterosexual intercourse an “ideology of pleasure”.According to descriptions in the sex manuals, the boundaries between the opposed genders are often fluid. Therefore the heterosexual union of opposed genders with binary defined sexualities becomes an unstable construction requiring constant stabilisation. During the second half of the 19th Century, when the criterion of reproduction diminished as the defining feature for reciprocal and loving sexual pleasure, the norm for heterosexual pleasure became stabilised by virtue of new arguments. These included the use of strong deterrents against same-gendered sexual activities or masturbation.By juxtaposing the connections between deterrents and taboos against deviant genders and sexualities with descriptions of the division and heterosexual union of the two genders, this investigation makes an empirical contribution to the feminist analysis of the intersection between gender, class and ethnicity in the construction of a heterosexual norm.
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39.
  • Ley, David, et al. (författare)
  • High presence of extracellular hemoglobin in the periventricular white matter following preterm intraventricular hemorrhage
  • 2016
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 7:AUG
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe cerebral intraventricular hemorrhage (IVH) in preterm infants continues to be a major clinical problem, occurring in about 15-20% of very preterm infants. In contrast to other brain lesions the incidence of IVH has not been reduced over the last decade, but actually slightly increased. Currently over 50% of surviving infants develop post-hemorrhagic ventricular dilatation and about 35% develop severe neurological impairment, mainly cerebral palsy and intellectual disability. To date there is no therapy available to prevent infants from developing either hydrocephalus or serious neurological disability. It is known that blood rapidly accumulates within the ventricles following IVH and this leads to disruption of normal anatomy and increased local pressure. However, the molecular mechanisms causing brain injury following IVH are incompletely understood. We propose that extracellular hemoglobin is central in the pathophysiology of periventricular white matter damage following IVH. Using a preterm rabbit pup model of IVH the distribution of extracellular hemoglobin was characterized at 72 h following hemorrhage. Evaluation of histology, histochemistry, hemoglobin immunolabeling and scanning electron microscopy revealed presence of extensive amounts of extracellular hemoglobin, i.e., not retained within erythrocytes, in the periventricular white matter, widely distributed throughout the brain. Furthermore, double immunolabeling together with the migration and differentiation markers polysialic acid neural cell adhesion molecule (PSA-NCAM) demonstrates that a significant proportion of the extracellular hemoglobin is distributed in areas of the periventricular white matter with high extracellular plasticity. In conclusion, these findings support that extracellular hemoglobin may contribute to the pathophysiological processes that cause irreversible damage to the immature brain following IVH.
  •  
40.
  • Mossberg, Anki, et al. (författare)
  • HAMLET Treatment Delays Bladder Cancer Development.
  • 2010
  • Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 183, s. 1590-1597
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. MATERIALS AND METHODS: Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. RESULTS: HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. CONCLUSIONS: Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development.
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41.
  • Na, Manli, et al. (författare)
  • Adenovirus assembly is impaired by BMI1-related histone deacetylase activity.
  • 2014
  • Ingår i: Virology. - : Elsevier BV. - 1096-0341 .- 0042-6822. ; 456:Apr 17, s. 227-237
  • Tidskriftsartikel (refereegranskat)abstract
    • Polycomb ring finger oncogene BMI1 (B cell-specific Moloney murine leukemia virus integration site 1) plays a critical role in development of several types of cancers. Here, we report an inverse relationship between levels of BMI1 expression and adenovirus (Ad) progeny production. Enforced BMI1 expression in A549 cells impaired Ad progeny production. In contrast, knocking-down of endogenous BMI1 expression enhanced progeny production of a conditionally replicating Ad and wild-type Ad5 and Ad11p. Ad vectors overexpressing BMI1 were not impaired in the replication of progeny genomes and in the expression of E1A and Ad structural proteins. However, 293 cells infected by Ad vector overexpressing BMI1 contained a large proportion of morphologically irregular Ad particles. This effect was reversed in 293 cells pre-treated with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) in parallel with the production of infectious Ad particles. Our findings suggest an inhibitory role of BMI1 in Ad morphogenesis that can be implied in Ad tropism and Ad-mediated cancer therapy.
  •  
42.
  • Nielsen, Henrietta, et al. (författare)
  • Binding and Uptake of A beta 1-42 by Primary Human Astrocytes In Vitro
  • 2009
  • Ingår i: GLIA. - : Wiley. - 1098-1136 .- 0894-1491. ; 57:9, s. 978-988
  • Tidskriftsartikel (refereegranskat)abstract
    • Clearance of the amyloid-P peptide (A beta) as a remedy for Alzheimer's disease (AD) is a major target in on-going clinical trials. In vitro studies confirmed that A beta is taken up by rodent astrocytes, but knowledge on human astrocyte-mediated A beta clearance is sparse. Therefore, by means of flow cytometry and confocal laser scanning microscopy (CLSM), we evaluated the binding and internalization of A beta 1-42 by primary human fetal astrocytes and adult astrocytes, isolated from nondemented subjects (n = 8) and AD subjects (n = 6). Furthermore, we analyzed whether alpha 1-antichymotrypsin (ACT), which is found in amyloid plaques and can influence A beta fibrillogenesis, affects the A beta uptake by human astrocytes. Upon over night exposure of astrocytes to FAM-labeled A beta 1-42 (10 mu M) preparations, (80.7 +/- 17.7)% fetal and (52.9 +/- 20.9)% adult A beta-positive astrocytes (P = 0.018) were observed. No significant difference was found in A beta 1-42 uptake between AD and non-AD astrocytes, and no influence of ApoE genotype on A beta 1-42 uptake was observed in any group. There was no difference in the percentage of A beta-positive cells upon exposure to A beta 1-42 (10 mu M) combined with ACT (1,000:1, 100:1, and 10:1 molar ratio), versus A beta 1-42 alone. CLSM revealed binding of A beta 1-42 to the cellular surfaces and cellular internalization of smaller A beta 1-42 fragments. Under these conditions, there was no increase in cellular release of the proinflammatory chemokine monocyte-chemoattractant protein 1, as compared with nontreated control astrocytes. Thus, primary human astrocytes derived from different sources can bind and internalize A beta 1-42, and fetal astrocytes were more efficient in A beta 1-42 uptake than adult astrocytes. (C) 2008 Wiley-Liss, Inc.
  •  
43.
  • Ny, Lars, 1967, et al. (författare)
  • A magnetic resonance imaging study of intestinal dilation in Trypanosoma cruzi-infected mice deficient in nitric oxide synthase.
  • 2008
  • Ingår i: The American journal of tropical medicine and hygiene. - 1476-1645. ; 79:5, s. 760-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Infection with Trypanosoma cruzi causes megasyndromes of the gastrointestinal (GI) tract. We used magnetic resonance imaging (MRI) to monitor alterations in the GI tract of T. cruzi-infected mice, and to assess the role of nitric oxide (NO) in the development of intestinal dilation. Brazil strain-infected C57BL/6 wild-type (WT) mice exhibited dilatation of the intestines by 30 days post-infection. Average intestine lumen diameter increased by 72%. Levels of intestinal NO synthase (NOS) isoforms, NOS2 and NOS3, were elevated in infected WT mice. Inflammation and ganglionitis were observed in all infected mice. Intestinal dilation was observed in infected WT, NOS1, NOS2, and NOS3 null mice. This study demonstrates that MRI is a useful tool to monitor intestinal dilation in living mice and that these alterations may begin during acute infection. Furthermore, our data strongly suggests that NO may not be the sole contributor to intestinal dysfunction resulting from this infection.
  •  
44.
  • Ortenlöf, Niklas, et al. (författare)
  • Characterization of choroid plexus in the preterm rabbit pup following subcutaneous administration of recombinant human IGF-1/IGFBP-3
  • 2023
  • Ingår i: Fluids and Barriers of the CNS. - 2045-8118. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. Importantly, preterm birth is associated with reduced serum levels of IGF-1 as compared to in utero levels. Using a preterm rabbit pup model, we investigated the uptake of systemic recombinant human (rh) IGF-1 in complex with its main binding protein IGF-binding protein 3 (BP-3) to the brain parenchyma via the choroid plexus. Five hours after subcutaneous administration, labeled rhIGF-1/rhIGFBP-3 displayed a widespread presence in the choroid plexus of the lateral and third ventricle, however, to a less degree in the fourth, as well as in the perivascular and subarachnoid space. We found a time-dependent uptake of IGF-1 in cerebrospinal fluid, decreasing with postnatal age, and a translocation of IGF-1 through the choroid plexus. The impact of systemic rhIGF-1/rhIGFBP-3 on IGF-1 receptor activation in the choroid plexus decreased with postnatal age, correlating with IGF-1 uptake in cerebrospinal fluid. In addition, choroid plexus gene expression was observed to increase with postnatal age. Moreover, using choroid plexus in vitro cell cultures, gene expression and protein synthesis were further investigated upon rhIGF-1/rhIGFBP-3 stimulation as compared to rhIGF-1 alone, and found not to be differently altered. Here, we characterize the uptake of systemic rhIGF-1/rhIGFBP-3 to the preterm brain, and show that the interaction between systemic rhIGF-1/rhIGFBP-3 and choroid plexus varies over time.
  •  
45.
  • Persson, Oscar, et al. (författare)
  • Distribution, cellular localization, and therapeutic potential of the tumor-associated antigen Ku70/80 in glioblastoma multiforme.
  • 2010
  • Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 97, s. 207-215
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibodies specifically targeting tumor-associated antigens have proved to be important tools in the treatment of human cancer. A desirable target antigen should be unique to tumor cells, abundantly expressed, and readily available for antibody binding. The Ku70/80 DNA-repair protein is expressed in the nucleus of most cells; it is, however, also present on the cell surface of tumor cell lines, and antibodies binding Ku70/80 at the cell surface were recently shown to internalize into tumor cells. To evaluate the potential of Ku70/80-antigen as a therapeutic target for immunotoxins in glioblastoma multiforme, we investigated binding and localization of Ku70/80-specific antibodies in tissue samples from glioblastomas and normal human brains, and in glioma cell cultures. Furthermore, the internalization and drug-delivery capacity were evaluated by use of immunotoxicity studies. We demonstrate that Ku70/80 is localized on the cell plasma membrane of glioma cell lines, and is specifically present in human glioblastoma tissue. Antibodies bound to the Ku70/80 antigen on the cell surface of glioma cells were found to internalize via endocytosis, and shown to efficiently deliver toxins into glioblastoma cells. The data further imply that different antibodies directed against Ku70/80 possess different abilities to target the antigen, in relation to its presentation on the cell surface or intracellular localization. We conclude that Ku70/80 antigen is uniquely presented on the plasma membrane in glioblastomas, and that antibodies specific against the antigen have the capacity to selectively bind, internalize, and deliver toxins into tumor cells. These results imply that Ku70/80 is a potential target for immunotherapy of glioblastoma multiforme.
  •  
46.
  • Rebetz, Johan, et al. (författare)
  • Fiber mediated receptor masking in non-infected bystander cells restricts adenovirus cell killing effect but promotes adenovirus host co-existence.
  • 2009
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:12
  • Tidskriftsartikel (refereegranskat)abstract
    • The basic concept of conditionally replicating adenoviruses (CRAD) as oncolytic agents is that progenies generated from each round of infection will disperse, infect and kill new cancer cells. However, CRAD has only inhibited, but not eradicated tumor growth in xenograft tumor therapy, and CRAD therapy has had only marginal clinical benefit to cancer patients. Here, we found that CRAD propagation and cancer cell survival co-existed for long periods of time when infection was initiated at low multiplicity of infection (MOI), and cancer cell killing was inefficient and slow compared to the assumed cell killing effect upon infection at high MOI. Excessive production of fiber molecules from initial CRAD infection of only 1 to 2% cancer cells and their release prior to the viral particle itself caused a tropism-specific receptor masking in both infected and non-infected bystander cells. Consequently, the non-infected bystander cells were inefficiently bound and infected by CRAD progenies. Further, fiber overproduction with concomitant restriction of adenovirus spread was observed in xenograft cancer therapy models. Besides the CAR-binding Ad4, Ad5, and Ad37, infection with CD46-binding Ad35 and Ad11 also caused receptor masking. Fiber overproduction and its resulting receptor masking thus play a key role in limiting CRAD functionality, but potentially promote adenovirus and host cell co-existence. These findings also give important clues for understanding mechanisms underlying the natural infection course of various adenoviruses.
  •  
47.
  • Svensson, Majlis, et al. (författare)
  • Acute pyelonephritis and renal scarring are caused by dysfunctional innate immunity in mCxcr2 heterozygous mice.
  • 2011
  • Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 80:10, s. 1064-1072
  • Tidskriftsartikel (refereegranskat)abstract
    • The CXCR1 receptor and chemokine CXCL8 (IL-8) support neutrophil-dependent clearance of uropathogenic Escherichia coli from the urinary tract. CXCR1 is reduced in children prone to pyelonephritis, and heterozygous hCXCR1 polymorphisms are more common in this patient group than in healthy individuals, strongly suggesting a disease association. Since murine CXCR2 (mCXCR2) is functionally similar to human CXCR1, we determined effects of gene heterozygosity on the susceptibility to urinary tract infection by infecting heterozygous (mCxcr2(+/-)) mice with uropathogenic Escherichia coli. Clearance of infection and tissue damage were assessed as a function of innate immunity in comparison to that in knockout (mCxcr2(-/-)) and wild-type (mCxcr2(+/+)) mice. Acute sepsis-associated mortality was increased and bacterial clearance drastically impaired in heterozygous compared to wild-type mice. Chemokine and neutrophil responses were delayed along with evidence of neutrophil retention and unresolved kidney inflammation 1 month after infection. This was accompanied by epithelial proliferation and subepithelial fibrosis. The heterozygous phenotype was intermediate, between knockout and wild-type mice, but specific immune cell infiltrates that accompany chronic infection in knockout mice were not found. Hence, the known heterozygous CXCR1 polymorphisms may predispose patients to acute pyelonephritis and urosepsis.
  •  
48.
  •  
49.
  • Thorén, Matilda Munksgaard, et al. (författare)
  • Integrin α10, a novel therapeutic target in glioblastoma, regulates cell migration, proliferation, and survival
  • 2019
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • New, effective treatment strategies for glioblastomas (GBMs), the most malignant and invasive brain tumors in adults, are highly needed. In this study, we investigated the potential of integrin α10Β1 as a therapeutic target in GBMs. Expression levels and the role of integrin α10Β1 were studied in patient-derived GBM tissues and cell lines. The effect of an antibody-drug conjugate (ADC), an integrin a10 antibody conjugated to saporin, on GBM cells and in a xenograft mouse model was studied. We found that integrin α10Β1 was strongly expressed in both GBM tissues and cells, whereas morphologically unaffected brain tissues showed only minor expression. Partial or no overlap was seen with integrins α3, α6, and α7, known to be expressed in GBM. Further analysis of a subpopulation of GBM cells selected for high integrin α10 expression demonstrated increased proliferation and sphere formation. Additionally, siRNA-mediated knockdown of integrin α10 in GBM cells led to decreased migration and increased cell death. Furthermore, the ADC reduced viability and sphere formation of GBM cells and induced cell death both in vitro and in vivo. Our results demonstrate that integrin α10Β1 has a functional role in GBM cells and is a novel, potential therapeutic target for the treatment of GBM.
  •  
50.
  • Van der Veeken, Lennart, et al. (författare)
  • Long-term neurological effects of neonatal caffeine treatment in a rabbit model of preterm birth
  • 2020
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 87:6, s. 1011-1018
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neonatal caffeine treatment might affect brain development. Long-term studies show conflicting results on brain-related outcomes. Herein we aimed to investigate the long-term effects of neonatal caffeine administration in a rabbit model of preterm birth. Methods: Preterm (born day 29) and term (day 32) pups were raised by wet nurses and allocated to treatment with saline or caffeine for 7 or 17 days. At pre-puberty, neurobehavioral tests were performed and brains were harvested for immunostaining of neurons, synapses, myelin, and astrocytes. Results: Survival was lower in preterm saline pups than in controls, whereas caffeine-treated preterm pups did not differ from term control pups. Preterm saline pups covered less distance compared to controls and were more likely to stay in the peripheral zone of the open field. Corresponding differences were not seen in preterm caffeine pups. Preterm animals had lower neuron density compared to controls, which was not influenced by caffeine treatment. Synaptic density, astrocytes, and myelin were not different between groups. Conclusion: Caffeine appeared to be safe. All preterm rabbits had lower neuron density but anxious behavior seen in preterm saline rabbits was not seen in caffeine-treated preterm pups.
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