| 1. |
- Pettersson, Ann, et al.
(författare)
-
Chromogranins can be measured in samples from cats and dogs
- 2014
-
Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Methods for objective evaluation of stress in animals are important, but clinically difficult. An alternative method to study the sympathetic activity may be to investigate Chromogranin A (CGA), Chromogranin B (CGB) and Secretogranin II (SG2). The aim of this study was to investigate the cross-reactivity of CGA, CGB and SG2 between man, cat and dog and to explore possibilities to measure these proteins in samples from cats and dogs. Results: Adrenal gland extracts from feline and canine species were measured by region-specific radioimmunoassays in different dilution steps to explore possible inter species cross reactivity. High cross reactivity was found for cats in the CGA17-38, CGA324-337, CGA361-372, CGB and SG2 assays. High cross reactivity was found for dogs in the CGA17-38, CGA361-372, CGB and SN assays. The method measuring the intact CGA was not useful for measurements in cats and dogs. Conclusions: Region-specific assays measuring defined parts of CGA, CGB and SG2 can be used for measurements in samples from cats and dogs. These results are promising and will allow for further studies of these proteins as possible clinical biomarkers in cats and dogs. Keywords: Chromogranin, Secretogranin, Canine, Feline, Human, Radioimmunoassay
|
|
| 2. |
- Johansson, Anna Maria, et al.
(författare)
-
Variation in the VWF Gene in Swedish Patients with Type 1 von Willebrand Disease.
- 2011
-
Ingår i: Annals of Human Genetics. - : Wiley. - 1469-1809 .- 0003-4800. ; 75, s. 447-455
-
Tidskriftsartikel (refereegranskat)abstract
- The spectrum of mutations in the von Willebrand factor (VWF) gene in a Swedish type 1 von Willebrand disease (VWD) population was investigated. To gain more knowledge about the dynamics of VWD mutations, the data were analyzed from a population genetics perspective. The VWF gene was resequenced in 54 Swedish patients diagnosed with type 1 VWD. Fifty-five variable sites were located in exons, 10 in the promoter and 38 in introns. The spectrum of mutations was similar to a European study, but included 10 new candidate mutations. The synonymous sites were evenly distributed along the coding sequence, whereas nonsynonymous sites were located into three clusters. Overall, 44% of patients had no mutations or candidate mutations and no promoter haplotype was significantly associated with disease. In 11 patients (20%), more than one mutation or candidate mutation was detected. The allelic identity for the putative disease-causing mutations was approximately 0.1, compatible with an overall disease frequency of 1%. VWF sequences for exon 28 from eight monkey species were compared with the variable positions found in our patients. Positions classified as mutations were overrepresented among sites that were fixed in all eight monkey species. No general increase of the mutation rate was found for the pseudogene region.
|
|
| 3. |
- Fryknäs, Mårten, et al.
(författare)
-
Iron chelators target both proliferating and quiescent cancer cells
- 2016
-
Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Poorly vascularized areas of solid tumors contain quiescent cell populations that are resistant to cell cycle-active cancer drugs. The compound VLX600 was recently identified to target quiescent tumor cells and to inhibit mitochondrial respiration. We here performed gene expression analysis in order to characterize the cellular response to VLX600. The compound-specific signature of VLX600 revealed a striking similarity to signatures generated by compounds known to chelate iron. Validation experiments including addition of ferrous and ferric iron in excess, EXAFS measurements, and structure activity relationship analyses showed that VLX600 chelates iron and supported the hypothesis that the biological effects of this compound is due to iron chelation. Compounds that chelate iron possess anti-cancer activity, an effect largely attributed to inhibition of ribonucleotide reductase in proliferating cells. Here we show that iron chelators decrease mitochondrial energy production, an effect poorly tolerated by metabolically stressed tumor cells. These pleiotropic features make iron chelators an attractive option for the treatment of solid tumors containing heterogeneous populations of proliferating and quiescent cells.
|
|
| 4. |
- Rotter Sopasakis, Victoria, 1972, et al.
(författare)
-
Elevated Glucose Levels Preserve Glucose Uptake, Hyaluronan Production, and Low Glutamate Release Following Interleukin-1 beta Stimulation of Differentiated Chondrocytes
- 2019
-
Ingår i: Cartilage. - : SAGE Publications. - 1947-6035 .- 1947-6043. ; 10:4, s. 491-503
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Chondrocytes are responsible for remodeling and maintaining the structural and functional integrity of the cartilage extracellular matrix. Because of the absence of a vascular supply, chondrocytes survive in a relatively hypoxic environment and thus have limited regenerative capacity during conditions of cellular stress associated with inflammation and matrix degradation, such as osteoarthritis (OA). Glucose is essential to sustain chondrocyte metabolism and is a precursor for key matrix components. In this study, we investigated the importance of glucose as a fuel source for matrix repair during inflammation as well as the effect of glucose on inflammatory mediators associated with osteoarthritis. Design To create an OA model, we used equine chondrocytes from 4 individual horses that were differentiated into cartilage pellets in vitro followed by interleukin-1 beta (IL-1 beta) stimulation for 72 hours. The cells were kept at either normoglycemic conditions (5 mM glucose) or supraphysiological glucose concentrations (25 mM glucose) during the stimulation with IL-1 beta. Results We found that elevated glucose levels preserve glucose uptake, hyaluronan synthesis, and matrix integrity, as well as induce anti-inflammatory actions by maintaining low expression of Toll-like receptor-4 and low secretion of glutamate. Conclusions Adequate supply of glucose to chondrocytes during conditions of inflammation and matrix degradation interrupts the detrimental inflammatory cycle and induces synthesis of hyaluronan, thereby promoting cartilage repair.
|
|
| 5. |
- Svala, Emilia, et al.
(författare)
-
Characterisation of lubricin in synovial fluid from horses with osteoarthritis.
- 2017
-
Ingår i: Equine veterinary journal. - : Wiley. - 2042-3306 .- 0425-1644. ; 49:1, s. 116-123
-
Tidskriftsartikel (refereegranskat)abstract
- The glycoprotein lubricin contributes to the boundary lubrication of the articular cartilage surface. The early events of osteoarthritis involve the superficial layer where lubricin is synthesised.To characterise the glycosylation profile of lubricin in synovial fluid from horses with osteoarthritis and study secretion and degradation of lubricin in an in vitro inflammation cartilage model.In vitro study.Synovial fluid samples collected from horses with joints with normal articular cartilage and structural osteoarthritic lesions; with and without osteochondral fragments, were analysed for the lubricin glycosylation profiles. Articular cartilage explants were stimulated with or without interleukin-1β for 25 days. Media samples collected at 3-day intervals were analysed by quantitative proteomics, western blot and enzyme-linked immunosorbent assay.O-glycosylation profiles in synovial fluid revealed both Core 1 and 2 O-glycans, with Core 1 O-glycans predominating. Synovial fluid from normal joints (49.5 ± 1.9%) contained significantly lower amounts of monosialylated Core 1 O-glycans compared with joints with osteoarthritis (53.8 ± 7.8%, P = 0.03) or joints with osteochondral fragments (57.3 ± 8.8%, P = 0.001). Additionally, synovial fluid from normal joints (26.7 ± 6.7%) showed higher amounts of disialylated Core 1 O-glycan than from joints with osteochondral fragments (21.2 ± 4.9%, P = 0.03). A C-terminal proteolytic cleavage site in lubricin was found in synovial fluid from normal and osteochondral fragment joints and in media from interleukin-1β stimulated and unstimulated articular cartilage explants.This is the first demonstration of a change in the glycosylation profile of lubricin in synovial fluid from diseased equine joints compared with that from normal joints. We demonstrate an identical proteolytic cleavage site of lubricin both in vitro and in vivo. The reduced sialation of lubricin in synovial fluid from diseased joints may affect the boundary lubricating ability of the superficial layer of articular cartilage and could be one of the early events in the progression of osteoarthritis.
|
|
| 6. |
- Hansson, Elisabeth, 1955, et al.
(författare)
-
Coupled cell networks are target cells of inflammation, which can spread between different body organs and develop into systemic chronic inflammation
- 2015
-
Ingår i: Journal of Inflammation-London. - : Springer Science and Business Media LLC. - 1476-9255. ; 12
-
Forskningsöversikt (refereegranskat)abstract
- Several organs in the body comprise cells coupled into networks. These cells have in common that they are excitable but do not express action potentials. Furthermore, they are equipped with Ca2+ signaling systems, which can be intercellular and/or extracellular. The transport of small molecules between the cells occurs through gap junctions comprising connexin 43. Examples of cells coupled into networks include astrocytes, keratinocytes, chondrocytes, synovial fibroblasts, osteoblasts, connective tissue cells, cardiac and corneal fibroblasts, myofibroblasts, hepatocytes, and different types of glandular cells. These cells are targets for inflammation, which can be initiated after injury or in disease. If the inflammation reaches the CNS, it develops into neuroinflammation and can be of importance in the development of systemic chronic inflammation, which can manifest as pain and result in changes in the expression and structure of cellular components. Biochemical parameters of importance for cellular functions are described in this review.
|
|
| 7. |
- Broberg, Anders, et al.
(författare)
-
Labradorins with antibacterial activity produced by Pseudomonas sp.
- 2017
-
Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 22
-
Tidskriftsartikel (refereegranskat)abstract
- The urgent need for new antibacterial drugs has led to renewed interest in microorganisms, which historically have been the main source of previously discovered antibiotics. The present study describes the discovery of two new antibacterial oxazolylindole type alkaloids, labradorins 5 (1) and 6 (2), which were isolated and characterized from two isolates of Pseudomonas sp., along with four previously known tryptophane derived alkaloids. The structures of 1 and 2 were determined by NMR spectroscopy and MS, and confirmed by synthesis. During bioassay-guided isolation using several human bacterial pathogens, 1 and 2 displayed activity towards Staphylococcus aureus and Acinetobacter baumannii. The minimal inhibitory concentrations (MIC) of compounds 1 and 2 against S. aureus were 12 mu g.mL(-1) and 50 mu g.mL(-1), respectively, whereas the MICs against A. baumannii were > 50 mu g.mL(-1). The CC50 values of compound 1 towards a liver cell line (HEP-G2) and a T-cell line (MT4) were 30 mu g.mL(-1) and 20 mu g.mL(-1), respectively, and for compound 2 were > 100 mu g.mL(-1) and 20 mu g.mL(-1), respectively. Due to the limited potency of compounds 1 and 2, along with their toxicity, the compounds do not warrant further development towards new antibiotics.
|
|
| 8. |
- Carlsson, Magnus L.R., et al.
(författare)
-
Expression, Purification and Initial Characterization of Functional α1-Microglobulin (A1M) in Nicotiana benthamiana
- 2020
-
Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- α1-Microglobulin (A1M) is a small glycoprotein that belongs to the lipocalin protein family. A major biological role of A1M is to protect cells and tissues against oxidative damage by clearing free heme and reactive oxygen species. Because of this, the protein has attracted great interest as a potential pharmaceutical candidate for treatment of acute kidney injury and preeclampsia. The aim of this study was to explore the possibility of expressing human A1M in plants through transient gene expression, as an alternative or complement to other expression systems. E. coli, insect and mammalian cell culture have previously been used for recombinant A1M (rA1M) or A1M production, but these systems have various drawbacks, including additional complication and expense in refolding for E. coli, while insect produced rA1M is heavily modified with chromophores and mammalian cell culture has been used only in analytical scale. For that purpose, we have used a viral vector (pJL-TRBO) delivered by Agrobacterium for expression of three modified A1M gene variants in the leaves of N. benthamiana. The results showed that these modified rA1M protein variants, A1M-NB1, A1M-NB2 and A1M-NB3, targeted to the cytosol, ER and extracellular space, respectively, were successfully expressed in the leaves, which was confirmed by SDS-PAGE and Western blot analysis. The cytosol accumulated A1M-NB1 was selected for further analysis, as it appeared to have a higher yield than the other variants, and was purified with a yield of ca. 50 mg/kg leaf. The purified protein had the expected structural and functional properties, displaying heme-binding capacity and capacity of protecting red blood cells against stress-induced cell death. The protein also carried bound chromophores, a characteristic feature of A1M and an indicator of a capacity to bind small molecules. The study showed that expression of the functional protein in N. benthamiana may be an attractive alternative for production of rA1M for pharmaceutical purposes and a basis for future research on A1M structure and function.
|
|
| 9. |
- Eriksson, Staffan
(författare)
-
Thymidine kinase 1 expression in atypical ductal hyperplasia significantly differs from usual ductal hyperplasia and ductal carcinoma in situ: A useful tool in tumor therapy management
- 2009
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 2, s. 923-929
-
Tidskriftsartikel (refereegranskat)abstract
- Thymidine kinase 1 (TK1) is an enzyme involved in the synthesis of DNA precursors. In studies using immunohistochemistry, it was reported to be a more useful proliferation marker than Ki-67 and PCNA in breast, lung and colorectal carcinoma. In this study, we extend the work of prior breast carcinoma studies by investigating the expression of TK1 in 132 patients with usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). TK1 and Ki-67 expression were determined with monoclonal antibodies using the SP technique. The expression of TK1 was found to be significantly increased in the breast ductal carcinomas in the following manner: UDH
|
|
| 10. |
- Frøbert, Anne Mette, et al.
(författare)
-
Hypothyroidism in hibernating brown bears
- 2023
-
Ingår i: Thyroid Research. - : BioMed Central (BMC). - 1756-6614. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- Brown bears hibernate throughout half of the year as a survival strategy to reduce energy consumption during prolonged periods with scarcity of food and water. Thyroid hormones are the major endocrine regulators of basal metabolic rate in humans. Therefore, we aimed to determine regulations in serum thyroid hormone levels in hibernation compared to the active state to investigate if these are involved in the adaptions for hibernation.We used electrochemiluminescence immunoassay to quantify total triiodothyronine (T3) and thyroxine (T4) levels in hibernation and active state in paired serum samples from six subadult Scandinavian brown bears. Additionally, we determined regulations in the liver mRNA levels of three major thyroid hormone-binding proteins; thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin, by analysis of previously published grizzly bear RNA sequencing data.We found that bears were hypothyroid when hibernating with T4 levels reduced to less than 44% (P = 0.008) and T3 levels reduced to less than 36% (P = 0.016) of those measured in the active state. In hibernation, mRNA levels of TBG and albumin increased to 449% (P = 0.031) and 121% (P = 0.031), respectively, of those measured in the active state. TTR mRNA levels did not change.Hibernating bears are hypothyroid and share physiologic features with hypothyroid humans, including decreased basal metabolic rate, bradycardia, hypothermia, and fatigue. We speculate that decreased thyroid hormone signaling is a key mediator of hibernation physiology in bears. Our findings shed light on the translational potential of bear hibernation physiology to humans for whom a similar hypometabolic state could be of interest in specific conditions.
|
|
