Browsing by Subject "bone"

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  • Helsingin yliopisto, kulttuurien tutkimuksen laitos, arkeologia (The University of Helsinki, Institute for Cultural Research, Archaeology, 2002)
  • Helsingin yliopisto, kulttuurien tutkimuksen laitos, arkeologia (The University of Helsinki, Institute for Cultural Research, Archaeology, 2002)
  • Purisha, Zenith; Karhula, Sakari S.; Ketola, Juuso H.; Rimpeläinen, Juho; Nieminen, Miika T.; Saarakkala, Simo; Kröger, Heikki; Siltanen, Samuli (2019)
    X-ray tomography is a reliable tool for determining the inner structure of 3-D object with penetrating X-rays. However, traditional reconstruction methods, such as Feldkamp-Davis-Kress (FDK), require dense angular sampling in the data acquisition phase leading to long measurement times, especially in X-ray micro-tomography to obtain high-resolution scans. Acquiring less data using greater angular steps is an obvious way for speeding up the process and avoiding the need to save huge data sets. However, computing 3-D reconstruction from such a sparsely sampled data set is difficult because the measurement data are usually contaminated by errors, and linear measurement models do not contain sufficient information to solve the problem in practice. An automatic regularization method is proposed for robust reconstruction, based on enforcing sparsity in the 3-D shearlet transform domain. The inputs of the algorithm are the projection data and a priori known expected degree of sparsity, denoted as 0 <C-pr
  • Arvola, Samuli; Seppänen, Marko; Malaspina, Simona; Mätzke, Sorjo; Raiko, Juho; Timonen, Kirsi L.; Ettala, Otto; Jambor, Ivan; Anttinen, Mikael; Kuisma, Anna; Löyttyniemi, Eliisa; Boström, Peter J.; Sohlberg, Antti; Noponen, Tommi (2022)
    Objective The aim of this study was to compare reprojected bone SPECT/CT (RBS) against planar bone scintigraphy (BS) in the detection of bone metastases in breast and prostate cancer patients. Methods Twenty-six breast and 105 prostate cancer patients with high risk for bone metastases underwent Tc-99m-HMDP BS and whole-body SPECT/CT, 1.5-T whole-body diffusion-weighted MRI and F-18-NaF or F-18-PSMA-1007 PET/CT within two prospective clinical trials (NCT01339780 and NCT03537391). Consensus reading of all imaging modalities and follow-up data were used to define the reference standard diagnosis. The SPECT/CT data were reprojected into anterior and posterior views to produce RBS images. Both BS and RBS images were independently double read by two pairs of experienced nuclear medicine physicians. The findings were validated against the reference standard diagnosis and compared between BS and RBS on the patient, region and lesion levels. Results All metastatic patients detected by BS were also detected by RBS. In addition, three metastatic patients were missed by BS but detected by RBS. The average patient-level sensitivity of two readers for metastases was 75% for BS and 87% for RBS, and the corresponding specificity was 79% for BS and 39% for RBS. The average region-level sensitivity of two readers was 64% for BS and 69% for RBS, and the corresponding specificity was 96% for BS and 87% for RBS. Conclusion Whole-body bone SPECT/CT can be reprojected into more familiar anterior and posterior planar images with excellent sensitivity for bone metastases, making additional acquisition of planar BS unnecessary.
  • Salminen, Anniina (Helsingin yliopisto, 2022)
    Osteoporoosi on luuston sairaus, jossa luun rakenne on heikentynyt lisäten murtumariskiä. Perimällä on keskeinen rooli luuston kehityksessä. Osteoporoosin ajatellaan olevan polygeneettinen tauti, mutta on tunnistettu myös yksittäisiä geenejä, joiden muutokset voivat johtaa osteoporoosin. KIF26B-geenin on raportoitu olevan uusi luuston terveydelle merkittävä tekijä ja sen yhden nonsense-variantin (p.Q287X) on raportoitu aiheuttavan primaaria osteoporoosia. Tämän tutkimuksen tarkoituksena oli kuvata kattava kirjallisuuskatsaus luuston terveyteen vaikuttavista ja osteoporoosin kehittymiselle altistavista geneettisistä tekijöistä sekä kuvata KIF26B-geenin varianttien luonnetta ja yleisyyttä primaari osteopoorosipotilailla. Aineisto koostui yhteensä 21:stä primaari osteoporoosia sairastavasta potilaasta (10 miestä; ikäjakauma 8–71 v). Heiltä kaikilta Sanger-sekvensointiin koko KIF26B-geeni. Sekvensoinnissa havaittiin 17 varianttia, joista 14 sijaitsi eksonin alueella. Eksonin alueella sijainneista varianteista viisi oli missense-varianttia, aiheuttaen muutoksen kodonin koodaamassa aminohapossa. Varianttien tarkemman analysoinnin perusteella varianteista neljä viidestä oli beningnejä. Yksi varianteista (P.Pro1775Arg) voisi mahdollisesti olla proteiinin toiminnan kannalta haitallinen, mutta variantin mahdollinen patogeenisuus jäi avoimeksi tämän tutkimuksen puitteissa. Potilailta ei löytynyt aiemmin havaittua primaaria osteoporoosia aiheuttavaa nonsense-varianttia (p.Q287X). Tutkimuksessa ei löydetty muita potentiaalisia, patogeeniksi tutkittavia variantteja selittämään potilaiden primaaria osteoporoosia.
  • Tolkachov, Alexander; Fischer, Cornelius; Ambrosi, Thomas H.; Bothe, Melissa; Han, Chung-Ting; Muenzner, Matthias; Mathia, Susanne; Salminen, Marjo; Seifert, Georg; Thiele, Mario; Duda, Georg N.; Meijsing, Sebastiaan H.; Sauer, Sascha; Schulz, Tim J.; Schupp, Michael (2018)
    The transcription factor GATA2 is required for expansion and differentiation of hematopoietic stem cells (HSCs). In mesenchymal stem cells (MSCs), GATA2 blocks adipogenesis, but its biological relevance and underlying genomic events are unknown. We report a dual function of GATA2 in bone homeostasis. GATA2 in MSCs binds near genes involved in skeletal system development and colocalizes with motifs for FOX and HOX transcription factors, known regulators of skeletal development. Ectopic GATA2 blocks osteoblastogenesis by interfering with SMAD1/5/8 activation. MSC-specific deletion of GATA2 in mice increases the numbers and differentiation capacity of bone-derived precursors, resulting in elevated bone formation. Surprisingly, MSC-specific GATA2 deficiency impairs the trabecularization and mechanical strength of bone, involving reduced MSC expression of the osteoclast inhibitor osteoprotegerin and increased osteoclast numbers. Thus, GATA2 affects bone turnover via MSC-autonomous and indirect effects. By regulating bone trabecularization, GATA2 expression in the osteogenic lineage may contribute to the anatomical and cellular microenvironment of the HSC niche required for hematopoiesis.
  • Imhof, Thomas; Balic, Anamaria; Heilig, Juliane; Chiquet-Ehrismann, Ruth; Chiquet, Matthias; Niehoff, Anja; Brachvogel, Bent; Thesleff, Irma; Koch, Manuel (2021)
    The continuously growing mouse incisor provides a fascinating model for studying stem cell regulation and organ renewal. In the incisor, epithelial and mesenchymal stem cells assure lifelong tooth growth. The epithelial stem cells reside in a niche known as the cervical loop. Mesenchymal stem cells are located in the nearby apical neurovascular bundle and in the neural plexus. So far, little is known about extracellular cues that are controlling incisor stem cell renewal and guidance. The extracellular matrix protein tenascin-W, also known as tenascin-N (TNN), is expressed in the mesenchyme of the pulp and of the periodontal ligament of the incisor, and is closely associated with collagen 3 fibers. Here, we report for the first time the phenotype of tenascin-W/TNN deficient mice, which in a C57BL/6N background exhibit a reduced body weight and lifespan. We found major defects in the alveolar bone and periodontal ligament of the growing rodent incisors, whereas molars were not affected. The alveolar bone around the incisor was replaced by a dense scar-like connective tissue, enriched with newly formed nerve fibers likely leading to periodontal pain, less food intake and reduced body weight. Using soft food to reduce mechanical load on the incisor partially rescued the phenotype. In situ hybridization and Gli1 reporter mouse experiments revealed decreased hedgehog signaling in the incisor mesenchymal stem cell compartment, which coordinates the development of mesenchymal stem cell niche. These results indicate that TNN deficiency in mice affects periodontal remodeling and increases nerve fiber branching. Through periodontal pain the food intake is reduced and the incisor renewal and the neurovascular sonic hedgehog secretion rate are reduced. In conclusion, tenascin-W/TNN seems to have a primary function in rapid periodontal tissue remodeling and a secondary function in mechanosensation.
  • Laakso, Saila; Borchers, Joonatan; Toiviainen-Salo, Sanna; Pekkinen, Minna; Mäkitie, Outi (2020)
    Objective: Immunological abnormalities, the resulting endocrinopathies and their treatments may impact bone health in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS1). The aim of the present study was to describe skeletal characteristics in patients with APECED and the prevalence and risk factors of compromised bone health. Patients and methods: We performed a cross-sectional study on 44 patients (27 females) with APECED and 82 age-, gender- and ethnicity-matched control subjects (54 females). We determined the prevalence of osteoporosis by dual-energy X-ray absorptiometry and skeletal characteristics by peripheral quantitative computed tomography at radius and tibia. Results: Patients were examined at the median age of 37.8 years (range, 7.0-70.1). Dual-energy X-ray absorptiometry indicated osteoporosis in four adult patients (9%); radiographs showed vertebral fractures in three patients. The prevalence of multiple non-spinal fractures was higher in patients than in controls. On peripheral quantitative computed tomography, bone characteristics at distal and proximal radius did not differ between the groups. At distal tibia, patients had lower total (p = 0.009) and trabecular (p = 0.033) volumetric bone mineral density. At the proximal tibia, patients had lower cortical thickness (p <0.001) than controls. Severity of APECED phenotype influenced both radial and tibial characteristics: cortical thickness and total and trabecular volumetric bone mineral density were lower in patients with >= 7 disease manifestations as compared with more mildly affected patients, whose values were similar to controls. Conclusions: APECED associated with bone structural alterations, especially in patients with a high number of disease manifestations. This may increase the risk of fractures with aging, but symptomatic osteoporosis was rare.
  • Richardt, Sampo (Helsingin yliopisto, 2021)
    Recently, mutations in the SGMS2 gene were shown to result in a rare disease known as osteoporosis with calvarial doughnut lesions. Affected patients present with severe, early-onset osteoporosis or skeletal dysplasia depending on the underlying mutation. In addition to the skeletal manifestations, patients also exhibit neurological symptoms, most commonly transient, spontaneously remitting, and recurring cranial nerve palsies. Similar neurological characteristics have previously been described in another rare condition known as Melkersson-Rosenthal syndrome (MRS). The objectives of this thesis were to provide a comprehensive review of literature on the role of sphingomyelin (SM) metabolism in the skeletal and central nervous systems and characterize the nature and prevalence of SGMS2 variants in cohorts of 14 Finnish MRS patients and 47 Finnish primary osteoporosis patients. The literature review explores the currently available data on SM metabolism in basic and clinical research. In bone, SM is suggested to hold a key role as a source of inorganic phosphate needed during mineralization and several studies have shown that aberrant SM metabolism leads to defective bone mineralization. In the central nervous system, SM metabolism has been shown to be altered in various pathologies, though the underlying pathophysiological mechanisms and their significance remain elusive. Genetic analyses of the cohorts were performed by extracting DNA from the patients’ whole blood, amplifying the coding and noncoding regions of the SGMS2 gene with PCR and using capillary sequencing to read the genetic code. Altogether 13 discrete single nucleotide variants were found, of which one was a missense variant present in two patients. The variant is relatively rare, has a high CADD score and is predicted probably damaging by computational software. The medical records of the two patients revealed nothing significantly deviating from the cohort norm. This thesis establishes that SGMS2 variants are not a common cause of primary osteoporosis or MRS in these two cohorts of Finnish patients. The significance of the identified missense variant warrants further studies.
  • Helsingin yliopisto, kulttuurien tutkimuksen laitos, arkeologia (The University of Helsinki, Institute for Cultural Research, Archaeology, 2002)
  • Fabritius, Anita (Helsingin yliopisto, 2023)
    The study consists of two parts: examining the accumulation of americium and plutonium to human ribs, and the accumulation to murine osteoblasts. In the cellular studies stable europium was used as an actinide analogue. After removing the organic material from the bones, americium and plutonium were separated from the dissolved bones by using extraction chromatographic methods. DOWEX, U/TEVA, and TRU resins were used to separate plutonium and americium from impurities. The sample activities were measured using alpha spectrometry. On average, 23.03 mBq/kg of plutonium-238, 12.58 mBq/kg of plutonium-239,240 and 9.81 mBq/kg of americium-241 were measured in the bone samples. The activity concentrations are calculated using the wet weight of the bone. Murine preosteobasts (MC3T3-E1) were mineralized for 12 days. The mineral was subsequently collected for SEM/EDS analysis. Non-mineralized cell fractions were collected for a fractioning study, where the cell internalized europium, membrane bound europium and extracellular europium fractions were collected and measured with MP-AES and ICP-MS. The used europium concentrations were below minimum detectable activity of the MP-AES, but measuring the samples on the ICP-MS showed that the percentage of the internalized europium increases at higher europium concentrations in cell culture media. At 0.2 μM europium concentration, on average, 28.6% of the europium was inside the cells and 71.4% in the media, while at 2.0 μM europium concentration, 30.8% of the europium was inside the cells and 68.5% in the media.
  • Gera, Sonia; Sampathi, Sunitha; Maddukuri, Sravya; Dodoala, Sujatha; Junnuthula, Vijayabhaskarreddy; Dyawanapelly, Sathish (2022)
    Naringenin (NRG) is a flavonoid and has been reported as an anti-osteoporotic agent. However, poor bioavailability may limit the anti-osteoporotic potential of the drug. The purpose of the study was to compare the anti-osteoporotic activity of naringenin nanosuspension (NRG-NS) with the NRG and standard therapeutic drug, raloxifene hydrochloride (RLX). Here, NRG-NS showed anti-osteoporotic activity in MG-63 cells by upregulating the osteocalcin levels. The in vivo anti-osteoporotic activity of NRG-NS was further investigated in an osteoporotic rat model to mimic the post-menopausal condition. The animals were randomized and separated into six groups. The animals were treated with RLX (p.o., 5.4 mg/kg), NRG (p.o., 20 mg/kg), NRG-NS (p.o., 20 mg/kg), and blank-NS for 60 days after completion of a 30-day post-surgery period and compared with control and ovariectomized (OVX) groups. After the treatment, body and uterine weights, biochemical estimation in serum (calcium, phosphorus, acid phosphatase, alkaline phosphatase, osteocalcin), bone parameters (length, diameter, dry weight, density, ash weight, bone mineral content) and bone microarchitecture by histopathology were determined. The results showed the protective effects of NRG-NS on osteoblast-like MG-63 cells. The biochemical estimations confirmed the normalization of parameters viz., alkaline phosphatase, calcium concentrations, and bone density with a decrease in levels of acid phosphatase and inorganic phosphorus with NRG-NS as compared to plain NRG. The results indicated that the oral administration of NRG-NS could be a potential therapeutic formulation for the treatment of osteoporosis.