| 1. |
- af Klint, Erik, et al.
(author)
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Evaluation of arthroscopy and macroscopic scoring.
- 2009
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 11:3
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Arthroscopy is a minimally invasive technique for retrieving synovial biopsies in rheumatology during the past 20 years. Vital for its use is continual evaluation of its safety and efficacy. Important for sampling is the fact of intraarticular variation for synovial markers. For microscopic measurements scoring systems have been developed and validated, but for macroscopic evaluations there is a need for further comprehensive description and validation of equivalent scoring systems.METHODS: We studied the complication rate and yield of arthroscopies performed at our clinic between 1998 and 2005. We also created and evaluated a macroscopic score set of instructions for synovitis.RESULTS: Of 408 procedures, we had two major and one minor complication; two haemarthrosis and one wound infection, respectively. Pain was most often not a problem, but 12 procedures had to be prematurely ended due to pain. Yield of biopsies adequate for histology were 83% over all, 94% for knee joints and 34% for smaller joints. Video printer photographs of synovium taken during arthroscopy were jointly and individually reviewed by seven raters in several settings, and intra and inter rater variation was calculated. A macroscopic synovial scoring system for arthroscopy was created (Macro-score), based upon hypertrophy, vascularity and global synovitis. These written instructions were evaluated by five control-raters, and when evaluated individual parameters were without greater intra or inter rater variability, indicating that the score is reliable and easy to use.CONCLUSIONS: In our hands rheumatologic arthroscopy is a safe method with very few complications. For knee joints it is a reliable method to retrieve representative tissue in clinical longitudinal studies. We also created an easy to use macroscopic score, that needs to be validated against other methodologies. We hope it will be of value in further developing international standards in this area.
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| 2. |
- af Klint, Johan, 1939-
(author)
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The Barabudur : A Synopsis of Buddhism
- 2021
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Doctoral thesis (other academic/artistic)abstract
- The aim of this PhD-dissertation is – on the one hand – to present in a critical and comprehensive manner an update of recent findings among Western scholars regarding the Barabudur monument and its illustrations of various Buddhist traditions, and – on the other hand – to throw some light on some of the outstanding issues regarding this monument. Focus has been laid on the religious aspects with a view of ascertaining which forms of Buddhism are most prominently represented on the monument.The Barabudur is the largest Buddhist monument in the world – being built on Central Java during the late eighth century CE. The Barabudur is constructed in four successively higher galleries with an area on top with three round terraces. The terraces encompass 72 latticed stupas, each containing Buddha Vairocana in dharmacakramudra large stupa is in the center. Each side of the squarely built monument is at the ground level around 123 meters. The height of the monument is believed to originally have been 41.81 meters. The walls and the balustrades of the galleries encompass 1,460 bas-reliefs representing various sutras, such as the Mahakarmavibhanga Sutra, the Lalitavistara, the Gandavyuha Sutra, the Dasabhumika Sutra and the Bhadracari. In addition, the Barabudur seems also to have been influenced by ideas from the ensuing Indonesian esoteric text the Sang Hyang Kamahayanikan, as well as by the esoteric Buddhist texts of the Mahavairocana Sutra, the Tattvasamgraha and the Prajnaparamita in 150 verses. The Barabudur thus presents aspects from the main three Buddhist traditions – the Sravakayana, the Mahayana and an early esoteric form of the Vajrayana.The main problem in studying the Barabudur is the lack of historical information. No dedicatory inscription has yet been found. The Barabudur was built during the Sailendra interregnum on Java. Their contacts with the Abhayagirivihara on Sri Lanka and with the Pala dynasty in Bengal, indicate that some early form of Vajrayana Buddhism existed on Java during the eighth century CE. In addition, some concepts from the esoteric Buddhism developed by the Three Monks in China during this period could well also have been introduced on Java.The Barabudur, together with the Candi Mendut, are supposed to represent the Twin-mandala – thus representing the “non-duality” between “Truth” and “Wisdom”. Dharmakaya Mahavairocana is in the center of both these Twin-mandalas symbolizing the amalavijnana.In conclusion, the Barabudur may be regarded as a holy monument, where the Buddha is present, and where the devotee may be taught directly by the Buddha.
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| 3. |
- Boeth, Heide, et al.
(author)
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Association between changes in molecular biomarkers of cartilage matrix turnover and changes in knee articular cartilage : a longitudinal pilot study
- 2019
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In: Journal of Experimental Orthopaedics. - : Springer Science and Business Media LLC. - 2197-1153. ; 6:1
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Journal article (peer-reviewed)abstract
- Background: An early detection of Osteoarthritis is urgently needed and still not possible until today. The aim of the study was to assess whether molecular biomarkers of cartilage turnover are associated with longitudinal change in knee cartilage thickness during a 2 year period in individuals with increased risk of developing knee osteoarthritis. A secondary aim was to assess whether prior knee injury or subjective patient-reported outcomes at baseline (BL) were associated with articular cartilage changes. Nineteen volleyball players (mean age 46.5 ± 4.9 years, 47% male) with a 30-year history of regular high impact training were recruited. The serum biomarkers Cpropeptide of type II procollagen (CPII), cartilage oligomeric matrix protein (COMP), collagenase generated carboxy-terminal neoepitope of type II collagen (sC2C), cartilage intermediate layer protein 2 (CILP-2), and the urine biomarkers C-telopeptide of type II collagen (CTX-II) and collagenase-generated peptide(s) of type II collagen (C2C-HUSA) were assessed at BL and at 2 year follow up (FU). Femorotibial cartilage thinning, thickening and absolute thickness change between BL and FU was evaluated from magnetic resonance imaging. Subjective clinical status at BL was evaluated by the International Knee Documentation Committee Subjective Knee Form and the Short-Form 36 Physical Component Score. Results: CILP-2 was significantly higher at FU and linearly associated with the absolute cartilage thickness change during the experimental period. Prior injury was a predictor of increased absolute cartilage thickness change. Conclusion: Measuring the change in the cartilage biomarker CILP-2 might be a valid and sensitive method to detect early development of knee osteoarthritis as CILP-2 appears to be related to cartilage thickness loss in certain individuals with increased risk of developing knee osteoarthritis. Prior knee injury may be predictive of increased articular cartilage thickness change.
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| 4. |
- Bonow, Johan M., et al.
(author)
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A multi-disciplinary study of Phanerozoic landscape development in West Greenland
- 2007
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In: Geological Survey of Denmark and Greenland Bulletin: Review of Survey activities 2006. - 1604-8156. ; :13, s. 33-36
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Journal article (peer-reviewed)abstract
- The western margin of the Greenland craton has been muchless stable in the Phanerozoic than previously thought. Thisnew insight has come from close integration of independentdata sets: geomorphological analysis of large-scale landscapes,apatite fission track analysis (AFTA), onshore and offshorestratigraphy and analysis of onshore fault and fracture sys -tems. Each data set records specific and unique parts of theevent chronology and is equally important to establish a con-sistent model. A key area for understanding the Mesozoic-Cenozoic landscape evolution and into the present is theuplifted part of the Nuussuaq Basin, where remnants of pla-nation surfaces cut across the Cretaceous to Eocene sedimen-tary and volcanic rocks. Our integrated analysis concludedthat the West Greenland mountains were formed by lateNeogene tectonic uplift (Fig. 1) and also provided newinsight into early Phanerozoic development. To understandour model, we present the different methods and the resultsthat can be deduced from them.
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| 5. |
- Carlberg, Konstantin, et al.
(author)
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Integrated Single Cell and Spatial Transcriptomics Reveal Autoreactive Differentiated B Cells in Joints of Early Rheumatoid Arthritis
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Other publication (other academic/artistic)abstract
- Rheumatoid Arthritis (RA) is a prevalent autoimmune disease characterized by inflammation of peripheral joints. Patients can be subdivided by the presence or absence of Rheumatoid Factor and anti-citrullinated protein antibodies (ACPA) in their circulation. Inflammation of the joint tissue is associated with infiltration of leukocytes from the blood, which can result in generation of lymphoid structures composed of B and T cells. Previous studies have shown that both memory B cells and antibody-secreting plasma cells populate the rheumatic joint tissue when captured from established and often long-standing disease. However, it has remained unclear, whether these cells are autoreactive and whether the associated lymphoid structures are present at the site of inflammation already at the time of diagnosis. Here, we used an integrated single cell and spatial transcriptomic approach to study B and plasma cells in synovial tissue of ACPA- and ACPA+ RA patients at this early time point. We found evidence for T cell help to B cells and presence of memory B and plasma cell pools in ACPA- as well as in ACPA+ RA. Our results demonstrated common supportive microenvironments in both patient subgroups, clonal relationships between the memory B and plasma cell pools and autoreactivity within the plasma cell compartment. These findings challenge our understanding of the dynamics of local adaptive immune responses in the RA joint of ACPA- and ACPA+ patients at the time of diagnosis, with direct implications for B and T cell targeting therapies for both patient subgroups.
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| 6. |
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| 7. |
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| 8. |
- Hardt, Uta, et al.
(author)
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Integrated single cell and spatial transcriptomics reveal autoreactive differentiated B cells in joints of early rheumatoid arthritis
- 2022
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Journal article (peer-reviewed)abstract
- B cells play a significant role in established Rheumatoid Arthritis (RA). However, it is unclear to what extent differentiated B cells are present in joint tissue already at the onset of disease. Here, we studied synovial biopsies (n = 8) captured from untreated patients at time of diagnosis. 3414 index-sorted B cells underwent RNA sequencing and paired tissue pieces were subjected to spatial transcriptomics (n = 4). We performed extensive bioinformatics analyses to dissect the local B cell composition. Select plasma cell immunoglobulin sequences were expressed as monoclonal antibodies and tested by ELISA. Memory and plasma cells were found irrespective of autoantibody status of the patients. Double negative memory B cells were prominent, but did not display a distinct transcriptional profile. The tissue architecture implicate both local B cell maturation via T cell help and plasma cell survival niches with a strong CXCL12-CXCR4 axis. The immunoglobulin sequence analyses revealed clonality between the memory B and plasma cell pools further supporting local maturation. One of the plasma cell-derived antibodies displayed citrulline autoreactivity, demonstrating local autoreactive plasma cell differentiation in joint biopsies captured from untreated early RA. Hence, plasma cell niches are not a consequence of chronic inflammation, but are already present at the time of diagnosis.
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| 9. |
- Iivanainen, Erika, et al.
(author)
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Intra- and extracellular signaling by endothelial neuregulin-1
- 2007
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In: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 313:13, s. 2896-2909
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Journal article (peer-reviewed)abstract
- Suppression of tumor growth by inhibition of ErbB receptor signaling is well documented. However, relatively little is known about the ErbB signaling system in the regulation of angiogenesis, a process necessary for tumor growth. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) is expressed by vascular endothelial cells (EC) and promotes endothelial recruitment of vascular smooth muscle cells (SMC). To assess whether other members of the EGF-family regulate angiogenesis, the expression of 10 EGF-like growth factors in primary ECs and SMCs was analyzed. In addition to HB-EGF, neuregulin-1 (NRG-1) was expressed in ECs in vitro and in vivo. Endothelial NRG-1 was constitutively processed to soluble extracellular and intracellular signaling fragments, and its expression was induced by hypoxia. NRG-1 was angiogenic in vivo in mouse corneal pocket and chicken chorioallantoic membrane (CAM) assays. However, consistent with the lack of NRG-1 receptors in several primary EC lines, NRG-1 did not directly stimulate cellular responses in cultured ECs. In contrast, NRG-1 promoted EC responses in vitro and angiogenesis in CAM in vivo by mechanisms dependent on VEGF-A and VEGFR-2. These results indicate that NRG-1 is expressed by ECs and regulates angiogenesis by mechanisms involving paracrine up-regulation of VEGF-A.
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