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101.
Hellquist A Zucchelli M Kivinen K Saarialho-Kere U Koskenmies S Widen E Julkunen H Wong A Karjalainen-Lindsberg ML Skoog T Vendelin J Cunninghame-Graham DS Vyse TJ Kere J Lindgren CM 《Journal of medical genetics》2007,44(5):314-321
Background
Several members of the GIMAP gene family have been suggested as being involved in different aspects of the immune system in different species. Recently, a mutation in the GIMAP5 gene was shown to cause lymphopenia in a rat model of autoimmune insulin‐dependent diabetes. Thus it was hypothesised that genetic variation in GIMAP5 may be involved in susceptibility to other autoimmune disorders where lymphopenia is a key feature, such as systemic lupus erythematosus (SLE).Material and methods
To investigate this, seven single nucleotide polymorphisms in GIMAP5 were analysed in five independent sets of family‐based SLE collections, containing more than 2000 samples.Result
A significant increase in SLE risk associated with the most common GIMAP5 haplotype was found (OR 1.26, 95% CI 1.02 to 1.54, p = 0.0033). In families with probands diagnosed with trombocytopenia, the risk was increased (OR 2.11, 95% CI 1.09 to 4.09, p = 0.0153). The risk haplotype bears a polymorphic polyadenylation signal which alters the 3′ part of GIMAP5 mRNA by producing an inefficient polyadenylation signal. This results in higher proportion of non‐terminated mRNA for homozygous individuals (p<0.005), a mechanism shown to be causal in thalassaemias. To further assess the functional effect of the polymorphic polyadenylation signal in the risk haplotype, monocytes were treated with several cytokines affecting apoptosis. All the apoptotic cytokines induced GIMAP5 expression in two monocyte cell lines (1.5–6 times, p<0.0001 for all tests).Conclusion
Taken together, the data suggest the role of GIMAP5 in the pathogenesis of SLE. 相似文献102.
Abhisek Bhattarai Behdad Pouran Janne T. A. Mäkelä Rubina Shaikh Miitu K. M. Honkanen Mithilesh Prakash Heikki Kröger Mark W. Grinstaff Harrie Weinans Jukka S. Jurvelin Juha Töyräs 《Journal of orthopaedic research》2020,38(10):2230-2238
Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P < .05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent. 相似文献
103.
Fausto Biancari Juha Saarnio Ari Mennander Linda Hypén Paulina Salminen Kari Kuttila Mikael Victorzon Camilla Böckelman Enrico Tarantino Olivier Tiffet Vesa Koivukangas Jon Arne Søreide Asgaut Viste Luigi Bonavina Halla Vidarsdóttir Tomas Gudbjartsson 《World journal of surgery》2014,38(4):902-909
Background
Recent studies have suggested that stent-grafting may improve the treatment outcome of patients with esophageal perforation, but evidence on this is still lacking.Methods
Data on 194 patients who underwent conservative (43 patients), endoclip (4 patients) stent-grafting (63 patients) or surgical treatment (84 patients) for esophageal perforation were retrieved from nine medical centers.Results
In-hospital/30-day mortality was 17.5 %. Three-year survival was 67.1 %. Age, coronary artery disease, and esophageal malignancy were independent predictors of early mortality. Chi squared automatic interaction detection analysis showed that patients without coronary artery disease, without esophageal malignancy and younger than 70 years had the lowest early mortality (4.1 %). Surgery was associated with slightly lower early mortality (conservative 23.3, endoclips 25.0 %, stent-grafting 19.0 %, surgery 13.1 %; p = 0.499). One center reported a series of more than 20 patients treated with stent-grafting which achieved an early mortality of 7.7 % (2/26 patients). Stent-grafting was associated with better survival with salvaged esophagus (conservative 76.7 %, endoclips 75.0 %, stent-grafting 77.8 %, surgery 56.0 %; p = 0.019). Propensity score adjusted analysis showed that stent-grafting achieved similar early mortality (p = 0.946), but significantly higher survival with salvaged esophagus than with surgical treatment (p = 0.001, OR 0.253, 95 % CI 0.110–0.585). Primary surgical repair was associated with somewhat lower early mortality (14.6 vs. 19.0 %; p = 0.561) and better survival with salvaged esophagus (85.4 vs. 77.8 %; p = 0.337) than stent-grafting.Conclusions
Esophageal perforation was associated with a rather high mortality rate in this all-comers population. Stent-grafting failed to decrease operative mortality, but it improved survival with salvaged esophagus. The results of one of the centers indicate that increasing experience with this less invasive procedure may possibly improve the outcome of these patients. 相似文献104.
105.
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107.
Kaisa Nieminen Juha Immanen Marjukka Laxell Leila Kauppinen Petr Tarkowski Karel Dolezal Sari Thtiharju Annakaisa Elo Mlanie Decourteix Karin Ljung Rishikesh Bhalerao Kaija Keinonen Victor A. Albert Yk Helariutta 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(50):20032-20037
Although a substantial proportion of plant biomass originates from the activity of vascular cambium, the molecular basis of radial plant growth is still largely unknown. To address whether cytokinins are required for cambial activity, we studied cytokinin signaling across the cambial zones of 2 tree species, poplar (Populus trichocarpa) and birch (Betula pendula). We observed an expression peak for genes encoding cytokinin receptors in the dividing cambial cells. We reduced cytokinin levels endogenously by engineering transgenic poplar trees (P. tremula × tremuloides) to express a cytokinin catabolic gene, Arabidopsis CYTOKININ OXIDASE 2, under the promoter of a birch CYTOKININ RECEPTOR 1 gene. Transgenic trees showed reduced concentration of a biologically active cytokinin, correlating with impaired cytokinin responsiveness. In these trees, both apical and radial growth was compromised. However, radial growth was more affected, as illustrated by a thinner stem diameter than in WT at same height. To dissect radial from apical growth inhibition, we performed a reciprocal grafting experiment. WT scion outgrew the diameter of transgenic stock, implicating cytokinin activity as a direct determinant of radial growth. The reduced radial growth correlated with a reduced number of cambial cell layers. Moreover, expression of a cytokinin primary response gene was dramatically reduced in the thin-stemmed transgenic trees. Thus, a reduced level of cytokinin signaling is the primary basis for the impaired cambial growth observed. Together, our results show that cytokinins are major hormonal regulators required for cambial development. 相似文献
108.
Kirsten D. Bentsen Thomas Horn Juha Risteli Leila Risteli Anna Engstrm-Laurent Kim Hrslev-Petersen Ib Lorenzen 《Liver international》1987,7(6):339-346
ABSTRACT— Serum concentrations of the aminoterminal propeptide of type III procollagen and of the 7S domain of type IV collagen, presumed to reflect fibrotic activity in liver tissue, and of the glycosamonoglycan hyaluronan, were obtained from 40 alcohol abusers, at the time of liver biopsy. The serological results were related to morphological findings in liver tissue, i.e. no fibrosis, fibrosis without cirrhosis, micronodular cirrhosis and macronodular cirrhosis, and to ultrastructural indications of perisinusoidal fibrosis in the acinar zone 3. All patients with fibrosis and cirrhosis on light microscopy had elevated serum levels of the type III procollagen peptide as well as of the 7S domain of type IV collagen. However, due to a considerable overlap between the groups, no relations could be demonstrated to the severity of the fibrosis, supporting the assumption that these serological markers reflect the current fibrotic activity and not the amount of fibrotic tissue previously deposited. Among patients without fibrosis on light microscopy, a relation between the propeptide levels and ultrastructural perisinusoidal zone 3 fibrosis was observed, suggesting that type III procollagen peptide may be valuable in detecting very early liver fibrosis. A positive correlation was demonstrated between the serum concentrations of type III procollagen peptide and hyaluronan. As hyaluronan is degraded in the liver endothelial cells, it is suggested that the liver is involved, not only in the synthesis, but also in the degradation of the propeptide. 相似文献
109.
Perkiomaki JS Zareba W Greenberg HM Moss AJ;Thrombogenic Factors Recurrent Coronary Events Investigators 《The American journal of cardiology》2002,90(3):205-209
Comprehensive information about the independent value of different electrocardiographic (ECG) variables in predicting cardiac events after acute myocardial infarction (AMI) in the era of modern therapy is limited. Patients (n = 1,034) underwent standard electrocardiography from 5 to 7 days after an AMI. Several time intervals and PQRST abnormalities were analyzed from the electrocardiogram. During a mean +/- SD follow-up of 752 +/- 301 days on average, 42 patients (4%) experienced cardiac death, and 259 patients (25%) a cardiac death, nonfatal AMI, or unstable angina. Several ECG variables had a significant association with cardiac events in univariate comparisons. After adjustment for all risk variables in the Cox hazards model, lateral ST-segment depression (hazard ratio [HR] 4.76, 95% confidence interval [CI] 2.40 to 9.44, p <0.0001) and atrial abnormality with a terminal deflection of the P wave > or =0.1 mV deep and > or =40 ms in duration in lead V(1) (HR 2.46, 95% CI 1.25 to 4.82, p = 0.009) were the only ECG variables that independently predicted cardiac death. Lateral ST-segment depression also predicted the combined end point of cardiac death/nonfatal AMI/unstable angina in this model (HR 1.49, 95% CI 1.14 to 1.94, p = 0.003). In conclusion, lateral ST depression and atrial abnormality on the electrocardiogram are independent predictors of cardiac death after AMI. Lateral ST depression is also associated with ischemic cardiac events. 相似文献
110.
Matti Aarnio Sari Lindblom-Ylänne Juha Nieminen Eeva Pyörälä 《Advances in health sciences education : theory and practice》2014,19(3):329-345
Recent research on problem-based learning (PBL) has shown that students need support when dealing with conflicting ideas in PBL-tutorial discussions. In the present study, we examined tutor facilitation during tutorial discussions, and particularly how the facilitation helped students to collaboratively resolve conflicts on knowledge. The study involved four PBL-tutorial sessions that included altogether 33 first-year medical and dental students. The sessions were videotaped and analysed using qualitative interaction analysis. Our aim was to find out how the tutor interventions encouraged students to elaborate on conflicting ideas, and how the interventions differed between conflict and non-conflict situations. We also examined how the tutors intervened during conflicts about factual or conceptual knowledge. The tutorial discussions included 92 tutor intervention episodes and 43 conflict episodes. The tutors intervened during 24 of the conflict episodes and resolved 13 of these episodes. Generally, the tutors often intervened by confirming what the students had said or by giving explanations, but they rarely asked questions that would stimulate the elaboration of knowledge. During conflicts on knowledge the tutors gave more explanations, but did little to encourage the students to deal with conflicting ideas. The tutors more often resolved conflicts on factual knowledge than conceptual knowledge. The findings suggest that tutor training should focus on promoting tutors’ understanding on when to give direct explanations, and when and how to encourage students to collaboratively elaborate on conflicting ideas. 相似文献