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Sökning: WFRF:(Kjellén G.)

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2.
  • Andersson-Engels, Stefan, et al. (författare)
  • Identification of brain tumours in rats using laser-induced fluorescence and haematoporphyrin derivative
  • 1989
  • Ingår i: Lasers in Medical Science. - 0268-8921. ; 4:4, s. 241-249
  • Tidskriftsartikel (refereegranskat)abstract
    • Laser-induced fluorescence has been used for the identification of brain tumours in rats, which have been previously given tumour-seeking haematoporphyrin derivative. A pulsed nitrogen laser (λ=337 nm) was used in conjunction with an optical multichannel analyzer. For both inoculated RG-2 and TCVC rat-brain-tumour models, the blue autofluorescence was strongly reduced in the tumour compared with normal brain tissue, and at the same time the characteristic red-drug signal increased. The contrast between tumour and normal tissue was strongly enhanced by forming the ratio between the two signals. Implications for possible improvement of tumour delineation in brain tumour surgery are discussed.
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3.
  • Andersson-Engels, S., et al. (författare)
  • Tissue diagnostics using laser-induced fluorescence
  • 1989
  • Ingår i: Berichte der Bunsengesellschaft für Physikalische Chemie. - : Wiley. - 0005-9021. ; 93:3, s. 335-342
  • Tidskriftsartikel (refereegranskat)abstract
    • We have performed extensive investigations of laser-induced fluorescence in animal and human tissue aimed at instant tissue characterization. Autofluorescence, as well as specific fluorescence from HPD/DHE and other photosensitizers, has been utilized. The studies have been focused on the demarcation of malignant tumours and atheroscleortic plaques. A nitrogen laser or an excimer-pumped dye laser was used to induce fluorescence, which was analysed with an intensified optical multichannel system. A fibre-optic sensor system was developed for the clinical work. Multi-colour fluorescence imaging has also been demonstrated along a line and equipment for two-dimensional imaging is being constructed. Dimensionless spectroscopic functions, which are not affected by factors that are clinically uncontrollable have been employed for optimum tissue discrimination. The investigations have so far been performed in a time-integrated mode, but time-resolved studies are now being initiated to fully exploit the diagnostic power of tissue laser-induced fluorescence. In addition to a presentation of our own work a brief review of tissue fluorescence studies performed by other groups is also given.
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  • Andersson, P. S., et al. (författare)
  • TISSUE CHARACTERIZATION USING LASER-INDUCED FLUORESCENCE.
  • 1987
  • Ingår i: Conference on Lasers and Electro-Optics. - 0936659491 ; 14, s. 46-48
  • Konferensbidrag (refereegranskat)abstract
    • In cancer tumor detection, tissue autofluorescence and characteristic features of injected hematoporphyrin derivative (HPD) can be utilized. The authors have studied the importance of the excitation wavelength for the achievable contrast between tumor and surrounding tissue using a rat tumor model. They have also compared the relative merits of two HPD preparations for tumor fluorescence detection. The real-time capability of the fluorescence technique is discussed.
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  • Bjurberg, Maria, et al. (författare)
  • Early changes in 2-deoxy-2-[18F]fluoro-D-glucose metabolism in squamous-cell carcinoma during chemotherapy in vivo and in vitro.
  • 2009
  • Ingår i: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 24:3, s. 327-332
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: The aim of this study was to investigate early changes in uptake of 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) in vivo and in vitro in a squamous-cell carcinoma (SCC) cell line originating from a human head and neck SCC during cytotoxic therapy with respect to metabolism in tumor cells and in surrounding stromal tissue. MATERIALS AND METHODS: In 60 nude mice with xenografted SCC, 50 animals were treated with cisplatin. Early changes in the tumor FDG uptake following therapy were evaluated sequentially with phosphor imaging. Using this technique, areas with focal hypermetabolism were detected. The cells creating the focal hypermetabolism were then identified histopathologically on the corresponding sections. In addition, early FDG uptake versus the number of viable tumor cells was measured in vitro following cisplatin treatment. RESULTS: An early transient increase in FDG uptake in tumor cells was seen on day 1 in treated tumors, followed by a rapid decrease confirmed by subsequent tumor regression. This metabolic flare was present in all treated tumors but not in the controls. In vitro, an increase in FDG uptake per cell was observed. CONCLUSIONS: Our results provide new insights into the early metabolic changes in squamous-cell carcinomas subjected to cytotoxic therapy and thus contribute to the discussion on the feasibility of early predictive PET studies.
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  • Bjurberg, Maria, et al. (författare)
  • Prediction of patient outcome with 2-deoxy-2-[(18)F]fluoro-D-glucose-positron emission tomography early during radiotherapy for locally advanced cervical cancer
  • 2009
  • Ingår i: International Journal of Gynecological Cancer. - Philadelphia : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 19:9, s. 1600-1605
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: It is difficult to assess the individual response of locally advanced cervical cancer to chemoradiation therapy during the course of treatment. We have investigated the predictive value of positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) early during treatment in relation to progression-free survival.Methods: This prospective single-center clinical trial included women with locally advanced cervical cancer from 2004 to 2008. 2-Deoxy-2-[(18)F]fluoro-D-glucose-PET/computed tomography was performed at baseline, during the third week of treatment and, finally, 3 months after the completion of treatment. The images were evaluated visually, semiquantitatively with the maximum standardized uptake value, and by calculating the metabolic rate of FDG. Thirty-two patients were eligible for full evaluation.Results: The median follow-up time was 28 months (range, 5-53 months). Visual metabolic complete response on FDG-PET, after a mean irradiation dose of 23 Gy (range, 16-27 Gy), was found in 7 patients, none of which relapsed. Eleven of the 25 patients with remaining malignant hypermetabolism on the second FDG-PET relapsed. Neither maximum standardized uptake value nor metabolic rate of FDG could further discriminate between patients with low risk and patients with high risk of relapse. The follow-up FDG-PET performed 3 months after the completion of treatment identified a group of patients with poor prognosis.Conclusions: In conclusion, FDG-PET early during chemoradiation therapy identified a small number of patients with an excellent prognosis. However, FDG-PET at this early point in time during treatment failed to predict the outcome for most patients. Future clinical trials to determine the optimal timing of predictive FDG-PET are thus warranted.
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11.
  • Brun, Eva, et al. (författare)
  • Early prediction of treatment outcome in head and neck cancer with 2-18FDG PET
  • 1997
  • Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 36:7, s. 741-747
  • Tidskriftsartikel (refereegranskat)abstract
    • The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.
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12.
  • Brun, Eva, et al. (författare)
  • FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma.
  • 2002
  • Ingår i: Head and Neck. - : Wiley. - 1043-3074. ; 24:2, s. 127-135
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2-[(18) F] fluoro-2-deoxy-D-glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC. METHODS: Between 1993 and 1999 47 patients underwent PET before (PET(1)) and after (PET(2)) 1 to 3 weeks of radical treatment with evaluation of metabolic rate (MR) and standardized uptake value (SUV) of FDG. All patients received radiotherapy, and 10 also received neoadjuvant chemotherapy. Median follow-up time was 3.3 years. RESULTS: Low and high MR FDG at PET(2), with median value as cutoff, was associated with complete remission in 96% and 62% (p =.007), with 5-year overall survival in 72% and 35% (p =.0042) and with local control in 96% and 55% (p =.002), respectively. CONCLUSIONS: FDG PET in the early phase of treatment of HNSCC is associated with tumor response, survival, and local control. Copyright 2002 John Wiley & Sons, Inc.
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13.
  • Dierker, Tabea, et al. (författare)
  • Altered heparan sulfate structure in Glce(-/-) mice leads to increased Hedgehog signaling in endochondral bones
  • 2016
  • Ingår i: Matrix Biology. - : Elsevier BV. - 0945-053X .- 1569-1802. ; 49, s. 82-92
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the key regulators of endochondral ossification is Indian hedgehog (Ihh), which acts as a long-range morphogen in the developing skeletal elements. Previous studies have shown that the distribution and signaling activity of Ihh is regulated by the concentration of the extracellular glycosaminoglycan heparan sulfate (HS). An essential step during biosynthesis of HS is the epimerization of D-glucuronic to L-iduronic acid by the enzyme glucuronyl C5-epimerase (Hsepi or Glce). Here we have investigated chondrocyte differentiation in Glce deficient mice and found increased regions of proliferating chondrocytes accompanied by a delayed onset of hypertrophic differentiation. In addition, we observed increased expression levels of the Ihh target genes Patched1 (Ptch1) and Parathyroid hormone related peptide (Pthrp; Parathyroid hormone like hormone (Pthlh)) indicating elevated Ihh signaling. We further show that Ihh binds with reduced affinity to HS isolated from Glce(-/-) mice. Together our results strongly indicate that not only the level, but also the structure of HS is critical in regulating the distribution and signaling activity of Ihh in chondrocytes.
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  • Henriksson, Eva, et al. (författare)
  • 2-deoxy-2-[F-18]fluoro-D-glucose uptake and correlation to intratumoral heterogeneity
  • 2007
  • Ingår i: Anticancer research. - 1791-7530. ; 27:4B, s. 2155-2159
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the pattern of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake in relation to the intratumoral histopathological appearance. Materials and Methods: Intratumoral distribution of FDG in nude mice with xenografted tumours originating from an established head and neck squamous cell carcinoma was studied. FDG uptake and the con-elation to histopathological appearance was evaluated in four separate quarters of each tumour. Results: Variations in FDG uptake correlating to the presence of tumour cells was demonstrated. Quarters containing more than 50% tumour cells showed a significantly higher FDG uptake (p=0.028) than quarters with more stromal tissue and necrosis. Conclusion: This Study shows that the heterogenic FDG uptake within a tumour correlates to histopathological findings and that the variable appearance of tracer uptake on the PET scan depends on distribution of different tissue components in the tumour. This intratumoral heterogeneity calls for caution when evaluating a PET scan where median values of larger areas will be misguiding and thus small areas with high uptake should be regarded as the regions of interest.
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20.
  • Henriksson, Eva, et al. (författare)
  • Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck
  • 2009
  • Ingår i: Journal of Experimental & Clinical Cancer Research. - : Springer Science and Business Media LLC. - 1756-9966. ; 28
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The survival of patients with locally advanced head and neck cancer is still poor, with 5-year survival rates of 24-35%. The identification of prognostic and predictive markers at the molecular and cellular level could make it possible to find new therapeutic targets and provide "taylor made" treatments. Established cell lines of human squamous cell carcinoma (HNSCC) are valuable models for identifying such markers. The aim of this study was to establish and characterize a series of cell lines and to compare the cisplatin sensitivity and 18F fluoro-2 deoxy 2 glucose (18F-FDG) uptake of these cell lines with other cellular characteristics, such as proliferation parameters and TP53 and CCND1 status. Methods: Explant cultures of fresh tumour tissue were cultivated, and six new permanent cell lines were established from 18 HNSCC cases. Successfully grown cell lines were analysed regarding clinical parameters, histological grade, karyotype, DNA ploidy, and index and S-phase fraction (Spf). The cell lines were further characterized with regard to their uptake of 18F-FDG, their sensitivity to cisplatin, as measured by a viability test ( crystal violet), and their TP53 and CCND1 status, by fluorescence in situ hybridization (FISH), polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) with DNA sequencing and, for cyclin D1, by immunohistochemistry. Results: Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test. Their tumours also showed more complex karyotypes than tumours from which cell lines could not be established. No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity. However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake. Conclusion: In vitro growth of HNSCC cells seem to be an independent prognostic factor, with cell lines being more readily established from aggressive tumours, a phenomenon more dependent on the molecular genetic characteristics of the tumour cells than on tumour location or TNM status.
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21.
  • Hu Frisk, Jun Mei, et al. (författare)
  • Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells
  • 2017
  • Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 199, s. 4132-4141
  • Tidskriftsartikel (refereegranskat)abstract
    • Copper has previously been implicated in the regulation of immune responses, but the impact of this metal on mast cells is poorly understood. In this article, we address this issue and show that copper starvation of mast cells causes increased granule maturation, as indicated by higher proteoglycan content, stronger metachromatic staining, and altered ultrastructure in comparison with nontreated cells, whereas copper overload has the opposite effects. In contrast, copper status did not impact storage of histamine in mast cells, nor did alterations in copper levels affect the ability of mast cells to degranulate in response to IgER cross-linking. A striking finding was decreased tryptase content in mast cells with copper overload, whereas copper starvation increased tryptase content. These effects were associated with corresponding shifts in tryptase mRNA levels, suggesting that copper affects tryptase gene regulation. Mechanistically, we found that alterations in copper status affected the expression of microphthalmia-associated transcription factor, a transcription factor critical for driving tryptase expression. We also found evidence supporting the concept that the effects on microphthalmia-associated transcription factor are dependent on copper-mediated modulation of MAPK signaling. Finally, we show that, in MEDNIK syndrome, a condition associated with low copper levels and a hyperallergenic skin phenotype, including pruritis and dermatitis, the number of tryptase-positive mast cells is increased. Taken together, our findings reveal a hitherto unrecognized role for copper in the regulation of mast cell gene expression and maturation.
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  • Isidor, Bertrand, et al. (författare)
  • Mesomelia-Synostoses Syndrome Results from Deletion of SULF1 and SLCO5A1 Genes at 8q13
  • 2010
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 87:1, s. 95-100
  • Tidskriftsartikel (refereegranskat)abstract
    • Mesomelia-synostoses syndrome (MSS) or mesomelic dysplasia with acral synostoses Verloes-David-Pfeiffer type is a rare autosomal-dominant disorder characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations. So far, five patients in four unrelated families have been reported worldwide with MMS. By using whole-genome oligonucleotide array CGH, we have identified an interstitial deletion at 8q13 in all patients. The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1, encoding the heparan sulfate 6-O-endosulfatase 1, and SLCO5A1, encoding the solute carrier organic anion transporter family member 5A1. SULF1 acts as a regulator of numerous growth factors in skeletal embryonic development whereas the function of SLCO5A1 is yet unknown. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Real-time quantitative RT-PCR analysis showed the highest levels of SULF1 transcripts in human osteoblasts and cartilage whereas SLCO5A1 was highly expressed in human fetal and adult brain and heart. Our results strongly suggest that haploinsufficiency of SULF1 contributes to this mesomelic chondrodysplasia, highlighting the critical role of endosulfatase in human skeletal development. Codeletion of SULF1 and SLCO5A1-which does not result from a low-copy repeats (LCRs)-mediated recombination event in at least two families-was found in all patients, so we suggest that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS.
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24.
  • Kjellén, G., et al. (författare)
  • Esophageal function, radiography, and dysphagia in Sjögren's syndrome
  • 1986
  • Ingår i: Digestive Diseases and Sciences. - : Kluwer Academic Publishers. - 0163-2116 .- 1573-2568. ; 31:3, s. 225-229
  • Tidskriftsartikel (refereegranskat)abstract
    • Esophageal function and anatomy were investigated with manometry, acid perfusion test, acid clearing test, and x-ray in 11 patients with primary Sjögren's syndrom (SS) and in 11 with secondary SS. The manometric investigation revealed minor motor differences in the SS patients as compared to 16 controls, ie, shorter peristaltic contraction time of the whole esophagus, and faster peristaltic velocity preferably in the distal part of the esophagus, while the results from the reflux tests did not differ between patients and controls. Radiographic examination revealed upper esophageal webs in 10% (2/20), and hiatal hernia in 25% (5/20). The dysphagia as reported by 73% of the patients cannot be explained by webs or impaired motor function and is regarded to be secondary to lack of saliva, making the solid bolus passage difficult.
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  • Kjellén, G., et al. (författare)
  • Scintigraphy, radiography, and acid clearing in dysphagia patients after anti-reflux surgery
  • 1984
  • Ingår i: Scandinavian Journal of Gastroenterology. - 0036-5521 .- 1502-7708. ; 19:8, s. 1022-1026
  • Tidskriftsartikel (refereegranskat)abstract
    • Oesophageal emptying was studied with scintigraphy, radiography, and the acid clearing test (ACT) in 18 patients reporting dysphagia and previously operated on with fundoplication. Radiography with contrast medium, isodense with water, revealed abnormalities in either motility or emptying capacity in 39% (7/18). A A barium meal showed abnormalities--that is, a tight repair, disruption of the fundoplication, or recurrence of the hernia--in 56% (10/18). The ACT was prolonged in 40% (6/15) of the patients. Pathological findings at scintigraphy with a solid bolus were found in 67% (12/18). Even if scintigraphy with a solid bolus is the method that identifies the highest number of patients with impaired oesophageal function among the tests used, it cannot differentiate between functional and anatomical disorders. A barium meal examination is the method of choice when an anatomical disorder is suspected.
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26.
  • Kjellén, Nils, et al. (författare)
  • Population trends in Swedish raptors demonstrated by migration counts at Falsterbo, Sweden 1942-97
  • 2000
  • Ingår i: Bird Study. - 0006-3657. ; 47:2, s. 195-211
  • Tidskriftsartikel (refereegranskat)abstract
    • The autumn migration of raptors at Falsterbo, Sweden has been studied since the early 1940s, and from 1973 standardized counts were made. Here we present data for 15 species over a 39-year period from 1942-97. These are discussed in the context of available information on population trends in Sweden and neighbouring countries. Although annual numbers and concentration rate vary considerably between species, population changes are very well reflected in the migration figures from Falsterbo. Most raptors showed stable populations at a fairly high level during the 1940s, hilt a marked decline was already obvious in White-tailed Eagle Haliaeetus albicilla and Peregrine Falcon Falco peregrinus. During the 1950s and 1960s, a more or less steep decline occurred in most species. Four species started to increase during the 1960s, but the real change came during the 1970s. At that time, decreased human persecution and a reduction ill the effects from pesticides resulted ill a general increase in Scandinavian raptors, with only Honey Buzzard Pernis apivorus continuing to decrease. The increases continued during the 1980s, but in the 1990s many raptors seem to have reached stable numbers or to have started to decline again. Two species, Marsh Harrier Circus aeruginosus and Montagu's Harrier C. pygargus show a positive trend through the study period. Numbers of Northern Harrier Circus cyaneus, Rough-legged Buzzard Buteo lagopus and Eurasian Kestrel Falco tinnunculus stabilized during Me 1980s and show a clear decline since then, most probably due to a general lack of rodent peaks in Northern Scandinavia since 1982. Most species of raptors scent to he doing reasonably well at the moment, brit a continuous decline in Honey Blizzard and Common Buzzard Buteo buteo is disturbing, and is possibly due to declining proportions of old deciduous forest and grazed meadows in Scandinavia. Since a general census programme of birds of prey does not exist in Sweden, the migration counts at Falsterbo is the best general method of monitoring population changes.
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27.
  • Krebs, C. J., et al. (författare)
  • Terrestrial trophic dynamics in the Canadian Arctic
  • 2003
  • Ingår i: Canadian Journal of Zoology-Revue Canadienne De Zoologie. ; 81, s. 827-843
  • Tidskriftsartikel (refereegranskat)abstract
    • The Swedish Tundra Northwest Expedition of 1999 visited 17 sites throughout the Canadian Arctic. At 12 sites that were intensively sampled we estimated the standing crop of plants and the densities of herbivores and predators with an array of trapping, visual surveys, and faecal-pellet transects. We developed a trophic-balance model using ECOPATH to integrate these observations and determine the fate of primary and secondary production in these tundra ecosystems, which spanned an 8-fold range of standing crop of plants. We estimated that about 13% of net primary production was consumed by herbivores, while over 70% of small-herbivore production was estimated to flow to predators. Only 9% of large-herbivore production was consumed by predators. Organization of Canadian Arctic ecosystems appears to be more top-down than bottom-up. Net primary production does not seem to be herbivore-limited at any site. This is the first attempt to integrate trophic dynamics over the entire Canadian Arctic.
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28.
  • Wiklund, Christer G., et al. (författare)
  • Lemming predators on the Siberian tundra
  • 1999
  • Ingår i: Ambio. - 0044-7447 .- 1654-7209. ; 28:3, s. 281-286
  • Tidskriftsartikel (refereegranskat)abstract
    • In the Eurasian Arctic, the most common lemming species are the Siberian lemming (Lemmus sibiricus) and the collared lemming (Dicrostonyx torquatus). Lemmings constitute the main food item for 5 common predators in the area: arctic fox; snowy owl; rough-legged buzzard; long-tailed skua; and pomarine skua. Hence, these predators form a foraging guild. We have studied factors influencing the structure of this guild. When comparing cooccurrence of the predators between 17 sites across Siberia, there were positive associations between the snowy owl and the two skuas, and a negative association between snowy owl and rough-legged buzzard. There was also a large variation in local population density among the predators, conceivably, due to the risk of intra-guild predation as well as the variation in food supply. There were significant relationships between lemming abundance and the abundance of each predator. An analysis of the predatory response by the arctic fox indicated a response pattern similar to that of a delayed numerical response to lemming abundance. For this and other reasons, we propose that the arctic fox is a resident specialist predator on microtine rodents. Further, the birds appeared to be nomadic specialist predators with, perhaps, one exception, the rough-legged buzzard.
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