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Sökning: WFRF:(WILLEN H)

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1.
  • Guerova, G., et al. (författare)
  • National Status Reports
  • 2020
  • Ingår i: Advanced GNSS Tropospheric Products for Monitoring Severe Weather Events and Climate. - Cham : Springer International Publishing. - 9783030139001 ; , s. 403-481
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • In this section a summary of the national progress reports is given. GNSS4SWEC Management Committee (MC) members provided outline of the work conducted in their countries combining input from different partners involved. In the COST Action paticipated member from 32 COST countries, 1 Near Neighbour Country and 8 Intrantional Partners from Australia, Canada, Hong Kong and USA. The text reflects the state as of 1 January 2018.
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2.
  • Tallini, G, et al. (författare)
  • Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group
  • 2002
  • Ingår i: Journal of Pathology. - : Wiley. - 0022-3417. ; 196:2, s. 194-203
  • Tidskriftsartikel (refereegranskat)abstract
    • The evaluation of chondroid lesions requires full integration of clinical, radiographic, and pathological data; tumour typing is often a challenge for the diagnostic pathologist. Although a variety of chromosomal abnormalities have been documented in chondroid lesions, the potential usefulness of cytogenetic analysis remains unclear. This study has critically reviewed and analysed 117 karyotyped samples from 100 patients with cartilaginous and chordoid tumours. Cases were selected based on successful chromosomal analysis and adequacy of clinical, radiographic, and pathological information. To ensure objective evaluation, the cytogenetic results were correlated in a double-blind setting with consensus diagnoses independently determined on each case, after complete review of the histological, radiographic, and clinical findings. Karyotypic aberrations were identified in 41/92 cartilaginous tumours (5/11 osteochondromas, 2/3 chondromyxoid fibromas, 0/4 chondroblastomas, 11/29 chondromas, 0/3 chondroid tumours of undetermined malignant potential, 22/40 chondrosarcomas and 1/2 miscellaneous cartilaginous lesions) and 5/8 chordomas. Complex karyotypic changes were a feature of malignant tumours (chondrosarcoma and chordoma) and of chondrosarcoma among cartilaginous tumours, where they correlated with high tumour grade. Among primary well-differentiated cartilaginous lesions of bone, the finding of an abnormal karyotype was consistently associated with a grade 1 chondrosarcoma diagnosis. Among karyotypically abnormal cartilaginous tumours, loss of distal 8q was associated with osteochondroma, +5 with synovial chondroma/chondromatosis and parosteal or soft tissue chondroma, alterations of chromosome arm 6q with chondromyxoid fibroma, +7 with bone chondrosarcoma, and 17pl alterations with grade 3 chondrosarcoma. Alterations involving 12q13 characterized synovial chondroma/chondromatosis in the chondroma group and myxoid chondrosarcoma of bone in the chondrosarcoma group. In conclusion, cytogenetic abnormalities in chondroid lesions are common and are not randomly distributed. They are associated with malignancy/tumour grade as well as with specific diagnoses in many cases, and can therefore be of potential value for tumour typing.
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3.
  • Tsiantoulas, D., et al. (författare)
  • APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 597, s. 92-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Atherosclerotic cardiovascular disease causes heart attacks and strokes, which are the leading causes of mortality worldwide(1). The formation of atherosclerotic plaques is initiated when low-density lipoproteins bind to heparan-sulfate proteoglycans (HSPGs)(2) and become trapped in the subendothelial space of large and medium size arteries, which leads to chronic inflammation and remodelling of the artery wall(2). A proliferation-inducing ligand (APRIL) is a cytokine that binds to HSPGs(3), but the physiology of this interaction is largely unknown. Here we show that genetic ablation or antibody-mediated depletion of APRIL aggravates atherosclerosis in mice. Mechanistically, we demonstrate that APRIL confers atheroprotection by binding to heparan sulfate chains of heparan-sulfate proteoglycan 2 (HSPG2), which limits the retention of low-density lipoproteins, accumulation of macrophages and formation of necrotic cores. Indeed, antibody-mediated depletion of APRIL in mice expressing heparan sulfate-deficient HSPG2 had no effect on the development of atherosclerosis. Treatment with a specific anti-APRIL antibody that promotes the binding of APRIL to HSPGs reduced experimental atherosclerosis. Furthermore, the serum levels of a form of human APRIL protein that binds to HSPGs, which we termed non-canonical APRIL (nc-APRIL), are associated independently of traditional risk factors with long-term cardiovascular mortality in patients with atherosclerosis. Our data reveal properties of APRIL that have broad pathophysiological implications for vascular homeostasis.
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6.
  • Mertens, F, et al. (författare)
  • Cytogenetic findings in 33 osteosarcomas
  • 1993
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 55:1, s. 44-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Thirty-three osteosarcomas (OS) were analyzed cytogenetically. Clonal chromosome changes were detected in 17 cases. Six tumors had chromosome numbers in the diploid range, 6 in the triploid range, 1 in the tetraploid range and 1 in the pentaploid range, while 3 tumors had multiple clones with different ploidy levels. Including the present 17 tumors, a total of 27 OS with clonal aberrations have been reported. The recognizable structural rearrangements in these 27 tumors clustered to chromosome arms 1p, 1q, 3p, 3q, 7q, 11p, 17p and 22q. Chromosome bands 1q11, 1q21, 1q42 and 7q11 were the most frequently rearranged, and the most common numerical rearrangements were -3, -10, -13 and -15. Supernumerary ring chromosomes, in 2 tumors as the sole change, were found in all 3 parosteal OS, which is in agreement with the findings in 1 previously reported parosteal OS. The association between ring formation and parosteal morphology represents the first cytogenetic-morphologic entity among OS.
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9.
  • Choong, P F, et al. (författare)
  • Prognostic value of Ki-67 expression in 182 soft tissue sarcomas. Proliferation--a marker of metastasis?
  • 1994
  • Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - 1600-0463. ; 102:12, s. 915-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Soft tissue sarcomas (STS) are characterized by deregulated proliferation. Ki-67 is a cell cycle antigen which may be elevated in proliferative states. We analysed Ki-67 expression in fixed and embedded tissues from STS in order to examine associations between proliferation, primary tumour characteristics, and metastasis. One hundred and eighty-two adult patients with trunk wall or extremity STS were treated at our institution between 1980 and 1992 (35 developed local recurrence and 56 developed metastases). Median follow-up time for survivors was 6 years (1-13). We used a semiquantitative score to the assess percentage of Ki-67-positive cells: < or = 10% (n = 86), > 10-25% (n = 57), > 25-50% (n = 30), > 50-75% (n = 7), > 75-100% (n = 2). Increasing Ki-67 expression correlated positively with tumour size, malignancy grade, necrosis, vascular invasion, S-phase fraction, and metastasis. A Ki-67 index Ki-D < or = 10% (n = 86) and > 10% (n = 96) defined two groups who had 84% and 56% 3-year metastasis-free survival (p = 0.0001), respectively. Tumours with Ki-D > 10 were typically large, high grade, necrotic, DNA aneuploid, and had intravascular invasion and a higher S-phase fraction. Ki-67 expression may be helpful in predicting survival of patients with soft tissue sarcomas.
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12.
  • Fritzell, Peter, et al. (författare)
  • Cost-effectiveness of lumbar fusion and nonsurgical treatment for chronic low back pain in the Swedish lumbar spine study : A multicenter, randomized, controlled trial from the Swedish Lumbar Spine Study Group
  • 2004
  • Ingår i: Spine. - : Lippincott Williams & Wilkins. - 0362-2436 .- 1528-1159. ; 29:4, s. 421-434
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Design. A cost-effectiveness study was performed from the societal and health care perspectives. Objective. To evaluate the costs-effectiveness of lumbar fusion for chronic low back pain (CLBP) during a 2-year follow-up. Summary of Background Data. A full economic evaluation comparing costs related to treatment effects in patients with CLBP is lacking. Patients and Methods. A total of 284 of 294 patients with CLBP for at least 2 years were randomized to either lumbar fusion or a nonsurgical control group. Costs for the health care sector ( direct costs), and costs associated with production losses ( indirect costs) were calculated. Societal total costs were identified as the sum of direct and indirect costs. Treatment effects were measured using patient global assessment of improvement, back pain ( VAS), functional disability (Owestry), and return to work. Results. The societal total cost per patient ( standard deviations) in the surgical group was significantly higher than in the nonsurgical group: Swedish kroner (SEK) 704,000 ( 254,000) vs. SEK 636,000 ( 208,000). The cost per patient for the health care sector was significantly higher for the surgical group, SEK 123,000 ( 60,100) vs. 65,200 ( 38,400) for the control group. All treatment effects were significantly better after surgery. The incremental cost-effectiveness ratio ( ICER), illustrating the extra cost per extra effect unit gained by using fusion instead of nonsurgical treatment, were for improvement: SEK 2,600 ( 600 - 5,900), for back pain: SEK 5,200 ( 1,100 - 11,500), for Oswestry: SEK 11,300 ( 1,200 - 48,000), and for return to work: SEK 4,100 ( 100 21,400). Conclusion. For both the society and the health care sectors, the 2-year costs for lumbar fusion was significantly higher compared with nonsurgical treatment but all treatment effects were significantly in favor of surgery. The probability of lumbar fusion being cost-effective increased with the value put on extra effect units gained by using surgery.
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14.
  • Gustafson, Pelle, et al. (författare)
  • Flow cytometric S-phase fraction in soft-tissue sarcoma: prognostic importance analysed in 160 patients
  • 1997
  • Ingår i: British Journal of Cancer. - 1532-1827. ; 75:1, s. 94-100
  • Tidskriftsartikel (refereegranskat)abstract
    • We could determine the S-phase fraction (SPF) by flow cytometric DNA analysis of paraffin archival material in 160 of 260 patients with soft-tissue sarcoma of extremity and trunk wall. The prognostic value of SPF was compared with other clinicopathological factors. The median follow-up time was 16 (6-31) years. In a univariate analysis, deep tumour location, increasing tumour size and histological malignancy grade, microscopic tumour necrosis, vascular invasion, DNA non-diploidy and high SPF (>3.0%) were associated with poor metastasis-free survival. In a multivariate analysis, microscopic tumour necrosis and high SPF were independently prognostic for metastasis. Used in combination with tumour size, microscopic tumour necrosis and vascular invasion, SPF could identify a group of patients with a 5-year metastasis-free survival rate of 0.97. This group constituted one-quarter of all patients. Patients with low SPF who did recur had a prolonged clinical course both as regards metastases and local recurrence. We conclude that SPF is a valuable adjunct in prognostication in soft-tissue sarcoma.
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16.
  • Götlind, Yu-Yuan Chiu, 1964, et al. (författare)
  • Interplay between Th1 and Th17 effector T cell pathways in the pathogenesis of spontaneous colitis and colon cancer in the Gai2-deficient mouse
  • 2013
  • Ingår i: International Immunology. - Oxford, United Kingdom : Oxford University Press. - 0953-8178 .- 1460-2377. ; 25:1, s. 35-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Gαi2-deficient mice spontaneously develop colitis. Using xMAP technology and RT-PCR, we investigated cytokine/chemokine profiles during histologically defined phases of disease: (i) no/mild, (ii) moderate, (iii) severe colitis without dysplasia/cancer and (iv) severe colitis with dysplasia/cancer, compared with age-matched wild-type (WT) littermates. Colonic dysplasia was observed in 4/11 mice and cancer in 1/11 mice with severe colitis. The histology correlated with progressive increases in colon weight/cm and spleen weight, and decreased thymus weight, all more advanced in mice with dysplasia/cancer. IL-1β, IL-6, IL-12p40, IL-17, TNF-α, CCL2 and CXCL1 protein levels in colons, but not small intestines increased with colitis progression and were significantly increased in mice with moderate and severe colitis compared with WT mice, irrespective of the absence/presence of dysplasia/cancer. CCL5 did not change during colitis progression. Colonic IL-17 transcription increased 40- to 70-fold in all stages of colitis, whereas IFN-γ mRNA was gradually up-regulated 12- to 55-fold with colitis progression, and further to 62-fold in mice with dysplasia/cancer. IL-27 mRNA increased 4- to 15-fold during the course of colitis, and colonic IL-21 transcription increased 3-fold in mice with severe colitis, both irrespective of the absence/presence of dysplasia/cancer. FoxP3 transcription was significantly enhanced (3.5-fold) in mice with moderate and severe colitis, but not in mice with dysplasia/cancer, compared with WT mice. Constrained correspondence analysis demonstrated an association between increased protein levels of TNF-α, CCL2, IL-1β, IL-6 and CXCL1 and dysplasia/cancer. In conclusion, colonic responses are dominated by a mixed T(h)1/T(h)17 phenotype, with increasing T(h)1 cytokine transcription with progression of colitis in Gαi2(-/-) mice.
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  • Järnerot, G, et al. (författare)
  • Familial occurrence of microscopic colitis: a report on five families
  • 2001
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 36:9, s. 959-962
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The etiology and pathogenesis of microscopic colitis is unknown. Whether genetic predisposition is of importance, as in many other gastrointestinal diseases, is unknown. Familial occurrence of collagenous colitis has earlier been reported only in two families. METHODS: Familial occurrence of microscopic colitis was searched for in a Swedish national microscopic colitis register. RESULTS: Familial occurrence of microscopic colitis was identified in five families. In all families a sister-sister relationship was found. Two sisters with collagenous colitis had been living apart in different Nordic countries for many years before developing the disease. In one pair, the smoking sister had collagenous colitis and the never smoking sister had lymphocytic colitis. CONCLUSIONS: Considering the relative rarity of microscopic colitis, these findings indicate that a genetic predisposition may be of importance.
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19.
  • Koul, A., et al. (författare)
  • BRCA1 and BRCA2 mutations in ovarian cancer : Covariation with specific cytogenetic features
  • 2000
  • Ingår i: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 10:4, s. 289-295
  • Tidskriftsartikel (refereegranskat)abstract
    • We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.
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20.
  • Koul, Bansi, et al. (författare)
  • Pulmonary sequelae of prolonged total venoarterial bypass: evaluation with a new experimental model
  • 1991
  • Ingår i: Annals of Thoracic Surgery. - 1552-6259. ; 51:5, s. 794-799
  • Tidskriftsartikel (refereegranskat)abstract
    • Total normothermic venoarterial bypass was established in 6 healthy pigs over a period of 18 hours. A heparin-coated closed extracorporeal system was used and no heparin was administered systemically. During the bypass period the main pulmonary artery was occluded and the heart was maintained in a beating state. All the animals maintained stable hemodynamics and normal blood gases during the entire period of bypass. In the postbypass period, the central hemodynamics continued to be stable while the arterial oxygen tension (inspired oxygen fraction = 0.21) decreased significantly (p less than or equal to 0.05). The total body oxygen uptake, on the other hand, remained unaltered. All the animals died within 4 hours after weaning off the venoarterial bypass circuit on account of pulmonary edema in 2 and cardiac arrest in 4. Death was preceded by progressive pulmonary hypertension and lactacidosis in all the animals. Histological examination of the lungs showed pulmonary parenchymal damage ranging from interstitial edema to intraalveolar hemorrhage and parenchymal necrosis involving more than 80% of the pulmonary parenchyma. A normothermic total venoarterial bypass of 18 hours duration or more produces pulmonary edema of varying severity, pulmonary hypertension, pulmonary parenchymal necrosis, and lactacidosis in healthy juvenile pigs, resulting uniformly in their death. Despite these sequelae the systemic arterial hypoxemia may only be mild to moderate.
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21.
  • Koul, Bansi, et al. (författare)
  • Venoarterial extracorporeal membrane oxygenation--how safe is it? Evaluation with a new experimental model
  • 1992
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - 1097-685X. ; 104:3, s. 579-584
  • Tidskriftsartikel (refereegranskat)abstract
    • This study was undertaken to find out if about 25% right cardiac output is sufficient for preservation of lung function during prolonged periods of venoarterial extracorporeal membrane oxygenation. Six healthy pigs weighing 57 kg were subjected to 18-hour venoarterial extracorporeal membrane oxygenation. During this period 1200 ml/min venous blood was delivered to the lungs through the pulmonary artery with the help of a separate roller pump and with use of the animal's own right ventricle to generate the pulse. Animals were observed for 6 hours after weaning from the venoarterial extracorporeal membrane oxygenation. At the sixth hour after extracorporeal membrane oxygenation, arterial oxygen tension, venous oxygen tension, lung compliance, and cardiac output had decreased significantly. Pulmonary vascular resistance and pulmonary clearance of technetium 99m-diethylenetriamine pentaacetic acid increased significantly also. The systemic arterial and venous carbon dioxide tensions, pH, and the base excess remained unchanged, as did the blood pressure and the systemic vascular resistance. Histopathology of the lung specimens revealed focal alveolar wall thickening and alveolar capillary congestion. The major portion of the pulmonary parenchyma looked normal. Alterations in pulmonary parameters cited were, to a major extent, explained on the basis of the experimental protocol followed and were believed to be reversible. This study suggests that about 25% of the systemic cardiac output should be diverted into the pulmonary artery for prevention of irreversible physiologic and histopathologic changes in the lungs during 18-hour normothermic venoarterial extracorporeal membrane oxygenation in healthy juvenile pigs.
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26.
  • Odenbring, S., et al. (författare)
  • Cartilage regeneration after proximal tibial osteotomy for medial gonarthrosis : An arthroscopic, roentgenographic, and histologic study
  • 1992
  • Ingår i: Clinical Orthopaedics and Related Research. - 0009-921X. ; :277, s. 210-216
  • Tidskriftsartikel (refereegranskat)abstract
    • High tibial osteotomy for medial gonarthrosis was performed in 28 patients (28 knees). At the time of surgery, arthroscopy was also performed and a cartilage-bone biopsy was obtained. Postoperatively, 15 patients were randomized to a cylinder plaster cast, whereas 13 patients had a hinged cast brace for early knee mobilization. At follow-up examination, two years after surgery, 16 patients accepted an arthroscopic examination with a cartilage- bone biopsy. In overcorrected knees, cartilage regeneration was found in eight of 14 patients on the medial tibial condyle and in nine of 14 on the medial femoral condyle. The main repair feature was proliferation of fibrocartilage, which covered bone and areas of fibrillated cartilage and filled vertical clefts in hyaline cartilage. The hyaline cartilage showed an increased cellularity with numerous nests of proliferating chondrocytes. No correlation was found between clinical outcome and the degree of cartilage regeneration as observed by arthroscopy, biopsy, or roentgenography. Knees with a brace postoperatively had better knee flexion two years after surgery. No difference in cartilage regeneration was recorded between knees with a plaster cast or a cast brace postoperatively.
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28.
  • Rohner, M., et al. (författare)
  • Sub-f(t) gain resonance of InP/InGaAs-HBTs
  • 2002
  • Ingår i: IEEE Transactions on Electron Devices. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9383 .- 1557-9646. ; 49:2, s. 213-220
  • Tidskriftsartikel (refereegranskat)abstract
    • Advanced npn-InP/InGaAs HBTs are often operated at high current levels for optimum high-speed performance. Because of velocity modulation effects, these transistors may operate in base-pushout although measurements of the cut-off frequency f(t) indicate the opposite. We show that the low mobility of the holes has a strong effect on the transistor operation in this regime, which is only revealed from a dynamic analysis: The unilateral power gain peaks far below f(t) followed by a -40 dB/dec roll-off. The effect was thoroughly analyzed and as a result, we present a simple equivalent circuit model that successfully describes transistors operating in pushout up to very high frequencies.
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29.
  • Rohner, M., et al. (författare)
  • Velocity-modulation and transit-time effects in InP/InGaAs HBTs
  • 2001
  • Ingår i: IEEE Electron Device Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 0741-3106 .- 1558-0563. ; 22:9, s. 417-419
  • Tidskriftsartikel (refereegranskat)abstract
    • The base-collector capacitance C-bc and the collector transit time delay tau
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30.
  • Rohner, M., et al. (författare)
  • Velocity modulation in III/V-HBTs
  • 2003
  • Ingår i: IEEE Transactions on Electron Devices. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9383 .- 1557-9646. ; 50:5, s. 1205-1213
  • Tidskriftsartikel (refereegranskat)abstract
    • Velocity modulation is shown to have a strong impact on the base/collector capacitance and the collector transit-time delay which dominate the high-speed performance of state-of-the-art HBTs. The authors present a theoretical analysis of the velocity modulation effects, which is the base of a method to assess their strength from measured S-parameters. Monte Carlo simulations are in good agreement with the measurements, providing strong support for the theory. As a consequence, the authors find that the carrier velocity is much lower than estimated from transit-time measurements when neglecting velocity modulation and that base-pushout occurs at much lower current levels than commonly expected.
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31.
  • Schwarz, V., et al. (författare)
  • 56 Gbit/s analogue PLL for clock recovery
  • 2001
  • Ingår i: Electronics Letters. - : Institution of Engineering and Technology (IET). - 0013-5194 .- 1350-911X. ; 37:22, s. 1336-1338
  • Tidskriftsartikel (refereegranskat)abstract
    • A clock-recovery circuit is reported that employs a phase-locked. loop (PLL) at 56.88 Gbit/s. and is demonstrate by locking to a 28.44 GHz sinosoidal signal while two additional circuits with adapted on-chip passive components are locked to 29 and 39 Gbit/s pseudorandom bit sequences, To the knowledge of the authors, this is the First demonstration of an integrated PLL integrated circuit for clock recovery at a data rate well above 40 Gbit/s.
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33.
  • Smeland, S, et al. (författare)
  • Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders
  • 2003
  • Ingår i: European Journal of Cancer. - 1879-0852. ; 39:4, s. 488-494
  • Tidskriftsartikel (refereegranskat)abstract
    • From 1990 to 1997, 113 eligible patients with classical osteosarcoma received neo-adjuvant chemotherapy consisting of high-dose methotrexate, cisplatin and doxorubicin. Good histological responders continued to receive the same therapy postoperatively, while poor responders received salvage therapy with an etoposide/ifosfamide combination. With a median follow-up of 83 months, the projected metastasis-free and overall survival rates at 5 years are 63 and 74%, respectively. Independent favourable prognostic factors for outcome were tumour volume < 190 ml, 24-h serum methotrexate > 4.5 muM and female gender. The etoposide/ifosfamide replacement combination did not improve outcome in the poor histological responders. In conclusion, this intensive multi-agent chemotherapy results in > 70% of patients with classical osteosarcoma surviving for 5 years. The data obtained from this non-randomised study do not support discontinuation and exchange of all drugs used preoperatively in histological poor responders. As observed in previous Scandinavian osteosarcoma studies, female gender appears to be a strong predictor of a favourable outcome. (C) 2003 Elsevier Science Ltd. All rights reserved.
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34.
  • Sturegård, Erik, et al. (författare)
  • Severe gastritis in guinea-pigs infected with Helicobacter pylori
  • 1998
  • Ingår i: Journal of Medical Microbiology. - 0022-2615. ; 47:12, s. 1123-1129
  • Tidskriftsartikel (refereegranskat)abstract
    • An appropriate animal model is essential to study Helicobacter pylori infection. The aim of this study was to investigate if H. pylori can colonise the guinea-pig stomach and whether the infection causes gastritis and a serological response similar to that observed in man. Guinea-pigs were infected either with fresh H. pylori isolates from human gastric biopsies or with a guinea-pig passaged strain. When the animals were killed, 3 and 7 weeks after inoculation, samples were taken for culture, histopathology and serology. H. pylori was cultured from 22 of 29 challenged animals. All culture-positive animals exhibited a specific immune response against H. pylori antigens in Western blotting and gastritis in histopathological examination. Antibody titres in enzyme immunoassay were elevated among animals challenged with H. pylori. The inflammatory response was graded as severe in most animals and consisted of both polymorphonuclear leucocytes and lymphocytes. Erosion of the gastric epithelium was found in infected animals. These results suggest that the guinea-pig is suitable for studying H. pylori-associated diseases. Moreover, guinea-pigs are probably more similar to man than any other small laboratory animal as regards gastric anatomy and physiology.
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35.
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36.
  • Wang, X, et al. (författare)
  • Infection of BALB/c A mice by spiral and coccoid forms of Helicobacter pylori
  • 1997
  • Ingår i: Journal of Medical Microbiology. - 0022-2615. ; 46:8, s. 657-663
  • Tidskriftsartikel (refereegranskat)abstract
    • Helicobacter pylori exists in two different morphological forms, spiral and coccoid. This study demonstrated that both forms can infect BALB/c A mice. The animals were inoculated orally three times at 2-day intervals with 10(8) cfu of both spiral and coccoid forms of strain CCUG 17874 (NCTC 11637), strain 25 and strain 553/93. Infection was followed over a 30-week period by histological scoring of the grade of inflammation in gastric biopsies. At each time point sera were collected for analysis in ELISA and immunoblot analysis. Both spiral and coccoid forms of all H. pylori strains gave significantly higher inflammation scores than a control group of animals 1 week after inoculation. The histological evidence persisted throughout the entire 30 weeks. The inflammation was most severe in the pylorus and duodenum. Infection with strain 553/93 displayed the most severe gastritis. The spiral form of strain CCUG 17874 gave an immune response after only 4 weeks, whereas its coccoid form as well as strains 25 and 553/93 (spiral and coccoid forms) gave a significant increase in antibody response in ELISA and immunoblot after 16 weeks. It is concluded that both spiral and coccoid forms of H. pylori can cause acute gastritis in BALB/c A mice.
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37.
  • Willen, Bo G., et al. (författare)
  • Experimental evaluation of the InP-InGaAs-HBT power-gain resonance
  • 2002
  • Ingår i: IEEE Electron Device Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 0741-3106 .- 1558-0563. ; 23:10, s. 579-581
  • Tidskriftsartikel (refereegranskat)abstract
    • An InP-InGaAs HBT has been evaluated that exhibits resonant hole modulation effects at a sufficiently low frequency for the resonance to be completely characterized by network analyzer measurements. It is shown that the frequency dependence of both the unilateral power gain and the current gain are modified by this effect, thus affecting the associated cutoff frequencies f(max) and f(T). A new power gain expression G(P) based on measured small-signal parameters is introduced to circumvent the ambiguity in the unilateral power gain. Finding f(max) and f(T) by means of extrapolation of G(P) and h(21), respectively, from a region below the,resonance frequency is proposed to yield appropriate estimates of the figures-of-merit for device applications.
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38.
  • Willen, Bo G., et al. (författare)
  • Improved automatic parameter extraction of InP-HBT small-signal equivalent circuits
  • 2002
  • Ingår i: IEEE transactions on microwave theory and techniques. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9480 .- 1557-9670. ; 50:2, s. 580-583
  • Tidskriftsartikel (refereegranskat)abstract
    • An improved automatic extraction technique for determination of the element values of an InP heterojunction-bipolar-transistor small-signal T-model is presented. Numerical optimization is shown to yield reproducible and physically relevant results when using a suitable figure-of-merit. The outcome of such an extraction is displayed for a range of operation points and the resulting bias dependencies of the element values is shown to be in good agreement with theoretical effects. The technique is further used to validate the quality of the extraction itself by showing a significant sensitivity to a deliberate error in the value of each element.
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39.
  • Willen, Bo G., et al. (författare)
  • Unilateral power gain limitations due to dynamic base widening effects
  • 2001
  • Ingår i: IEEE Electron Device Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 0741-3106 .- 1558-0563. ; 22:8, s. 370-372
  • Tidskriftsartikel (refereegranskat)abstract
    • It is shown that the maximum frequency of oscillation of an InP-HBT may be limited by the low velocity of the holes when operated in the base push-out regime since modulation of the extended base will be delayed by the hole transit time, having an effect also on the electron current. The resulting delay of the current response causes a peaking of the unilateral power gain followed by a -40 dB/decade roll-off, being a source for a strong overestimation of the extrapolated cut-off frequency when neglected,An extended equivalent small-signal circuit is proposed that takes these effects into account.
  •  
40.
  • Willén, Katarina, et al. (författare)
  • Heterogeneous Association of Alzheimer's Disease-Linked Amyloid-β and Amyloid-β Protein Precursor with Synapses
  • 2017
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 60:2, s. 511-524
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease (AD) is increasingly viewed as a disease of synapses. Loss of synapses correlates better with cognitive decline than amyloid plaques and neurofibrillary tangles, the hallmark neuropathological lesions of AD. Soluble forms of amyloid-β (Aβ) have emerged as mediators of synapse dysfunction. Aβ binds to, accumulates, and aggregates in synapses. However, the anatomical and neurotransmitter specificity of Aβ and the amyloid-β protein precursor (AβPP) in AD remain poorly understood. In addition, the relative roles of Aβ and AβPP in the development of AD, at pre- versus post-synaptic compartments and axons versus dendrites, respectively, remain unclear. Here we use immunogold electron microscopy and confocal microscopy to provide evidence for heterogeneity in the localization of Aβ/AβPP. We demonstrate that Aβ binds to a subset of synapses in cultured neurons, with preferential binding to glutamatergic compared to GABAergic neurons. We also highlight the challenge of defining pre- versus post-synaptic localization of this binding by confocal microscopy. Further, endogenous Aβ42 accumulates in both glutamatergic and GABAergic AβPP/PS1 transgenic primary neurons, but at varying levels. Moreover, upon knock-out of presenilin 1 or inhibition of γ-secretase AβPP C-terminal fragments accumulate both pre- and post-synaptically; however earlier pre-synaptically, consistent with a higher rate of AβPP processing in axons. A better understanding of the synaptic and anatomical selectivity of Aβ/AβPP in AD can be important for the development of more effective new therapies for this major disease of aging.
  •  
41.
  • Willen, R, et al. (författare)
  • Similarity of uterine mucosa changes in patients treated by Raloxifen and Tamoxifen
  • 2002
  • Ingår i: Anticancer research. - 1791-7530. ; 22:2B, s. 1121-1125
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Selective estrogen receptor modulators (SERMS) like Tamoxifen and Raloxifen are used for menopausal symptoms, prevention of cardio-vascular diseases, osteoporosis and mammary carcinoma. Tamoxifen acts as an estrogen inhibitor on the mammary gland, but stimulates postmenopausal uterine mucosa in about 25% of cases while decreasing the risk of osteoporosis. Materials, Methods and Results: In three menopausal women, 56, 79 and 62 years of age, we found uterine mucosal changes similar to what is found in Tamoxifen-treated patients. Using light microscopy and immuno-histopathological techniques, partly cystic mucosa with both atrophic and proliferating glands was found. Strong stromal proliferation was also seen with the typical sharp-edged form of stromal cells and mitoses. A strong ostrogen and progesterone reaction was revealed with immuno-histopathological techniques in both gland and stromal parts. Conclusion: Taking into account the variable amount of different estrogen-receptor types in the uterine mucosa, we can not in the long run expect that no patient will react with estrogen-stimulation features on SERMs like Raloxifen. Further studies and thorough observations are needed to elucidate the true frequency of Raloxifen impact on the uterine mucosa.
  •  
42.
  • Öhman, Lena, 1967, et al. (författare)
  • Acellular Bordetella pertussis vaccine enhances mucosal interleukin-10 production, induces apoptosis of activated Th1 cells and attenuates colitis in Galphai2-deficient mice.
  • 2005
  • Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 141:1, s. 37-46
  • Tidskriftsartikel (refereegranskat)abstract
    • Mice deficient for the inhibitory G protein subunit alpha2 (Galphai2(-/-)) spontaneously develop a progressive inflammatory bowel disease resembling ulcerative colitis, and have a T helper 1 (Th1)-dominated immune response prior to onset of colitis, which is further augmented after the onset of disease. The present study was performed to investigate whether the Galphai2(-/-) mice were able to down-regulate the Th1-dominated inflammatory mucosal immune response and/or induce an anti-inflammatory Th2/T regulatory response and thereby diminish the severity of colitis following treatment with acellular Bordetella pertussis vaccine. The acellular vaccine against B. pertussis, the causative agent of whooping cough, has been demonstrated to induce a Th2-mediated response in both man and mice. We therefore treated Galphai2(-/-) mice intraperitoneally with a three-component acellular B. pertussis vaccine. The treated Galphai2(-/-) mice showed significantly increased interleukin (IL)-10 production in intestinal tissue, associated with significantly reduced colitis and decreased mortality, compared to untreated Galphai2(-/-) mice. The attenuation of colitis in Galphai2(-/-) mice was due, at least partly, to the B. pertussis surface antigen filamentous haemagglutinin (FHA), which almost completely inhibited proliferation of CD4(+) T cells and stimulated apoptosis of activated CD4(+) T helper 1 cells. In conclusion, the three-component acellular B. pertussis vaccine containing filamentous haemagglutinin increases the production of IL-10 in the intestinal mucosa, induces apoptosis of activated Th1 cells and attenuates colitis in Galphai2(-/-) mice.
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