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Sökning: WFRF:(Michael H) > (1990-1999)

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1.
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3.
  • Bremer, Kåre, et al. (författare)
  • An ordinal classification for the families of flowering plants
  • 1998
  • Ingår i: ANNALS OF THE MISSOURI BOTANICAL GARDEN. - : MISSOURI BOTANICAL GARDEN. - 0026-6493. ; 85:4, s. 531-553
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Recent cladistic analyses are revealing the phylogeny of flowering plants in increasing detail, and there is support for the monophyly of many major groups above the family level. With many elements of the major branching sequence of phylogeny established
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4.
  • Chan, H C, et al. (författare)
  • Angiotensin II receptor type I-regulated anion secretion in cystic fibrosis pancreatic duct cells.
  • 1997
  • Ingår i: The Journal of membrane biology. - 0022-2631. ; 156:3, s. 241-9
  • Tidskriftsartikel (refereegranskat)abstract
    • The beta-adrenergic (cAMP-dependent) regulation of Cl- conductance is defective in cystic fibrosis (CF). The present study explored alternative regulation of anion secretion in CF pancreatic ductal cells (CFPAC-1) by angiotensin II (AII) using the short-circuit current (ISC) technique. An increase in ISC could be induced in CFPAC-1 cells by basolateral or apical application of AII in a concentration-dependent manner (EC50 at 3 microm and 100 nm, respectively). Angiotensin receptor subtypes were identified using specific antagonists, losartan and PD123177, for AT1 and AT2 receptors, respectively. It was found that losartan (1 microm) could completely inhibit the AII-induced ISC, whereas, PD123177 exerted insignificant effect on the ISC, indicating predominant involvement of AT1 receptors. The presence of AT1 receptors in CFPAC-1 cells was also demonstrated by immunohistochemical studies using specific antibodies against AT1 receptors. Confocal microscopic study demonstrated a rise in intracellular Ca2+ upon stimulation by AII indicating a role of intracellular Ca2+ in mediating the AII response. Depletion of intracellular but not extracellular pool of Ca2+ diminished the AII-induced ISC. Treatment of the monolayers with a Cl- channel blocker, DIDS, markedly reduced the ISC, indicating that a large portion of the AII-activated ISC was Cl--dependent. AII-induced ISC was also observed in monolayers whose basolateral membranes had been permeabilized by nystatin, suggesting that the ISC was mediated by apical Cl- channels. Our study indicates an AT1-mediated Ca2+-dependent regulatory mechanism for anion secretion in CF pancreatic duct cells which may be important for the physiology and pathophysiology of the pancreas.
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5.
  • Fu, Michael, 1963, et al. (författare)
  • Agonist-like activity of anti-peptide antibodies directed against an autoimmune epitope on the heart muscarinic acetylcholine receptor.
  • 1994
  • Ingår i: Receptors & channels. - 1060-6823. ; 2:2, s. 121-30
  • Tidskriftsartikel (refereegranskat)abstract
    • A synthetic peptide corresponding to amino acids 169-193 of the second extracellular loop of the M2 human muscarinic receptor was used to raise antibodies in rabbits. Affinity purified antibodies specifically recognized a major band with a molecular weight of about 80 kDa on the electrotransferred membrane proteins of both rat ventricles and chinese hamster ovary cells expressing recombinant muscarinic receptors. Incubation of these antibodies with rat myocardial membranes resulted not only in a decrease in the maximal binding capacity, but also in a decrease in receptor antagonist affinity. These antibodies could also mimic the effects of agonist stimulation as demonstrated by inhibition of isoproterenol-stimulated cAMP accumulation and by a negative chronotropic effect on cultured cardiomyocytes. These results suggest that the second extracellular loop of the M2 muscarinic receptor is an immunologically and functionally important domain with properties comparable to those found for autoantibodies against the same domain in idiopathic dilated cardiomyopathy. It strengthens the hypothesis that the second extracellular loop of the members of the superfamily of G-protein coupled membrane receptors could be the main immunogenic region responsible for a pathogenic autoimmune response.
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6.
  • Shattuck Eidens, Donna, et al. (författare)
  • A Collaborative Survey of 80 Mutations in the BRCA1 Breast and Ovarian Cancer Susceptibility Gene : Implications for Presymptomatic Testing and Screening
  • 1995
  • Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 273:7, s. 535-541
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES:To report the initial experience of an international group of investigators in identifying mutations in the BRCA1 breast and ovarian cancer susceptibility gene, to assess the spectrum of such mutations in samples from patients with different family histories of cancer, and to determine the frequency of recurrent mutations.DESIGN:Nine laboratories in North America and the United Kingdom tested for BRCA1 mutations in DNA samples obtained from a total of 372 unrelated patients with breast or ovarian cancer largely chosen from high-risk families. Three of these laboratories also analyzed a total of 714 additional samples from breast or ovarian cancer cases, including 557 unselected for family history, for two specific mutations that had been found to recur in familial samples.PARTICIPANTS:A total of 1086 women with either breast or ovarian cancer.MAIN OUTCOME MEASURE:The detection of sequence variation in patients' DNA samples that is not found in sets of control samples.RESULTS:BRCA1 mutations have now been identified in a total of 80 patient samples. Thirty-eight distinct mutations were found among 63 mutations identified through a complete screen of the BRCA1 gene. Three specific mutations appeared relatively common, occurring eight, seven, and five times, respectively. When specific tests for the two most common mutations were performed in larger sets of samples, they were found in 17 additional patients. Mutations predicted to result in a truncated protein accounted for 86% of the mutations detected by complete screening.CONCLUSIONS:The high frequency of protein-terminating mutations and the observation of many recurrent mutations found in a diverse set of samples could lead to a relatively simple diagnostic test for BRCA1 mutations. More data must be accumulated to address specifically the sensitivity and specificity of such a diagnostic testing procedure and to better estimate the age-specific risk for breast and ovarian cancer associated with such mutations.
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7.
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8.
  • Bishop, Kevin, et al. (författare)
  • The hydrology of the covered catchment
  • 1998
  • Ingår i: Experimental Reversal of Acid Rain Effects: the Gårdsjön Project. - : John Wiley & Sons. ; , s. 109-135
  • Bokkapitel (refereegranskat)
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9.
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10.
  • Chang, W, et al. (författare)
  • Parathyroid Ca(2+)-conducting currents are modulated by muscarinic receptor agonists and antagonists.
  • 1997
  • Ingår i: The American journal of physiology. - 0002-9513. ; 273:5 Pt 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Parathyroid cells express Ca(2+)-conducting cation currents, which are activated by raising the extracellular Ca2+ concentration ([Ca2+]o) and blocked by dihydropyridines. We found that acetylcholine (ACh) inhibited these currents in a reversible, dose-dependent manner (50% inhibitory concentration approximately equal to 10(-8) M). The inhibitory effects could be mimicked by the agonist (+)-muscarine. The effects of ACh were blunted by the antagonist atropine and reversed by removing ATP from the pipette solution (+)-Muscarine enhanced the adenosine 3',5'-cyclic monophosphate (cAMP) production by 30% but had no effect on inositol phosphate accumulation in parathyroid cells. Oligonucleotide primers, based on sequences of known muscarinic receptors (M1-M5), were used in reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify receptor cDNA from parathyroid poly (A)+ RNA. RT-PCR products displayed > 90% nucleotide sequence identity to human M2- and M4-receptor cDNAs. Expression of M2-receptor protein was further confirmed by immunoblotting and immunocytochemistry. Thus parathyroid cells express muscarinic receptors of M2 and possibly M4 subtypes. These receptors may couple to dihydropyridine-sensitive, cation-selective currents through the activation of adenylate cyclase and ATP-dependent pathways in these cells.
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11.
  • Dannetun, Per, et al. (författare)
  • New Results on Metal-Polymer Interfaces
  • 1993
  • Ingår i: Molecular Crystals and Liquid Crystals. - : Taylor & Francis. - 1542-1406 .- 1563-5287. ; 228:1, s. 43-48
  • Tidskriftsartikel (refereegranskat)abstract
    • New results on studies of the early stages of formation of the aluminum-poly(p-phenylenevinylene) interface are presented.
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12.
  • Dannetun, Per, et al. (författare)
  • Proceedings of the International Conference on Science and Technology of Synthetic Metals The chemical and electronic structure of the interface between aluminum and conjugated polymers or molecules
  • 1993
  • Ingår i: Synthetic metals. - : Elsevier. - 0379-6779 .- 1879-3290. ; 55:1, s. 212-217
  • Tidskriftsartikel (refereegranskat)abstract
    • The interaction between aluminum and α-ω-diphenyltetradecaheptaenee (DP7), α-sexithienyl (6T), and poly(p-phenylenevinylene) (PPV), respectively have been studied using both X-ray Photoelectron Spectroscopy (XPS) and Ultraviolet Photoelectron Spectroscopy (UPS). The UPS valence band spectra, are interpreted with the help of quantum chemical calculations based upon Modified Neglect of Diatomic Overlap (MNDO), Valence Effective Hamitonian (VEH) and ab initio Hartree-Fock methods. DP7 is a model molecule for polyacetylene, while 6T is a model molecule (an oligomer) of polythiophene. The results indicate that aluminum reacts strongly with the surfaces of all of the materials studied. The Ï€-electronic structure of each material was strongly modified. Furthermore, aluminum reacts preferentially with the polyene partof DP7, with the vinylene part of PPV, and with the α-carbons of the thiophene nits of 6T.
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13.
  • Dannetun, Per, et al. (författare)
  • The evolution of charge-induced gap states in degenerate and non-degenerate conjugated molecules and polymers as studied by photoelectron spectroscopy
  • 1994
  • Ingår i: Synthetic metals. - : Elsevier. - 0379-6779 .- 1879-3290. ; 67:1, s. 81-86
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the results of ultraviolet photoelectron spectroscopy (UPS) studies of the interaction between sodium and conjugated systems for a series of diphenylpolyees and diffrent oligomers of poly(p-phenylenevinylene) (PPV). The diphenylpolyenes include molecules containing two (i.e., stilbene) to 14 carbon atoms in the polyene part; stilbene itself can also be considered as a phenyl-capped monomer of PPV. Furthermore, a PPV oligomer with three phenylene units, as well as PPV itself, has been studied. The experimental results are interpreted with the help of quantum-chemical calculations using the Hartree-Fock semi-empirical Austin Model 1 (AM1) and valence-effective Hamiltonian (VEH) methods. An important result is that all the systems react strongly with sodium; at high doping levels two new doping-induced states are detected above the valence band edge of the pristine material. In the case of saturation-doped diphenylpolyenes (i.e., two sodiums per molecule), the new states can be discussed in terms of soliton-antisoliton pairs confined within the polyene part of the molecules; in contrast, the self-localized states induced in PPV and its oligomers have to be referred to as bipolarons.
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14.
  • de Jong, H W, et al. (författare)
  • The influence of backscatter material on 99mTc and 201Tl line source responses
  • 1999
  • Ingår i: Physics in Medicine and Biology. - 1361-6560. ; 44:3, s. 665-679
  • Tidskriftsartikel (refereegranskat)abstract
    • SPECT projections are contaminated by scatter, resulting in reduced image contrast and quantitative errors. When tissue is present behind the source, some of the detected photons backscatter via this tissue. Particularly in dual-isotope SPECT and in combined emission-transmission SPECT, backscatter constitutes a major part of the down-scatter contamination in lower-energy windows. In this paper, the effects of backscatter material were investigated. Planar images of 99mTc and 201Tl line sources between varying numbers of Perspex slabs were analysed using the photopeak windows and various scatter windows. In the 99mTc photopeak window no significant change in total counts due to backscatter material was measured. In the 201Tl photopeak window an increase of about 10% in total counts was observed. In the scatter windows an even more explicit influence of backscatter material was measured. For instance, at a forward depth of 10 cm, total counts of a 99mTc source detected in the 72 keV window eventually doubled with increasing backscatter material, compared with the situation without backscatter material. The backscatter contribution plateaued when more than 5-10 cm of scatter material was placed behind the source. In conclusion, backscatter should be taken into account, particularly in model-based down-scatter correction methods in dual-isotope SPECT and combined emission-transmission SPECT.
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16.
  • Fu, Michael, 1963, et al. (författare)
  • Agonist-like activity of antibodies to angiotensin II receptor subtype 1 (AT1) from rats immunized with AT1 receptor peptide.
  • 1999
  • Ingår i: Blood pressure. - 0803-7051. ; 8:5-6, s. 317-24
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study, rats were immunized with angiotensin II receptor subtype 1 (AT1) receptor peptides for 3 months to see if the immunization produced specific anti-AT1 receptor antibodies and if continuous stimulation for 3 months affected blood pressure or induced morphological changes in the organs containing AT1 receptors. Our results showed that there were constant high levels of circulating antibodies throughout the study period in all rats of the immunized group, but not in the control rats, and that there were almost no significant cross-reactions of antisera with AT2 receptor peptide and alpha1 adrenoceptor peptide, except in four rats, which showed low cross-reactions with alpha1 adrenoceptor and AT2 receptor peptides. When an affinity-purified anti-AT1 receptor antibody was used, it specifically displayed the AT1-stimulatory positive chronotropic effect and also localized AT1 receptors. However, in the immunized group, saturation binding of AT1 in homogenates from kidneys showed no difference either in maximal binding sites (Bmax) or in antagonist affinity (Kd). No difference in mRNA of AT1a was found in either kidney or heart, and no morphological changes in the organs were observed, as compared with the control group. Furthermore, immunization did not cause hypertension. In conclusion, the synthetic peptide corresponding to the second extra-cellular loop of the human AT1 receptor was able to produce highly specific and functionally active anti-AT1 receptor antibodies, but unable to induce pathological structural changes or hypertension.
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17.
  • Garkavij, Michael, et al. (författare)
  • Improving radioimmunotargeting of tumors: the impact of preloading unlabeled L6 monoclonal antibody on the biodistribution of 125I-L6 in rats
  • 1994
  • Ingår i: Journal of nuclear biology and medicine (Turin, Italy : 1991). - 0368-3249. ; 38:4, s. 594-600
  • Tidskriftsartikel (refereegranskat)abstract
    • In the radioimmunotherapy of malignancies the uptake of monoclonal antibodies (MoAb) is commonly low in tumors compared with normal tissue. Several methods have been suggested to increase the tumor-to-normal tissue (T/N) ratio. In this study we have investigated the biodistribution of different amounts of 125I-L6-biotin MoAb in combination with a preload of unlabeled L6 MoAb. Nude rats were injected with 50 micrograms or 250 micrograms of unlabeled L6 24 hours prior to the injection of 10 micrograms, 50 micrograms or 250 micrograms of 125I-L6, antipancarcinoma MoAb. Dissections were performed 24 hours after the injection of radiolabeled MoAb. The maximal enhancement of tumor uptake with simultaneously decreased uptake in normal tissues was with 250 micrograms of 125I-L6 preceded by a preload of 50 micrograms unlabeled L6. Mean T/N ratios were improved by a factor of 2.9 for bone marrow, 3.4 for liver, 3.7 for lungs and 2.3 for kidneys as compared with the corresponding controls. This study demonstrated that preinjection of optimal amounts of unlabeled L6 MoAb may increase the uptake of 125I-L6 by tumor and improve the T/N ratios. Based on present data, preloading with unlabeled MoAb should be considered in future clinical studies with immunoconjugates to improve the radioimmunotargeting of tumors. It is essential to titrate an appropriate amount of the preload, thus avoiding possible tumor antigen saturation of unlabeled MoAbs but simultaneously decreasing the uptake of subsequently injected radiolabeled MoAb in normal tissues.
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18.
  • Holgersson, J, et al. (författare)
  • Blood group A glycolipid antigen expression in kidney, ureter, kidney artery, and kidney vein from a blood group A1Le(a-b+) human individual. Evidence for a novel blood group A heptaglycosylceramide based on a type 3 carbohydrate chain.
  • 1990
  • Ingår i: The Journal of biological chemistry. - 0021-9258. ; 265:34, s. 20790-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Kidney, ureter, kidney artery, and kidney vein tissue were obtained from a single human transplant specimen. The donors erythrocyte blood group phenotype was A1Le(a-b+). Total non-acid glycolipid fractions were isolated and individual glycolipid components were identified by immunostaining thin layer plates with a panel of monoclonal antibodies and by mass spectrometry of the permethylated and permethylated-reduced total glycolipid fractions. The dominating glycolipids in all tissues were mono- to tetraglycosylceramides. In the kidney, ureter, and artery tissue less than 1% of the glycolipids were of blood group type, having more than 4 sugar residues. In contrast, 14% of the vein glycolipids were of blood group type, and the dominating components were type 1 chain blood group H pentaglycosylceramides and A hexaglycosylceramides. Trace amounts of structurally different blood group A glycolipids (type 1 to 4 core saccharide chains) with up to 10 sugar residues were found in the kidney, ureter, and vein tissues, including evidence for a novel blood group A heptaglycosylceramide based on the type 3 chain in the vein. The only detected A glycolipid antigen in the artery tissue was the blood group A difucosyl type 1 chain heptaglycosylceramide (ALeb) structure. Blood group Lewis and related antigens (Lea, Leb, and ALeb) were expressed in the kidney, ureter, and artery, but were completely lacking in the vein, indicating that the Le gene-coded alpha 1-4-fucosyltransferase was not expressed in this tissue. The X and Y antigens (type 2 chain isomers of the Lea and Leb antigens) were detected only in the kidney tissue.
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20.
  • Holtbäck, U, et al. (författare)
  • Receptor recruitment: a mechanism for interactions between G protein-coupled receptors.
  • 1999
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 96:13, s. 7271-5
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a great deal of evidence for synergistic interactions between G protein-coupled signal transduction pathways in various tissues. As two specific examples, the potent effects of the biogenic amines norepinephrine and dopamine on sodium transporters and natriuresis can be modulated by neuropeptide Y and atrial natriuretic peptide, respectively. Here, we report, using a renal epithelial cell line, that both types of modulation involve recruitment of receptors from the interior of the cell to the plasma membrane. The results indicate that recruitment of G protein-coupled receptors may be a ubiquitous mechanism for receptor sensitization and may play a role in the modulation of signal transduction comparable to that of the well established phenomenon of receptor endocytosis and desensitization.
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22.
  • Jerkeman, Mats, et al. (författare)
  • CHOP versus MACOP-B in aggressive lymphoma--a Nordic Lymphoma Group randomised trial
  • 1999
  • Ingår i: Annals of Oncology. - 1569-8041. ; 10:9, s. 1079-1086
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The long-term survival of patients with advanced stage aggressive lymphoma has not improved significantly during the last twenty years. In a randomised trial, the efficacy of MACOP-B, a six-drug weekly chemotherapy regimen, was compared to CHOP, the current standard regimen, in terms of overall and failure-free survival, toxicity and health related quality of life. PATIENTS AND METHODS: Four hundred five patients with aggressive lymphoma, stage II-IV, age 18-67, were randomised to receive either 12 weeks of MACOP-B or 8 courses of CHOP over 24 weeks. Special emphasis was put in the definition of Ann Arbor stage in extranodal disease. A subset of 95 patients also entered a quality of life study, based on the EORTC QLQ-C30. RESULTS: Thirty-one patients were ineligible. Among the remaining 374 patients, the median age was 52 years. According to the age-adjusted International Prognostic Index, 37% were 'high-intermediate' or 'high-risk' patients. No difference could be demonstrated, either in overall survival (60% at five years in the MACOP-B group and 59% in the CHOP group) or in failure-free survival (47% at five years with MACOP-B and 44% with CHOP). In terms of quality of life, physical function and global quality of life were more impaired in patients receiving MACOP-B, who also exhibited more non-haematological toxicity. CONCLUSION: No superiority of MACOP-B compared to CHOP could be demonstrated. CHOP remains the treatment of choice in low-risk patients. At present, intensified or experimental treatment should be reserved for high-risk disease.
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23.
  • Leung, P S, et al. (författare)
  • Angiotensin II receptors, AT1 and AT2 in the rat epididymis. Immunocytochemical and electrophysiological studies.
  • 1997
  • Ingår i: Biochimica et biophysica acta. - 0006-3002. ; 1357:1, s. 65-72
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous work from our laboratory has provided evidence for the presence of a tissue renin-angiotensin system in the rat epididymis. In the current investigation, the regional localization of angiotensin II receptors, type I (AT1) and type II (AT2) was studied immunocytochemically using specific anti-peptide antibodies against the second extracellular loops of AT1 and AT2 receptors, and pharmacologically using specific receptor antagonists in conjunction with the short-circuit current technique. The immunocytochemical results showed that AT1 and AT2 immunoreactivities were predominantly localized in the basal region of the epididymal epithelium. Electrophysiological studies using the short-circuit current technique demonstrated a stimulatory effect of basolaterally applied angiotensin II on the epididymal electrogenic ion transport. This effect was inhibitable by the addition of AT1 antagonist, losartan but not by AT2 antagonist, PD123177, indicating a functional role of AT1 in epididymal electrolyte transport. The present finding suggests that angiotensin II receptors may play an important role in the regulation of epididymal function.
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24.
  • Leung, P S, et al. (författare)
  • Angiotensin II receptors: localization of type I and type II in rat epididymides of different developmental stages.
  • 1997
  • Ingår i: The Journal of membrane biology. - 0022-2631. ; 157:1, s. 97-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies from our laboratory have provided evidence for the existence of a local renin-angiotensin system in the rat epididymis. Evidence has also accumulated, indicating that locally formed angiotensin II from the rat epididymis may play a paracrine and/or autocrine role in regulating epididymal electrolyte and fluid transport. In the present study, specific anti-peptide antibodies against the second extracellular loops of angiotensin II type I (AT1) and type II (AT2) receptors were used to localize immunocytochemically these receptors in the rat cauda epididymides of three developmental stages, namely, immature (2-week), early mature (6-week) and fully mature (10-week). The immunostaining intensity for AT1 receptors was found to be stronger than that for AT2 receptors throughout rat epididymides of all stages. However, the immunostaining for both AT1 and AT2 receptors observed in the fully mature rat epididymis was much more intense than that observed in the epididymides of the two younger stages. While the immunostaining for both AT1 and AT2 receptors in the younger rat epididymides appeared to be distributed in both basal and apical regions, the immunostaining in the fully mature epididymis was predominantly localized in the basal region. The present finding of the differential patterns of angiotensin II receptor immunoreactivity in three different stages of the rat epididymis may reflect the fine tuning of rat epididymal function by angiotensin II, acting as a paracrine or autocrine agent, during the course of development.
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25.
  • Leung, P S, et al. (författare)
  • Differential gene expression of angiotensin II receptor subtypes in the epididymides of mature and immature rats.
  • 1998
  • Ingår i: Life sciences. - 0024-3205. ; 62:5, s. 461-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have suggested that epididymal and sperm functions are subject to control by a local renin-angiotensin II system (RAS) in the rat epididymis. Type-1 angiotensin II receptor, AT1 and type-2 receptor, AT2 were localized in epididymal epithelium, indicating that RAS may act in a paracrine or autocrine fashion to regulate fluid secretion, probably through the basally placed membrane-bound AT1 protein as revealed by immunocytochemical and electrophysiological studies. In the present work, the expression of the angiotensin II receptor subtypes in the rat epididymis was showed by western blot analysis and reverse-transcription polymerase chain reaction (RT-PCR) using specific primers for the angiotensin II receptor subtypes. Western blot analysis showed the expression of AT1 receptor in the rat epididymis. Results from RT-PCR, using specific primers based on the corresponding angiotensin II receptor subtype genes for AT1a, AT1b and AT2 , demonstrated the differential expression of mRNAs from these receptor subtypes in the epididymides of mature and immature rats. Both the genes for AT1a and AT1b, but not that for AT2, are predominantly expressed in the epididymides of mature rat. In contrast, only AT1a and AT2 were highly expressed in the epididymides of immature rat. These results suggest that the expression of type-1 and type-2 angiotensin II receptor subtypes are developmentally regulated. Type-1 subtype may play a role in regulation of electrolyte and fluid transport in mature rat whereas type-2 subtype may be important in growth and development in the immature rat.
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26.
  • Liu, H R, et al. (författare)
  • Screening of serum autoantibodies to cardiac beta1-adrenoceptors and M2-muscarinic acetylcholine receptors in 408 healthy subjects of varying ages.
  • 1999
  • Ingår i: Autoimmunity. - 0891-6934. ; 29:1, s. 43-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Autoantibodies to cardiac beta1-adrenoceptors and M2-muscarinic receptors have mainly been found in the sera of patients with idiopathic dilated cardiomyopathy (DCM). In order to elucidate the pathological significance of these autoantibodies in DCM, it is necessary to understand their characteristic distribution in a healthy population of different genders and ages. The peptides corresponding to the sequences of the second extracellular loops of the human beta1-adrenoceptor and M2-muscarinic receptors were therefore used as antigens to screen the sera of 408 healthy subjects of different ages (ranging from 0.5 to 85 years). Of 408 sera, 41 (10.0%) and 46 (11.3%) recognized the beta1-adrenoceptor and M2-muscarinic receptor peptides respectively. Of the positive sera for beta1-adrenoceptors and M2-muscarinic receptors, up to 63.4% and 56.5% had both anti-beta1-adrenoceptor and anti-M2-muscarinic receptor autoantibodies respectively. The antibody titres of the positive sera of healthy subjects were all of a low level, with a geometric mean titre of 1:42+/-1.9 for anti-beta1-adrenoceptor antibodies and 1:51+/-1.7 for anti-M2-muscarinic receptor antibodies. The frequency of occurrence of autoantibodies to both receptors in the sera of healthy subjects increased significantly with age. In conclusion, the autoantibodies to beta1-adrenoceptors and M2-muscarinic receptors in the sera of healthy subjects are characterized by a low frequency of occurrence and low titre, with the frequency of occurrence increasing with age.
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27.
  • Lohmander, L. S., et al. (författare)
  • Temporal patterns of stromelysin-1, tissue inhibitor, and proteoglycan fragments in human knee joint fluid after injury to the cruciate ligament or meniscus
  • 1994
  • Ingår i: Journal of Orthopaedic Research. - 0736-0266. ; 12:1, s. 21-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Stromelysin-1, tissue inhibitor of metalloproteinases-1 (TIMP-1), and proteoglycan fragments were quantified in knee synovial fluid samples in a cross-sectional study of patients who had injury to the anterior cruciate ligament or the meniscus. The average concentrations of stromelysin-1 and TIMP-1 increased 25-fold and 10-fold within the first day after the trauma, respectively, and the concentration of proteoglycan fragments increased 4- fold. From approximately 1-6 months after injury, the levels of these markers were higher after injury to the cruciate ligament than after injury to the meniscus. From 6 months to 18 years after trauma, however, the levels of stromelysin-1 and TIMP-1 in patients who had an injury to the ligament were the same as the levels in patients who had a meniscal lesion, but the levels were increased compared with those for a reference group of healthy volunteers. The molar balance of stromelysin-1 to TIMP-1 in synovial fluid in both groups of injured joints changed from a balance representing an excess of free inhibitor in the normal joint to one representing an excess of free enzyme in the injured joint. The increased release of these markers to joint fluid both early and late after trauma may be caused by a change in the loading patterns in the knee with an injured ligament or meniscus or by synovitis induced by bleeding. The increased release may be associated with the frequent development of posttraumatic osteoarthritis in patients with these injuries.
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30.
  • Mardirossian, G, et al. (författare)
  • A new rectal model for dosimetry applications
  • 1999
  • Ingår i: Journal of Nuclear Medicine. - 0161-5505. ; 40:9, s. 1524-1531
  • Tidskriftsartikel (refereegranskat)abstract
    • A revised geometric representative model of the lower part of the colon, including the rectum, the urinary bladder and prostate, is proposed for use in the calculation of absorbed dose from injected radiopharmaceuticals. The lower segment of the sigmoid colon as described in the 1987 Oak Ridge National Laboratory mathematical phantoms does not accurately represent the combined urinary bladder/rectal/prostate geometry. In the revised model in this study, the lower part of the abdomen includes an explicitly defined rectum. The shape of sigmoid colon is more anatomically structured, and the diameters of the descending colon are modified to better approximate their true anatomic dimensions. To avoid organ overlap and for more accurate representation of the urinary bladder and the prostate gland (in the male), these organs are shifted from their originally defined positions. The insertion of the rectum and the shifting of the urinary bladder will not overlap with or displace the female phantom's ovaries or the uterus. In the adult male phantom, the prostatic urethra and seminal duct are also included explicitly in the model. The relevant structures are defined for the newborn and 1-, 5-, 10- and 15-y-old (adult female) and adult male phantoms. METHODS: Values of the specific absorbed fractions and radionuclide S values were calculated with the SIMDOS dosimetry package. Results for 99mTc and other radionuclides are compared with previously reported values. RESULTS: The new model was used to calculate S values that may be crucial to calculations of the effective dose equivalent. For 131I, the S (prostate<--urinary bladder contents) and S (lower large intestine [LLI] wall<--urinary bladder contents) are 6.7 x 10(-6) and 3.41 x 10(-6) mGy/MBq x s, respectively. Corresponding values given by the MIRDOSE3 computer program are 6.23 x 10(-6) and 1.53 x 10(-6) mGy/MBq x s, respectively. The value of S (rectum wall<--urinary bladder contents) is 4.84 x 10(-5) mGy/MBq x s. For 99mTc, we report S (testes<--prostate) and S (LLI wall<--prostate) of 9.41 x 10(-7) and 1.53 x 10(-7) mGy/MBq x s versus 1.33 x 10(-6) and 7.57 x 10(-6) mGy/MBq x s given by MIRDOSE3, respectively. The value of S (rectum wall<--prostate) for 99mTc is given as 4.05 x 10(-6) mGy/MBq x s in the present model. CONCLUSION: The new revised rectal model describes an anatomically realistic lower abdomen region, thus giving improved estimates of absorbed dose. Due to shifting the prostate gland, a 30%-45% reduction in the testes dose and the insertion of the rectum leads to 48%-55% increase in the LLI wall dose when the prostate is the source organ.
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31.
  • Rydberg, Lennart, 1944, et al. (författare)
  • ABO-incompatible kidney transplantation (A2 to O). Qualitative and semiquantitative studies of the humoral immune response against different blood group A antigens.
  • 1990
  • Ingår i: Transplantation. - 0041-1337. ; 49:5, s. 954-60
  • Tidskriftsartikel (refereegranskat)abstract
    • The humoral immune response against blood group A antigens with different core saccharide structures has been investigated in four blood group O recipients transplanted with kidneys from two blood group A2 donors. Radioimmunoassay and thin-layer chromatogram binding assay studies showed that different individuals responded differently to the same antigenic stimulus. Antibodies were produced in the recipient that bound to the terminal trisaccharide of the blood group A antigens. In some cases antibodies that bound to a larger antigen epitope, including the fourth and fifth sugar in the polysaccharide core chain, also occurred. Immunoglobulin class-specific, as well as subclass specific, responses were seen. The antibody response in the blood group O recipients receiving an A2 graft seem to be dependent on the antigenic expression in the transplanted kidney. In view of the recent findings of individuality of A antigen expression in kidneys within the A1 and A2 subgroups, an extended typing of A2 donors may be important. The humoral immune response in the recipient may also be dependent on earlier contacts with ABO incompatible pregnancies, vaccinations, or infections. A possible correlation between pre- and posttransplant findings was noted in one case and deserves further notice.
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32.
  • Sjöstrand, Torbjörn, et al. (författare)
  • PYTHIA and HERWIG for linear collider physics
  • 1999
  • Ingår i: Physics and experiments with future linear e+ e- colliders. Proceedings, 4th Workshop, LCWS'99, Sitges, Spain, April 28-May 5, 1999. Vol. 2: Machines and detectors. ; , s. 757-760
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • An overview is given of general-purpose event generators, especially PYTHIA and HERWIG. The current status is summarized, some recent physics improvements are described, and planned future projects are outlined.
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33.
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34.
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35.
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36.
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37.
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38.
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39.
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40.
  • Strand, Sven-Erik, et al. (författare)
  • A general extracorporeal immunoadsorption method to increase tumor-to-tissue ratio
  • 1994
  • Ingår i: Cancer. - 1097-0142. ; 73:3 Suppl, s. 1033-1037
  • Tidskriftsartikel (refereegranskat)abstract
    • The idea of applying extracorporeal immunoadsorption (ECIA) in radioimmunodiagnosis and radioimmunotherapy has been proposed previously. The authors here report on the development of new concept using a general method for ECIA based on biotinylated MoAb adsorbed on an avidin column. Athymic rats heterotransplanted with either human melanomas or human lung carcinoma were injected with iodine-125-labeled biotinylated 96.5 or L6 MoAb, respectively. At 24 or 48 hours after the injection, ECIA was performed by pumping blood through a hollow-fiber plasma filter. The separated plasma then was passed through an absorbent (avidin-agarose) column. The whole ECIA procedure lasted for 3 hours. By this ECIA method, the tumor-to-normal tissue ratios were increased in various tissues (i.e., radiosensitive and blood rich organs) by a factor of four to five.
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41.
  • Sundeman, H., et al. (författare)
  • Effects of desflurane on the pig intestinal circulation during hypotension
  • 1999
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 43:10, s. 1069-77
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aim of the present study was to analyze the perfusion pressure dependency for the splanchnic vascular effects of desflurane (DES). METHODS: We measured portal blood flow (QPORT, perivascular ultrasound) and jejunal mucosal perfusion (JMP; laser Doppler) in pentobarbital-anesthetized pigs (n=10). Experimentally, decreases in mean arterial pressure (MAP) were produced by pericardial infusions of dextran. The protocol included sets of measurements at incremental doses of DES (1, 2, 4 and 6%) prior to and during pericardial infusions. RESULTS: Although QPORT and JMP decreased significantly during pericardial infusions, DES, irrespective of dose, did not reduce QPORT until MAP had decreased below 65-70 mm Hg. In higher MAP ranges, vasodilation in pre-portal tissues was powerful enough to maintain QPORT in spite of concurrent decreases in driving arterial pressure, as produced by either DES or pericardial infusion, or by a combination of both. We found no effects of DES on JMP even at very low MAP (about 40 mm Hg during pericardial infusion), indicating that the normal physiological response of the small intestine to redistribute blood flow from deeper to more superficial layers during hypotension was unimpaired by DES. CONCLUSIONS: Our data suggest a wide dose-tolerability of DES as regards the splanchnic circulation during hypotensive states.
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42.
  • Sundeman, H., et al. (författare)
  • The effects of desflurane on cardiac function as measured by conductance volumetry in swine
  • 1998
  • Ingår i: Anesthesia and Analgesia. - : Ovid Technologies (Wolters Kluwer Health). - 0003-2999 .- 1526-7598. ; 87:3, s. 522-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the investigation was to assess the effects of desflurane (DES) on left ventricular heart function during basal barbiturate anesthesia in a closed-pericardium, closed-chest acute swine model. The study was performed in 11 normoventilated adult pigs. Hemodynamic measurements were obtained using arterial, central venous, and pulmonary artery catheters, as well as a conductance volumetry and tip manometry catheter placed in the left ventricle. Hemodynamic measurements were recorded during basal pentobarbital anesthesia and with the addition of 1%, 2%, 4%, and 6% DES. DES dose-dependently decreased mean arterial pressure, systemic vascular resistance, left ventricular end-systolic pressure, dP/dtMAX and dP/dtMIN. At doses >1%, decreases in CO, stroke volume, ejection fraction, end-systolic elastance, preload recruitable stroke work, preload adjusted maximal power, and peak filling rate were observed. Heart rate decreased at 4% and 6% DES. Isovolumetric relaxation time increased only at 6% DES. We conclude that smaller doses of DES have a significant cardiodepressive effect in the setting of barbiturate infusion, as measured by conductance volumetry. IMPLICATIONS: Desflurane, in very small doses, depressed cardiac function during pentobarbital anesthesia with ketamine and benzodiazepine premedication in swine, as assessed by conductance volumetry and left ventricular pressure and volume relationship analysis. These results suggest that desflurane, in combination with certain anesthetics, can be cardiodepressive even in very small doses.
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43.
  • Tulldahl, H. Michael, et al. (författare)
  • Analytical waveform generation from small objects in lidar bathymetry
  • 1999
  • Ingår i: Applied Optics. - 0003-6935 .- 1539-4522. ; 38:6, s. 1021-1039
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a model to simulate receiver waveforms from an airborne sea-depth-sounding lidar to compare the influence that is due to different shapes of objects placed on the sea bottom. The objects are of size 1 m(3), and the bottom depths are 5-12 m. We use an existing analytical beam-propagation model and divide the bottom into squares. For each element on the bottom grid we create a transmitted and a reflected waveform. The waveforms are summed, yielding a total contribution from all bottom elements. We compare two object types, cylinder and cube, and find that the difference in the receiver waveform is small between these objects. Simulated waveforms are compared with experimental data from the Swedish Hawk Eye system and show good agreement.
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44.
  • Ulfvin, A, et al. (författare)
  • Expression of glycolipid blood group antigens in single human kidneys: change in antigen expression of rejected ABO incompatible kidney grafts.
  • 1993
  • Ingår i: Kidney international. - 0085-2538. ; 44:6, s. 1289-97
  • Tidskriftsartikel (refereegranskat)abstract
    • Total neutral glycolipid fractions were separated into molecular species on thin-layer chromatography plates and detected by immunostaining with monoclonal anti-blood group antibodies. Blood group A antigens based on type 1, 2, 3 and 4 carbohydrate core saccharides were present in kidneys of A1 and A1B individuals. Blood group A2 individuals expressed only small amounts of A antigen compared to A1 individuals especially of the type 3 and 4 compounds. Kidneys from non-secretor individuals contained less A antigen compared to secretor individuals, and in both groups a variation in the antigen expression between single individuals was noted. Blood group A type 2 and 3 (which is an extension of A type 2) antigens were present both as basic 6 and 9 sugar structures as well as extended saccharide chains migrating in the 8 to 11 sugar interval. In contrast, the type 1 chain based A and Lewis antigens were only present as their basic 5 to 7 sugar chains, and no elongated structures were found. Four cases of A2 kidneys initially transplanted into O recipients and removed after 5, 12, 21 days and 4 years, respectively, were also analyzed. Two of these kidneys, originating from the same donor, showed a difference in A antigen expression. The kidney functioning for four years (lost due to chronic rejection) completely lacked X antigen with five sugar residues (present in all other individuals) and contained a large amount of A antigens.(ABSTRACT TRUNCATED AT 250 WORDS)
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45.
  • Waldeck, A. Reginald, et al. (författare)
  • Electron paramagnetic resonance studies of succinate:ubiquinone oxidoreductase from Paracoccus denitrificans : Evidence for a magnetic interaction between the 3Fe-4S cluster and cytochrome b
  • 1997
  • Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 1083-351X .- 0021-9258.
  • Tidskriftsartikel (refereegranskat)abstract
    • Electron paramagnetic resonance (EPR) studies of succinate:ubiquinone oxidoreductase (SQR) from Paracoccus denitrificans have been undertaken in the purified and membrane-bound states, Spectroscopic ''signatures'' accounting for the three iron-sulfur clusters (2Fe-2S, 3Fe-4S, and 4Fe-4S), cytochrome b, flavin, and protein-bound ubisemiquinone radicals have been obtained in air-oxidized, succinate-reduced, and dithionite-reduced preparations at 4-10 K. Spectra obtained at 170 K in the presence of excess succinate showed a signal typical of that of a flavin radical, but superimposed with another signal. The superimposed signal originated from two bound ubisemiquinones, as shown by spectral simulations, Power saturation measurements performed on the air-oxidized enzyme provided evidence for a weak magnetic dipolar interaction operating between the oxidized 3Fe-4S cluster and the oxidized cytochrome b. Power saturation experiments performed on the succinate- and dithionite-reduced forms of the enzyme demonstrated that the 4Fe-4S cluster is coupled weakly to both the 2Fe-2S and the 3Fe-4S clusters, Quantitative interpretation of these power saturation experiments has been achieved through redox calculations. They revealed that a spin-spin interaction between the reduced 3Fe-4S cluster and the cytochrome b (oxidized) may also exist. These findings form the first direct EPR evidence for a close proximity (less than or equal to 2 nm) of the high potential 3Fe-4S cluster, situated in the succinate dehydrogenase part of the enzyme, and the low potential, low spin b-heme in the membrane anchor of the enzyme.
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46.
  • Wallukat, G, et al. (författare)
  • Autoantibodies against M2 muscarinic receptors in patients with cardiomyopathy display non-desensitized agonist-like effects.
  • 1999
  • Ingår i: Life sciences. - 0024-3205. ; 64:6-7, s. 465-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating autoantibodies against the human M2 muscarinic receptors have been previously shown in 38% of patients with idiopathic dilated cardiomyopathy. The functional properties of these autoantibodies are reported herein. They were able to decrease the cell beating frequency of myocytes in cultured neonatal rat heart cells in a dose-dependent manner without desensitization over a period of more than 5 hours whereas the non-specific muscarinic receptor agonist carbachol also inhibited the heart cell beating frequency but was desensitized within 1 hour. In the same cell culture, anti-M2 muscarinic receptor autoantibodies were not able to induce internalization of muscarinic receptor whereas carbachol did. These results demonstrate for the first time that anti-M2 muscarinic receptor autoantibodies from patients with idiopathic dilated cardiomyopathy have stimulatory muscarinic activity in vitro, which differ from normal muscarinic agonists by non-desensitization.
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47.
  • Wang, W Z, et al. (författare)
  • Effects of anti-peptide antibodies against human M2 muscarinic receptors on cardiac function in rats in vivo.
  • 1996
  • Ingår i: Blood pressure. Supplement. - 0803-8023. ; 3, s. 25-7
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of anti-peptide antibodies (Ab) against the second extracellular loop of human muscarinic receptor-2 on cardiac function in rats in vivo were studied. These effects were compared with those of the muscarinic receptor agonist, carbachol (Carb). It was shown that: (1) both Carb and Ab administered intravenously in the same doses of 0.4 nmol, 1.0 nmol, and 2.0 nmol were able to inhibit the maximal rate of rise of ventricular pressure (+dp/dt max) in a dose-dependent manner. (2) The isoproterenol (Iso)-induced increase in HR and +dp/dt max were also markedly inhibited by Carb and Ab. Administration of 1.0 nmol Carb decreased the Iso-stimulated increase of HR from 13.6 +/- 2.0 to 4.9 +/- 0.7% and decreased the increase of +dp/dt max from 27.9 +/- 3.2 to 4.8 +/- 0.6%, respectively; whereas Ab decreased the HR to 6.5 +/- 1.1% and +dp/dt max to 13.5 +/- 1.2%, respectively. (3) Both the inhibitory effects of Carb and Ab could be significantly blocked by atropine (1.4 nmol). These findings suggest that the Ab display a stimulatory muscarinic activity similar to Carb in inhibiting the cardiac function as evidenced by its negative chronotropic and inotropic effects.
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48.
  • Wang, W Z, et al. (författare)
  • Effects of anti-peptide antibodies against human M2 muscarinic receptors on the cAMP generating system in guinea pig ventricles.
  • 1996
  • Ingår i: Blood pressure. Supplement. - 0803-8023. ; 3, s. 22-4
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of anti-peptide antibodies (Ab) against the second extracellular loop of human muscarinic receptor-2 on the cAMP generating system in guinea pig ventricles were studied. These effects were compared with those of the muscarinic receptor agonist carbachol (Carb). It was shown that: (1) both Carb and Ab were able to inhibit the isoproterenol (Iso)-stimulated cAMP production of ventricles in a dose-dependent manner. Carb at 2 microM, 10 microM and 50 microM decreased Iso-stimulated cAMP production by 8.0 +/- 1.1, 15.8 +/- 1.2 and 28.4 +/- 1.7%, respectively; whereas Ab at 50 nM, 100 nM and 400 nM decreased it by 5.8 +/- 0.4, 16.8 +/- 1.4 and 30.6 +/- 2.5%, respectively. (2) Both Carb and Ab could also inhibit the basal cAMP content of ventricles significantly. Carb at 10 microM and Ab at 100 nM decreased it by 46.9 +/- 4.2% and 60.2 +/- 4.6%, respectively. (3) The inhibitory effects of both Ab and Carb on Iso-stimulated cAMP production were significantly prevented by atropine at 1.5 microM. (4) The inhibitory effect of Ab at 100 nM was almost completely abolished by the peptide (700 nM) used as immunogen. These findings suggest that the antibodies exhibit a stimulatory muscarinic activity similar to carbachol in the inhibitory modulation of cAMP production.
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49.
  • Wennerberg, Anders B.A., et al. (författare)
  • The structure of the rodent and porcine neuropeptide galanin and antagonists as determined by FTIR and CD spectroscopy
  • 1994
  • Ingår i: Canadian journal of chemistry (Print). - : Canadian Science Publishing. - 0008-4042 .- 1480-3291. ; 72:6, s. 1495-1499
  • Tidskriftsartikel (refereegranskat)abstract
    • FT-IR spectroscopy was used to study the conformation of the porcine neuropeptide galanin, fragments 1−16 of the porcine and human peptides and the antagonists M15 and M35. All peptides were shown to be structureless in aqueous solution. Upon addition to SDS micelles, only porcine galanin and the fragment consisting of amino acids 1−16 showed any evidence of interaction, adopting a helical structure. No interaction could be demonstrated with zwitterionic lipids for any peptide except M15 which formed a thermally unstable helical conformation which unfolded promoting aggregation at around 45 °C.Additional studies on rat galanin in various solvent systems were made by using circular dichroism spectroscopy. The results obtained support the observations made by FT-IR spectroscopy.
  •  
50.
  • Zhu, L, et al. (författare)
  • Immunocytochemical studies of M2 muscarinic receptors in guinea pig atria and ventricles using anti-peptide antibodies.
  • 1996
  • Ingår i: Blood pressure. Supplement. - 0803-8023. ; 3, s. 19-21
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The localization and density of M2 muscarinic receptors in guinea pig atria and ventricles were studied by immunocytochemical techniques, with anti-peptide antibodies against the second extracellular loop of human muscarinic receptor-2. It was shown that the positive immunoreaction of M2 muscarinic receptor was characterized by brown-yellow granules of variable size and shape, which were located mainly on the cell surface and in the cytoplasm far from nuclei. The positive immunoreactive substances appeared in both atrial and ventricular myocytes, with the density being greater in atria than in ventricles. Pre-incubation with atropine, but not carbachol, significantly reduced the intensity of positive immunoreactivity. This indicates that the binding of antibody to receptor site can be partially blocked by M2 muscarinic receptor antagonist.
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