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Showing papers by "Lund University published in 1994"


Journal ArticleDOI
K. Hagiwara, Ken Ichi Hikasa1, Koji Nakamura, Masaharu Tanabashi1, M. Aguilar-Benitez, Claude Amsler2, R. M. Barnett3, Patricia R. Burchat4, C. D. Carone5, C. Caso, G. Conforto6, Olav Dahl3, Michael Doser7, Semen Eidelman8, Jonathan L. Feng9, L. K. Gibbons10, Maury Goodman11, Christoph Grab12, D. E. Groom3, Atul Gurtu7, Atul Gurtu13, K. G. Hayes14, J. J. Herna`ndez-Rey15, K. Honscheid16, Christopher Kolda17, Michelangelo L. Mangano7, David Manley18, Aneesh V. Manohar19, John March-Russell7, Alberto Masoni, Ramon Miquel3, Klaus Mönig, Hitoshi Murayama3, Hitoshi Murayama20, S. Sánchez Navas12, Keith A. Olive21, Luc Pape7, C. Patrignani, A. Piepke22, Matts Roos23, John Terning24, Nils A. Tornqvist23, T. G. Trippe3, Petr Vogel25, C. G. Wohl3, Ron L. Workman26, W-M. Yao3, B. Armstrong3, P. S. Gee3, K. S. Lugovsky, S. B. Lugovsky, V. S. Lugovsky, Marina Artuso27, D. Asner28, K. S. Babu29, E. L. Barberio7, Marco Battaglia7, H. Bichsel30, O. Biebel31, Philippe Bloch7, Robert N. Cahn3, Ariella Cattai7, R. S. Chivukula32, R. Cousins33, G. A. Cowan34, Thibault Damour35, K. Desler, R. J. Donahue3, D. A. Edwards, Victor Daniel Elvira, Jens Erler36, V. V. Ezhela, A Fassò7, W. Fetscher12, Brian D. Fields37, B. Foster38, Daniel Froidevaux7, Masataka Fukugita39, Thomas K. Gaisser40, L. Garren, H.-J. Gerber12, Frederick J. Gilman41, Howard E. Haber42, C. A. Hagmann28, J.L. Hewett4, Ian Hinchliffe3, Craig J. Hogan30, G. Höhler43, P. Igo-Kemenes44, John David Jackson3, Kurtis F Johnson45, D. Karlen, B. Kayser, S. R. Klein3, Konrad Kleinknecht46, I.G. Knowles47, P. Kreitz4, Yu V. Kuyanov, R. Landua7, Paul Langacker36, L. S. Littenberg48, Alan D. Martin49, Tatsuya Nakada7, Tatsuya Nakada50, Meenakshi Narain32, Paolo Nason, John A. Peacock47, Helen R. Quinn4, Stuart Raby16, Georg G. Raffelt31, E. A. Razuvaev, B. Renk46, L. Rolandi7, Michael T Ronan3, L.J. Rosenberg51, Christopher T. Sachrajda52, A. I. Sanda53, Subir Sarkar54, Michael Schmitt55, O. Schneider50, Douglas Scott56, W. G. Seligman57, Michael H. Shaevitz57, Torbjörn Sjöstrand58, George F. Smoot3, Stefan M Spanier4, H. Spieler3, N. J. C. Spooner59, Mark Srednicki60, A. Stahl, Todor Stanev40, M. Suzuki3, N. P. Tkachenko, German Valencia61, K. van Bibber28, Manuella Vincter62, D. R. Ward63, Bryan R. Webber63, M R Whalley49, Lincoln Wolfenstein41, J. Womersley, C. L. Woody48, O. V. Zenin 
Tohoku University1, University of Zurich2, Lawrence Berkeley National Laboratory3, Stanford University4, College of William & Mary5, University of Urbino6, CERN7, Budker Institute of Nuclear Physics8, University of California, Irvine9, Cornell University10, Argonne National Laboratory11, ETH Zurich12, Tata Institute of Fundamental Research13, Hillsdale College14, Spanish National Research Council15, Ohio State University16, University of Notre Dame17, Kent State University18, University of California, San Diego19, University of California, Berkeley20, University of Minnesota21, University of Alabama22, University of Helsinki23, Los Alamos National Laboratory24, California Institute of Technology25, George Washington University26, Syracuse University27, Lawrence Livermore National Laboratory28, Oklahoma State University–Stillwater29, University of Washington30, Max Planck Society31, Boston University32, University of California, Los Angeles33, Royal Holloway, University of London34, Université Paris-Saclay35, University of Pennsylvania36, University of Illinois at Urbana–Champaign37, University of Bristol38, University of Tokyo39, University of Delaware40, Carnegie Mellon University41, University of California, Santa Cruz42, Karlsruhe Institute of Technology43, Heidelberg University44, Florida State University45, University of Mainz46, University of Edinburgh47, Brookhaven National Laboratory48, Durham University49, University of Lausanne50, Massachusetts Institute of Technology51, University of Southampton52, Nagoya University53, University of Oxford54, Northwestern University55, University of British Columbia56, Columbia University57, Lund University58, University of Sheffield59, University of California, Santa Barbara60, Iowa State University61, University of Alberta62, University of Cambridge63
TL;DR: This biennial Review summarizes much of Particle Physics using data from previous editions, plus 2205 new measurements from 667 papers, and features expanded coverage of CP violation in B mesons and of neutrino oscillations.
Abstract: This biennial Review summarizes much of Particle Physics. Using data from previous editions, plus 2205 new measurements from 667 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. This edition features expanded coverage of CP violation in B mesons and of neutrino oscillations. For the first time we cover searches for evidence of extra dimensions (both in the particle listings and in a new review). Another new review is on Grand Unified Theories. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http://pdg.lbl.gov.

5,143 citations


Journal ArticleDOI
TL;DR: There was a high prevalence of APC resistance among young persons with a history of venous thrombosis, and this resistance appeared to be inherited as an autosomal dominant trait.
Abstract: Background In three families with various forms of venous thrombosis, we observed an apparently inherited poor response to the anticoagulant activated protein C (APC). The condition was due to a deficiency in a previously unrecognized anticoagulant factor that functioned as a cofactor to activated protein C. Methods We conducted the present study to determine the prevalence of resistance to APC in patients with venous thrombosis. We compared 104 consecutive patients with venous thrombosis confirmed by objective tests with 130 controls. In addition, 211 members of 34 families of persons with resistance to APC were studied. The anticoagulant response to APC was measured with a modified version of the activated partial-thromboplastin time test; the results were expressed as APC ratios. Results Forty-five percent of patients had a family history of thrombosis. A significant (P<0.001) difference in APC ratios was observed between the controls and the patients with thrombosis. For 33 percent of patients, the AP...

1,077 citations


Journal ArticleDOI
TL;DR: In this article, the interactions of three proteoglycans of the decorin family, decorin, biglycan and fibromodulin, with transforming growth factor beta (TGF-beta) were analyzed.
Abstract: We have analysed the interactions of three proteoglycans of the decorin family, decorin, biglycan and fibromodulin, with transforming growth factor beta (TGF-beta). The proteoglycan core proteins, expressed from human cDNAs as fusion proteins with Escherichia coli maltose-binding protein, each bound TGF-beta 1. They showed only negligible binding to several other growth factors. Intact decorin, biglycan and fibromodulin isolated from bovine tissues competed with the fusion proteins for the TGF-beta binding. Affinity measurements suggest a two-site binding model with Kd values ranging from 1 to 20 nM for a high-affinity binding site and 50 to 200 nM for the lower-affinity binding site. The stoichiometry indicated that the high-affinity binding site was present in one of ten proteoglycan core molecules and that each molecule contained a low-affinity binding site. Tissue-derived biglycan and decorin were less effective competitors for TGF-beta binding than fibromodulin or the non-glycosylated fusion proteins; removal of the chondroitin/dermatan sulphate chains of decorin and biglycan (fibromodulin is a keratan sulphate proteoglycan) increased the activities of decorin and biglycan, suggesting that the glycosaminoglycan chains may hinder the interaction of the core proteins with TGF-beta. The fusion proteins competed for the binding of radiolabelled TGF-beta to Mv 1 Lu cells and endothelial cells. Affinity labelling showed that the binding of TGF-beta to betaglycan and the type-I receptors in Mv 1 Lu cells and to endoglin in endothelial cells was reduced, but the binding to the type-II receptors was unaffected. TGF-beta 2 and 3 also bound to all three fusion proteins. Latent recombinant TGF-beta 1 precursor bound slightly to fibromodulin and not at all to decorin and biglycan. The results show that the three decorin-type proteoglycans each bind TGF-beta isoforms and that slight differences exist in their binding properties. They may regulate TGF-beta activities by sequestering TGF-beta into extracellular matrix.

932 citations


Journal ArticleDOI
TL;DR: This, to the authors' knowledge, is the second example, besides the thrombin receptor, of a proteolytically activated seven-transmembrane G-protein-coupled receptor, and is provisionally named proteinase activated receptor 2.
Abstract: A DNA sequence encoding a G-protein-coupled receptor was isolated from a mouse genomic library. The predicted protein is similar in structure to the thrombin receptor and has a similar activation mechanism. When expressed in Xenopus laevis oocytes, the receptor was activated by low concentrations of trypsin (EC 3.4.21.4) and by a peptide (SLIGRL) derived from the receptor sequence, but was not activated by thrombin (EC 3.4.21.5). Trypsin failed to activate a mutant receptor in which the presumed cleavage site Arg-34-Ser-35 was changed to an Arg-Pro sequence. The agonist peptide (SLIGRL) activated equally well mutant and wild-type receptors. Northern blot analysis demonstrated receptor transcripts in highly vascularized tissues such as kidney, small intestine, and stomach. Because this, to our knowledge, is the second example, besides the thrombin receptor, of a proteolytically activated seven-transmembrane G-protein-coupled receptor, we have provisionally named it proteinase activated receptor 2.

904 citations


Journal ArticleDOI
TL;DR: All three groups were characterized by a significant preponderance of men, and there was a significant increase in the incidence of clavicular fracture, both overall and sports-related, between 1952 and 1987.
Abstract: The age- and gender-specific incidences were calculated in 2035 cases of fracture of the clavicle. The fractures were classified in three groups according to the Allman system. Each group was further divided into undisplaced and displaced fracture subgroups, with an extra subgroup of comminuted midclavicular fractures in Group I. Seventy-six percent of the fractures were classified as Allman Group I. The median age in this group was 13 years. There were significant differences in age- and gender-specific incidence between the undisplaced, displaced, and comminuted fracture subgroups. Twenty-one percent were classified as Allman Group II. The median age of the patients was 47 years, and there was no difference in age between the undisplaced and displaced fracture subgroups. Three percent were classified as Allman Group III, and the median age of the patients in this group was 59 years. All three groups were characterized by a significant preponderance of men, and there was a significant increase in the incidence of clavicular fracture, both overall and sports-related, between 1952 and 1987.

575 citations


Journal ArticleDOI
Olle Lindvall1, Zaal Kokaia1, Johan Bengzon, Eskil Elmér, Merab Kokaia1 
TL;DR: Insight into the regulation and role of the neurotrophins after brain insults should increase the understanding of pathophysiological mechanisms in epileptogenesis and cell death, and could lead to new therapeutic strategies.

573 citations


Journal ArticleDOI
01 Jan 1994-Nature
TL;DR: In this article, the structure of ETS-10 was solved using a combination of high-resolution electron microscopy, electron and powder X-ray diffraction, solid-state NMR, molecular modelling and chemical analysis.
Abstract: INORGANIC microporous framework solids such as zeolites are of considerable technological importance as shape-selective catalysts, ion-exchange materials and molecular sieves1. Most microporous materials known until recently were silicates, aluminosilicates1 or aluminophosphates2–4, all of which contain tetrahedrally coordinated metal atoms. In 1989, a family of microporous titanosilicates (generically denoted ETS) was discovered in which the metal atoms (Ti4+) are octahedrally coordinated5–8. A full understanding of the potential of any microporous solid to act as a molecular sieve and selective catalyst, and of the nature of the catalytic centres, requires that its structure be known. But that of the ETS materials has proved elusive because of the considerable degree of disorder that they contain. Using a combination of high-resolution electron microscopy, electron and powder X-ray diffraction, solid-state NMR, molecular modelling and chemical analysis, we have now been able to solve the structure of a prominent member of this family, ETS-10. This structure comprises corner-sharing SiO4 tetrahedra and TiO6 octahedra linked through bridging oxygen atoms. The pore system contains 12-membered rings and displays a considerable degree of disorder. Many ordered variants of ETS-10 exist, some of which are chiral.

515 citations


Journal Article
TL;DR: An increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk in peripheral blood lymphocytes, according to an ongoing Nordic cohort study of cancer incidence.
Abstract: Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange or micronuclei in PBL. In order to standardize for the interlaboratory variation, the results were trichotomized for each laboratory into three strata: low (1-33 percentile), medium (34-66 percentile), or high (67-100 percentile). In this second follow-up, a total of 85 cancers were diagnosed during the observation period (1970-1991). There was no significant trend in the standardized incidence ratio with the frequencies of sister chromatid exchange or micronuclei, but the data for these parameters are still too limited to allow firm conclusions. There was a statistically significant linear trend (P = 0.0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk.

510 citations


Journal ArticleDOI
TL;DR: The results indicate that grafts of embryonic dopamine neurons can survive, grow, and exert functional effects up to at least 3 years after surgery in the parkinsonian brain, despite an ongoing disease process leading to degeneration of the intrinsic dopamine system.
Abstract: Two patients with idiopathic Parkinson's disease (Patients 3 and 4 in our series) were followed up to 3 years after grafting of human embryonic dopamine-rich mesencephalic tissue unilaterally into the putamen. During the first postoperative year both patients showed significant amelioration of parkinsonian symptoms and increased 6-L-[18F]-fluorodopa uptake in the grafted putamen, as assessed with positron emission tomography. Three years after grafting the patients still exhibited increased fluorodopa uptake in the grafted putamen and significant clinical improvements, evidenced by a reduction of the severity of symptoms and of the time spent in the "off" phase, and by a prolongation of the effect of a single dose of L-dopa. Between 1 and 3 years after surgery, Patient 3 showed only minor changes of parkinsonian symptoms on the side contralateral to the graft, whereas there was a worsening on the ipsilateral side. Fluorodopa uptake decreased in the nongrafted putamen but was unchanged in the grafted putamen. Patient 4 continued to improve after the first postoperative year and L-dopa was withdrawn after 32 months. The reduction of parkinsonian symptoms on the side contralateral to the graft became more pronounced between 1 and 3 years after surgery. Fluorodopa uptake further increased in the grafted putamen, whereas no change was detected on the non-grafted side. These results indicate that grafts of embryonic dopamine neurons can survive, grow, and exert functional effects up to at least 3 years after surgery in the parkinsonian brain, despite an ongoing disease process leading to degeneration of the intrinsic dopamine system.

426 citations


Journal ArticleDOI
TL;DR: Investigation of Swedish families with inherited APC resistance for the factor V gene mutation found it to be present in 47 of them and perfect cosegregation between a low APC ratio and the presence of mutation was seen in 40 families, but co-segregation was not perfect as 12 out of 57 APC-resistant family members were found to lack the mutation.
Abstract: Resistance to activated protein C (APC) is the most prevalent inherited cause of venous thrombosis. The APC resistance phenotype is associated with a single point mutation in the factor V gene, changing Arg506 in the APC cleavage site to a Gln. We have investigated 50 Swedish families with inherited APC resistance for this mutation and found it to be present in 47 of them. Perfect cosegregation between a low APC ratio and the presence of mutation was seen in 40 families. In seven families, the co-segregation was not perfect as 12 out of 57 APC-resistant family members were found to lack the mutation. Moreover, in three families with APC resistance, the factor V gene mutation was not found, suggesting another still unidentified cause of inherited APC resistance. Of 308 investigated families members, 146 were normal, 144 heterozygotes, and 18 homozygotes for the factor V gene mutation and there were significant differences in thrombosis-free survival curves between these groups. By age 33 yr, 8% of normals, 20% of heterozygotes, and 40% of homozygotes had had manifestation of venous thrombosis.

422 citations


Journal ArticleDOI
TL;DR: Eighty basal cell carcinomas, 10 lesions of Bowen's disease, and four lesions of cutaneous T‐cell lymphoma in two patients, were treated with photodynamic laser therapy (PDT), using topical application of the haem precursor δ‐amino levulinic acid (ALA).
Abstract: Eighty basal cell carcinomas (BCCs) in 21 patients, 10 lesions of Bowen's disease in three patients, and four lesions of cutaneous T-cell lymphoma in two patients, were treated with photodynamic laser therapy (PDT), using topical application of the haem precursor delta-amino levulinic acid (ALA). The diagnoses were confirmed histologically prior to treatment. Fifty-five of the BCCs were superficial lesions, and 25 were nodular. Of the 80 BCCs, 39 (49%) were located on the trunk, 36 (45%) on the head and neck region, four (15%) on the leg and one on the arm. The two principal locations of the 10 Bowen's disease lesions were the leg (50%) and the trunk (40%). The T-cell lymphoma lesions were located on the shoulder and on the arm. A water-in-oil based cream containing 20% ALA was applied to the lesions, with a margin of about 10-20 mm beyond the visible tumour border, 4-6 h before the laser procedure. During this period of time the highly fluorescent and photodynamically active substance protoporphyrin IX (Pp IX) is synthesized via the haem cycle. Laser-induced fluorescence (LIF) was used for real-time monitoring of the Pp IX distribution in the tumour and in the normal surrounding skin, before and after treatment in all patients. Before laser treatment the Pp-IX distribution demonstrated by LIF showed a demarcation between tumour and normal skin of about 15:1 for BCC and Bowen's disease, and 5:1 for T-cell lymphomas. Laser light from a pulsed frequency-doubled Nd:YAG laser pumping a dye laser with light emission at 630 nn was used for the therapy. The power density in the irradiation was kept below 110 mW/cm(2), in order to avoid hyperthermal effects. A total energy of 60 J/cm(2) was delivered for 10-20 min, depending on the tumour size. A complete response rate of 100% in superficial BCCs and 64% in nodular BCCs occurred after a single laser treatment, and a response rate of 100% was achieved after one additional. treatment in the nodular BCCs. in the Bowen's disease lesions a complete response of 90% was obtained with a single treatment. Two of the four T-cell lymphomas resolved completely. The follow-up time was between 6 and 14 months. (Less)

Journal ArticleDOI
24 Mar 1994-Nature
TL;DR: The atomic structure of COMT is solved to 2.0 Å resolution, which provides new insights into the mechanism of the methyl transfer reaction, and the co-enzyme-binding domain is strikingly similar to that of an AdoMet-dependent DNA methylase10, indicating that all Ado met methylases may have a common structure.
Abstract: Catechol O-methyltransferase (COMT, EC 2.1.1.6) is important in the central nervous system because it metabolizes catecholamine neurotransmitters such as dopamine. The enzyme catalyses the transfer of the methyl group from S-adenosyl-L-methionine (AdoMet) to one hydroxyl group of catechols. COMT also inactivates catechol-type compounds such as L-DOPA. With selective inhibitors of COMT in combination with L-DOPA, a new principle has been realized in the therapy of Parkinson's disease. Here we solve the atomic structure of COMT to 2.0 A resolution, which provides new insights into the mechanism of the methyl transfer reaction. The co-enzyme-binding domain is strikingly similar to that of an AdoMet-dependent DNA methylase, indicating that all AdoMet methylases may have a common structure.

Journal ArticleDOI
TL;DR: Linkage between APC resistance and the factor V gene in a large kindred with familial thrombophilia and a point mutation changing Arg506 in the APC cleavage site to a Gln was found suggestfactor V gene mutation to be the most common genetic cause of thromBophilia.

Journal ArticleDOI
TL;DR: Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methioninelabelled recombinant GAD.
Abstract: Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n = 10) and control (n = 50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. Binding levels were not normally distributed (p < 0.0001) and therefore, the diagnostic accuracy of GAD antibodies was analysed by the ROC plots in population-based, consecutively-diagnosed, recent onset, 0-14 year-old patients (n = 105), and matched, healthy control subjects (n = 157). The ROC plots showed that the diagnostic sensitivity of GAD65 antibodies was 77% and the specificity 92% compared with 8% and 98%, respectively for GAD67 antibodies. In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89% (72 of 81) without a correlation between the autoantibody levels. Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methionine-labelled recombinant GAD.

Journal ArticleDOI
TL;DR: This paper focuses on food properties in cereal and legume products that affect metabolic responses to starch and correlates well with glycemic and insulinemic indices for several starchy foods.

Journal ArticleDOI
TL;DR: The crystal structure of Thermus thermophilus elongation factor G without guanine nucleotide was determined and it was found that this GTPase has five domains with overall dimensions and the GTP binding domain has a core common to other GTPases with a unique subdomain which probably functions as an intrinsic nucleotide exchange factor.
Abstract: The crystal structure of Thermus thermophilus elongation factor G without guanine nucleotide was determined to 2.85 A. This GTPase has five domains with overall dimensions of 50 x 60 x 118 A. The GTP binding domain has a core common to other GTPases with a unique subdomain which probably functions as an intrinsic nucleotide exchange factor. Domains I and II are homologous to elongation factor Tu and their arrangement, both with and without GDP, is more similar to elongation factor Tu in complex with a GTP analogue than with GDP. Domains III and V show structural similarities to ribosomal proteins. Domain IV protrudes from the main body of the protein and has an extraordinary topology with a left-handed cross-over connection between two parallel beta-strands.

Journal ArticleDOI
TL;DR: In this paper, a new method for measuring the rate of in-vitro starch digestion in products with a structure "as eaten" is introduced, where an equivalent amount of potentially available starch from each product was chewed by subjects, expectorated into a beaker and incubated with pepsin.

Journal ArticleDOI
TL;DR: Factor V is shown not only to express procoagulant properties after its activation by thrombin but also to play an important part in the anticoagULant system as cofactor to APC.
Abstract: Recently, our laboratory described a defect in anticoagulant response to activated protein C (APC). This response, APC resistance, was shown to be inherited and associated with familial thrombophilia. As other possible mechanisms were excluded, APC resistance was hypothesized to be due to deficiency of a previously unrecognized cofactor of APC. The aim of the present study was to isolate and characterize this factor. Plasma from an individual with pronounced inherited APC resistance was used as test plasma in a biological assay which monitored APC cofactor activity during its isolation from normal plasma. A purification procedure was devised that yielded a protein which was shown to be identical to coagulation factor V. It proved impossible to separate the APC cofactor activity from factor V, even by affinity chromatography using a monoclonal antibody against factor V. The affinity-purified factor V corrected the poor anticoagulant response to APC of APC-resistant plasma in a dose-dependent manner. Because the APC-resistant plasma contained normal levels of factor V procoagulant activity, the results indicated APC resistance to be due to a selective defect in the anticoagulant function of factor V. The present results show factor V not only to express procoagulant properties after its activation by thrombin but also to play an important part in the anticoagulant system as cofactor to APC.

Journal ArticleDOI
TL;DR: Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), and near-normal glycemia can be obtained by a combination of met formin and sulfonylurea, even in advanced NIDDM.
Abstract: OBJECTIVE To assess and compare the therapeutic efficacy and safety of metformin (M) and sulfonylurea (glyburide, G), alone and in various combinations, in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS Of 165 patients (fasting blood glucose [FBG] ≥ 6.7 mmol/l) initially treated with diet alone, 144 (FBG still ≥6.7 mmol/l) were randomized to double-blind, double-dummy controlled treatment with M, G, or primary combination therapy (MG). The dose was titrated, withFBG RESULTS The FBG target was achieved in 9% of patients after diet alone. Single-drug therapy was insufficient in 36% and MGL in 25% (NS) of the randomized patients. There was further improvement in glucose control by the high-dose combinations. Mean FBG ± SE was reduced ( P = 0.001) from 9.1 ± 0.4 to 7.0 ± 0.2 mmol/l in those maintained on single-drug treatment or low-dose primary combination. Those treated with different high-dose combinations had a large mean FBG reduction, from 13.3 ± 0.8 to 7.8 ± 0.6 mmol/l. HbA 1c levels showed corresponding reductions, and glycemic levels rose after drug discontinuation. Fasting C-peptide rose during treatment with G and MGL but not with M, while fasting insulin was not significantly changed. Meal-stimulated C-peptide and insulin levels were unchanged by M but increased by G and, to a lesser extent, by MGL. There were no significant insulin or C-peptide differences between the different high-dose combinations (M/G, G/M, and MGH). Body weight did not change following treatment with M or combination but increased by 2.8 ± 0.7 kg following G alone. Blood pressure was unchanged. Overall effects on plasma lipids were small, with no significant differences between groups. Drug safety was satisfactory, even if the reporting of (usually modest) adverse events was high; the profile, but not the frequency, differed between groups. CONCLUSIONS Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.

Journal ArticleDOI
TL;DR: To perform an economic analysis of primary healing and healing with amputation in diabetic patients with foot ulcers, a comparison study of nine cases of amputation and three cases of partial amputation is performed.
Abstract: . Objectives. To perform an economic analysis of primary healing and healing with amputation in diabetic patients with foot ulcers. Design. A retrospective economic analysis based on a prospective study of consecutively presenting diabetic patients admitted to the Department of Internal Medicine because of foot ulcer. Setting. A multidisciplinary foot-care team. Subjects. A total of 314 consecutively presenting diabetic patients with foot ulcers. Forty patients died before healing occurred. In those patients who healed primarily (n = 197) or after amputation (n = 77), a retrospective economic analysis was performed. Interventions. All patients were treated by a multi-disciplinary foot care team consisting of diabetologist, orthopaedic surgeon, diabetes nurse, podiatrist and orthotist both as in- and out-patients. The patients were followed by the team from admittance until final outcome, i.e. primary healing or healing with amputation or death. Main outcome measures. Data from both the prospectively collected patient material and from patient records were used to estimate the cost for hospital care, antibiotics, surgery, out-patient care, staff attendance, drugs and material for ulcer dressings, and orthopaedic appliances. Results. The total costs were SEK 51000 (3000–808000) for patients with primary healing and SEK 344000 (27000–992000) for healing with amputation. Costs for in-patient care were 37% of total average costs for primary healing and 82% for patients with amputation. The costs for topical treatment of the ulcers in out-patient care were 45% of the total average cost for primary healed and 13% for patients who healed with amputation. The costs for products used for ulcer dressings were 21% of total costs for topical treatment, i.e. 9% and 3% of total average costs for primary healing and healing with amputation, respectively. Costs for visits to the foot care team, antibiotics and orthopaedic appliances were low in relation to total costs. Conclusion. Treatment of diabetic patients with foot ulcers in a multidisciplinary system was associated with relatively low costs. Healing with amputation was associated with high costs mainly due to multiple and extended hospitalization. These findings indicate the potential cost savings of preventive and multi-disciplinary foot care.

Journal ArticleDOI
TL;DR: The results suggest that factor V and protein S work in synergy as phospholipid-bound cofactors to APC.


Journal ArticleDOI
Pelle Gustafson1
TL;DR: In this paper, the authors evaluated epidemiology, prognosis and the association between metastases and local recurrence in a series of adult patients with soft tissue sarcoma (STS) of the extremity and trunk wall.
Abstract: We have evaluated epidemiology, prognosis and the association between metastases and local recurrence in a series of adult patients with soft tissue sarcoma (STS) of the extremity and trunk wall. 508 patients were diagnosed in the Southern Swedish Health Care Region from 1964 through 1989. The series was population-based, i.e., all patients within a defined area were included, irrespective of where treated, thereby avoiding selection bias in referral and follow-up. Epidemiology. The annual incidence was 18 per million. The median age was 64 years. One third of the tumors were subcutaneous, and these were smaller than the deep-seated tumors. Malignant fibrous histiocytoma and grade IV were the commonest. Differences were noted in clinicopathologic features among histotypes. The 5-year metastasis-free survival rate (MFSR) was 0.6. The crude local recurrence rate was 0.3. The majority of metastases and local recurrences occurred within 3 years. The referral pattern to the tumor center has become more favorable over time; in the last 5 years half of the subcutaneous and four fifths of the deep-seated tumors were referred before surgery. Prognostic factors. Tumor size, tumor necrosis, and vascular invasion were strong and independent prognostic factors for metastasis in a histologically mixed series. In MFH, storiform and pleomorphic subtype, tumor necrosis and tumor size were associated with a poor prognosis. Tumor necrosis and vascular invasion independently worsened the prognosis in leiomyosarcoma. In liposarcoma, tumor necrosis and in synovial sarcoma, tumor size were the only important prognostic factors. Tumor size, tumor necrosis, and vascular invasion were used in a prognostic system which identified two thirds of all patients with a 5-year MFSR of 0.8 and one third of the patients with a 5-year MFSR of 0.3. Metastasis and local recurrence. The causal association proposed for local recurrence and metastasis should be interpreted with caution. We suggest that highly malignant tumors combine local and distant aggressiveness, and that local recurrence is a marker of risk, and not necessarily a cause of, metastasis. Conclusions. 1. Population-based series are preferable when studying epidemiology in soft tissue sarcoma. 2. We propose that tumor size, tumor necrosis, and vascular invasion are strong and reliable factors that can be used to improve prognostic accuracy. 3. There is a growing body of evidence against a causal relationship between local recurrence and metastasis.

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TL;DR: Theoretical considerations of eye design allow us to find routes along which the optical structures of eyes may have evolved, if selection constantly favours an increase in the amount of detectable spatial information.
Abstract: Theoretical considerations of eye design allow us to find routes along which the optical structures of eyes may have evolved. If selection constantly favours an increase in the amount of detectable spatial information, a light-sensitive patch will gradually turn into a focused lens eye through continuous small improvements of design. An upper limit for the number of generations required for the complete transformation can be calculated with a minimum of assumptions. Even with a consistently pessimistic approach the time required becomes amazingly short: only a few hundred thousand years.

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TL;DR: It is shown how nonmonotonic inferences may elegantly be interpreted in terms of underlying expectations, and it is shown that by using the notion of expectation, one can unify the treatment of the theory of belief revision and that of nonMonotonic inference relations.

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TL;DR: A survey of studies using molecular markers to investigate genet diversity and structure in clonal plants is presented in this paper, where only two were studied by DNA methods, the rest by isozyme markers.
Abstract: We present a literature survey of studies using molecular markers to investigate genet diversity and structure in clonal plants. The data from 40 studies comprised 45 species of which only two were studied by DNA methods, the rest by isozyme markers. Less than one third of the studies provided information about the spatial distribution of individual genets within populations, and only 12.5% of the studies used mapping of all ramets within plots or part of the population in combination with identification of multilocus genotypes. We also present two case studies. InGlechoma hederacea morphological criteria were used to select clones. Multi-samples of ramets within these “clones” turned out to be variable using isozymes indicating that these “clones” in most cases consisted of several genets. One individual multilocus genotype covered tens of square metres. InHylocomium splendens samples from 10×10 cm plots usually consisted of a mixture of multilocus genotypes, but occasionally the whole plot consisted of one genet.

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TL;DR: It is concluded that ZOO–FISH can be used to generate comparative chromosome maps of a large number of mammalian species.
Abstract: Comparative chromosome painting, termed ZOO-FISH, using DNA libraries from flow sorted human chromosomes 1,16,17 and X, and mouse chromosome 11 discloses the presence of syntenic groups in distantly related mammalian Orders ranging from primates (Homo sapiens), rodents (Mus musculus), even-toed ungulates (Muntiacus muntjak vaginalis and Muntiacus reevesi) and whales (Balaenoptera physalus). These mammalian Orders have evolved separately for 55-80 million years (Myr). We conclude that ZOO-FISH can be used to generate comparative chromosome maps of a large number of mammalian species.

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TL;DR: The studies support earlier findings that have found that ultrasonographically determined intima-media thickness is a valid way to study early atherosclerosis and increase significantly with increasing plaque score.
Abstract: To evaluate ultrasonographically determined intima-media thickness as a measure of early atherosclerosis, three studies were performed. Ultrasound measurements of intima-media thickness in the carotid artery were directly validated by comparing the same thickness measured by light microscopy. The values were closely correlated (r = .82, P < .001). Intima-media thickness determined by light microscopy was consistently smaller than that determined by ultrasound, probably due to shrinkage during histological preparation. As an indirect validation, mean intima-media thickness was calculated in three large groups of patients with no plaque (n = 224), one plaque (n = 105), and one circumferential or two or more plaques (n = 54) in the carotid bifurcation. Intima-media thickness increased significantly with increasing plaque score, indicating that diffuse intima-media thickening is more pronounced with more severe atherosclerosis. The intima-media thickness also increased with increasing multifactorial cardiovascular risk, reflecting a positive relation between signs of early atherosclerosis and the burden of known risk factors for the disease. Our studies support earlier findings that have found that ultrasonographically determined intima-media thickness is a valid way to study early atherosclerosis.

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TL;DR: A potential neuroprotective effect of nimodipine by preventing calcium overload in ischaemic neurons may have been outweighed by detrimental haemodynamic effects in the ischaemia area.
Abstract: A randomised, double-blind, placebo-controlled trial of intravenous nimodipine was conducted in 295 patients with acute ischaemic stroke. Nimodipine was given as an intravenous infusion of 1 or 2 mg/h for 5 days followed by an oral dose of 120 mg daily for a total treatment period of 21 days. Patients with a clinical diagnosis of ischaemic stroke in the carotid artery territory within 24 h entered the study at 34 centres, involving 11 European countries: 100 were randomly assigned to placebo, 101 to nimodipine with an initial intravenous dose of 1 mg/h and 94 patients to an initial dose of 2 mg/h. The trial, initially aiming at a patient inclusion of 600, was terminated because of concerns arising from safety monitoring. Primary efficacy variables were neurological outcome according to the Orgogozo scale and functional outcome according to the Barthel scale at day 21. There were apparent differences between the groups in neurological and functional outcome with a better outcome in the placebo group. The differences between the placebo group and the 2-mg/h group were statistically significant (p = 0.0005 for the Orgogozo scale and p = 0.0033 for the Barthel scale). The differences were even more pronounced at the final follow-up at 24 weeks (p = 0.0001 and p = 0.0002, respectively). There were no statistically significant differences in mortality between the groups. There were statistically significant differences between the groups regarding the effect of the first few days of intravenous treatment on systolic and diastolic blood pressure with the most pronounced reduction in the 2-mg/h nimodipine treatment group at day 2 (p = 0.0001). An explorative analysis indicated a correlation between diastolic blood pressure reduction in the nimodipine-treated groups and unfavourable neurological outcome (p = 0.0005). A potential neuroprotective effect of nimodipine by preventing calcium overload in ischaemic neurons may thus have been outweighed by detrimental haemodynamic effects in the ischaemic area.

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Mats Urde1
TL;DR: Brand orientation means that the formulation of company strategy is based on brands as mentioned in this paper, and it is management's task and challenge to synchronize these concepts with a view to generating added value and brand loyalty.
Abstract: Brand orientation means that the formulation of company strategy is based on brands. By focussing the company′s commitment and resources on building, developing and nurturing brands, a platform for a sustainable competitive strategy is achieved. Presents a model of a brand‐oriented company using the concepts of product, trademark, corporate name, corporate identity, positioning, target group and brand vision. It is management′s task and challenge to synchronize these concepts with a view to generating added value and brand loyalty. The case of the Pharmacia Nicorette provides an illustration of the transition from product focus to brand orientation. The importance of brand orientation for industry and commerce is enhanced by three drivers: decreasing product divergence, increasing media costs and continuing market integration. A corporate management capable of exploiting the potential of brands may obtain long term competitive advantages – a strategy for survival in a growing number of companies.