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  • 1
    Electronic Resource
    Electronic Resource
    Differential effects of leflunomide on leukocytes: Inhibition of ratin vivo adhesion and humanin vitro oxidative burst without affecting surface marker modulation (1994)
    Springer
    Inflammation research 41 (1994), S. C276 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leflunomide has been shown to combat effectively autoimmune diseases in a number of animal models, as well as chronic polyarthritis of humans. Here we report on the effects of this novel drug on the adherence of leukocytes to endothelium, an essential event in establishment and maintenance of inflammation. The entry of cells into tissues is dependent on interactions of adhesion molecules. The process of diapedesis, which these molecules control, involves three phases: tethering, triggering of receptors on endothelial cells and firm attachment of leukocytes to these cells. The interaction of LECAM-1 (constitutively expressed on circulating leukocytes) and P- and E-selectins on the vessel wll leads to rolling of leukocytes along the endothelium. Using anin vivo system (rat peritoneum) we found that leflunomide effectively inhibits the rolling of leukocytes along the vessel wall after formyl-methionyl peptide (FMLP) induction. Leflunomide's inhibition of FMLP-induced rolling does not appear to be due to its effects on either LECAM-1 or CD11b, because their modulation was unaltered by this drug. We did, though, find that leflunomide strongly inhibited the FMLP-induced induction of the oxidative burst in these cells. Although we have not yet obtained data on leflunomide's effects on the other phases of diapedesis, our results indicate that this drug has effects on leukocyte activation and adhesion, key events in the initiation and maintenance of chronic inflammation and pathological tissue damage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01987668
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  • 2
    Electronic Resource
    Electronic Resource
    The influence of leflunomide on cell cycle, IL-2-receptor (IL-2-R) and its gene expression (1994)
    Springer
    Inflammation research 41 (1994), S. C204 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leflunomide is a novel immunomodulatory drug shown to be very effective in animal models of autoimmune diseases and transplantation rejection, as well as in human rheumatoid arthritis. Leflunomide's main metabolite, A77 1726, has been shown to be reversibly antiproliferativein vitro. Pursuing this, we performed cell cycle analysis by flow cytometry of a B-cell lymphoma line and found that at concentrations 〉2.5 μM cells accumulated in the early S-phase. In order to determine A77 1726's effects on cell activation, human peripheral blood lymphocytes (PBL) were cultured in the presence of PHA or OKT 3 antibody. Flow cytometric evaluation of IL-2 and transferrin receptor expression exhibited a dose-dependent inhibition of these activation markers (10–100 μM). Further, using the polymerase chain reaction, we investigated the ability of leflunomide to impair the transcription of the IL-2-R gene. We found that A77 1726 did not significantly decrease IL-2-R α-chain mRNA expression regardless of stimulation. It seems that leflunomide's main metabolite did not affect IL-2-R at the level of gene transcription, and thus its effects could be due to impairment of post-translational events. Taken together, these studies demonstrate that leflunomide: (1) impairs activation of quiescent lymphocytes (reduction of IL-2-R expression), without inhibiting IL-2-R mRNA formation; (2) reversibly inhibits proliferation by holding resting lymphocytes in the G0-phase and activated cells in the early S-phase of the cell cycle. Thus, this compound may exert its effects through influencing two important aspects of an immune response, i.e. activation and proliferation of lymphocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01987638
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  • 3
    Electronic Resource
    Electronic Resource
    The influence of leflunomide on cell cycle, IL-2-receptor (Il-2-R) and its gene expression (1995)
    Springer
    Inflammation research 44 (1995), S. 143-143 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01782026
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  • 4
    Electronic Resource
    Electronic Resource
    Sequence polymorphism in kringle IV 37 in linkage disequilibrium with the apolipoprotein (a) size polymorphism (1995)
    Springer
    Human genetics 〈Berlin〉 95 (1995), S. 275-282 
    Details
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apolipoprotein(a) [apo(a)] contains a variable number of identical (K-IV A/B) or nearly identical (K-IV 1, K-IV 30–37) kringle repeats that are homologous to K-IV from plasminogen. The sizes of 414 apo(a) alleles were determined by pulsed-field gel electrophoresis (PFGE) of KpnI-digested DNA. Furthermore, sequence variation in the apo(a) K-IV 30–37 domain was analysed. Reverse transcription/polymerase chain reaction (RT-PCR) cloning of human liver poly A+ RNA followed by sequencing revealed a single nucleotide exchange in the ultimate K-IV (K-IV 37) of apo(a) (codon 4168); this results in an ATG (Met) to ACG (Thr) substitution. A PCR-based restriction assay of genomic DNA demonstrated that this substitution represents a common polymorphism. In 231 unrelated Tyroleans, the frequencies for the K-IV 37 Thr and K-IV 37 Met alleles were 0.66 and 0.34, respectively. The phase between the K-IV 37 Met/Thr and the KpnI size polymorphism was determined for 224 alleles. A significant linkage disequilibrium was detected between the sequence and size polymorphisms of apo(a). K-IV 37 Met was significantly associated with KpnI allele no. 18 (D AB= 0.0267 + 0.0101; χ2 = 10.09, df = 1). The Met/Thr polymorphism was further used to test whether deletions or duplications of K-IV 37 occur frequently in the apo(a) gene. Some 40 apo(a) alleles, 22 of which were from subjects that appeared to be double heterozygotes for K-IV repeat number and the Met/Thr variation were separated by PFGE and analysed for the 4168 Met/Thr polymorphism. The Met and Thr sequences were always present on different size alleles and no evidence for a duplication or deletion of K-IV 37 was obtained. This suggests that the copy number of K-IV 37 is invariable, in contrast to the highly variable K-IV A/B domain of the gene. The 4168 Met/Thr polymorphism had no effect on Lp(a) concentration, neither did it influence the lysine-binding property of the Lp(a) particle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00225193
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  • 5
    Electronic Resource
    Electronic Resource
    The value of family investigations in newly detected Charcot-Marie-Tooth disease in children (1995)
    Springer
    European journal of pediatrics 154 (1995), S. S40 
    Details
    ISSN: 1432-1076
    Keywords: Charcot-Marie-Tooth disease 1A ; Duplication on chromosome 17p11.2 ; Variable clinical phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Charcot-Marie-Tooth disease (CMT) was diagnosed by nerve conduction velocity and histology of the sural nerve in two boys aged 3 and 6 years with clinical signs of a severe neuromuscular disease. DNA analysis revealed the typical duplication on chromosome 17p 11.2 (2.7 kb allele) for CMT 1A. Although none of their family members reported symptoms of neuromuscular disease, the nerve conduction velocity was reduced in three members (father and two aunts). They were homozygous for the 2.7 kb allele and were assumed to carry three copies of this allele. The very differing clinical picture from one generation to the next in patients with identical neurophysiological and genetic results is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02191504
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  • 6
    Electronic Resource
    Electronic Resource
    Chain length and pressure dependence of lipid translational diffusion (1987)
    Springer
    European biophysics journal 14 (1987), S. 485-491 
    Details
    ISSN: 1432-1017
    Keywords: Lipid diffusion ; free volume ; excimers ; pressure ; model membranes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract The translational diffusion of pyrene, pyrene butyric acid and pyrene decanoic acid has been determined in phosphatidylcholine bilayers of different chain length and under pressure up to 200 bars. In the liquid crystalline phase and at a given temperature the diffusion decreases with increasing chain length. At a constant reduced temperature, T red (about 10 K above the transition temperature), long chain lipids exhibit the fastest diffusion which is in disagreement with hydrodynamic models but favours free volume models for diffusion in lipid bilayers. The volume of activation, V act, calculated from the decrease of the diffusion coefficient with pressure, ∂ln D/∂P, depends on lipid chain length. V act decreases with decreasing lipid chain length at a given temperature, T=65°C, and increases at the reduced temperature. These results are again in agreement with the dependence of the diffusion on lipid chain length and therefore with the free volume model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00293258
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  • 7
    Electronic Resource
    Electronic Resource
    Increased prevalence of minor anomalies in childhood malignancy (1985)
    Springer
    European journal of pediatrics 144 (1985), S. 243-249 
    Details
    ISSN: 1432-1076
    Keywords: Childhood malignancy ; Leukaemia ; Malformation ; Minor anomalies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Body measurements were taken and the prevalence of major malformations and of 57 minor anomalies was determined in 106 children with malignant disease, in 81 of their sibs, and in 106 control subjects matched to the patients according to sex, age and ethnic origin. Leukaemic children had a significantly smaller head circumference than the corresponding control children, but no significant differences in height, anthropometric and syndromologic indices were found. No differences were observed in the frequency of associated major malformations including renal malformations detectable by sonography. The prevalence of minor anomalies was significantly higher in the patients with malignant disease and their sibs than in the control children: 69.2% of the patients, 63.0% of the sibs and 34.6% of the control subjects had at least one minor anomaly. When two and more minor anomalies were considered, the prevalence figures were 36.5%, 29.6% and 12.5%, respectively. Among the single minor anomalies only the Sydney line was significantly more frequent in patients with solid tumours. No specific association of an individual dysplasia or a pattern of minor anomalies with a given tumour could be established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00451951
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  • 8
    Electronic Resource
    Electronic Resource
    Order parameter and packing studies in nematic and smectic A phases by x-ray diffraction (1988)
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 89 (1988), S. 3317-3322 
    Details
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: X-ray diffraction measurements have been made on the nematic phase of T15 (4-cyano-4'-n-pentyl-p-terphenyl), as well as on the nematic and smectic A phases of RNO2 [4'-nitrophenyl-4-(4'-n-hexyloxy-benzoyloxy)-cinnamate]. The x-ray equipment used allows comparably high resolution measurements of liquid crystals. The inner reflexes show that both compounds possess a bilayer structure supposed as overlapping of polar cyano or nitro group of one molecule and the phenyl ring of the neighboring molecule. The molecular orientational distribution function f (β) has been calculated on the basis of intensity simulations of the outer reflexes. The orientational order parameter P2(cos β), P4(cos β), 〈P2〉 and 〈P4〉 have been determined from f (β). A strong decrease of 〈P2〉 and 〈P4〉 is observed at the smectic A–nematic phase transition temperature of RNO2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.454939
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  • 9
    Electronic Resource
    Electronic Resource
    Chemi-Luminescence and Chemi-Electron Emission from Alkali Azides (1965)
    [s.l.] : Nature Publishing Group
    Nature 207 (1965), S. 1073-1075 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] AT elevated temperatures, Audubert et al.l~5 observed a faint emission of ultra-violet light from various azides by means of a photosensitive Geiger-Miiller counter. They ascribed the emission to the thermal decomposition of the specimens and assumed that the intensity of the radiation was a direct ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/2071073a0
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  • 10
    Electronic Resource
    Electronic Resource
    Electron microscopy samples: replication using dental inlay wax (1981)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of oral rehabilitation 8 (1981), S. 0 
    Details
    ISSN: 1365-2842
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A two-stage replication technique for electron microscopy is described using indirect dental inlay wax. Its application has particular value in the study of dental polymeric materials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2842.1981.tb00492.x
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