Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor alpha and interleukin-1 in rheumatoid arthritis

OBJECTIVE: To investigate the regulation of expression of the angiogenic cytokine vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA), in order to determine whether new blood vessel formation could be a potential therapeutic target in RA. METHODS: Dissociated RA synovial membrane cells were cultured in the presence of cytokine inhibitors, or under hypoxic conditions. Serum VEGF levels were serially measured in RA patients enrolled in clinical trials of anti-tumor necrosis factor alpha (anti-TNFalpha) monoclonal antibody treatment. RESULTS: Combined neutralization of TNFalpha and interleukin-1 (IL-1) in RA synovial membrane cultures reduced VEGF release by 45% (P < 0.05 versus control), although blockade of either TNFalpha or IL-1 activities alone resulted in only small inhibitory effects. In addition, release of VEGF from RA synovial membrane cells was selectively up-regulated by hypoxia. Serum VEGF levels were significantly elevated in RA patients relative to control subjects, and correlated with disease activity. Treatment of RA patients with anti-TNFalpha significantly decreased serum VEGF, and this effect was enhanced by cotreatment with methotrexate. CONCLUSION: Inhibition of TNFalpha and IL-1 activity in vivo could reduce the drive to new blood vessel formation, and hence pannus mass, adding to other therapeutic effects of anti-TNFalpha therapy in RA.     

Application of the fracture mechanics safety analysis to structural steel sections

This contribution presents a fracture mechanics safety analysis with finite element models applied on I-beams with defects in the tension flange. The moment rotation at room temperature was observed in the light of the toughness behaviour in front of initial notches. The results show very early crack initiation due to very large initial defects. The experiments were accompanied by a fracture mechanics safety analysis employing FEM. However, in temperature ranges of buildings plastically designed beams are subjected to sufficient rotation capacity, i.e. rotational ductility could be found.     

Voltage-controlled SAW filter on berlinite

An electrically tunable narrow-bandwidth SAW filter described. This new device works similarly as a SAW voltage controlled oscillator. Because of stability requirements ar recent availability, experiments are reported on berlini (AlPO4) crystal.     

Probleme der Rohstoffversorgung bei stahlveredelnden Schwer- und Sondermetallen

Problems regarding the raw material supply of steel improving heavy and minor alloy metals . The supply situation of steel improving heavy and minor alloy metals reveals that the absolute and relative concentration of the raw material output as well as the regional supply agglomeration in developing countries is much more marked as is the case with crude oil. Future development is expected to increase even the import dependence of few large producing countries in the Third World, thus increasing the risk of short-term availability bottlenecks, shortcomings in deliveries and cartelizations in view of a sharply rising demand of alloy metals and a shortage of Europe's own production. Besides the promotion of industrial potentialities to ensure a better adaptability to given supply situations – particularly recycling, substitution and stockpiling – there is a need for a government flanking raw material policy with national and international objectives.     

Prospective study of risk factors in natural rubber latex hypersensitivity

Five hundred sixty-nine subjects routinely underwent skin prick tests for latent sensitization to latex. The study of risk factors included skin tests to inhalant allergens, to diagnose atopy, and a questionnaire aimed at revealing frequent exposure to latex such as the wearing of gloves, multiple surgical procedures, or urinary catheterization. The subjects were categorized into five groups: group I, subjects with no risk factor (n = 272); group II, nonatopic subjects exposed to latex (n = 73); group III, atopic subjects not exposed (n = 180); group IV, exposed atopic subjects (n = 44); and group V, subjects with a history of intraoperative anaphylactic shock caused by latex (n = 13). Twenty-five subjects had spina bifida and were in either group II (14 subjects) or group IV (11 subjects). The questionnaire identified a probable allergy to latex in 18 subjects: 16 cases were confirmed by skin test, but responses were not informative in 23 patients who were sensitive to latex. Positive prick tests to latex were obtained in 0.37% of group I, 6.85% of group II, 9.44% of group III, and 36.36% of group IV. Of the children with spina bifida, 32% had positive skin test results. As risk factors, atopy and exposure were synergistic. We recommend predictive prick tests not only in children with spina bifida but also in any atopic subject or in any patient with a history of frequent exposure to latex. Latex could be considered a habitual allergen. The use of latex urinary catheters should be avoided in patients who are catheterized on a daily basis.     

Efficient adenoviral infection with IkappaB alpha reveals that macrophage tumor necrosis factor alpha production in rheumatoid arthritis is NF-kappaB dependent

Tumor necrosis factor (TNF) alpha has been shown to be a major therapeutic target in rheumatoid arthritis with the success of anti-TNFalpha antibody clinical trials. Although signaling pathways leading to TNFalpha expression have been studied in some detail, there is evidence for considerable differences between individual cell types. This prompted us to investigate the intracellular signaling pathways that result in increased TNFalpha synthesis from macrophages in the diseased synovial joint tissue. Using an adenoviral system in vitro we report the successful delivery of genes to more than 95% of normal human macrophages. This permitted us to show, by using adenoviral transfer of IkappaB alpha, the natural inhibitor of NF-kappaB, that induction of TNFalpha in normal human macrophages by lipopolysaccharide, but not by some other stimuli, was inhibited by 80%. Furthermore the spontaneous production of TNFalpha from human rheumatoid joint cell cultures was inhibited by 75%, indicating that the NF-kappaB pathway is an essential step for TNFalpha synthesis in synovial macrophages and demonstrating that NF-kappaB should be an effective therapeutic target in this disease.     

Sframe: An efficient system for detailed DC simulation of bipolar analog integrated circuits using continuation methods

This work describes a simulation package for detailed studies of biasing networks for bipolar transistors. A sophisticated transistor model is introduced which captures many second-order effects, but which causes convergence difficulties for many existing methods used for computing an operating point. Artificial parameter numerical continuation techniques are introduced, then, as a robust and efficient means of solving bias networks employing our model. Sensitivity studies and natural parameter continuation studies based on the computed operating point (or points) are also discussed.     

New charge transfer recursive filter

A new fully integrated recursive charge transfer filter is described using the concept of passive recirculation of charges. This is a novel solution for voice channel or data filters in digital communications.     

Influence of cigarette smoking on rate of reopening of the infarct-related coronary artery after myocardial infarction: a multivariate analysis

OBJECTIVES: This study sought to determine whether the reopening of the infarct-related vessel is related to clinical characteristics or cardiovascular risk factors, or both. BACKGROUND: In acute myocardial infarction, thrombolytic therapy reduces mortality by restoring the patency of the infarct-related vessel. However, despite the use of thrombolytic agents, the infarct-related vessel remains occluded in up to 40% of patients. METHODS: We studied 295 consecutive patients with an acute myocardial infarction who underwent coronary angiography within 15 days (mean [+/- SD] 6.7 +/- 3.2 days) of the onset of symptoms. Infarct-related artery patency was defined by Thrombolysis in Myocardial Infarction trial flow grade > or = 2. Four cardiovascular risk factors--smoking, hypertension, hypercholesterolemia and diabetes mellitus--and eight different variables-age, gender, in-hospital death, history of previous myocardial infarction, location of current myocardial infarction, use of thrombolytic agents, time interval between onset of symptoms, thrombolytic therapy and coronary angiography--were recorded in all patients. RESULTS: Thrombolysis in current smokers and anterior infard location on admission were the three independent factors highly correlated with the patency of the infarct-related vessel (odds ratios 3.2, 3.0 and 1.9, respectively). In smokers, thrombolytic therapy was associated with a higher reopening rate of the infard vessel, from 35% to 77% (p < 0.001). Nonsmokers did not benefit from thrombolytic therapy, regardless of infarct location. CONCLUSIONS: These observational data, if replicated, suggest that in patients with acute myocardial infarction, thrombolytic therapy may be most effective in current smokers, whereas nonsmokers and ex-smokers may require other management strategies, such as emergency percutaneous transluminal coronary angioplasty.     

Non-Intercepting Ion Phase Measuring Equipment of the Isochronous Cyclotrons at Karlsruhe and Julich

A non-intercepting ion phase measuring equipment is in use at the Karlsruhe cyclotron. Five phase signals, steadily and simultaneously displayed are presenting a good survey of phase width and phase distribution versus radius. High noise immunity is obtained by the use of differential electrostatic pickup probes. Concerning the Jülich cyclotron a similar device with twelve double electrostatic probes is in construction.