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[Bewund're doch, o Mensch, dies Wunder. A poetry of Barthold Heinrich Brockes: Der Zahn (The tooth)].
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Structure of the Atmosphere of Jupiter: Galileo Probe Measurements
Temperatures and pressures measured by the Galileo probe during parachute descent into Jupiter's atmosphere essentially followed the dry adiabat between 0.41 and 24 bars, consistent with the absence of a deep water cloud and with the low water content found by the mass spectrometer. From 5 to 15 bars, lapse rates were slightly stable relative to the adiabat calculated for the observed H2/He ratio, which suggests that upward heat transport in that range is not attributable to simple radial convection. In the upper atmosphere, temperatures of >1000 kelvin at the 0.01-microbar level confirmed the hot exosphere that had been inferred from Voyager occultations. The thermal gradient increased sharply to 5 kelvin per kilometer at a reconstructed altitude of 350 kilometers, as was recently predicted. Densities at 1000 kilometers were 100 times those in the pre-encounter engineering model.
[Thrombolytic therapy and balloon dilatation. The effect on infarct time, reperfusion and reocclusion].
127 patients, admitted within six hours of onset of symptoms of acute transmural myocardial infarction, received at first 250 000 U streptokinase intravenously over 20 min, followed by an intracoronary infusion of 250 000 U after coronary angiographic demonstration of the infarct vessel. Those in whom the infarct vessel was closed were randomized into two groups. An attempt at recanalization was made either by thrombolysis alone, through a specially developed 3F catheter (group I, 64 patients), or by thrombolysis and dilatation with 4F Grüntzig balloon catheter (group II, 63 patients). There was no significant difference between the two groups with regard to sex, age, infarct site, creatine-kinase level and interval between onset of symptoms and treatment. Re-perfusion rate for group I was 92% (59 patients), for group II 89% (56 patients). Re-occlusion during the hospital stay occurred in 10 of 59 patients in group I, in 9 of 55 in group II. Re-occlusion occurred in only 8% (3 patients) after successful dilatation, but in 35% (6 patients) after failed dilatation. In the subsequent six months further occlusions were observed in seven group I and two group II patients. Combined drug-mechanical recanalization thus increased the re-perfusion rate, shortened the infarction time and made possible full revascularization by subsequent dilatation which led to a reduction in the re-occlusion rate.
Incidence, determinants, and clinical course of reinfarction in-hospital after index acute myocardial infarction (results from the pooled data of the maximal individual therapy in acute myocardial infarction [MITRA], and the myocardial infarction registry [MIR]).
There are few data about the incidence, determinants, and clinical course of in-hospital repeat acute myocardial infarction (RE-AMI) after an index AMI. From June 1994 to June 1998, 22,613 patients with AMI as an index event were registered by the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) and Myocardial Infarction Registries (MIR). Of these, 1,071 (4.7%) had a RE-AMI. For the index event, 9,143 patients (40.5%) were treated with thrombolysis, 1,707 (7.5%) with primary angioplasty, and 443 (2.0%) with a combination of both. Multivariate analysis showed that previous AMI (odds ratio [OR] 1.59; 95% confidence intervals [CI] 1.35 to 1.86), age >70 years (OR 1.57; 95% CI 1.36 to 1.81), diagnostic first electrocardiogram (OR 1.37; 95% CI 1.19 to 1.59), and female gender (OR 1.14; 95% CI 1.05 to 1.32) were independently associated with a higher incidence of RE-AMI. The incidence of RE-AMI was higher when patients received thrombolysis (OR 1.36; 95% CI 1.15 to 1.61), and it was lower when they underwent primary angioplasty (OR 0.74; 95% CI 0.53 to 1.03) or received beta blockers (OR 0.84; 95% CI 0.72 to 0.97). Patients with RE-AMI had higher hospital mortality compared with those without RE-AMI (OR 4.35; 95% CI 3.83 to 4.95). Multivariate logistic regression analysis showed an independent association of RE-AMI with in-hospital death (OR 6.60; 95% CI 5.61 to 7.70), repeat revascularization (OR 2.91; 95% CI 2.42 to 3.50), low workload capacity on the bicycle ergometry test (OR 2.17; 95% CI 1.71 to 2.76), and ejection fraction <40% (OR 1.72; 95% CI 1.38 to 2.14) at discharge. Thus, RE-AMI occurs in 4.7% of patients after an AMI. Previous AMI, age >70 years, diagnostic first electrocardiogram, and female gender are independent determinants for RE-AMI. Thrombolysis is associated with a higher and beta blockers with a lower incidence of RE-AMI. Once a RE-AMI occurs, it is a strong predictor of in-hospital mortality and morbidity.
DNA damage by PAH and repair in a marine sponge.
The sponge Tethya lyncurium from the Northern Adriatic has been used as an experimental species. A method is outlined for preparation of DNA which yields a highly purified DNA with a double-strand (ds) molecular weight of 25 M-dalton between single-strand (ss) breaks, which when properly damaged can be cut opposite to ss-breaks with nuclease S1. The molecular weights of the resulting ds-DNA pieces and their distribution has been evaluated by electron microscope photographs. Sponges exposed to benzo[a]pyrene (BaP) in the dark only incorporate BaP-derivatives (BaPD) in small amounts, if any. However, in the presence of light, derivatization to BaP derivatives enables effective coupling to occur, as shown previously (R.K. Zahn et al., 1981). Sponges were exposed to radiolabeled BaP in the presence of light. Coupling of BaPD to the DNA as well as the induction of ss-breaks were measured. Light-mediated coupling is concentration dependent from 0.01-20 ppb BaP with a correlation coefficient of r = 0.84. Under conditions of possible repair, ss-breaks completely disappear from sponge DNA in the course of three weeks while a substantial fraction of the BaP derivatives persists. Double label experiments show that substantial DNA synthesis occurs during this time. Pollution causes a decrease of the molecular weight of unnicked DNA, re-incubation in clean water an increase. A DNA species of 24 M-dalton seems to play a critical role. If its percentage in the DNA population drops below a critical level, recovery is not longer possible. DNA damage by PAH and repair in sponges seems to differ from that of most eucaryotes.
Virtual DNA analysis--a new tool for combination and standardised evaluation of SSO, SSP and sequencing-based typing results.
In order to obtain reliable information on HLA types, DNA typing with sequence-specific oligonucleotide/primer (SSO/SSP) typing sets or sequencing-based typing (SBT) is increasingly performed. The quality of the evaluation depends on the presence of a complete listing of all typed alleles as well as on the ability of detecting all corresponding alleles/allele pairs. We have developed the concept of virtual DNA analysis (VDA), which is able to combine all types of SSO/SSP/SBT results and evaluate this typing in combination according to the latest published allele sequence lists. The concept is based on the target DNA recognised by the respective typing techniques. All SSO/SSP or SBT results are transformed to a virtual sample DNA, which subsequently is analysed. Evaluation of generic or allele-specific DNA typing or the combination of both is supported. Due to this flexible approach, all kinds of SSO/SSP sets, as far as the respective SSO/SSP sequences are available, can be entered and evaluated immediately. The combination of collected data of different typing sets and procedures leads to the highest possible typing resolution. If more than one possible allele combination persists, the program reduces the result to the most specific common denominator in a stepwise manner. VDA offers the possibility of re-evaluation of former SSO/SSP/SBT results, alone or in combination. No solutions are omitted. This might be a first step towards standardisation of evaluating DNA-based HLA typing results or transfer of the respective typing data for later evaluation.
"Real life" use of sirolimus-eluting coronary stents in Germany. Results from the prospective multi-centre German Cypher Registry.
BACKGROUND: Drugeluting stents (DES) are currently judged to be a "break-through" technology for the prevention of restenosis after percutaneous coronary interventions (PCI). However, experience is limited to randomised controlled clinical trials (RCT) in selected lesions and the currently available DES are more expensive compared to conventional "bare" stents. Therefore, actual clinical practice may be very different to RCT. METHODS: We analysed the data of the German Cypher trade mark Registry, a nationwide registry which was initiated in parallel to the launch of the first DES, the Cypher trade mark sirolimus-eluting coronary stent, in April 2002. RESULTS: From April 2002 until March 2003, 1638 procedures at 88 hospitals were included in the German Cypher trade mark Registry. The mean inclusion rate per centre and month remained low (<3 procedures/month and participating hospital) during the whole inclusion period. Most patients presented with stable angina pectoris (45.8%); however, 6.4% of patients were treated for a non-ST elevation myocardial infarction, 10.3% of patients for ST elevation myocardial infarction and 1.7% in cardiogenic shock. In patients without ST elevation myocardial infarction, a de novo stenosis was treated in 68.4% of cases, a restenosis in 4.1%, and an in-stent restenosis in 25.5% of cases. Chronic total occlusions were treated in 6.1% of patients. Predilatation was performed in 68.3% of patients and 1.05 +/- 0.35 Cypher trade mark stents were implanted per patient with a median (quartiles) stent length of 18 (13-21) mm. PCI-related death occurred in 0.1% of patients and a Q-wave myocardial infarction in 1.1%. Urgent re-PCI before hospital discharge was performed in 1.3% and urgent bypass surgery in 0.1% of cases. CONCLUSIONS: The use of the sirolimus-eluting coronary stents in this "real life" registry was found to be safe concerning acute complications. In about one half of the registry patients, the DES was implanted in lesions that were excluded from RCTs.
IL-5-Induced JAB-JAK2 interaction.
Receptor activation by the haematopoietic growth factor proteins interleukin 5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) leads to phosphorylation of JAK2 as a key trigger of signal transduction. JAB has recently been identified as a regulator of JAK2 phosphorylation and activity by binding phosphorylated JAK2 and inducing its degradation. As part of our effort to define molecular recognition networks that lead to signalling, we investigated the effect of JAB on both JAK2 phosphorylation and JAK2 interaction state that ensue upon IL-5 stimulation in recombinant 293T cells cotransfected 293T cells with IL-5R alpha, beta c and hJAK2 either with or without JAB. Without JAB, stimulation with wild-type and re-engineered single chain (sc) IL-5 induced a time-dependent phosphorylation of JAK2. In the presence of JAB cotransfection, no phospho-JAK2 was observed, and JAB was observed co-immunoprecipitated with non-phosphorylated JAK2. The time dependence of JAB co-immunoprecipitation correlated with the time dependence of JAK2 phosphorylation when JAB was absent. Since JAB has already been shown to bind JAK2 via a phosphorylated tyrosine, the current data suggest that JAB binds to phosphorylated JAK2, enhances JAK2 dephosphorylation and remains associated in a complex, with dephosphorylated JAK2, that may be a precursor leading to irreversible JAK2 degradation.
Large-scale protein expression for proteome research.
Access to pure and soluble recombinant proteins is essential for numerous applications in proteome research, such as the production of antibodies, structural characterization of proteins, and protein microarrays. Through the German cDNA Consortium we have access to more than 1500 ORFs encoding uncharacterized proteins. Preparing a large number of recombinant proteins calls for the careful refinement and re-evaluation of protein purification tools. The expression and purification strategy should result in mg quantities of protein that can be employed in microarray-based assays. In addition, the experimental set-up should be robust enough to allow both automated protein expression screening and the production of the proteins on a mg scale. These requirements are best fulfilled by a bacterial expression system such as Escherichia coli. To develop an efficient expression strategy, 75 different ORFs were transferred into suitable expression vectors using the Gateway cloning system. Four different fusion tags (E. coli transcription-termination anti-termination factor (NusA), hexahistidine tag (6xHis), maltose binding protein (MBP) and GST) were analyzed for their effect on yield of induced fusion protein and its solubility, as determined at two different induction temperatures. Affinity-purified fusion proteins were confirmed by MALDI-TOF MS.