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Biomedical subjects

K Nagel

Publications and source records attributed to K Nagel.

At least 19 recordsLinked to original sources

Supporting perception in the service of dynamic decision making.

Skilled performers in complex environments rely heavily on heuristic strategies to cope with the time pressure and complexity of dynamic tasks. We suggest that the use of task simplification strategies based largely on perception and pattern recognition is fundamental to the novice-expert shift in dynamic decision making. We therefore suggest that interface training interventions should support the development of highly effective and robust heuristic strategies, rather than the development of more abstract, cognitively intensive strategies. A pair of empirical studies are presented that investigated the benefits of training interventions aimed at supporting perceptual and pattern-recognitional activities in dynamic environments. Results suggest that the acquisition of skilled performance in dynamic environments can be accelerated by supporting perceptual activities in the service of dynamic decision making. Implications of these results for training, aiding, and interface design are discussed.

Adult↗

Regulation of the uncoupled GTPase activity of elongation factor G (EF-G) by the conformations of the ribosomal subunits.

The elongation factor G (EF-G) GTPase activity is induced by either 70S ribosomes or 50S ribosomal subunits. The GTPase activity induced by 50S ribosomal subunits is predominant at low concentrations of monovalent cations and decreases with increasing concentrations of K+ or NH4+. Double-logarithmic plots of the data reveal straight lines with different slopes for low and high concentrations of monovalent cations, respectively, intersecting at the same concentration of monovalent cations where maximal EF-G GTPase activity is measured in the presence of both ribosomal subunits. Substantially the same curves are obtained when 50S ribosomal subunits are substituted by 50S CsCl-core particles partially reconstituted by addition of purified 50S split proteins L7/L12. Intact 30S ribosomal subunits, but not 30S CsCl-core particles are able to associate with 50S ribosomal subunits and to modulate ribosome-dependent EF-G GTPase activity. Therefore, our data clearly show that the biphasic courses of the NH4+ and K+ curves of EF-G GTPase activity induced by 50S ribosomal subunits are not due to contaminations with 30S ribosomal subunits but result from different conformations of EF-G/50S ribosomal-subunit complexes at low and high concentrations of monovalent cations, respectively. CD spectra of 50S ribosomal subunits measured under different salt conditions have shown that the conformation of the 50S ribosomal subunits is strongly dependent on the concentration of monovalent cations. The conformation of 30S ribosomal subunits is, however, considerably stronger influenced by the Mg2+ than by the concentration of monovalent cations. The salt effects on the conformation of the 30S ribosomal subunits correspond to the salt effects on the association of ribosomal subunits and the modulation of EF-G GTPase activity by 30S ribosomal subunits. Since, in the presence of both ribosomal subunits, EF-G GTPase activity is maximal at the same concentration of monovalent cations where obviously a spontaneous conformation change of 50S ribosomal subunits takes place, we postulate that EF-G GTPase primarily acts on the ribosomes by changing the conformation of 50S ribosomal subunits. The resulting model is based on the assumption that EF-G GTPase activity is considerably more strongly induced by the 'substrate conformation' ('state I') than by the 'product conformation' of the 50S ribosomal subunits ('state II'). A spontaneous transformation of 'state II' to 'state I' is expected to occur in the absence of mRNA, aminoacyl-tRNA and EF-T especially under salt conditions favouring state I.

Cations↗

Regulation of elongation factor G GTPase activity by the ribosomal state. The effects of initiation factors and differentially bound tRNA, aminoacyl-tRNA, and peptidyl-tRNA.

The elongation factor G (EF-G) is responsible for the translocation of the ribosome along the mRNA chain. Under in vitro conditions, EF-G exhibits a very active uncoupled GTPase activity which is dependent on the presence of ribosomes and is modulated by mRNA-dependent binding of tRNA. In the absence of tRNA, uncoupled EF-G GTPase is inhibited by initiation factors IF1 and IF3, but not by initiation factor IF2. In the presence of N-fMet-tRNAfMet and poly(A,U,G) or in the presence of N-acetyl-Phe-tRNAPhe and poly(U), initiation factor IF2 causes an additional decrease of the uncoupled EF-G GTPase activity. This effect, however, is dependent on the presence of IF1 and IF3 and is obviously due to the mRNA- and initiation factor-dependent binding of N-fMet-tRNAfMet and N-acetyl-Phe-tRNAPhe, respectively, to the ribosomal P-site. Non-enzymatic binding of N-fMet-tRNAfMet and N-acetyl-Phe-tRNAPhe, however, causes a stimulation of uncoupled EF-G GTPase activity. The same effects are observed for Met-tRNA, Phe-tRNAPhe and uncharged tRNA. These findings are discussed in the light of the three-site model of the ribosome and the mechanism of translocation.

Chromatography, DEAE-Cellulose↗

An inhibitor of elongation factor G (EF-G) GTPase present in the ribosome wash of Escherichia coli: a complex of initiation factors IF1 and IF3?

An inhibitor of elongation factor G (EF-G) GTPase isolated from the ribosome wash of Escherichia coli was shown to stimulate the poly(A,U,G)- and initiation factor 2 (IF2)-dependent binding of N-formyl-[35S]Met-tRNAfMet to ribosomes. In the presence of saturating amounts of the EF-G GTPase inhibitor, neither addition of initiation factor 1 (IF1) nor addition of initiation factor 3 (IF3) caused a further stimulation of the formation of N-formyl-[35S]Met-tRNAfMET/poly(A,U,G)/ribosome complexes. Both IF1 and IF3 were shown to inhibit ribosome-dependent EF-G GTPase, especially when both initiation factors were added either in absence or in the presence of initiation factor 2 (IF2), poly(A,U,G) and N-formyl-Met-tRNAfMet. Therefore, we conclude that the EF-G GTPase inhibitor consisting of two polypeptide subunits with apparent molecular masses of 23,000 and 10,000 Da is a complex of initiation factors IF1 and IF3. The inhibition of EF-G GTPAse by IF3, but not the effects of IF1 in the presence or absence of IF3 could be reversed by increasing the Mg(2+)-concentration as already shown for the EF-G GTPase inhibitor. Therefore, IF1 as well as the EF-G GTPase inhibitor do not influence the ribosome-dependent EF-G GTPase by affecting the association of ribosomal subunits.

Bacterial Proteins↗

[Late results following implantation of aortic bifurcation prosthesis].

From January 1976 to December 1986 181 patients with chronic arterial occlusive disease were provided with an Y-prosthesis of the aorta. In a retrospective study we reviewed the history of these patients. From 130 (72%) patients we obtained information about the further course of the disease, 83 (46%) patients were reexamined. Depending on the preoperative stage (Fontaine-Ratschow classification) of the chronic arterial occlusive disease, patients in higher stages had a greater benefit from the implantation by shifting into a more satisfactory stage. The majority of patients without any postoperative complaints (48%) belonged to the group, preoperatively classified into stage II B. Depending on the type of occlusion the best results were obtained in unique occlusions of the aorto-iliac vascular segment. 50% of the reexamined patients had no complaints although in 61% of these cases the superficial femoral artery was occluded in the mean time. 47 patients deceased during the interval of observation. In most cases death was caused by other manifestations of the basic disease (e.g. cardiac infarction or cerebral apoplexy). The 10-year-survival rate was 59%. The majority of patients with chronic occlusive disease of the pelvic arteries profited from the implantation of an aortal Y-prosthesis. The long-term success of this operation with its low lethality depends on the preoperative stage and the extent of the occlusive process.

Aorta, Abdominal↗

Lithium carbonate and mood disorder in recently detoxified alcoholics: a double-blind, placebo-controlled pilot study.

The effects of lithium carbonate were assessed in a double-blind, placebo-controlled study of a small group of recently detoxified alcoholics. The patients were treated during their 2nd and 3rd week of abstinence. A previous study demonstrated the existence in these patients of a syndrome of mildly elevated psychomotor rate, including irritability, grandiosity, an increased need for social contact, loquaciousness, and sexual preoccupation. The intensity of this syndrome was significantly decreased by treatment with low dose lithium carbonate, with no effect of placebo treatment.

Adult↗

[Results of endoscopic perforant vein dissection].

A new endoscopic technique allows insufficient perforating veins to be sectioned under direct visual control with minimal trauma. The endoscopical sectioning of perforating veins was performed on 61 patients in 86 legs. Perforating veins have most frequently been separated in the area of the Cockett group (185), the 24-cm perforating vein (74), and the Boyd group (63). Two patients showed disturbances of wound healing after the operation. By a follow-up examination 2 years postoperatively, insufficient perforating veins were not found in any of the 86 legs operated on. New varices were seen in six legs. With respect to a staging of chronic venous insufficiency, it can be said that in 90% of cases a more favorable stage or complete healing is reached.

Endoscopes↗

[Results of endoscopic perforating vein dissection].

The subfascial discision of insufficient perforating veins is considered the most effective therapeutic principle for the treatment of postthrombotic disturbances of the skin as well as for trophic disturbances caused by varicose. A new endoscopic technique allows to be sectioned them under direct view control with little trauma. In the period from November 1986 to April 1990 61 patients underwent an endoscopic sectioning of perforating veins. Perforating veins have most frequently been separated in the area of the Cockett group (153), the 24 cm perforating vein (74) and in the area of the Boyd group (63). Two patients (3.3%) with trophic disturbances of the skin in the area of the shank showed disturbances of wound healing after the operation. First results of the follow-up examination 3-37 months postoperative have proved good (45%) to very good (40%) results. Criteria, which were observed, were pains in the leg, disturbances of sensibility, swellings and relapsed varices. Only two patients proved a bad result. Insufficient perforating veins in the area of the shank were not found by one of the 61 operated patients. Referring to a staging of chronic venous insufficiency it can be said that with the exception of the two patients above mentioned there is a ranging to a more favourable stage or to a complete treating.

Adult↗

Isolation and characterization of an inhibitor of ribosome-dependent GTP hydrolysis by elongation factor G.

Two inhibitors of ribosome-dependent GTP hydrolysis by elongation factor (EF)G were found in the ribosome wash of Escherichia coli strain B. One of these inhibitors was purified to homogeneity and characterized. The isolated inhibitor was found to consist of two polypeptide subunits with apparent molecular masses of 23 kDa and 10 kDa. Inhibition of EF-G GTPase could not be overcome by increasing amounts of the elongation factor or high concentrations of GTP, but was reversed by large amounts of ribosomes. The effect of the inhibitor was reduced by increasing concentrations of either 30S or 50S ribosomal subunits. EF-G-dependent GTPase of 50S ribosomal subunits was not affected by the inhibitor. These findings clearly show that the inhibitor interferes with the modulation of EF-G GTPase activity by the interactions between 30S and 50S ribosomal subunits. Under conditions, where 30S CsCl core particles are able to associate with 50S subunits and to stimulate EF-G GTPase, the effect of the inhibitor was considerably reduced when intact 30S ribosomal subunits were substituted by 30S CsCl core particles. This finding indicates that 30S CsCl split proteins are important for the action of the inhibitor and that the inhibitor does not affect the EF-G GTPase merely by interfering with the association of ribosomal subunits. Furthermore, poly(U)-dependent poly(phenylalanine) synthesis was considerably less sensitive to the inhibitor than EF-G GTPase. When ribosomes were preincubated with poly(U) and Phe-tRNA(Phe), poly(phenylalanine) synthesis was considerably less affected by the inhibitor, whereas EF-G GTPase was still sensitive.

Chromatography, DEAE-Cellulose↗

[Quantification of changes in the skeletal muscle blood circulation following revascularization using a 99m technetium-labeled tracer].

A new 99mTc-labelled tracer (99mTc-Sestamibi) was used for the first time to demonstrate the perfusion of the skeletal muscle. In 16 patients with obstructive atherosclerosis of the lower limbs the change of perfusion of thigh and lower leg was studied with SPECT before and after vascular surgery (n = 11) or percutaneous transluminal angioplasty (n = 5). Comparative results of scintigraphic measurements and clinical observations (ankle-arm pressure, treadmill test) in 10 surgical patients (14 operated legs) showed correct positive or negative results in 86% (12/14).

Aged↗

[The results and complications of 616 percutaneous transhepatic biliary drainages].

During nine years, percutaneous transhepatic biliary drainage was carried out 616 times on 563 patients in the Department of Radiology, University of Mainz Medical School. 50.3% were pre-operative and 39% were palliative. More than 80% were necessitated by malignant lesions. Subsequent improvements in biochemical measurements were observed in 82.4% of patients. Complications of the procedure led to the death of five patients (0.8%) and required surgery in nine patients (1.5%). The following complications were observed: biliary peritonitis in 0.6%, sepsis in 1.9%, bleeding in 1.9% and fever higher than 38 degrees C in 16.2%.

Biliary Tract↗