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Biomedical subjects

R Lutz

Publications and source records attributed to R Lutz.

At least 19 recordsLinked to original sources

[The therapeutic concept of euthymic treatment. The little school of pleasure].

With the aid of euthymic treatment, patients can learn to open up to, and enjoy, positive occurrences, to create their own space for well-being, and to develop a higher level of self-care. Changes in both the cognitive and the sensual planes in particular, are goals to be aimed at. The concept of euthymic therapy has developed on the basis of research on enjoyment and a therapeutic program known as the "little school of pleasure." Today, this program is being applied in a variety of different categories of patients, for example, depressives, alcoholics, schizophrenics, neurological, traumatized and chronic-pain patients, as well as those hospitalized in psychosomatic and psychiatric institutions.

Adaptation, Psychological↗

[B-flow and contrast medium-enhanced power Doppler (Optison(R))--preoperative diagnosis of high-grade stenosis of the internal carotid artery].

PURPOSE: To improve sonographic diagnosis of high-grade stenosis of the internal carotid artery (ICA) by vascular sonography in "B-flow"-mode and in contrast medium (Optison(R))-enhanced power Doppler (PD). MATERIAL AND METHODS: 88 patients suspected of a high-grade stenosis of the extracranial ICA were examined by independent examiners with color-coded Doppler (CCD), B-flow and PD to compare the methods for morphology and degree of stenosis. In 21 cases contrast medium was used in PD. Sonographic results of all 88 patients were compared with selective angiography (DSA), in 53 cases with operative findings. RESULTS: A complete occlusion was found in 9 patients and a 50 - 70 % degree non-exulcerated stenosis in 26 cases. 53 of 88 patients presented findings in both sonography and DSA leading to operation of the ICA. Among these 47 had a stenosis > 70 % and 6 a stenosis of 60 - 70 % with exulcerated plaques. Even a small dose of contrast medium (0.3 ml) gave a significant signal increase in PD improving flow detection even in extensive vascular calcification. In both the early phase (up to the first minute p. i.) flow contrast was optimal and without significant artifacts. Thus, the extent and the morphology of the stenosis was better appreciated. Hypoechogenic plaques, ulcerations and thrombi are as easily recognized by B-flow as flow in preocclusive stenosis, free of vibration and blooming artifacts. This gave a better correlation with DSA and a higher diagnostic accuracy in grading a stenosis than CCD and PD. Circular calcifications or vessel kinking made diagnosis of flow more difficult. CONCLUSION: B-flow allows a reliable diagnosis of the degree of stenosis of ICA and a better appreciation of plaque morphology than CCD. In some cases with extensive calcifications contrast medium-enhanced PD is able to detect better intrastenotic flow. Only small quantities of contrast medium (Optison(R)) are required.

Aged↗

[Preoperative wire localisation of breast lesions by tissue harmonic imaging (THI) sonography].

PURPOSE: To obtain a fast and reliable preoperative wire localisation of occult lesions in dense breast tissue by tissue harmonic imaging (THI) sonography when localisation by mammography is not reliable enough. MATERIAL AND METHODS: In addition to biplane mammography for breast screening or for follow-up examination after breast-saving therapy, ultrasound was performed by two independent radiologists in 350 patients with mastopathic or fibrotic breast tissue. Using a multifrequency probe (5 - 10 MHz), lesions were documented by conventional B-mode and by THI in similar projections. In 25 lesions not precisely identified in mammography sonographically guided puncture with wire localisation was performed. RESULTS: In 22 of 350 patients 25 circumscribed suspicious lesions with an average diameter of 8 mm were identified, regarded suspicious by ultrasound but not by mammography. Nineteen of 25 lesions found by M-Mode and THI, an additional 6 only by THI. Guided puncture and wire localisation was achieved in 10 minutes on the average. In B-mode, the course of needle and wire was reliably seen in 16 of 25 cases, in THI in all cases. After surgical removal of tissue, histopathology revealed a ductal or lobular carcinoma in 19 cases, metastasis in three cases and benign complicated cysts with fibrotic tissue in the remaining three cases. CONCLUSION: THI is superior to B-mode ultrasound in differentiating suspicious lesions in dense glandular breast tissue. If tumor signs in mammography are not reliable enough or if a precise localisation is not possible, sonographically guided puncture by THI can give reliable results and, furthermore, is faster and more comfortable for the patient than localisation by mammography.

Biopsy, Needle↗

Highly conserved amino acids in Pax and Ets proteins are required for DNA binding and ternary complex assembly.

Combinatorial association of DNA-binding proteins on composite binding sites enhances their nucleotide sequence specificity and functional synergy. As a paradigm for these interactions, Pax-5 (BSAP) assembles ternary complexes with Ets proteins on the B cell-specific mb-1 promoter through interactions between their respective DNA-binding domains. Pax-5 recruits Ets-1 to bind the promoter, but not the closely related Ets protein SAP1a. Here we show that, while several different mutations increase binding of SAP1a to an optimized Ets binding site, only conversion of Val68 to an acidic amino acid facilitates ternary complex assembly with Pax-5 on the mb-1 promoter. This suggests that enhanced DNA binding by SAP1a is not sufficient for recruitment by Pax-5, but instead involves protein-protein interactions mediated by the acidic side chain. Recruitment of Ets proteins by Pax-5 requires Gln22 within the N-terminal beta-hairpin motif of its paired domain. The beta-hairpin also participates in recognition of a subset of Pax-5-binding sites. Thus, Pax-5 incorporates protein-protein interaction and DNA recognition functions in a single motif. The Caenorhabditis elegans Pax protein EGL-38 also binds specifically to the mb-1 promoter and recruits murine Ets-1 or the C.elegans Ets protein T08H4.3, but not the related LIN-1 protein. Together, our results define specific amino acid requirements for Pax-Ets ternary complex assembly and show that the mechanism is conserved between evolutionarily related proteins of diverse animal species. Moreover, the data suggest that interactions between Pax and Ets proteins are an important mechanism that regulates fundamental biological processes in worms and humans.

Amino Acid Sequence↗

Dissecting the functional program of Escherichia coli promoters: the combined mode of action of Lac repressor and AraC activator.

The mode of action of regulated promoters is largely determined by kinetic parameters which govern the interaction between promoters and proteins involved in induction and repression of transcription. To gain insight into the interplay between positively and negatively acting transcriptional regulators, in this case AraC and LacR, we have generated a panel of promoter sequences derived from P(lac), the promoter of the Escherichia coli lac operon. The function of these promoters is limited at different steps and to various extents within the pathway of RNA polymerase (RNAP)/promoter interaction. Moreover, in all promoters the cAMP receptor protein binding site was replaced by the binding motif of AraC to prevent pleiotropic effects in vivo upon activation. Analyzing the activation of these promoters by AraC in vivo under conditions of repression by LacR and derepression yielded a three step model of transcription initiation which reveals mechanisms of AraC and LacR action. Our data show three distinct rate limiting steps at which AraC can exert its function. In general, the activator accelerates the formation of the first stable complex between RNAP and promoter. At most promoter sequences, however, its main impact is on the conversion of the closed to the open complex. However, AraC is also capable of eliminating limitations at steps following open complex formation.

AraC Transcription Factor↗

[B-Flow: sonographic assessment and therapy for femoral artery pseudoaneurysm].

PURPOSE: To evaluate the diagnostic accuracy of femoral artery pseudoaneurysm by B-flow, a new ultrasound method and the outcome of compression treatment. MATERIAL AND METHODS: 700 patients with radiological interventions (300 DSA, 355 PTA, 45 thrombolysis) have been examined by vascular ultrasound for possible bleeding at the puncture site to rule out pseudoaneurysms. The new B-flow ultrasound with a multi-frequency probe was used besides color-coded Doppler (CCD) and power Doppler (PD). RESULTS: No pseudoaneurysm was found in patients with diagnostic angiography and thrombolysis. In 25 of 355 patients a pseudoaneurysm was detected after PTA in 8 of them in the common and in 17 in the superficial femoral artery. The diameters were 1.5 to 4.5 cm, 3 cm on average. By ultrasound compression treatment of 20 minutes on the average 23 out of 25 pseudoaneurysms were occluded without any further complication. In B-flow the lesion of the vessel wall, the flow in the fistula and in the sack of the pseudoaneurysm were better demonstrated and without artifacts compared to both other methods. This makes treatment by compression much easier, first of all because remaining flow phenomena and the progression of intracavitary thrombosis can be controlled. CONCLUSION: The newly developed B-flow detects both slow and fast flow phenomena. Visualisation of the fistula canal and the aneurysm sack is more reliable and examiner-independent than other Doppler methods such as CCD and PD. This allows better compression treatment of the fistula canal.

Aneurysm, False↗

[Low-dose thrombolysis using rt-Pa in extensive peripheral vascular occlusion].

PURPOSE: To evaluate the efficacy of intra-arterial thrombolysis by rt-PA in acute and subacute extensive peripheral vascular occlusion. MATERIAL AND METHODS: 100 patients with acute and subacute occlusion of peripheral arteries were treated by catheter thrombolysis using 20 mg of rt-PA over a period of 20-24 hours. In all cases the occlusion extended to more than 20 cm and two stages of the extremity were involved. In 80 patients the original vessels (69/80 by thrombosis, 11/80 by embolization) and in 20 cases the femoro-popliteal bypass vessel was occluded. A catheter was inserted into the thrombus into which rt-PA and heparin were separately infused by two injectors. Heparin was given in a dose of 800-1000 U/h depending on the continuously monitored PTT levels. A control angiography was performed after 10 mg of rt-PA. After successful thrombolysis either PTA or aspiration thrombectomy was performed, if necessary, to reestablish a nearly normal vascular lumen. Open arteries of the thigh and at least one main vessel of lower leg was considered as success. RESULTS: Recanalization of the original vessels was successfully by thrombolysis, PTA or aspiration thrombectomy in 68/80 [85%] cases. Thrombolysis and PTA reestablished a normal lumen of the bypass vessel in 11/20 [65%] and in 6 more cases a recanalization with minor stenosis. In 13/15 patients with critical ischemia, thrombolysis probably helped to avoid amputation by reopening smaller collateral arteries. Bleeding at the puncture site, as a complication of thrombolysis, was the reason for stopping therapy in three cases. There was no retroperitoneal or cerebral bleeding. After successful thrombolysis, reocclusion occurred in 15 patients within one year, only in five cases amputation was necessary. CONCLUSION: Extensive occlusion of peripheral arteries or of a femoro-cural bypass can be successfully treated by low dose rt-PA thrombolysis with a low complication rate. Even partial reopening may prevent amputation.

Aged↗

Integrational plasmids for the tetracycline-regulated expression of genes in Streptococcus pneumoniae.

Plasmids for the tetracycline regulated gene expression in Streptococcus pneumoniae have been developed. The plasmids were used for the tetracycline-dependent production of firefly luciferase in streptococci. The production of luciferase can be induced fivefold by the addition of tetracycline. By using two promoters of different strength and depending on the presence or absence of tetracycline, an 80-fold range of luciferase activities can be covered. The system was also used to construct strains that depend on the addition of tetracycline for the production of the A subunit of DNA gyrase, an essential streptococcal protein. The growth of such a strain depends on the addition of tetracycline to the medium. In the absence of tetracycline, the cells cease to grow and are not viable. The system presented in this report should be useful for the characterization of gene networks in S. pneumoniae. It especially allows one to study the function of essential genes that can not be investigated by standard knock-out techniques.

Base Sequence↗

Construction and analysis of hybrid Escherichia coli-Bacillus subtilis dnaK genes.

The highly conserved DnaK chaperones consist of an N-terminal ATPase domain, a central substrate-binding domain, and a C-terminal domain whose function is not known. Since Bacillus subtilis dnaK was not able to complement an Escherichia coli dnaK null mutant, we performed domain element swap experiments to identify the regions responsible for this finding. It turned out that the B. subtilis DnaK protein needed approximately normal amounts of the cochaperone DnaJ to be functional in E. coli. The ATPase domain and the substrate-binding domain form a species-specific functional unit, while the C-terminal domains, although less conserved, are exchangeable. Deletion of the C-terminal domain in E. coli DnaK affected neither complementation of growth at high temperatures nor propagation of phage lambda but abolished degradation of sigma32.

Adenosine Triphosphatases↗

Postmortem distribution of dihydrocodeine and metabolites in a fatal case of dihydrocodeine intoxication.

A report of a fatal dihydrocodeine ingestion under substitution therapy is given. Quantitation of dihydrocodeine, dihydromorphine, N-nordihydrocodeine, dihydrocodeine-6-, dihydromorphine-6- and dihydromorphine-3-glucuronide was performed simultaneously after solid-phase extraction prior to HPLC analysis, and the analytes were detected using their native fluorescence. Postmortem concentrations of blood samples from different sampling sites as well as from liver, kidney and cerebrum are reported. A hair sample was investigated to prove long-term use of the substitute drug. Site-to-site differences of the analytes from blood samples were very small. The partition behavior of the opioid glucuronides depended on the hematocrit value of the particular blood sample. Most important findings seemed that dihydromorphine and dihydromorphine-6-glucuronide concentrations decisively contributed to the toxicity of dihydrocodeine. This case report outlines that in dihydrocodeine related deaths the concentrations of the pharmacologically active metabolites should additionally be determined for reliable interpretation.

Adult↗

A potent cell death activity associated with transient high level expression of BCL-2.

The BCL-2 proto-oncogene contains unusually long untranslated 5' and 3' sequences. Deletion of the sequences flanking the BCL-2 open reading frame dramatically increases the level of protein expression. Transient high level BCL-2 protein expression mediated by plasmid transfection or by infection with recombinant adenovirus results in potent apoptosis of several cell lines. Detailed mutational (deletion and add-back) analysis reveals that both 5'- and 3'-flanking sequences contribute to the negative modulation of protein expression from the BCL-2 open reading frame. It appears that these sequences exert the negative regulatory effect in an orientation-dependent manner. Analysis of BCL-2 RNA levels indicate that elevated levels of mRNA may be the primary cause of elevated levels of protein expression. Apoptosis induced by adenovirus vectors expressing elevated levels of BCL-2 can be readily inhibited by the caspase inhibitor z-VAD-fmk, suggesting that high levels of BCL-2 expression induce apoptosis via the caspase cascade. Mutational analysis of BCL-2 indicates that its pro-apoptotic activity is separable from its anti-apoptosis activity. Our results raise the possibility that oncogenic conversion of BCL-2 may require somatic mutations in the pro-apoptotic activity, in addition to other activating mutations that result in enhanced expression. Consistent with this hypothesis, a somatic mutation of BCL-2 observed in multiple human tumors results in reduced apoptosis activity.

Adenoviridae↗

Hemoglobin diffusion across a venous wall: an experimental study.

The aim of this study was to investigate the permeation behavior of a large molecule through a venous wall; hemoglobin was chosen as a model substance. In vitro experiments were performed using a Chien-Valia diffusion chamber. Postmortem, hemolyzed, and fresh nonhemolyzed blood samples were investigated as permeants. Vein patches from vena cava inferior and vena jugularis interna were used as diffusion barriers. Applying this technique, extravasation of hemoglobin was detectable. The portion of hemoglobin molecules passing through the vascular wall depended on time, vein type, and graduation of hemolysis. The passage of hemoglobin across the wall of a large vein suggests intravascular changes in drug concentrations from postmortem blood samples not to be restricted on the unbound portion of the particular drug.

Diffusion↗

Insulin injection sites: morphology and immunohistochemistry.

In a case of insulin suicide in a nondiabetic woman, insulin was detected in routinely formalin fixed and paraffin embedded subcutaneous injection marks, in spite of a post-morterm interval of 24 days. Around birefringent crystalline material, probably zinc phosphate, immunohistochemistry revealed granular insulin depots as well as an insulin staining along the lipocyte membranes. A cellular reaction of granulocytic character was present, with an uptake of insulin by inflammatory cells.

Autopsy↗

Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements.

Based on parameters governing promoter activity and using regulatory elements of the lac, ara and tet operon transcription control sequences were composed which permit the regulation in Escherichia coli of several gene activities independently and quantitatively. The novel promoter PLtetO-1 allows the regulation of gene expression over an up to 5000-fold range with anhydrotetracycline (aTc) whereas with IPTG and arabinose the activity of Plac/ara-1 may be controlled 1800-fold. Escherichia coli host strains which produce defined amounts of the regulatory proteins, Lac and Tet repressor as well as AraC from chromosomally located expression units provide highly reproducible in vivo conditions. Controlling the expression of the genes encoding luciferase, the low abundance E.coli protein DnaJ and restriction endonuclease Cfr9I not only demonstrates that high levels of expression can be achieved but also suggests that under conditions of optimal repression only around one mRNA every 3rd generation is produced. This potential of quantitative control will open up new approaches in the study of gene function in vivo, in particular with low abundance regulatory gene products. The system will also provide new opportunities for the controlled expression of heterologous genes.

Arabinose↗

An in vitro study on the effect of branch points on the stability of coronary artery flow.

Empirical correlations for the onset of turbulence in pulsatile flow through a straight tube and a 45 degrees T-bifurcation are presented. We pumped three different test fluids of kinematic viscosity 0.008-0.035 cm2 s-1 through four straight tubes 0.4-3.0 cm in diameter and three 45 degree T-bifurcations 0.45-2.2 cm in diameter. A Scotch yoke mechanism provided an oscillatory sine wave flow component of known stroke volume and frequency. To determine transition to turbulence, we adjusted the mean flow independently until we detected signal instabilities from hot film or electrochemical wall shear stress probes. The critical peak Reynolds number was found to correlate with two independent dimensionless groups: the Womersley parameter and the Strouhal number. We derived power low functions of these groups to provide an accurate and convenient method of predicting transition in both straight and bifurcating tubes. When compared to pulsatile flow through the straight tube, the presence of flow separation within the 45 degrees T-bifurcation induced flow instabilities at lower values of the peak Reynolds number. The correlation for the 45 degrees T-bifurcation is also a suitable model for predicting transition at coronary branch points, which we previously studied in an in vitro pulse duplicator. Flow instabilities at coronary branch points may play an important role in atherogenesis.

Arteriosclerosis↗

An in vitro experiment for postmortem vascular permeation. The passage of morphine and morphine glucuronides across a vascular wall.

A venous blood sample taken at autopsy cannot be considered to represent the antemortem blood concentration of a particular substance. Autolytic processes cause disintegration and increasing permeability of the physiological and anatomical barriers such as vascular walls and lead to changes in substance concentrations. In the present study, the experimental design represents an in vitro postmortem simulation of a drug substance crossing a venous wall. The postmortem behavior of morphine, morphine-3- and morphine-6-glucuronide was investigated. A Chien-Valia-diffusion chamber with a patch of inferior vena cava as diffusion barrier was used. For optimal simulation of postmortem events, vein sampling was restricted to selected autopsy cases. Parameters for the analysis of diffusion across the vascular tissue were dependence on time, temperature, and initial substance concentrations. The penetration behavior simulating venous efflux and influx of the substances was studied by different orientation of the venous wall in the experiments. Rhodamine B was used as a model substance to visualize the binding to the tissue and the passage across the venous wall. The permeation of morphine, morphine-3- and morphine-6-glucuronide across a vein tissue was found to be mainly dependent on the disintegration of the vascular wall and on the postmortem time period as well as on concentration gradients. From the data of this preliminary in vitro study, it can be concluded that a lag time for transvascular diffusion exists postmortem. However, it could be demonstrated, that adsorption to and penetration into the vascular tissue may alter intraluminal blood concentrations even at an early stage of the postmortem time period.

Biological Transport↗