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Biomedical subjects

M Langer

Publications and source records attributed to M Langer.

At least 91 records · Page 5Linked to original sources
PubMed2000

Melatonin and adolescent idiopathic scoliosis.

Scoliosis seen in the chicken after pinealectomy resembles adolescent idiopathic scoliosis in man. It has been suggested that in both species, deficiency of the pineal hormone, melatonin, is responsible for this phenomenon. In nine patients with adolescent idiopathic scoliosis and in ten age- and gender-matched controls, the circadian levels of serum melatonin and the excretion of urinary 6-hydroxy-melatonin-sulphate, the principal metabolite of melatonin, were determined. There were no statistically significant differences in the secretion of serum melatonin or the excretion of urinary 6-hydroxy-melatonin-sulphate between the patients and the control group. The hypothesis of melatonin deficiency as a causative factor in the aetiology of adolescent idiopathic scoliosis cannot be supported by our data.

Adolescent↗
PubMed1999

Site-specific mutagenesis of mistletoe lectin: the role of RIP activity in apoptosis.

Recombinant mistletoe lectin (rML) belongs to the class of type II ribosome-inactivating proteins (RIP) composed of a catalytically active A-chain with rRNA N-glycosidase activity and a B-chain with carbohydrate binding properties. To investigate the contribution of the enzymatic activity of the rML A-chain to the observed cytotoxic and apoptotic effects, an rMLA E166Q R169Q molecule was developed by means of site-specific mutagenesis. Following heterologous expression, the activity of mutant rMLA was measured in a cell-free assay for rRNA-N-glycosidase activity. Moreover, after generation of heterodimer, the activities of mutant rML E166Q R169Q and rML wild type were determined in a cytotoxicity and apoptosis assay. Although the reduction of activity as measured in the cell-free RIP assay was more pronounced (factor 237) than in both cellular assays (factors 20-22), the data clearly indicate a close correlation between cytotoxicity, apoptosis, and the enzymatic activity of the rML A-chain. Thus, RIP activity is an essential feature of rML and therefore a prerequisite for its biological function as an anticancer agent.

Apoptosis↗
PubMed1999

Pelvic floor descent: dynamic MR imaging using a half-Fourier RARE sequence.

Dynamic magnetic resonance imaging (MRI) using a single shot fast spin-echo technique was evaluated as a noninvasive alternative to cystourethography or colpocystorectography in patients with pelvic organ prolapse and/or urinary incontinence. Thirty-two patients were included in this prospective study. Colpocystorectography was performed in 10 patients who previously had undergone hysterectomy and in 2 patients without history of hysterectomy with clinical suspicion of rectoceles. Bead-chain cystourethrography was performed in 20 patients without hysterectomy. For dynamic MRI, a single-slice half-Fourier RARE sequence (imaging time 2 seconds) was used to depict the pelvic organs at different levels of pelvic strain. The results obtained with dynamic MRI were correlated with the x-ray findings. All 17 cystoceles, 10 rectoceles, 2 enteroceles, and 7 vaginal prolapses could be demonstrated on MRI. Diagnostic information gained from these images was equivalent to that obtained with colpocystorectography and superior to that obtained with cystourethrography; with the latter, important findings were missed (four rectoceles). We conclude that dynamic MRI of the pelvic floor with a half-Fourier RARE sequence can reliably detect descents of all three pelvic compartments, that it requires no contrast agent, and that no radiation exposure is involved.

Adult↗
PubMed1999

[RIS modality interfaces. From proprietary solutions to DICOM worklist management].

Radiologic information systems (RIS) and picture archiving and communication systems (PACS) are becoming increasingly widespread. This leads to new demands on the integration of the individual, formerly independent information systems (RIS, modalities, PACS). Possible ways of integrating individual systems are introduced. Besides the detailed description of different realizations of system communication, its role in the PACS at the university hospital in Freiburg is explained. The integration of different information systems still requires the use of proprietary interfaces. An appropriate integration generally has been realized in Freiburg. In the near future DICOM basic worklist management will standardize system integration and render an interdepartmental workflow concept possible. Even though an available communication standard exists, not all problems in the RIS-modality interface are solved. Different data models in the various RI systems and modalities demand certain degrees of freedom in the standard. Thus a satisfactory workflow cannot be guaranteed even when all involved systems conform with the standard.

Germany↗
PubMed1999

[Modern network technologies for data communication in the hospital].

Modern network technologies provide the basic infrastructure for information and communication systems in the hospital today. The goal to build up a universal network infrastructure which meets the broadly varied requirements. Analysis of data communication in the hospital and the evaluation of established network technologies, as well as new developments, leads to the switching concept as the suitable solution. Two technologies play the major role in building enterprise networks: the Ethernet family, based on frame switching, and ATM, based on cell switching. Orientation on established standards is the key to free system choice and grants interoperability between systems from different manufacturers. However, the network design must meet the application and system architecture of the information technology in order to achieve successful mapping of the involved communication profiles. This means scaling of the bandwidth as needed, suitable segmenting of the network and resilient links. In a further step, policy-based networking takes advantages of prioritizing critical applications and therefore reduces interdependencies across the network.

Computer Systems↗
PubMed1999

Chest wall infiltration by lung cancer: value of thin-sectional CT with different reconstruction algorithms.

The aim of this investigation was to evaluate whether thin-sectional CT with different reconstruction algorithms can improve the diagnostic accuracy with regard to chest wall invasion in patients with peripheral bronchogenic carcinoma. Forty-one patients with intrapulmonary lesions and tumor contact to the thoracic wall as seen on CT staging underwent additional 1-mm CT slices with reconstruction in a high-resolution (HR) and an edge blurring, soft detail (SD) algorithm. Five criteria were applied and validated by histological findings. Using the criteria of the intact fat layer, HRCT had a sensitivity of 81 % and a specificity of 79 %, SD CT had a sensitivity of 96 % and a specificity of 78 %, and standard CT technique had a sensitivity of 50 % and a specificity of 71 %, respectively. Regarding changes of intercostal soft tissue, HRCT achieved a sensitivity of 71 % and a specificity of 96 %, SD CT had a sensitivity of 94 % and a specificity of 96 % (standard CT technique: sensitivity 50 % and specificity 96 %). For the other criteria, such as pleural contact area, angle, and osseous destruction, no significant differences were found. Diagnostic accuracy of chest wall infiltration can be improved by using thin sectional CT. Especially the application of an edge-blurring (SD) algorithm increases sensitivity and specificity without additional costs.

Adult↗
PubMed1999

Results of a prospective multicenter study for evaluation of the diagnostic quality of an open whole-body low-field MRI unit. A comparison with high-field MRI measured by the applicable gold standard.

OBJECTIVE: To evaluate the diagnostic quality of an open whole-body low-field MRI scanner compared to high-field scanners. MATERIALS AND METHODS: Over a period of 3 months, 401 patients with diseases of the kidney (n = 78), the shoulder (n = 122), the spine (n = 105) and the cerebrum (n = 96) were prospectively evaluated in four participating centers. They all underwent clinical evaluation, low-field and high-field MRI examination and surgical or follow-up confirmation of diagnosis. Clinical, histopathologic, high-field and low-field MRI diagnoses were recorded in standardized questionnaires that were centrally evaluated. Statistical evaluation comprised two parts: ROC analysis assessed accuracy of MRI and clinical diagnoses; furthermore rates of concordance of high- and low-field MRI diagnosis were calculated. RESULTS: We found no statistically relevant difference in high-field MRI diagnosis compared to low-field MRI diagnostic accuracy measured by clinical or surgical gold standard in three of the four regions examined; in cerebral examinations there was a small yet significant advantage for the high-field systems (P = 0.01). CONCLUSION: We conclude that the open low-field scanner we evaluated using clinical and surgical gold standard as reference is able to achieve comparable diagnostic accuracy compared to high-field scanners at lower costs and greater patient comfort. Limitations due to field strength (signal-to-noise ratio, resolution, scan time) seem to be relevant only in a very small number of cases that warrant high-field examination.

Adult↗
PubMed1999

Cloning of the mistletoe lectin gene and characterization of the recombinant A-chain.

Mistletoe lectin I (MLI) is the major active constituent of mistletoe extracts, which are widely used for adjuvant tumour therapy. The 66-kDa heterodimeric disulphide-linked glycoprotein is classified as type II ribosome-inactivating protein (RIP) due to the rRNA-cleaving enzyme activity of the A-subunit, also referred to as toxic entity. MLI and the close relative ricin both belong to the family of the two-chain plant type II RIP proteins. Isolation of the glycosylated proteins from plant material yield inhomogeneous material probably due to post-translational modifications. The aim of this study was to prepare pure and homogeneous protein as a prerequisite for structural and mechanistic studies in order to gain insight into the mode of action of this cytotoxic plant protein on tumour and immune cells. Of particular interest was to explain whether the differences in toxicity of ML and ricin are the result of variations of their enzymatic activities. By investigating the sequence homologies between the active sites of different RIPs we were able to deduce a set of primers which were suitable for specific amplification of the mistletoe lectin gene. Applying this PCR strategy the full-length 1923 nucleotide DNA sequence coding for the prepro-protein was obtained showing the existence of a single intron-free gene. In order to elucidate the molecular basis for the observed differences in cytotoxicity within the family of RIP the enzymatic A-subunit was expressed in a heterologous system. Expression of the A-chain in E. coli BL21/pT7 resulted in production of insoluble inclusion bodies constituting 20-30% of total protein. Refolding led to a pure and homogeneous protein species with an apparent molecular mass of 27 kDa and a pI value of 6.4. The ribosome-inactivating activity of the unglycosylated recombinant A-chain (IC50 20.5 pM) protein was in the same range as that of the glycosylated plant-derived ML A-chain (IC50 3.7 pM), which was very similar to that of ricin A-chain (IC50 4.9 pM). Thus, the higher cytotoxicity of ricin cannot be accountable for differences in the enzymatic activities of the type II RIP A-chains.

Amino Acid Sequence↗
PubMed1999

Characterization of recombinant and plant-derived mistletoe lectin and their B-chains.

Mistletoe lectin I (pML) and its isoforms ML II and III constitute the active principle in extract preparations from mistletoe, commonly used as immunomodulator in adjuvant tumour therapy. The heterodimeric disulfide-linked cytotoxic protein is classified as type II ribosome inactivating protein (RIP). Recently, the sequence coding for the mistletoe lectin prepro-protein was identified and the existence of a single intron-free gene was shown [Eck, J., Langer, M., Möckel, B., Baur, A., Rothe, M., Zinke, H. & Lentzen, H. (1999) Eur. J. Biochem. 264, 775-784]. The aim of this study was to prepare pure and homogeneous rMLB-chain as well as rML heterodimer for studying the carbohydrate binding specificity of recombinant versus natural protein and its contribution to the observed cytotoxic effect. Expression in E. coli resulted in the production of insoluble protein (inclusion bodies). A procedure for generating correctly folded, biochemically and biologically active rMLB was established starting from the insoluble single chain. Carbohydrate binding and specificity of pMLB and rMLB were analysed by a competitive enzyme linked lectin assay (ELLA). Asialofetuin was able to compete with binding of both chains (50% at 0.8 microM). The specificity of the B-chains to lactose was more distinct with halfmaximal competition at 4.9 mM (pMLB) and > 90 mM (rMLB), respectively. Furthermore, in a coassociation process rMLA- and rMLB inclusion bodies were associated in one step by defined dilution yielding active rML-heterodimer. The activities of recombinant (rML) and plant derived mistletoe lectin (pML) were compared. Cytotoxicity was determined using MOLT-4 cells and enzymatic rRNA N-glycosidase activity was measured in a coupled transcription/translation assay. The IC50 values of the two heterodimers were similar in both assays; rMLB-chain did not show any cytotoxic effect. In the ELLA with lactose as a competitor 50% competition of binding to asialofetuin was achieved at 1.6 mM (rML) and 1.8 mM (pML). Hence, using three different assays we found no significant differences between the recombinant protein and the glycosylated form of ML. Comparing the biological activities of the single chains with those of the heterodimer we conclude, that both, lectin activity and the rRNA N-glycosidase activity, are prerequisites for the cytotoxic effects on target cells.

Asialoglycoproteins↗
PubMed1999

[Kinematic versus static MRI study of the cervical spine in patients with rheumatoid arthritis].

PURPOSE: The objective of this study was to compare the diagnostic value of cinematic magnetic resonance imaging with static MRI examinations in patients with rheumatoid arthritis and concomitant attack of the cervical spine. METHODS: Dynamic functional MRI examinations of the cervical spine were performed one five subjects without complaints and 20 patients with rheumatoid arthritis. For the functional studies, a positioning frame was used that allowed infinitely variable forward and backward inclinations of the head. RESULTS: Functional magnetic resonance imaging made possible a sufficiently good differentiation of the extension of pannus tissue cranial, ventral, and dorsal of the dens with possible displacing and impinging effects on the spinal cord during flexing and stretching movements. In addition, it is suitable for demonstration of the degree of instability in the atlanto-occipital and atlanto-axial planes. In contrast to conventional X-rays, CT, and static MRI, basilary impression as well as compressions and angulations of the cervical bone marrow are better visualized by cinematic magnetic resonance tomography. CONCLUSIONS: Functional magnetic resonance tomography is an important diagnostic method for the induction of the cervical spine in patients with rheumatoid arthritis. In particular, fusion and instabilities as well as compressions of the bone marrow often can only be detected with the help of functional MRI.

Cervical Vertebrae↗
PubMed1999

Homogenization and crystallization of histidine ammonia-lyase by exchange of a surface cysteine residue.

Histidase (histidine ammonia-lyase, EC 4.3.1.3) from Pseudomonas putida was expressed in Escherichia coli and purified. In the absence of thiols the tetrameric enzyme gave rise to undefined aggregates and suitable crystals could not be obtained. The solvent accessibility along the chain was predicted from the amino acid sequence. Among the seven cysteines, only one was labeled as 'solvent-exposed'. The exchange of this cysteine to alanine abolished all undefined aggregations and yielded readily crystals diffracting to 1.8 A resolution.

Crystallography↗
PubMed1999

Comparison between a screen-film system and a selenium radiography system. An ROC study using simulated thoracic lesions.

RATIONALE AND OBJECTIVES: To evaluate the diagnostic image quality of the hard copies of a commercially available selenium detector-based computed radiography system compared to that of a conventional screen-film system. METHODS: Ten radiographs of an anthropomorphic chest phantom with simulated nodular and linear-reticular lesions were produced using either system. Each radiograph was subdivided into 15 fields containing zero lesions, one nodular lesion, one linear-reticular lesion, or both lesions. The total of 150 fields for each modality was reviewed by six radiologists, and receiver operating analysis was performed. RESULTS: The conventional screen-film system performed significantly better for nodular lesions, whereas no statistically significant difference was found between the detection rates of both systems for linear-reticular lesions. CONCLUSIONS: The better detection of nodules with the dedicated selenium detector can be explained by the higher dynamic range of the system. Detection of linear-reticular lesions was slightly but not significantly better with the screen-film system, but the detection rate of the selenium detector might be further improved with a different image processing technique.

Humans↗
PubMed1999

MRI of heart morphology. Comparison of nongradient echo sequences with single- and multislice acquisition.

RATIONALE AND OBJECTIVES: A large variety of cardiac MRI sequences have been introduced for heart morphology evaluation. The aim of this study was to establish a practicable and robust examination protocol for standard high-field systems applying nongradient echo sequences with single- and multi-slice acquisition. METHODS: Fifty-one patients received electrocardiogramgated MRI of the heart with "black-blood" preparation, comparing three single-slice and three multislice sequences with a T1-weighted turbo spin echo reference sequence. Demarcation of the left ventricular myocardium and cavity and the extent of flow and motion artifacts were assessed. RESULTS: The myocardium and left ventricular cavity were depicted best with the single-slice T1- and T2-weighted turbo spin echo sequence. The nonbreath-hold multislice sequences produced marked artifacts and therefore were of poor diagnostic value. The TIRM haste sequence was best suited for fat suppression. The T2-weighted breath-hold single-shot sequence with half-Fourier imaging proved to be most appropriate for multislice imaging. CONCLUSIONS: Sufficient depiction of heart morphology with comprehensive evaluation of signal changes can be achieved using nongradient spin echo and turbo spin echo sequences with breath-holding. For rational imaging of myocardial and heart chamber morphology, multislice and single-slice sequences should be combined.

Adult↗
PubMed1999

Pelvic imaging with a selenium-based detector (Thoravision). Comparison with screen-film radiography in 75 patients.

OBJECTIVE: To evaluate whether the selenium detector (Thoravision) provides sufficient diagnostic confidence in digital pelvic imaging compared with a conventional screen-film combination. METHODS: In 75 patients, pelvic imaging with conventional screen-film and isodose selenium radiography using a dedicated postprocessing mode was compared independently by three radiologists. The depiction of cortical and cancellous bone was evaluated in the iliac wings, sacral and pubic bones, acetabulum, femoral head, and trochanter. Demarcation of soft tissue was assessed in the iliac and trochanteric region. RESULTS: Visualization of cortical bone and soft tissue in the iliac area as well as soft tissue and cortical and cancellous bone in the trochanteric region was significantly superior with the selenium detector. However, conventional imaging was better in the trabecular bone of the sacral region, where results with the selenium system were particularly poor. CONCLUSIONS: The selenium detector (Thoravision) is advantageous in imaging soft tissue adjacent to the iliac wings and the trochanter, but results for the cancellous sacral bone are poor. Further modifications of postprocessing modes may lead to improved depiction of this critical pelvic area.

Adult↗
PubMed1999

Cerebral and renal embolization after lymphography in a patient with non-Hodgkin lymphoma: case report.

An unusual case of lipid embolization to brain and kidney after lymphography in a patient with non-Hodgkin lymphoma of the upper anterior mediastinum is reported. Contrast material-enhanced echocardiography demonstrated a right-to-left shunt to the left atrium without evidence of a patent foramen ovale. Echo contrast particles were transiently present within the tumor surrounding the great vessels.

Adult↗
PubMed1999

Pharmacokinetic-pharmacodynamic modeling of tolerance to the prolactin-secreting effect of chlorprothixene after different modes of drug administration.

The objective of this study was the construction of a pharmacokinetic-pharmacodynamic model to describe the effects of chlorprothixene on prolactin secretion and the time-dependent alterations in the concentration-effect relationship due to tolerance development. Prolactin and chlorprothixene serum concentrations were determined in eight healthy men for up to 72 h after the intravenous and oral administration of chlorprothixene. An integrated pharmacokinetic model and a physiological indirect pharmacodynamic/tolerance model were applied to describe the prolactin-secreting effect of chlorprothixene. A three-compartment model served as pharmacokinetic model. The pharmacodynamic and tolerance model accounted for the baseline effect, the effect induced by the drug, and the regulatory mechanism that opposes the effect of the drug. This model adequately characterized the prolactin response after intravenous and oral drug administration of each individual by the sensitivity (dissociation constant), the efficacy (maximal prolactin secretion rate), the extent, and the rate of tolerance development. We speculate that this approach improves the quality of neuroendocrine challenge tests to determine the subject's sensitivity to drugs and the time course of adaptation.

Administration, Oral↗