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Biomedical subjects

A Franke

Publications and source records attributed to A Franke.

At least 19 recordsLinked to original sources

Mapping functional domains of the polycomb protein of Drosophila melanogaster.

In Drosophila the Polycomb group (Pc-G) proteins are responsible for the stable and heritable silencing of genes. The Pc-G apparently uses heterochromatin-like mechanisms to transcriptionally inactivate developmental regulators such as the homeotic genes. The Polycomb (Pc) protein is part of a large multimeric complex composed of other members of the Pc-G. We have identified functionally relevant domains of the Pc protein by sequencing different Pc alleles. Additionally, using a Pc-beta gal fusion protein with deleted internal histidine repeats, we found that this mutant protein cannot bind to four particular target loci, but otherwise does not change the remaining overall binding pattern. We show that, in contrast to the dotted subnuclear localization of the wild-type protein, the nuclear distribution of mutant proteins becomes homogeneous. Surprisingly, in Pc mutants the polyhomeotic protein, another member of the Pc-G, is also redistributed in the nucleus. Our results indicate that the appropriate subnuclear localization of the two proteins is critical for the silencing function of the Pc-G complex.

Alleles

gamma-Glutamyl transpeptidase-cellular expression in populations of normal human mononuclear cells and patients suffering from leukemias.

The expression of the ectoenzyme gamma-glutamyl transpeptidase (EC2.3.2.2., gamma GT) was investigated by flow cytometry on populations of peripheral blood mononuclear cells (PBMC) from healthy subjects and patients suffering from several types of leukemia before and under chemotherapy. In unstimulated PBMC, 28% of these cells were found to be gamma GT positive. The highest expression was measured on monocytes (CD14/gamma GT+ cells: 60%). Within the subsets of T lymphocytes (CD3/gamma GT+ cells: 18%) we saw no clear differences between CD4+ and CD8+ cells. B lymphocytes, NK cells, and activated cells showed low expressions (up to 10%). Treatment of PBMC with mitogens, alpha-IFN, IL-2, and GM-CSF did not affect the enzyme expression on normal mononuclear cells (MNC). However, a rapid increase of gamma GT+ cells was found in the presence of glutathione (GSH) and n-acetyl cysteine (nAC), particularly on monocytes, B cells, and NK cells. Comparing 40 healthy subjects and untreated patients suffering from leukemias, a significantly higher expression of gamma GT+ cells in the total MNC populations (B-CLL: 57%, CML: 62% gamma GT+ cells) was observed in B-chronic lymphocytic leukemia (B-CLL) and chronic myelogenous leukemia (CML), whereas other leukemias did not show clear differences. Most interestingly, the gamma GT expression was diminished in all populations of CML cells after 5 h of incubation in the presence of 10 units/ml IFN-alpha. These data suggest a possible protective role of gamma GT in MNC and a regulatory function of this enzyme in the development of CML.

Adult

Molecular characterization of the male-specific lethal-3 gene and investigations of the regulation of dosage compensation in Drosophila.

In Drosophila, dosage compensation occurs by transcribing the single male X chromosome at twice the rate of each of the two female X chromosomes. This hypertranscription requires four autosomal male-specific lethal (msl) genes and is negatively regulated by the Sxl gene in females. Two of the msls, the mle and msl-1 genes, encode proteins that are associated with hundreds of specific sites along the length of the male X chromosome. MLE and MSL-1 X chromosome binding are negatively regulated by Sxl in females and require the functions of the other msls in males. To investigate further the regulation of dosage compensation and the role of the msls in this process, we have cloned and molecularly characterized another msl, the msl-3 gene. We have found that MSL-3 is also associated with the male X chromosome. We have further investigated whether Sxl negatively regulates MSL-3 X-chromosome binding in females and whether MSL-3 X-chromosome binding requires the other msls. Our results suggest that the MLE, MSL-1 and MSL-3 proteins may associate with one another in a male-specific heteromeric complex on the X chromosome to achieve its hypertranscription.

Amino Acid Sequence

[Three-dimensional reconstruction of heart valves].

The reconstruction of three-dimensional data sets from two-dimensional echocardiographic images offers several fundamental advantages: 1. more complete data than present in the few standard 2D-view; 2. off-line generation of any desired plane, cut, or perspective after the data set has been acquired; 3. access to quantitative parameters like surface areas (e.g., of valve leaflets or portions of leaflets), volumes, and others, without geometric assumptions. The mitral valve has been the focus of several studies using various techniques of reconstruction of transthoracic or transesophageal images. These studies have shown the mitral annulus to be a non-planar, "saddle-shaped" structure, with an average distance of highest to lowest points of 14 mm in normals. This recognition of mitral annular non-planarity has led to a more stringent echocardiographic definition of mitral valve prolapse. Further studies have shown systolic shrinkage of mitral annular area by about 30% and systolic apico-basal translation of the annulus by approximately 1 cm in normals. In patients with dilated cardiomyopathy, the annulus is flattened, and both cyclic change in annular area and apico-basal translation are significantly reduced. 3D-studies of the left ventricular outflow tract in hypertrophic obstructive cardiomyopathy allow measurement of outflow tract and leaflet surface areas and dynamic spatial visualization of systolic anterior motion of the anterior mitral leaflet. Automated techniques to reconstruct the full grey value data set from a high number of parallel or rotational transesophageal planes allow impressive visualization of normal and diseased mitral and aortic valves or valve prostheses, with special emphasis on generating "surgical" views and perspectives, which cannot be obtained by conventional tomographic imaging.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve

[3-dimensional reconstruction of multiplanar transesophageal echocardiography images: a methodologic report with case examples].

First experience with the dynamic three-dimensional reconstruction of transesophageal echocardiographic images in more than 100 patients with various cardiac diseases are reported. Ninety different two-dimensional image planes were acquired for each reconstruction using a conventional multiplanar transducer, connected to a stepper motor and controlled by a computer-based image acquisition system with special software. Acquisition time for one data set was 2.3 +/- 0.9 min, and calculation time to achieve three-dimensional images was 20-45 min. Several cardiac structures were reconstructed and analyzed qualitatively and quantitatively (measurements of distances and areas, volume calculation by Simpson's rule). Image sequences showing three-dimensional depth by gray scale modification were generated. After image acquisition one can select any desired cut plane to achieve perspectives that cannot be obtained by two-dimensional technique. Advantages of three-dimensional echocardiography are the display and potential quantification of pathomorphology of the left ventricle and mitral valve, atrial septal defects, intracardiac masses (i.e., myxomas, vegetations), and direct spatial imaging of complex congenital heart diseases. In principle, three-dimensional data sets have advantages for the quantitative evaluation of irregular formed cardiac structures, since the three-dimensional data set is more complete than cross-sections used in conventional two-dimensional echocardiography. Currently, however, these advantages are limited by the necessity of human interaction to segment the structures of interest.

Adolescent

[Improved evaluation of prosthetic heart valve regurgitation with multiplanar transesophageal echocardiography].

UNLABELLED: To study the value of the newly introduced multiplane transesophageal transducer technology for the assessment of prosthetic valve regurgitation, 63 consecutive patients with 35 mitral and 33 aortic prostheses (23 bioprostheses and 45 mechanical prostheses) were examined. Transvalvular, paravalvular, and, in mechanical valves, normal or pathological transvalvular regurgitation were identified using first 0 degrees (transverse) and 90 degrees (longitudinal) planes combined with flexion of the echoscope tip and then additionally using multiple intermediary planes by transducer rotation. In a subgroup of 20 patients interobserver variability was evaluated. Both methods showed regurgitation in 56/58 valves; one additional case of regurgitation was seen by multiplane imaging only. However, there were 19 cases of regurgitation not clearly classifiable by biplane technique compared to only three using multiplane technique. Grading of severity was concordant by both modalities in 66 and discordant in only two cases. Observers disagreed on severity in 2/20 cases based on biplane imaging, but in none based on multiplane imaging; classification of regurgitation differed in 6/20 biplane and 1/20 multiplane images respectively. CONCLUSION: Multiplane transesophageal imaging improves classification of prosthetic regurgitation, but has little effect on severity grading.

Adult

[The management of adolescents and adults with congenital heart defects: 3 years experiences with interdisciplinary consultation].

UNLABELLED: Since September 1991, 204 patients (pts), 109 male and 95 female, mean age 27.3 +/- 10.6 years, were followed in a newly established interdisciplinary outpatient clinic combining both adult and pediatric cardiologists. 61 pts predominantly presented with left-to-right shunt congenital heart disease (CHD), 32 with valvar CHD, 20 with aortic coarctation, 23 with complex acyanotic, and 49 with cyanotic CHD. The population included 19 pts with Marfan syndrome. 106 pts had had previous cardiac surgery, 32 of them with up to three reoperations. Deficits and needs in medical and social care were analyzed in 100 pts using a standardized questionnaire at the time of first examination: One-third of pts were not or only incompletely informed about their CHD, previous surgical procedures and need for antibiotic prophylaxis of endocarditis. Only a minority of pts had had vocational advice (34%) or counseling concerning contraception (40%) or pregnancy (30%). Cardiac catheterization was performed in 37 pts (18%) after being first seen in our outpatient clinic, followed by a primary surgical intervention in 19 and reoperation in eight cases. Overall, 30 pts (15%) underwent surgery (28) or interventional procedures (one closure of the arterial duct, one AV node ablation after Mustard-operation) as a consequence of admission to our unit. Successful late Fontan operations were performed in four adults aged 21 to 35 years. There was 1/30 postoperative death (M. Ebstein, thrombosis of the mechanical prosthesis). The population includes five pts with severe pulmonary vascular disease (one waiting for lung transplantation) and two pts with pulmonary artery arborisation malformations not amenable to surgery. CONCLUSION: In a population of 204 adolescents and adults with CHD, we clearly found deficits in medical and social care and, in addition, an unexpected high percentage of necessary invasive investigations (18%) and surgical or interventional procedures (15%). Interdisciplinary management of these patients is mandatory combining the special facilities of adult and pediatric cardiologists.

Activities of Daily Living

[Patients in (post)modern society--does psychosomatic medicine still have concrete foundations?].

The paper describes the scientific development psychosomatic medicine has undergone in the last decades, as well as the politically induced changes in the German Health Care system. In three future scenarios the dangers of a) biological and b) voluntaristic schools of thought are presented along with the c) consequences of ecological destruction and economic power. The increasing trend for psychosomatic medicine to use salutogenetic models is discussed as a feasible approach for the prevention of fear-provoking perspectives.

Forecasting

Three-dimensional reconstruction of cardiac structures from transesophageal echocardiography.

Although tomographic imaging has been very successful in cardiology,the quantitation of volumes, surfaces, and masses,as well as understanding of complex morphologies would improve by three-dimensional imaging. This review focuses on approaches to 3-D reconstruction from transesophageal echocardiography. In the past, several attempts using either stepwise parallel translation or stepwise rotation of the transducer have been made. In vitro and, to a limited extent, in vivo studies have confirmed high accuracy in calculating left ventricular volumes in such manner. Complex cardiac structures and their motion, such as the mitral annulus, mitral leaflets, atrial septal defects, and others have been reconstructed from patient studies. Although potentially a powerful tool for cardiac imaging with promising quantitation capabilities, progress is needed in particular in the field of border detection to make 3-D imaging practical enough for clinical use.

Computer Graphics

Thiol-proteindisulfide-oxidoreductase (proteindisulfide isomerase): a new plasma membrane constituent of mature human B lymphocytes.

The thiol-proteindisulfide-oxidoreductase (TPO, EC 1.8.4.2., proteindisulfide isomerase, EC 5.3.4.1.) is known as an cytoplasmatic enzyme, and is thought to be involved in the post-translational folding of disulfide containing proteins. Using monoclonal and polyclonal antibodies the authors were able to prove that this enzyme or an unknown homologous protein is localized also to the plasma membrane of B lymphocytes. In peripheral blood from healthy donors 11% of the mononuclear cells (PBMNC) expressed this surface antigen whereas in PBMNC of patients with B-cell chronic lymphocytic leukaemia 76% of the MNC were positive. This value correlates well with the known B-cell markers CD19 and CD20. However, this antigen is different from all known clustered B-cell markers. Immunoprecipitation analysis of PHA-stimulated PBMNC and of cells from patients suffering from chronic lymphocytic leukaemia revealed a membrane protein with the same molecular weight (61 kDa) as the TPO. These data suggest that this enzyme is present not only in the cytoplasm but also on the surface of B cells and that it is possibly involved in the regulation of the SH-SS status of the cell membrane proteins of B lymphocytes.

Adult

Polycomb and polyhomeotic are constituents of a multimeric protein complex in chromatin of Drosophila melanogaster.

The polycomb group (Pc-G) genes are responsible for maintaining the repressed state of homeotic genes during development. It has been suggested that the Pc-G exerts its transcriptional control by regulating higher order chromatin structure. In particular, the finding of genetic and molecular similarities to components involved in heterochromatin formation, led to the proposal that homeotic genes are permanently repressed by mechanisms similar to those responsible for heterochromatin compaction. Because of synergistic effects, Pc-G gene products are thought to act in a multimeric complex. Using immunoprecipitation we show that two members of the Pc-G, Polycomb and polyhomeotic, are constituents of a soluble multimeric protein complex. Size fractionation indicates that a large portion of the two proteins are found in a distinct complex of molecular weight 2-5 x 10(6) Da. During embryogenesis the two proteins show the same spatial distribution. In addition, by double-immunofluorescence labelling we can demonstrate that Polycomb and polyhomeotic have exactly the same binding patterns on polytene chromosomes of larval salivary glands. We propose that some Pc-G proteins act in multimeric complexes to compact the chromatin of stably repressed genes like the homeotic regulators.

Animals

A short multilingual quality of life questionnaire--practicability, reliability and interlingual homogeneity.

International cooperative clinical trials require a multilingual quality of life questionnaire. The 'International Society for Chemo- and Immunotherapy' therefore designed a study to develop and test a 'health accentuated' quality of life questionnaire in the eight languages spoken in this society. The objective was to examine practicability, reliability and interlingual homogeneity. Versions of the questionnaire in Czech, German, Hungarian, Italian, Kroatian, Polish, Romanian and Slovakian have been prepared. The results are based on data of 1,104 adult patients. They demonstrate that the developed questionnaire is practicable. Patients need 10-15 min to answer it, usually without assistance. The proportion of missing values is for all but two questions less than 3%. The questionnaire also found high acceptance reflected by only 2.7% refusals. It is reasonably reliable in each language. Interlingual homogeneity could be shown by demonstration of strong structural similarities between the different versions using multidimensional scaling, factor analysis and comparison of mean profiles.

Adolescent

Analysis of the functional role of the Polycomb chromo domain in Drosophila melanogaster.

The chromo domain was identified as a homologous protein motif between Polycomb (Pc)--a member of the Pc-group genes encoding transcriptional repressors of the homeotic genes--and HP1--a heterochromatin-associated protein encoded by the suppressor of position effect variegation gene Su(var)205. Together with previous genetic studies, this molecular similarity supports the suggestion of a common mechanism used for generating heterochromatin and for repressing homeotic genes. The evolutionary conservation of the chromo domain throughout the animal and plant kingdoms implies an important functional role for this protein motif. We have used transgenic lines as well as transient expression assays employing Drosophila tissue culture cells to study the functional role of the Pc chromo domain. Wild-type Pc protein is endogenously expressed in SL2 cells and is found in large immunologically visible complexes. Mutated Pc proteins were expressed as Pc-beta-galactosidase fusion proteins, and their nuclear distribution was examined by indirect immunofluorescence in tissue culture cells and on polytene chromosomes of transgenic larvae. We show that carboxy-terminal truncations of the Pc protein do not affect chromosomal binding of the fusion protein. However, mutations affecting only the chromo domain including in vitro generated deletions, as well as point mutations, abolish chromosomal binding. Our results demonstrate for the first time that the chromo domain is important for the function of Pc and that it is absolutely required for binding of Pc protein to chromatin. Some of the nuclear patterns generated by the mutated forms of the fusion proteins suggest, furthermore, that the chromo domain could be involved in a packaging mechanism, essential for compacting chromosomal proteins within heterochromatin or heterochromatin-like complexes.

Alleles

Complicated duodenal ulcer, vagotomy or distal resection--own experience.

An analysis of clinical material through 10-year-period (1980-1989) is presented. There were 708 gastric operations performed for gastroduodenal ulcer disease. Most frequently distal gastric resections (585) were used, 233 in B. I. and 352 in B II. modification. Selective proximal vagotomy (SPV) was less frequently used (only 116 cases). Authors think there is no reason for a general use of SPV for each form of duodenal ulcer because of very serious competition with the H2 blockers. A different individual proved choice of the method as well as an appropriate subtle operating technique is considered to be essential.

Duodenal Ulcer

[Characterization of T lymphocyte defects in patients with Hodgkin's disease using enzyme chemical markers].

Patients suffering from lymphogranulomatosis were studied with respect to cellular immune deficiencies. For this purpose, mononuclear cells from venous blood were separated and subjected to analysis of lymphocyte markers. T-lymphocytes were enumerated by means of the sheep erythrocyte (SE) rosette test. T cell subpopulations were determined using enzyme cytochemical staining for dipeptidyl peptidase IV (DP IV) and unspecific acid alphanaphthylacetate esterase (ANAE). In 18 patients with M. Hodgkin a significant reduction in the T lymphocyte count in peripheral blood was found. This T cell defect is due to a selective decrease in the TM-subpopulation as identified by enzyme cytochemical markers DP IV and ANAE (focal reaction). From these results it is concluded that patients with lymphogranulomatosis have characteristic abnormalities in the immune system in the sense of a disturbed equilibrium of immune regulatory cells.

Adult

Electrostimulation of healing abdominal incisional hernias by low frequency, bipolar, symmetrical rectangular pulses. An experimental study.

A total of 107 male Wistar rats had abdominal hernias repaired (3 weeks after they had been artificially induced) by a two layer closure of the abdominal wall--the Mayo technique. The wounds of 56 rats were subjected to constant stimulation by an electric flow field. An implanted stimulation unit provided a low frequency (0.87 Hz), bipolar, symmetrical rectangular pulsed current (+/- 25 microA). A control group were given units that did not transmit current. In 39 of the 51 animals in the control group the muscle margins of the abdominal scars separated by between 1 and 5 mm. The scars of the electrostimulated animals were distinguished histologically by early formation of fibroblasts and deposition of collagen and the rapid maturation and longitudinal alignment of the collagen fibres. 46 of 56 of these scars were not separated. This technique may have a clinical application as adjuvant treatment for relapses of incisional hernias.

Abdominal Muscles

[Bipolar impulses or direct current as an adjuvant treatment of incisional hernia? Comparative experimental animal study].

The electrostimulation of the cicatricial healing in the abdominal wall were tested in 119 Wistar rats by means of bipolar rectangularly pulsed current (0.87 Hz, +/- 25 mu A) and direct current (1 mu A). Doubling of the fascia of an abdominal wall hernia was carried out in three groups of rats. In the first group the operational region was stimulated by rectangularly pulsed current, strong proliferated cicatrices were formed with premature production of fibroblasts and collagenous fibres, fast maturation, and high strength. In the second group it was stimulated by direct current, a less exact longitudinal orientation of the collagenous fibres and a slower cicatricial maturation were shown. The third group applied as a control showed a cicatricial distension up to 5 mm. The electrostimulation of the proliferation of connective tissue and cicatricial healing could be pointed out between different tissues (peritoneum and fascia).

Animals