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Biomedical subjects

A Heller

Publications and source records attributed to A Heller.

At least 19 recordsLinked to original sources

Continuous non-invasive blood pressure monitoring using concentrically interlocking control loops.

A new method and apparatus for non-disruptive blood pressure (BP) recording in the finger based on the vascular unloading technique is introduced. The instrument, in contrast to intermittent set point readjustments of the conventional vascular unloading technique, delivers BP without interruptions, thus refining the Penáz' principle. The method is based on concentrically interlocking control loops for correct long-term tracing of finger BP, including automatic set point adaptation, light control and separate inlet and outlet valves for electro-pneumatic control. Examples of long-term BP recordings at rest and during autonomic function tests illustrate the potential of the new instrument.

Blood Pressure Monitors↗

Multicolor fluorescence in situ hybridization (FISH) applied to FISH-banding.

During the last decade not only multicolor fluorescence in situ hybridization (FISH) using whole chromosome paints as probes, but also numerous chromosome banding techniques based on FISH have been developed for the human and for the murine genome. This review focuses on such FISH-banding techniques, which were recently defined as 'any kind of FISH technique, which provide the possibility to characterize simultaneously several chromosomal subregions smaller than a chromosome arm. FISH-banding methods fitting that definition may have quite different characteristics, but share the ability to produce a DNA-specific chromosomal banding'. While the standard chromosome banding techniques like GTG lead to a protein-related black and white banding pattern, FISH-banding techniques are DNA-specific, more colorful and, thus, more informative. For some, even high-resolution FISH-banding techniques the development is complete and they can be used for whole genome hybridizations in one step. Other FISH-banding methods are only available for selected chromosomes and/or are still under development. FISH-banding methods have successfully been applied in research in evolution- and radiation-biology, as well as in studies on the nuclear architecture. Moreover, their suitability for diagnostic purposes has been proven in prenatal, postnatal and tumor cytogenetics, indicating that they are an important tool with the potential to partly replace the conventional banding techniques in the future.

Bone Marrow Cells↗

Non-invasive beat-to-beat cardiac output monitoring by an improved method of transthoracic bioimpedance measurement.

The report describes a method of impedance cardiography using an improved estimate of thoracic volume. The formulas and their implementation in hardware and software are explained and new shortband electrodes are described which generate a good homogeneous thoracic field. Examples of stroke volume and cardiac output curves underline the capabilities of the monitoring system "Task Force Monitor". In several experiments, results are compared to thermodilution as well as to BioZ measurements: the new method excels in comparison with thermodilution and is comparable to the BioZ device. Compared to traditional electrodes, the new shortband electrodes are shown to provide better reproducibility.

Cardiac Output↗

[Dynamic decision making in emergency medicine. Example of paraplegia after a traffic accident].

Dynamic decision making is one of the key skills in crew resource management training in aviation. In emergency medicine it is important to practice this skill as a prerequisite for effective treatment of patients. We report a case of paraplegia after a road traffic accident and cervical spine injury. During the prehospital treatment the patient's state was re-evaluated at different times. Although the patient was initially unconscious the physician at the scene decided not to intubate the trachea as the level of consciousness improved during resuscitation. In the emergency room a C5 fracture and a prolapsed intervertebral disc were diagnosed and immediate decompression and stabilisation of the cervical spine were performed. Dynamic decision-making has been in practise for a long time in aviation, similarities to decisions in medicine and the psychological background are described on the basis of the case report.

Accidents, Traffic↗

The hierarchically organized splitting of chromosome bands into sub-bands analyzed by multicolor banding (MCB).

To clarify the nature of chromosome sub-bands in more detail, the multicolor banding (MCB) probe-set for chromosome 5 was hybridized to normal metaphase spreads of GTG band levels at approximately 850, approximately 550, approximately 400 and approximately 300. It could be observed that as the chromosomes became shorter, more of the initial 39 MCB pseudo-colors disappeared, ending with 18 MCB pseudo-colored bands at the approximately 300-band level. The hierarchically organized splitting of bands into sub-bands was analyzed by comparing the disappearance or appearance of pseudo-color bands of the four different band levels. The regions to split first are telomere-near, centromere-near and in 5q23-->q31, followed by 5p15, 5p14, and all GTG dark bands in 5q apart from 5q12 and 5q32 and finalized by sub-band building in 5p15.2, 5q21.2-->q21.3, 5q23.1 and 5q34. The direction of band splitting towards the centromere or the telomere could be assigned to each band separately. Pseudo-colors assigned to GTG-light bands were resistant to band splitting. These observations are in concordance with the recently proposed concept of chromosome region-specific protein swelling.

Chromosome Banding↗

[Palliative culture in the stationary care for the elderly].

Nursing homes are challenged by a significant change in the patient-structure. To care for dying elderly people means to enable them to live in dignity till the end. Helpful therefore is to implement Palliative Care into existing structures. This requires personal and organizational learning and development. The first step is to make central differences and contradictions visible und communicable. We describe three organizational types which leads into different core-processes. Organizational measures supporting the development of a palliative culture and indicators of successful implementation are presented.

Adaptation, Psychological↗

Multitude multicolor chromosome banding (mMCB) - a comprehensive one-step multicolor FISH banding method.

Multicolor chromosome banding (MCB) using one single chromosome-specific MCB probe set per experiment was previously reported as powerful tool in molecular cytogenetics for the characterization of all kinds of human marker chromosomes. However, a quick analysis of karyotypes with highly complex chromosomal changes was hampered by the problem that up to 24 MCB experiments were necessary for a comprehensive karyotype description. To overcome that limitation the 138 available region-specific microdissection-derived libraries for all human chromosomes were combined to one single probe set, called multitude MCB (mMCB). A typical fluorescence banding pattern along the human karyotype is produced, which can be evaluated either by transforming these profiles into chromosome region-specific pseudo-colors or more reliably by studying the fluorescence profiles. The mMCB probe set has been applied on chromosomes of normal male and female probands, two primary myelodysplastic syndromes and two solid tumor cell lines. Additionally, a cell line of Gorilla gorilla (GGO) studied previously by single chromosome-specific MCB was reevaluated by the mMCB method. All results were in concordance with those obtained in parallel or by other cytogenetic and molecular cytogenetic approaches indicating that mMCB is a powerful multicolor FISH banding tool for fast characterization of complex karyotypes.

Animals↗

Evidence for a new microdeletion syndrome in 15q21.

We report on the fourth known case with an interstitial deletion in 15q21. In the present case the breakpoints have been determined by GTG-banding, microdissection and the recently developed multicolor banding (MCB) technique as 15q21.1-q21.3. Common features in all four cases are mental retardation, growth retardation, a beak-like nose with hypoplastic alae nasi and a thin upper lip. Additional frequent features are small hands and feet, hypotonia, low hair implantation, low set ears, clinodactyly and obesity. The possibility that a critical region for a new microdeletion-syndrome is situated in 15q21 is discussed.

Abnormalities, Multiple↗

Multicolor chromosome banding (MCB) with YAC/BAC-based probes and region-specific microdissection DNA libraries.

Multicolor chromosome banding (MCB) allows the delineation of chromosomal regions with a resolution of a few megabasepairs, i.e., slightly below the size of most visible chromosome bands. Based on the hybridization of overlapping region-specific probe libraries, chromosomal subregions are hybridized with probes that fluoresce in distinct wavelength intervals, so they can be assigned predefined pseudo-colors during the digital imaging and visualization process. The present study demonstrates how MCB patterns can be produced by region-specific microdissection derived (mcd) libraries as well as collections of yeast or bacterial artificial chromosomes (YACs and BACs, respectively). We compared the efficiency of an mcd library based approach with the hybridization of collections of locus-specific probes (LSP) for fluorescent banding of three rather differently sized human chromosomes, i.e., chromosomes 2, 13, and 22. The LSP sets were comprised of 107 probes specific for chromosome 2, 82 probes for chromosome 13, and 31 probes for chromosome 22. The results demonstrated a more homogeneous coverage of chromosomes and thus, more desirable banding patterns using the microdissection library-based MCB. This may be related to the observation that chromosomes are difficult to cover completely with YAC and/or BAC clones as single-color fluorescence in situ hybridization (FISH) experiments showed. Mcd libraries, on the other hand, provide high complexity probes that work well as region-specific paints, but do not readily allow positioning of breakpoints on genetic or physical maps as required for the positional cloning of genes. Thus, combinations of mcd libraries and locus-specific large insert DNA probes appear to be the most efficient tools for high-resolution cytogenetic analyses.

Chromosome Banding↗

Elevation of fetal dopamine following exposure to methamphetamine in utero.

The effect of methamphetamine on fetal dopaminergic function was examined following treatment of pregnant mice twice daily with 40 mg/kg methamphetamine from either gestational day (GD) 7-13 or from GD 7-15. Dopamine levels were elevated in fetal GD 16 corpus striatum and rostral mesencephalon following both treatment regimens. This increase in fetal dopamine is consistent with our findings that exposure to methamphetamine in utero results in adult dopaminergic neurons which are more responsive in terms of methamphetamine induced release of the neurotransmitter and more sensitive to the neurotoxic effects of the drug.

Animals↗

Induction of cell cycle arrest and morphological differentiation by Nurr1 and retinoids in dopamine MN9D cells.

Dopamine cells are generated in the ventral midbrain during embryonic development. The progressive degeneration of these cells in patients with Parkinson's disease, and the potential therapeutic benefit by transplantation of in vitro generated dopamine cells, has triggered intense interest in understanding the process whereby these cells develop. Nurr1 is an orphan nuclear receptor essential for the development of midbrain dopaminergic neurons. However, the mechanism by which Nurr1 promotes dopamine cell differentiation has remained unknown. In this study we have used a dopamine-synthesizing cell line (MN9D) with immature characteristics to analyze the function of Nurr1 in dopamine cell development. The results demonstrate that Nurr1 can induce cell cycle arrest and a highly differentiated cell morphology in these cells. These two functions were both mediated through a DNA binding-dependent mechanism that did not require Nurr1 interaction with the heterodimerization partner retinoid X receptor. However, retinoids can promote the differentiation of MN9D cells independently of Nurr1. Importantly, the closely related orphan receptors NGFI-B and Nor1 were also able to induce cell cycle arrest and differentiation. Thus, the growth inhibitory activities of the NGFI-B/Nurr1/Nor1 orphan receptors, along with their widespread expression patterns both during development and in the adult, suggest a more general role in control of cell proliferation in the developing embryo and in adult tissues.

Animals↗

Computer experiments to determine whether over- or under-counting necessarily affects the determination of difference in cell number between experimental groups.

Computer cell counting experiments were performed in order to examine the consequences of over- or under-counting. The three-dimensional reaggregate culture laboratory environment for cell counting was used as a model for computer simulation. The laboratory environment for aggregate and cell sizes, numbers and spatial placement in gelatin blocks was mimicked in the computer setup. However, in the computer, cell counting was set to be either ideally unbiased, or deliberately biased in regard to over- or under-counting so as to compare eventual results when using the various cell counting methods. It was found that there was no effect of the cell counting methods used in determining whether there was a significant difference in cell number between two experimental groups. In addition, it was found that under the conditions of these simulations, the optical dissector method behaved similarly, on the average, as the ideal method of counting cell centers and in both of those cases, the average ratio between actual cell number in a flask and estimated number was close to 1.00.

Animals↗

The Drosophila dorsoventral determinant PIPE contains ten copies of a variable domain homologous to mammalian heparan sulfate 2-sulfotransferase.

In Drosophila, the gene PIPE is expressed in follicle cells, the somatic cells that surround the forming egg during maturation, specifically on one side of the egg chamber. This asymmetry establishes the dorsoventral axis of the future embryo. Through the action of PIPE, the ligand SPATZLE, that is located in the perivitelline fluid of the embryo, is activated ventrally. This signal activates TOLL, a membrane-bound receptor. According to present knowledge, PIPE encodes two different transcripts, one of which restored ventral pattern elements to embryos when introduced into mutant pipe females. Here we show that PIPE is far more complex than previously reported. It encodes not two, but at least ten different transcripts, two of which are localized to ventral follicle cells. The transcripts contain one of ten copies of a variable domain, all homologous to heparan sulfate 2-sulfotransferase, an enzyme known to modify heparan sulfate proteoglycans, which are molecules that can bind ligands. The complex gene structure of PIPE thus evolved by duplications of one exon, a strategy used by genes of the immunoglobulin superfamily to generate molecular diversity. We show that PIPE transcripts can be eliminated by RNAi, although in this method double-stranded RNA is injected in embryos, while PIPE transcripts appear in the adult ovary. Our data suggest that at least two different PIPE transcripts redundantly provide the ventralizing PIPE function. 3' of PIPE we identified an enhancer element that drives a lacZ reporter gene specifically in ventral follicle cells. Since PIPE transcripts are found in salivary glands, and since expression of salivary gland genes is dependent on signaling molecules, we speculate that PIPE became localized to ventral follicle cells by a preexisting control system after acquiring a follicle cell enhancer.

Alternative Splicing↗