PubMed Health⌕ Search

Biomedical subjects

A Rapp

Publications and source records attributed to A Rapp.

At least 19 recordsLinked to original sources
PubMed2006

Humor and smiling: cortical regions selective for cognitive, affective, and volitional components.

BACKGROUND: The interrelationships among humor, smiling, and grinning have fascinated philosophers for millennia and neurologists for over a century. A functional dissociation between emotional facial expressions and those under voluntary control was suggested decades ago. Recent functional imaging studies, however, have been somewhat at odds with older studies with respect to the role of the right frontal cortex in the perception of humor. METHODS: Blood oxygen level-dependent (BOLD) activity was measured in 13 subjects during the presentation of "funny" vs "nonfunny" versions of essentially the same cartoons and compared with BOLD activity associated with "merely grinning" at similar nonfunny cartoons via fMRI. RESULTS: Humor perception was correlated with BOLD activity in the left temporo-occipitoparietal junction and left prefrontal cortex and humor-associated smiling (recorded with an MR-compatible video camera) with bilateral activity in the basal temporal lobes. Unexpectedly, both conditions were also accompanied by a decrease in BOLD activity in the right orbitofrontal cortex. Voluntary "grinning" in the absence of humorous stimuli was accompanied by bilateral activity in the facial motor regions. CONCLUSIONS: These results confirm the clinically derived hypothesis of separate cortical regions responsible for the production of emotionally driven vs voluntary facial expressions. The right orbitofrontal decrease reconciles inconsistencies between clinical and functional imaging findings and may reflect a disinhibition of facial emotional expression.

Adolescent↗
PubMed2006

UVA-induced apoptosis studied by the new apo/necro-Comet-assay which distinguishes viable, apoptotic and necrotic cells.

An adaptation of the Comet-assay was developed which enables the discrimination of viable, apoptotic and necrotic single cells by use of the common Annexin-V staining and a dye exclusion test on the cells already embedded in agarose gel on glass slides. Membrane integrity (Ethidium-Homodimer exclusion), cellular esterase activity (Calcein blue-AM) as well as translocation of phosphadidyl-serine (Annexin-V) were analysed using these stains. The advantage of the 'apo/necro-Comet-assay' is that the viability status of individual cells can be determined and correlated with the DNA fragmentation pattern (comet) formed by the same cells. Hence, DNA damage can be assessed and correlated with viable cells or cells undergoing early, mid- or late stage apoptosis or necrosis as identified by the staining pattern. The staining was verified using heat and etoposide-induced apoptosis. This technique, among others, was used to study whether apoptotic fragmentation interferes with repair kinetics measured with the comet assay following UVA exposure (doses up to 1,280 kJ/m(2)) in the cultured human keratinocytes (HaCaT). Therefore, a time course of apoptotic events (phosphatidyl translocation and TUNEL fragmentation) was established and correlated to the DNA fragmentation in the comet-assay. Apoptotic cells were detected more than 8 h later. The combined three-colour staining method with the comet assay showed that there was no significant interference of DNA repair by apoptotic fragmentation processes since DNA repair was almost completed before the onset of apoptotic fragmentation. The apo/necro-Comet-assay reduces the general problem of false-positive results in genotoxicity tests using the Comet-assay.

Annexin A5↗
PubMed2005

Comet-assay in combination with PNA-FISH detects mutagen-induced DNA damage and specific repeat sequences in the damaged DNA of transformed cells.

The Comet-assay was applied to three transformed cell lines (HT1080, CCRF-CEM line and CHO) which were treated with the cytostatics bleomycin (BLM) or mitomycin C (MMC). In addition, PNA probes for the telomere repeat (TTAGGG)(n) were used for detection of telomeric DNA sequences in the damaged DNA. Data were compared with previously obtained results from peripheral leukocytes. The amount of migrating DNA increased in all cell types in a dose-dependent manner after BLM exposure. CHO cells reacted sensitively at low doses of the mutagen, and leukocytes had the highest dose-related effect up to 25 IU/ml which, however, did not further increase. A rather linear dose response characterized the HT1080 cells, the effect was lowest for the CCRF-CEM cells. While MMC at lower doses increased the percentage of migrating DNA in a dose-dependent manner, the higher doses induced shorter comets, on average, than the lower ones in all cell lines. With PNA-Comet-FISH obvious differences were found between the studied cell lines with respect to quantitative head/tail distribution of telomeric signals after BLM exposure. A large number of signal spots of various sizes were found in CHO cells, very small signals could be detected in the comets of both neoplasia cell lines. Dose-dependence of telomeres in the tail was most pro-nounced in CCRF-CEM and normal leukocytes, less in HT1080. The steepest dose-related increase of telomeric signals in the tail was found in CHO cells. The ratio between the migrated DNA and the telomeric signals in the tail varied distinctly between the examined cell types from 3:1 to 1:1. Taken together, Comet-FISH can detect mutagenic effects on specific DNA sequences. This may be of high practical value if amplified DNA sequences will be addressed by those examinations in future.

Animals↗
PubMed2003

Putative colon cancer risk factors damage global DNA and TP53 in primary human colon cells isolated from surgical samples.

This study describes a novel in vitro method in genetic toxicology that is based on detection of chemical-induced DNA damage connected with altered migration of TP53 in primary human colonocytes. Techniques were developed to isolate high numbers of human epithelial colon cells from surgical tissues. High quantities of viable cells were obtained per donor. The primary cells were treated with the endogenous risk factors trans-2-hexenal, and hydrogen peroxide. Global DNA damage and repair were measured by single-cell gel electrophoresis (Comet assay). We compared responses of primary colon cells to HT29clone19A, a differentiated human colon tumour cell line, for which the karyotype was analysed with 24-colour FISH. Both compounds were genotoxic in both cell types and most of the induced DNA damage was repaired after 30 min. Specific migration of TP53 was determined by fluorescence in situ hybridization (Comet FISH). Using primary colon cells, we quantified the migration of TP53 signals into the comet tails. In these cells TP53 was more sensitive than global DNA for genotoxicity induced by trans-2-hexenal and H(2)O(2). HT29clone19A cells cannot be used for Comet FISH because of their aberrant karyotype. The approach described allows us to obtain more knowledge of putative risk factors in colon carcinogenesis.

Aged↗
PubMed2003

Labelling quality and chromosome morphology after low temperature FISH analysed by scanning far-field and near-field optical microscopy.

A non-enzymatic, low temperature fluorescence in situ hybridization (LTFISH) procedure was applied to metaphase spreads and interphase cell nuclei. In this context 'low temperature' means that the denaturation procedure of the chromosomal target DNA usually applied by heat treatment and chaotropic agents such as formamide was completely omitted so that the complete hybridization reaction took place at 37 degrees C. For LTFISH, the DNA probe had to be single-stranded, which was achieved by means of separate thermal denaturation of the DNA probe only. The DNA probe pUC1.77 was used for all LTFISH experiments. The labelling quality (number of binding sites, relative background intensity, relative intensity of major and minor binding sites) was analysed by confocal laser scanning microscopy (CLSM). An optimum in specificity and signal quality was obtained for 15 h hybridization time. For this hybridization condition of LTFISH, the chromosomal morphology was analysed by scanning near-field optical microscopy (SNOM). The results were compared with the morphology of chromosomes after (a) labelling of all centromeres using the same chemical treatment in the FISH procedure but with the application of target denaturation, and (b) labelling of all centromeres using a standard FISH protocol including thermal denaturation of the DNA probe and the chromosomal target. Depending on the FISH-procedure applied, SNOM images show substantial differences in the chromosome morphology. After LTFISH the chromosome morphology appeared to be much better preserved than after standard FISH. In contrast, the application of the LTFISH chemical treatment accompanied by heat denaturation had a very destructive influence on chromosomal morphology. The results indicate that, at least for certain DNA probes, specific chromosome labelling can be obtained without the usually applied heat and chemical denaturation of the DNA target, resulting in an apparently well preserved chromatin morphology as visualized by SNOM. LTFISH may be therefore a useful labelling technique whenever the chromosomal morphology had to be preserved after specific labelling of DNA regions. Binding mechanisms of single-stranded DNA probes to double-stranded DNA targets are discussed.

Cell Nucleus↗
PubMed2002

Self-organization of supramolecular helical dendrimers into complex electronic materials.

The discovery of electrically conducting organic crystals and polymers has widened the range of potential optoelectronic materials, provided these exhibit sufficiently high charge carrier mobilities and are easy to make and process. Organic single crystals have high charge carrier mobilities but are usually impractical, whereas polymers have good processability but low mobilities. Liquid crystals exhibit mobilities approaching those of single crystals and are suitable for applications, but demanding fabrication and processing methods limit their use. Here we show that the self-assembly of fluorinated tapered dendrons can drive the formation of supramolecular liquid crystals with promising optoelectronic properties from a wide range of organic materials. We find that attaching conducting organic donor or acceptor groups to the apex of the dendrons leads to supramolecular nanometre-scale columns that contain in their cores pi-stacks of donors, acceptors or donor-acceptor complexes exhibiting high charge carrier mobilities. When we use functionalized dendrons and amorphous polymers carrying compatible side groups, these co-assemble so that the polymer is incorporated in the centre of the columns through donor-acceptor interactions and exhibits enhanced charge carrier mobilities. We anticipate that this simple and versatile strategy for producing conductive pi-stacks of aromatic groups, surrounded by helical dendrons, will lead to a new class of supramolecular materials suitable for electronic and optoelectronic applications.

Journal Article↗
PubMed2002

Variations in cell surfaces of estrogen treated breast cancer cells detected by a combined instrument for far-field and near-field microscopy.

The response of single breast cancer cells (cell line T-47D) to 17beta-estradiol (E(2)) under different concentrations was studied by using an instrument that allows to combine far-field light microscopy with high resolution scanning near-field (AFM/SNOM) microscopy on the same cell. Different concentrations of E(2) induce clearly different effects as well on cellular shape (in classical bright-field imaging) as on surface topography (atomic force imaging) and absorbance (near-field light transmission imaging). The differences range from a polygonal shape at zero via a roughly spherical shape at physiological up to a spindle-like shape at un-physiologically high concentrations. The surface topography of untreated control cells was found to be regular and smooth with small overall height modulations. At physiological E(2) concentrations the surfaces became increasingly jagged as detected by an increase in membrane height. After application of the un-physiological high E(2) concentration the cell surface structures appeared to be smoother again with an irregular fine structure. The general behaviour of dose dependent differences was also found in the near-field light transmission images. In order to quantify the treatment effects, line scans through the normalised topography images were drawn and a rate of co-localisation between high topography and high transmission areas was calculated. The cell biological aspects of these observations are, so far, not studied in detail but measurements on single cells offer new perspectives to be empirically used in diagnosis and therapy control of breast cancers.

Breast Neoplasms↗
PubMed2002

Comet assay measurements of DNA damage in cells by laser microbeams and trapping beams with wavelengths spanning a range of 308 nm to 1064 nm.

DNA damage induced in NC37 lymphoblasts by optical tweezers with a continuous-wave Ti:sapphire laser and a continuous-wave Nd:YAG laser (60-240 mW; 10-50 TJ/m2; 30-120 s irradiation) was studied with the comet assay, a single-cell technique used to detect DNA fragmentation in genomes. Over the wavelength range of 750-1064 nm, the amount of damage in DNA peaks at around 760 nm, with the fraction of DNA damage within the range of 750-780 nm being a factor of two larger than the fraction of DNA damage within the range of 800-1064 nm. The variation in DNA damage was not significant over the range of 800-1064 nm. When the logarithm of damage thresholds measured in the present work, as well as values reported previously in the UV range, was plotted as a function of wavelength, a dramatic wavelength dependence became apparent. The damage threshold values can be fitted on two straight lines, one for continuous-wave sources and the other for pulsed sources, irrespective of the type of source used (e.g. classical lamp or laser). The damage threshold around 760 nm falls on the line extrapolated from values for UV-radiation-induced damage, while the data for 800-1064 nm fall on a line that has a different slope. The change in the slope between 320 and 340 nm observed earlier is consistent with a well-known change in DNA-damaging mechanisms. The change observed around 780 nm is therefore suggestive of a further change in the mechanism(s). The data from this work together with our previous measurements provide, to the best of our knowledge, the most comprehensive view available of the DNA damage produced by microfocused light.

Calibration↗
PubMed2001

Human placenta as a 'dual' biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 1: physiology, function and sampling of placenta for elemental characterisation.

Choice of specimen from human subjects for monitoring pollutants proven to be detrimental to human health depends on the criteria chosen, namely real-time monitoring (RTM) or long-term monitoring (LTM). Specimens such as whole blood, urine, saliva and breast milk are commonly used from living subjects for RTM of toxic metals. However, sampling blood requires an invasive procedure. On the other hand, hair (with some limitations), bone (especially for the assessment of bone seeking elements), adipose tissue (mainly for organic pollutants) and liver (for both organic and inorganic toxicants) are used as specimens for LTM. With the exception of hair, generally these specimens are obtained at post-mortem. In context of health-related biomonitoring, placenta as a specimen has not received as much attention as it deserves. It is a unique sample requiring no invasive procedure, and offers possibilities for RTM, in particular as a dual purpose specimen for evaluating the pollutant burden exerted on the mother as well as on the fetus. Obtaining representative samples of placenta for elemental composition studies is a difficult task, because of heterogeneous mix of placental cells and decidual matter tainted with maternal and fetal blood. Therefore, the present sampling practices for placental tissue, and guidelines to safeguard the validity of the sampled material have been reviewed in part 1 with the following conclusions: medico-legal and ethical matters should be properly addressed before collecting the placenta; it is advisable to collect the entire placenta even if it includes the umbilical cord; further preparatory work is to be carried out in a clean laboratory and depends upon the purpose of the investigation; homogenising the entire sample may prove to be technically challenging but this step is crucial to obtain representative samples, handling the entire sample may be unavoidable; and an alternative method of procuring representative samples would require random samples from multiple sites, pooled, homogenised and assayed to confirm homogeneity.

Adult↗
PubMed2001

Human placenta as a 'dual' biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 2: essential minor, trace and other (non-essential) elements in human placenta.

A survey of elemental composition of the human placenta was undertaken to evaluate reference values for minor and trace elements (essential and non-essential). The new data collection was narrowed down to results generated between the period of 1975-2000, since analytical methodology was becoming increasingly reliable with time for many elements. The search revealed the following results (microg/g, based on wet weight): Ca = 770; Cl = 1900; K = 1685; Mg = 100; Na = 360; P = 1700; and S = 350. However, Na, P and S need further confirmation. For a group of essential trace elements following average values were evaluated (microg/g, based on wet weight): Co = 0.007; Cr = 0.03; Cu = 0.9; Fe = 69; I = 0.005; Mn = 0.08; Mo = 0.02; Se = 0.2; and Zn = 10. However, the iodine value needs further confirmation. In addition, information values have been identified for a number of so-called non-essential elements such as Ag, Au, B, Ba, Br, Cs, F, La, Rb, Sb, Sc, Si, Sn, Sr, Ti, V and W. The survey results for toxic trace elements As, Cd, Hg, Ni and Pb are discussed in part 3 of this paper along with placenta as a biomonitor for toxic trace elements.

Adult↗
PubMed2001

Human placenta as a 'dual' biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 3: toxic trace elements in placenta and placenta as a biomarker for these elements.

The human placenta as a body component is exposed to several harmful substances, depending upon the environmental conditions encountered. In the case of toxic metals, placental tissue can be regarded as a dual biomarker to assess maternal and fetal health. The average range of concentrations for toxic trace elements in placenta based on wet weight are found to be: cadmium 1-6 ng/g; total mercury 2-13 ng/g; methyl mercury 1-14 microg/g; and lead 5-60 ng/g. The placenta appears to be at least a partial barrier for Cadmium. Cadmium transport includes a broad variety of mechanisms. Once in circulation, it mainly interferes with Ca and Zn transportation. On the other hand, placenta appears to be a weaker harrier for Pb than for Cd. In the case of Hg, predominantly the organic form is absorbed and readily crosses the placenta. In fetal blood, the organic mercury content is equal or even greater than in maternal blood, raising questions on normal fetal development. Placenta as a biomarker could be taken as an alternative to repeated maternal blood sampling for assessing lead exposure in utero. Placenta samples are usually obtained at the time of parturition, a one-time event. Hence, each pregnancy has to be looked upon as an RTM (real time monitoring) process since the affected species is exposed to the placental source of pollutants only during the course of that particular pregnancy.

Adult↗
PubMed2000

Fused bicyclic Gly-Asp beta-turn mimics with potent affinity for GPIIb-IIIa. Exploration of the arginine isostere.

6-[4-Amidinobenzoyl]amino]-tetralone-2-acetic acid is a potent antagonist of GPIIb-IIIa. Substitution in the meta position of the benzamidine, or replacement with a heteroaryl amidine was tolerated in this series. Use of an acyl-linked 4-alkyl piperidine as an arginine isostere also provided active compounds. Compounds from this series provided substantial systemic exposure in the rat following oral administration.

Acetates↗
PubMed2000

UV-A breakage sensitivity of human chromosomes as measured by COMET-FISH depends on gene density and not on the chromosome size.

COMET-FISH, a single cell-based combination of COMET-assay (also known as single cell gel electrophoresis (SCGE)) with fluorescence in situ hybridization (FISH) allows region specific studies on DNA stability and damage. COMET-FISH can be used to investigate UV-A-induced DNA damage of selected whole chromosomes. In the present work, a modified COMET-FISH protocol with whole chromosome painting probes was used to study whether UV-A-induced DNA damage is distributed randomly over the whole genome or occurs at preferred sites. The study was performed with 12 different chromosome painting probes (for chromosomes 1, 2, 3, 8, 9, 11, 14, 18, 19, 21, X and Y). The results on human lymphocytes irradiated with 500 kJ/m2 at a wavelength of 365 nm indicate that the induced number of chromatin strand breaks does not correlate with the chromosome size. They therefore are distributed in a non-random manner. For example, fragments of the gene-rich chromosome chromosome 1 were found in the comet tail in only 3% of the examined cells, and thus chromosome 1 is rather stable, whereas fragmentation of the gene-poor chromosome 8 was observed in 25% of all comets. On the basis of all 12 chromosomes analyzed, an inverse correlation between the density of active genes and the sensitivity toward UV-A radiation is found.

Cells, Cultured↗
PubMed1999

Fused bicyclic Gly-Asp beta-turn mimics with specific affinity for GPIIb-IIIa.

Disubstituted isoquinolones 2 and 3 have affinity for GPIIb-IIIa and represent leads for further structural evaluation. Structure-activity studies centered on the bicyclic beta-turn mimic contained in these molecules indicated that this moiety could accommodate a variety of modifications. Specifically, monocyclic, 6, 5-bicyclic, and 6,7-bicyclic structures provide compounds with affinity for GPIIb-IIIa. Within the 6,6-series, isoquinoline, tetralin, tetralone, and benzopyran nuclei yield potent antagonists that are specific for GPIIb-IIIa. Attachment of the arginine isostere (benzamidine) to the supporting nucleus can be accomplished with an ether or amide linkage, although the latter enhances activity. Several compounds in this series provided measurable blood levels after oral dosing. Conversion of the acid moiety in these molecules to an ester generally provided compounds which gave greater systemic exposure after oral administration. Absolute bioavailabilities in the rat for the ethyl ester prodrug derivatives of the tetralin, tetralone, and benzopyran analogues of 3 were 28%, 23%, and 24%, respectively.

Administration, Oral↗
PubMed1998

Volatile flavour of wine: correlation between instrumental analysis and sensory perception.

The aroma of wine consists of 600 to 800 aroma compounds from which especially those, typical for the variety, are already present in the grapes. There are significant varietal differences between the aromagrams ('fingerprint patterns'). Thus the amount of some flavour compounds ('key substances') shows typical dependence on the variety. Especially monoterpene compounds play an important role in the differentiation of wine varieties. The German white wines can be differentiated into three groups only by quantitative determination of 12 monoterpenes ('terpene profile'). These groups are: 'Riesling type', 'Muscat type' and 'Silvaner-Weissburgunder type'. Such 'terpene profiles' are also useful for the separation of real Riesling wines from others called Riesling (e.g. Welschriesling, Kap Riesling, Emerald Riesling) but not produced from grapes of the variety Riesling. Including further components and by means of statistical methods (discriminant analysis) even the different varieties within the mentioned groups for instance the 'Riesling'-group (e.g. Riesling, Kerner, Ehrenfelser, Bacchus, Müller-Thurgau) can be separated from each other. An analytical characterization of the neutral ('Silvaner-type') grape varieties Silvaner, Ruländer (Pinot gris), Weissburgunder (Pinot blanc) is also possible with about 20 compounds (e.g. monoterpenes, alcohols). Computing at the same time free and glycosidically bound aroma components (monoterpenes, alcohols, norisoprenes) in discriminant analysis the characterization of the neutral grape varieties can be considerably improved. To identify compounds causing 'off-flavours' sniffing technique is the method of choice. The off-flavour is pinpointed during gas chromatographic separation of the complex aroma mixture by effluent sniffing. Once allocated, the chemical nature of the off-flavours is elucidated by spectroscopic methods. Substances contributing to the green pepper taint, the strawberry note, moussiness, corkiness, etc. in wine could be found in this way.

Humans↗