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Biomedical subjects

E Günther

Publications and source records attributed to E Günther.

At least 19 recordsLinked to original sources
PubMed2005

The photoionization-reduced energy in LSC.

The atomic rearrangement cascade that follows the electron-capture decay process in low-Z radionuclides involves X-rays which have high photoelectric interaction probabilities. When the K-shell binding energy of the ionized atom (e.g., hydrogen) is significantly lower than the energy of the X-ray photon, the detector response to a photon-equivalent energy electron and the whole photoionization process are very similar. This is not the case when the scintillator cocktail contains larger atoms (e.g., oxygen and phosphorus in Ultima Gold). For larger Z atoms, the reduced energy of the whole photoionization process is less than the reduced energy of the interacting photon due to the nonlinear effects of ionization quenching. This paper shows the convenience of including a more detailed simulation of the photoionization process in the atomic rearrangement detection model for electron-capture nuclides such as (55)Fe, (51)Cr and (54)Mn. The need for more elaborate atomic rearrangement models is a consequence of the analysis of (125)I data.

Journal Article↗
PubMed2003

Cytogenetic mapping and orientation of the rhesus macaque MHC.

Applying fluorescence in situ hybridisation (FISH), six cosmid clones of rhesus macaque origin containing the genes SACM2L, RING1, BAT1 and MIC2, MIC3, MICD, and MOG of the major histocompatibility complex (MHC) were localised to the long arm of the rhesus macaque chromosome 6 in 6q24, the orthologous region to human 6p21.3. Furthermore, centromere to telomere orientation of the rhesus macaque MHC as well as the internal order of the MHC genes tested are the same as in human. Fiber-FISH allows a rough estimate of distances between these MHC genes in the rhesus macaque, and, as in the human, the rhesus macaque MHC comprises about 3 to 4 Mb.

Animals↗
PubMed2001

Physical map and expression profile of genes of the telomeric class I gene region of the rat MHC.

The rat is an important model for studying organ graft rejection and susceptibility to certain complex diseases. The MHC, the RT1 complex, plays a decisive role in controlling these traits. We have cloned the telomeric class I region of the RT1 complex, RT1-C/E/M, of the BN inbred rat strain in a contig of overlapping P1-derived artificial chromosome clones encompassing approximately 2 Mb, and present a physical map of this MHC region. Forty-five class I exon 4-hybridizing BAM:HI fragments were detected, including the previously known rat class I genes RT1-E, RT-BM1, RT1-N, RT1-M2, RT1-M3, and RT1-M4. Twenty-six non-class I genes known to map to the corresponding part of the human and mouse MHC were tested and could be fine mapped in the RT1-C/E/M region at orthologous position. Four previously known microsatellite markers were fine mapped in the RT1-C/E/M region and found to occur in multiple copies. In addition, a new, single-copy polymorphic microsatellite has been defined. The expression profiles of several class I genes and the 26 non-class I genes were determined in 13 different tissues and exhibited restricted patterns in most cases. The data provide further molecular information on the MHC for analyzing disease susceptibility and underline the usefulness of the rat model.

Animals↗
PubMed2001

The major histocompatibility complex of the rat (Rattus norvegicus).

This review of the RT1 complex, the major histocompatibility complex (MHC) of the rat, focuses on genetic, genomic, evolutionary, and functional aspects at the molecular level. The class I, class II, and framework genes are listed. The physical map of the RT1 complex as revealed by analysis of clonal contigs is compared with the human and mouse MHC, and the degree of orthologous relationship is outlined. Elucidation of the RT1 complex provides important information for using the rat as a model of experimental transplantation and complex diseases.

Animals↗
PubMed2001

Standardisation and decay data of 177Lu and 188Re.

The activity values of 177Lu and 188Re standard sources were measured using the 4pibeta-gamma-coincidence method and by liquid scintillation counting. The X- and gamma-ray emission probabilities per disintegration were determined by means of photon spectrometry with calibrated Ge and Si(Li) detectors and using the pertinent activity values. The half-lives were measured with ionization chambers, yielding T(1/2)(177Lu) = 6.646(5) d and T(1/2)(188Re) = 0.70848(9) d.

Absorptiometry, Photon↗
PubMed2001

Genomic analysis of MIC genes in rhesus macaques.

MIC genes map to the major histocompatibility complex (MHC) and are distantly related to MHC class I genes. Recently, MICA/MICB-like genes have been described in nonhuman primates. In Macaca mulatta, three MICA/B-like genes could be identified: Mamu-MIC1, Mamu-MIC2, and Mamu-MIC3. We show here the isolation and characterization of rhesus macaque cosmid clones which carry the Mamu-MIC2 and Mamu-MIC3 genes. Neither the MIC2- and MIC3-coding sequences nor respective flanking sequences can be aligned unambiguously to either the human HLA-MICA or -MICB subregions, although MIC2 was found at a similar distance to the BAT1 gene as known for MICB in human. Thus, the characteristics allowing for a classification of primate MIC genes as being of the MICA or MICB types appear to have evolved after the separation of humans and rhesus monkeys from a common ancestor. Furthermore, also Mamu-MICD-containing cosmids could be isolated. In contrast to Mamu-MIC2 and Mamu-MIC3, the Mamu-MICD gene and its flanking sequences are highly conserved and orthologous to the human MICD subregion.

Animals↗
PubMed2001

Genomic and funtional aspects of the rat MHC, the RT1 complex.

The major histocompatibility complex (MHC) plays a central role in controlling immune responsiveness, susceptibility to certain diseases and histo-incompatibility. A physical map of the complete rat MHC, the RTI complex, is presented based on a PAC clonal contig (RT1n haplotype). Expression profiling of various tissues of different inbred strains has been carried out for genes of the RT1-C/E/M region, and different types of variability of expression are shown. As an example of single gene analysis, the RT1-linked heat shock-inducible heat shock genes Hsp70-1 and Hsp70-2 have been studied. It is demonstrated that their gene products are able to increase lysability of target cells by cytotoxic T lymphocytes.

Animals↗
PubMed2000

Heat shock protein 70 is able to prevent heat shock-induced resistance of target cells to CTL.

Heat shock or transfection with heat shock protein 70 (Hsp70) genes has been shown to protect tumor cell lines against immune mechanisms of cytotoxicity. We have reported previously that heat shock confers resistance to CTL in the rat myeloma cell line Y3 that is Hsp70 defective. Evidence is now presented that Hsp70 is able to prevent the induction of the resistant phenotype. In Con A-stimulated lymphocytes and in lymphocyte x Y3 somatic cell hybrid clones a severe, non-Hsp70-inducing heat shock elicits resistance to CTL in contrast to a heat shock that results in Hsp70 expression. Thus, Hsp70 expression appears to be negatively associated with the development of resistance. Furthermore, loading of Y3 cells with recombinant Hsp70 protein before heat shock is able to prevent resistance. Because apoptosis induced in Y3 cells by heat shock is not affected, Hsp70 appears to interfere selectively with the CTL-induced lethal pathway that is found to be calcium but not caspase dependent. It is suggested that after heat shock Hsp70 enhances the CTL-induced apoptotic pathway by chaperoning certain proteins in the target cell that are involved in the execution of cell death. Thus, although shown to confer protection against many cytotoxic mechanisms, Hsp70 does not appear to be generally cytoprotective. This observation could also be of relevance when interpreting the effectiveness of tumor immunity.

Animals↗
PubMed2000

Physical mapping and evolution of the centromeric class I gene-containing region of the rat MHC.

We physically mapped the centromeric part of the BN rat MHC (RT1n haplotype) in a contig of overlapping P1-derived artificial chromosome (PAC) clones encompassing about 300 kb. The following genes were identified and ordered as: (Syngap, Hset, Daxx, Bing1)-Tapbp-Rgl2-Ke2-Bing4-B3galt4- Rps18-Sacm2l-RT1-A1-RT1-A2-RT1-A3-Ring1-Ring2-++ +Ke4-Rxrb-Col11a2-RT1-Hb-Ring3-RT1-DMb. Thus, in contrast to other RT1 haplotypes, RT1n contains three class I genes, RT1-A1, RT1-A2, and RT1-A3, mapping between the Sacm2l and Ring1 genes. Comparisons of the sequences flanking the Sacm2L and Ring1 genes in rat, human, and mouse suggest that the class I gene-containing region was inserted between these genes in rat and mouse at a similar position. Thus, this insertion is likely to have occurred in a common ancestor of these rodents, although the presence of a site particularly permissive for insertions cannot be excluded.

Animals↗
PubMed2000

Tissue transglutaminase in the small intestine of the mouse as a marker for apoptotic cells. Colocalization with DNA fragmentation.

Besides the morphological changes in cells undergoing apoptosis, such as chromatin condensation and cell shrinkage, histological demonstration of DNA fragmentation by in situ end labeling (ISEL) has been widely used for the demonstration of apoptotic cells in tissue sections. Although DNA fragmentation can be demonstrated in apoptotic cells and apoptotic bodies in most cases, there is no clear correlation of ISEL staining with apoptosis. It has often been demonstrated that, in many morphologically intact cells, nuclei with fragmented DNA can be found. Thus staining with ISEL for the detection of apoptosis is useful only in connection with other markers for apoptosis as, for example, characteristic morphological changes. Here we show that tissue transglutaminase protein is unequivocally expressed in apoptotic enterocytes as shown by DNA fragmentation and morphology. Tissue transglutaminase is not expressed in enterocytes with healthy morphology, although DNA fragmentation can be demonstrated in these cells. Thus the immunohistochemical demonstration of tissue transglutaminase may serve as a simple marker for apoptotic epithelial cells in tissue sections.

Animals↗
PubMed2000

Psychotherapy of panic syndrome: focusing on ecological aspects of relationships.

Cognitive Behavioral Therapy (CBT) has been shown to be an effective symptomatic treatment for panic attacks; however, this paper recommends complementing it with an approach based on an interactive ecological model. The approach is based on the thesis that a panic syndrome can occur if patients block an impending and/or already initiated development of their relationships, especially involving partners or work. The case may be that, over a period of years, phobic attitudes and behavior described further in the text have enabled patients to maintain a socially positive shaping of their personal niches. Later, phobic avoidance behavior is no longer adequate due to the requirements of the new stage of life. Unconsciously, patients configure an outer relationship situation that demands of them the realization of the impending step in development. Therapy should utilize this relationship configuration.

Adult↗
PubMed2000

Hearing threshold and frequency discrimination in the purely aquatic frog Xenopus laevis (Pipidae): measurement by means of conditioning.

Hearing threshold and frequency discrimination for underwater sound were measured in the clawed frog Xenopus laevis by means of conditioning. A go/no go discrimination procedure was used in which the test tone was presented concurrently with a wave on the surface of the water. The tone signalled whether or not the frog should respond to the wave. The hearing range of X. laevis was 200-4000 Hz. Similar thresholds of 92-96 dB re 1 microPa were found at 600 Hz, 1400-1800 Hz and 3200-3600 Hz. A high threshold at 1000-1300 Hz suggested that this was the frequency range between the sensitivities of the amphibian and basilar papillae. Relative frequency discrimination was approximately 5 % at 400-800 Hz, 45 % at 1000 Hz and 2.4-6 % at 1600-2500 Hz. This last range encompasses the dominant frequencies of the advertisement call of this species. High discrimination acuity at these frequencies may be used in distinguishing between calling males. The threshold for a one-third-octave bandpass noise centred at 600 Hz was 27.6 dB lower than that for a pure tone of 600 Hz, suggesting that sound intensity was integrated within this bandwidth, possibly by a critical-band mechanism.

Animals↗
PubMed1999

Heat-induced expression of MHC-linked HSP70 genes in lymphocytes varies at the single-cell level.

The expression of MHC-linked heat shock protein 70 (HSP70) genes HSP70-1 and HSP70-2 has been studied in human and rat lymphocytes and Concanavalin A (con A)-induced lymphoblasts by in situ hybridization and flow cytometry. In in vitro experiments transcripts of these genes were observed only after heat shock, and mitogen stimulation per se did not lead to induction. Heat shock-induced expression of HSP70-1 and HSP70-2 mRNA varied at the single-cell level. The fraction of HSP70-positive lymphocytes increased continuously with the severity of heat shock. However, 15-35% of the cells always remained HSP70 transcript negative. After fever induction in vivo similar variation of HSP70-1 and HSP70-2 mRNA expression could also be observed. Analysis of heat shocked lymphocytes by flow cytometry demonstrated that HSP70 induction varied also at the protein level, a fraction of cells always remaining unresponsive. Thus, HSP70 induction does not appear to occur in each cell and to a similar extent when a given cell population is exposed to the same stress.

Animals↗
PubMed1999

New N-(pyridin-4-yl)-(indol-3-yl)acetamides and propanamides as antiallergic agents.

A series of new N-(pyridin-4-yl)-(indol-3-yl)alkylamides 44-84 has been prepared in the search of novel antiallergic compounds. Synthesis of the desired ethyl (2-methyindol-3-yl)acetates 1-4 was achieved by indolization under Fischer conditions; Japp-Klingemann method followed by 2-decarboxylation afforded the ethyl (indol-3-yl)alkanoates 17-25. Amidification was successfully carried out by condensation of the corresponding acids or their N-aryl(methyl) derivatives with 4-aminopyridine promoted by 2-chloro-1-methylpyridinium iodide. Efforts to improve the antiallergic potency of the title series by variation of the indole substituents (R1, R2, R) and the length of the alkanoic chain (n = 1, 2, 3) led to the selection of N-(pyridin-4-yl)-[1-(4-fluorobenzyl)indol-3-yl]acetamide 45, out of 41 compounds. This amide was 406-fold more potent than astemizole in the ovalbumin-induced histamine release assay, using guinea pig peritoneal mast cells, with an IC50 = 0.016 microM. Its inhibitory activity in IL-4 production test from Th-2 cells was identical to that of the reference histamine antagonist (IC50 = 8.0 microM) and twice higher in IL-5 assay: IC50 = 1.5 and 3.3 microM, respectively. In vivo antiallergic activity evaluation confirmed efficiency of 45 in sensitized guinea pig late phase eosinophilia inhibition, after parenteral and oral administration at 5 and 30 mg/kg, respectively. Its efficiency in inhibition of microvascular permeability was assessed in two rhinitis models; ovalbumin and capsaicin-induced rhinorrhea could be prevented after topical application of submicromolar concentrations of 45 (IC50 = 0.25 and 0.30 microM); and it also exerted significant inhibitory effect in the first test after iv and oral administration, with ID50 = 0.005 and 0.46 mg/kg.

Acetylcholine↗
PubMed1999

Enhanced susceptibility to cytotoxic T lymphocytes without increase of MHC class I antigen expression after conditional overexpression of heat shock protein 70 in target cells.

Antigenic peptides have been found associated with heat shock proteins (HSP) including cytoplasmic HSP70 and heat shock cognate protein 70 as well as the endoplasmic reticulum-resident glucose-regulated protein 94. Recently, HSP70 transfection has been reported to increase MHC class I cell surface expression and antigen presentation on mouse melanoma B16 cells (Wells et al., Int. Immunol. 1998. 10: 609). To analyze the effect of HSP70 on MHC class I cell surface expression and lysability of target cells we transfected a human melanoma cell line with the rat Hsp70-1 gene using the Tet-On system for conditional overexpression of HSP70. Induction of HSP70 did not increase cell surface expression of HLA class I molecules in general or individual HLA-A and B antigens in particular. Nonetheless, induction of HSP70 enhanced susceptibility of these cells to lysis by allospecific CTL. The same effect was observed using an HLA-A2-restricted tyrosinase-specific CTL clone after pulsing the tyrosinase-negative target cells with the specific peptide. Thus, HSP70 induction can increase killing by CTL without affecting MHC class I cell surface expression or antigen processing. This effect of HSP70 appears to be different from the commonly found protection exerted by HSP70 against stress like heat shock, and might be mediated by improving CTL-induced apoptosis.

Animals↗