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Biomedical subjects

A Meister

Publications and source records attributed to A Meister.

At least 19 recordsLinked to original sources
PubMed2004

DNA damage processing and aberration formation in plants.

Various types of DNA damage, induced by endo- and exogenous genotoxic impacts, may become processed into structural chromosome changes such as sister chromatid exchanges (SCEs) and chromosomal aberrations. Chromosomal aberrations occur preferentially within heterochromatic regions composed mainly of repetitive sequences. Most of the preclastogenic damage is correctly repaired by different repair mechanisms. For instance, after N-methyl-N-nitrosourea treatment one SCE is formed per >40,000 and one chromatid-type aberration per approximately 25 million primarily induced O6-methylguanine residues in Vicia faba. Double-strand breaks (DSBs) apparently represent the critical lesions for the generation of chromosome structural changes by erroneous reciprocal recombination repair. Usually two DSBs have to interact in cis or trans to form a chromosomal aberration. Indirect evidence is at hand for plants indicating that chromatid-type aberrations mediated by S phase-dependent mutagens are generated by post-replication (mis)repair of DSBs resulting from (rare) interference of repair and replication processes at the sites of lesions, mainly within repetitive sequences of heterochromatic regions. The proportion of DSBs yielding structural changes via misrepair has still to be established when DSBs, induced at predetermined positions, can be quantified and related to the number of SCEs and chromosomal aberrations that appear at these loci after DSB induction. Recording the degree of association of homologous chromosome territories (by chromosome painting) and of punctual homologous pairing frequency along these territories during and after mutagen treatment of wild-type versus hyperrecombination mutants of Arabidopsis thaliana, it will be elucidated as to what extent the interphase arrangement of chromosome territories becomes modified by critical lesions and contributes to homologous reciprocal recombination. This paper reviews the state of the art with respect to DNA damage processing in the course of aberration formation and the interphase arrangement of homologous chromosome territories as a structural prerequisite for homologous rearrangements in plants.

Arabidopsis↗
PubMed2002

Whole blood impedance aggregometry for the assessment of platelet function in patients with congestive heart failure (EPCOT Trial).

OBJECTIVE: Data from small studies have shown the presence of platelet abnormalities in patients with congestive heart failure (CHF). We sought to characterize the diagnostic utility of the whole blood aggregometry (WBA) in a random outpatient CHF population. METHODS: Blood samples were obtained for measurement of whole blood aggregation, shear-induced closure time, platelet contractile force, expression of GP IIb/IIIa, and P-selectin in 100 consecutive patients with CHF. RESULTS: Substantial inter-individual variability of platelet characteristics exists in patients with CHF. There were no statistically significant differences when patients were divided by the incidence of vascular events, emergency revascularization needs, survival, or etiology of heart failure. Surprisingly, aspirin use did not affect instrument readings as well. Whole blood aggregometry correlates well with the closure time (r(2)=0.587), and with GP IIb/IIIa expression (r(2)=0.435). Significant but less strong correlation has been observed for the WBA with platelet P-selectin expression (r(2)=0.295), and no correlation was present for the platelet contractile force measures (r(2)=0.030). CONCLUSIONS: Despite the fact that patients with heart failure enrolled in the EPCOT trial exhibited marginal, sometimes oppositely directed changes, in their platelet characteristics, whole blood impedance aggregometry is indeed capable to serve as a valuable diagnostic tool, and may be successfully used as an established screening device in this population. Ability of the whole blood aggregometry to predict clinical outcomes, or for the monitoring of anti-platelet agents in CHF patients, will be evaluated in the ongoing clinical trials.

Aged↗
PubMed2002

Proliferation of glial cells induced by lithium in the neural lobe of the rat pituitary is enhanced by dehydration.

Rats dehydrated by 6 days of water deprivation had a low level of mitotic activity in the astrocytes ('pituicytes') of the neural lobe of the pituitary. Mitotic activity in the pituicytes was greatly increased when isotonic lithium was administered in the last 3 days of water deprivation. Rehydration on the last day of the experiment produced a further increase in mitoses. Isotonic solutions of sodium, potassium or rubidium chloride did not increase mitoses. This model of cell proliferation is of interest because the mitotic activity is related to a physiological attempt to maintain homeostasis rather than a response to injury or the development of neoplasia.

Animals↗
PubMed2001

Chromatin organization and its relation to replication and histone acetylation during the cell cycle in barley.

We have studied the replication time, nuclear organization and histone acetylation patterns of distinct chromatin domains [nucleolus organizers (NORs), centromeres, euchromatin and heterochromatin] of barley during the cell cycle. The Rabl orientation of chromosomes, with centromeres and telomeres located at opposite nuclear poles, was found to be maintained throughout interphase. Replication started at the rDNA loci within nucleoli and then proceeded from the euchromatic distal chromosome regions toward the heterochromatic pole. Centromere association frequently occurred in mid- and late S-phase, i.e., during and after centromere replication. Euchromatin, centromeres and heterochromatin were found to be enriched in acetylated histone H4 (except for lysine 16) during their replication; then deacetylation occurred. The level of deacetylation of H4 in heterochromatin was more pronounced than in euchromatin. Deacetylation is finished in early G2-phase (lysine 8) or may last until mitosis or even the next G1-phase (lysines 5 and 12). The NORs were found to be most strongly acetylated at lysines 5 and 12 of H4 during mitosis, independently of their potential activity in nucleolus formation and rDNA transcription. The acetylation pattern of chromosomal histone H3 was characterized by low acetylation intensity at centromeres (lysines 9/18) and pericentromeric regions (lysine 14) and more intense uniform acetylation of the remaining chromatin; it remained fairly constant throughout the cell cycle. These results have been compared with the corresponding data published for mammals and for the dicot Vicia faba. This revealed conserved features as well as plant- or species-specific peculiarities. In particular, the connection of acetylation intensity of H4 at microscopically identifiable chromatin domains with replicational but not with transcriptional activity during the cell cycle seems to be conserved among eukaryotes.

Acetylation↗
PubMed2001

Reconstruction of reproductive diversity in Hypericum perforatum L. opens novel strategies to manage apomixis.

The mode of reproduction was characterized for 113 accessions of the tetraploid facultative apomictic species Hypericum perforatum using bulked or single mature seeds in the flow cytometric seed screen (FCSS). This screen discriminates several processes of sexual or asexual reproduction based on DNA contents of embryo and endosperm nuclei. Seed formation in H. perforatum proved to be highly polymorphic. Eleven different routes of reproduction were determined. For the first time, individual seeds were identified that originated from two embryo sacs: the endosperm from an aposporous and the embryo from the legitimate meiotic embryo sac. Moreover, diploid plants were discovered, which apparently reproduce by a hitherto unknown route of seed formation, that is chromosome doubling within aposporous initial cells followed by double fertilization. Although most plants were tetraploid and facultative sexual/apomictic, diploid obligate sexuals and tetraploid obligate apomicts could be selected. Additionally, genotypes were detected which at a high frequency produced embryos either from reduced parthenogenetic or unreduced fertilized egg cells. The endosperm developed most frequently after fertilization of the central cell in aposporous embryo sacs (pseudogamy) but in few cases also autonomously. The genetic control of apomixis appears to be complex in H. perforatum. Basic material was developed for breeding H. perforatum, and strategies are suggested for elucidation of inheritance as well as evolution of apomixis and for molecular approaches of apomixis engineering.

Flow Cytometry↗
PubMed2000

Pertussis vaccine and pertussis toxin increase lithium levels in rats: possible role of G-proteins.

A single dose of lithium was injected intravenously or intraperitoneally in rats. Lithium levels in serum and tissues 5 or 24 hours later were elevated when the rats were pretreated with pertussis vaccine (PV). The vaccine was effective whether given locally (subcutaneous) or systemically (intravenous). Tests of heated (inactivated) PV suggested that pertussis toxin might be responsible for the effects of PV. Injection of purified pertussis toxin (PT) confirmed this suggestion. Elevation of serum urea nitrogen suggested that lithium levels were increased because the combination of PV or PT with lithium reduced renal excretory function which could cause retention of lithium. Inasmuch as PV and PT are known to inactivate the inhibitory G-proteins, these data suggest G-protein involvement in the elevation of lithium levels by PV and PT.

Animals↗
PubMed2000

An efficient screen for reproductive pathways using mature seeds of monocots and dicots.

Seed samples of 32 species (obligate and facultative sexuals and apomicts of monocots and dicots) were investigated by flow cytometry to reveal the pathway of reproduction. Ten different pathways of seed formation could be reconstructed considering whether the female and/or male gametes were reduced or unreduced, the embryos arose via the zygotic or parthenogenetic route and the endosperm via the pseudogamous or autonomous route. The screen is suited to select sporophytic or gametophytic mutants in sexual species, to identify pure sexual or obligate apomictic genotypes from facultative apomictic species, and to analyze the inheritance of the individual reproductive processes. Corresponding unique results are presented for Arabidopsis, Arabis, Hypericum and Poa. The screen of mature seeds by flow cytometry yielded more information about the reproductive behavior of individual plants than any other available test, and is very useful both in basic research and plant breeding.

Plant Physiological Phenomena↗
PubMed2000

[Radiotherapy for choroidal neovascularization (CNV) in age-related macular degeneration (AMD)].

AIM OF THE STUDY: Several pilot studies have indicated, that radiation therapy might have a beneficial effect on the course of CNV in AMD. This controlled study was aimed at the question, whether such treatment might halt progression of neovascular AMD and whether a low or a high radiation dose should be applied. METHODS AND PATIENTS: Enclosed were patients aged > or = 60 and < or = 85 and eyes with a VA of > or = 0.1 and < or = 0.6, revealing a juxta/subfoveal CNV either of the occult or the classic type. Treatment was performed with a linear accelerator at fractions of 2 Gy up to a total dose of 10 Gy or 36 Gy. 95 eyes had completed follow-up of > or = 12 < or = 24 months. RESULTS: Among eyes with occult CNV 8 received 36 Gy, 16 were treated with 10 Gy and 21 were in the control group. Mean visual loss was 3.5 lines after 12 months and 5 lines after 24 months with no difference between irradiated eyes and those in the control group. In the groups with classic CNV 8 eyes were treated with 36 Gy, 27 eyes received 10 Gy and 15 eyes were in the control group. Mean visual loss after 6 months was 2.2 lines in eyes of both groups treated with radiation and 5.7 lines in the control group. This was statistically significant (p < 0.05). VA was < 0.1 after 12 (24) months of follow-up in 50 (75)% of the cases with 36 Gy, in 48 (83)% with 10 Gy and in 60 (83)% of the controls. These results were statistically significant after 12 months only. DISCUSSION AND CONCLUSIONS: The natural course of occult CNV could not be improved by irradiation with 10 or 36 Gy. In eyes with classic CNV a VA of > or = 0.1 was maintained significantly more often in irradiated eyes than in those of the control group. Treatment with 36 Gy however was associated with an unacceptable incidence of radiation retinopathy.

Aged↗
PubMed2000

Cytologically integrated physical restriction fragment length polymorphism maps for the barley genome based on translocation breakpoints.

We have developed a new technique for the physical mapping of barley chromosomes using microdissected translocation chromosomes for PCR with sequence-tagged site primers derived from >300 genetically mapped RFLP probes. The positions of 240 translocation breakpoints were integrated as physical landmarks into linkage maps of the seven barley chromosomes. This strategy proved to be highly efficient in relating physical to genetic distances. A very heterogeneous distribution of recombination rates was found along individual chromosomes. Recombination is mainly confined to a few relatively small areas spaced by large segments in which recombination is severely suppressed. The regions of highest recombination frequency (</=1 Mb/cM) correspond to only 4.9% of the total barley genome and harbor 47.3% of the 429 markers of the studied RFLP map. The results for barley correspond well with those obtained by deletion mapping in wheat. This indicates that chromosomal regions characterized by similar recombination frequencies and marker densities are highly conserved between the genomes of barley and wheat. The findings for barley support the conclusions drawn from deletion mapping in wheat that for all plant genomes, notwithstanding their size, the marker-rich regions are all of similar gene density and recombination activity and, therefore, should be equally accessible to map-based cloning.

Chromosome Mapping↗
PubMed2000

N-Methyl-N-nitrosourea-induced DNA damage detected by the comet assay in Vicia faba nuclei during all interphase stages is not restricted to chromatid aberration hot spots.

The genotoxic effect of the monofunctional alkylating agent N:-methyl-N:-nitrosourea (MNU) on root-tip nuclei of the field bean, Vicia faba, has been tested by comparative application of three protocols of the comet assay. While the alkaline denaturation/alkaline electrophoresis (A/A) procedure proved to be most sensitive at low doses, the alkaline denaturation/neutral electrophoresis (A/N) procedure yielded an optimal dose-response curve within a wider dose range. With the neutral electrophoresis without alkaline denaturation (N/N) procedure only minimal response was found. MNU-mediated single-strand breaks occurred in nuclei of all interphase stages. Detection of tandemly repeated FOK:I elements on comets by fluorescence in situ hybridization showed an average involvement of these heterochromatin-specific sequences in MNU-mediated single-strand breaks. This, together with previous results, suggests that the pronounced clustering of chromosomal aberrations in heterochromatic regions after treatment with S phase-dependent mutagens is mainly due to an error-prone interference of recombinative repair and replication in damaged basic repeats of large tandem repeat arrays.

Alkylating Agents↗
PubMed2000

Histone H4 acetylation of euchromatin and heterochromatin is cell cycle dependent and correlated with replication rather than with transcription.

Reversible acetylation of nucleosomal histones H3 and H4 generally is believed to be correlated with potential transcriptional activity of eukaryotic chromatin domains. Here, we report that the extent of H4 acetylation within euchromatin and heterochromatic domains is linked with DNA replication rather than with transcriptional activity, whereas H3 acetylation remains fairly constant throughout the cell cycle. Compared with euchromatin, plant nucleolus organizers were more strongly acetylated at H4 during mitosis but less acetylated during S phase, when the nucleolus appeared to be (at least transiently) devoid of nucleosomes. Deposition-related acetylation of lysines 5 and 12 of H4 seems to be conserved in animals and plants and extended to K16 in plants. A possibly species-specific above-average acetylation at lysines 9/18 and 14 of H3 appeared in 4',6-diamidino-2-phenylindole (DAPI)-stained heterochromatin fractions. These results were obtained by combining immunodetection of all acetylatable isoforms of H3 and H4 on mitotic chromosomes and nuclei in G1, early S, mid-S, late S, and G2 phases of the field bean with identification of specific chromatin domains by fluorescence in situ hybridization or DAPI staining. In addition, the histone acetylation patterns of distinct domains were compared with their replication and transcription patterns.

Acetylation↗
PubMed2000

DNA content, rDNA loci, and DAPI bands reflect the phylogenetic distance between Lathyrus species.

The nuclear DNA content, the proportion of A+T base pairs, the chromosomal positions of 5S and 25S rRNA genes, as well as of DAPI (4,6-diamidino-2-phenylindole) bands are described for seven species belonging to three different sections of the genus Lathyrus. These data and chromosome measurements allowed to establish precise idiograms and to discriminate most of the chromosome pairs of the seven species. The karyotypic features correlate well with the phylogenetic distances between these species.

Chromosome Banding↗
PubMed1999

Quality of life in patients cured from a carcinoma of the head and neck by radiotherapy: the importance of the target volume.

PURPOSE: To assess the health-related quality of life (QOL) of long-term survivors of carcinomas of different subsites of the head and neck following curative radiotherapy (RT). PATIENTS AND METHODS: Patients continuously free from recurrence or second primary tumors treated 1988-1994 were contacted 5.1 to 5.9 years after RT and asked to fill in the EORTC QLQ-C30 core questionnaire and the H&N cancer module. RT had been restricted to the glottis (group A; carcinomas of the vocal cord T1-2 N0), or had included bilateral neck nodes and the primary tumor outside the nasopharynx (group B; AJC Stage II to IV) or within the nasopharynx, respectively (group C; Stage II to IV). Response rate was 97% (group A; n = 41), 69% (group B; n = 26) and 71% (group C; n = 12), respectively. The groups were different with respect to age (older in group A), alcohol consumption (absent in group C) and proportion of females (more in group C). RESULTS: Patients with nasopharyngeal cancer reported the highest morbidity on the H&N module (dry mouth, sticky saliva, trismus, problems with teeth, trouble eating). However, these symptoms did not have a high impact on global QOL or function scores on the QLQ-C30 core questionnaire. Patients in group B reported a lower global QOL but less severe symptoms on the module. CONCLUSION: The high morbidity of patients treated for a nasopharyngeal cancer may be explained by the location of the target volume which included the bilateral temporo-mandibular joints and the salivary glands. These patients require appropriate care during follow-up and will probably profit most from new RT techniques with sparing of normal tissues.

Aged↗
PubMed1999

The crystal structure of plasminogen activator inhibitor 2 at 2.0 A resolution: implications for serpin function.

BACKGROUND: Plasminogen activator inhibitor 2 (PAI-2) is a member of the serpin family of protease inhibitors that function via a dramatic structural change from a native, stressed state to a relaxed form. This transition is mediated by a segment of the serpin termed the reactive centre loop (RCL); the RCL is cleaved on interaction with the protease and becomes inserted into betasheet A of the serpin. Major questions remain as to what factors facilitate this transition and how they relate to protease inhibition. RESULTS: The crystal structure of a mutant form of human PAI-2 in the stressed state has been determined at 2.0 A resolution. The RCL is completely disordered in the structure. An examination of polar residues that are highly conserved across all serpins identifies functionally important regions. A buried polar cluster beneath betasheet A (the so-called 'shutter' region) is found to stabilise both the stressed and relaxed forms via a rearrangement of hydrogen bonds. CONCLUSIONS: A statistical analysis of interstrand interactions indicated that the shutter region can be used to discriminate between inhibitory and non-inhibitory serpins. This analysis implied that insertion of the RCL into betasheet A up to residue P8 is important for protease inhibition and hence the structure of the complex formed between the serpin and the target protease.

Amino Acid Sequence↗
PubMed1999

Antispasmodic activity of Thymus vulgaris extract on the isolated guinea-pig trachea: discrimination between drug and ethanol effects.

The effect of an extract of Thymus vulgaris on induced spasms was investigated on guinea-pig trachea preparations. By the experimental setup used, effects of ethanol as the vehicle could be differentiated from the activity of the herbal constituents. The extract reversibly and concentration-dependently antagonized the contraction of the Musculus transversus tracheae, provoked by four different spasmogens (BaCl2, carbachol, histamine, prostaglandin F2 alpha). The degree of the antispasmodic activity was dependent on the individual spasmogen with prostaglandin F2 alpha being most efficiently antagonized.

Animals↗
PubMed1998

Prevention of lithium nephrotoxicity in a novel one-hour model in rats.

It is well established that lithium can cause morphologically visible damage to the kidneys of humans and animals. Although the clinical significance of its nephrotoxicity is debatable, it would be desirable to find a method to prevent lithium's effect on the kidneys. Toward this end, we have developed a novel method for producing nephrotoxicity that will be useful for research on prevention. A single, large, toxic dose of lithium chloride (LiCl) caused necrosis of the distal convoluted tubules, which was visible by light microscopy in 30 min, had fully developed in 1 h, and had disappeared by the next day. The lesions were seen after i.p. or i.v. injections of fasted rats of three different strains. Equivalent doses of NaCl, KCl, MgCl2 and combinations thereof had no such effect, nor did they inhibit nephrotoxicity when incorporated into the LiCl solution. However, relatively small doses of LiCl injected by any route 3 or 24 h beforehand prevented the nephrotoxicity. The mechanism of prevention is not known, but it does not involve reduction of lithium levels in the kidneys.

Animals↗