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Biomedical subjects

T Koller

Publications and source records attributed to T Koller.

At least 19 recordsLinked to original sources

[Reoperations after LASIK].

BACKGROUND: Repeat operations after refractive surgery have increased in frequency during the past 10 years. The spectrum of the indications for repeat LASIK may have changed. METHODS: All cases of repeat operations after refractive surgery performed between May 1, 2004 and April 30, 2005 at the Institute of Refractive and Ophthalmic Surgery (IROC) were retrospectively investigated regarding indication for repeat surgery and visual and refractive results. The 1-month results were used to estimate the refractive and visual success rate. RESULTS: Of the 76 reoperations, 69 were performed as re-lifts, 3 eyes had new lamellae cut, and 3 cases needed keratoplasties. The reoperations took place 7.5 +/- 13 months after the primary operation (range 0.5 to 60 months). The most frequent indication was residual astigmatism of 0.5 D and more. Visual loss of more than 1 decimal line did not occur and unaided visual acuity increased from 0.64 to 1.05. No complications were reported, however, 3 eyes needed additional enhancement. CONCLUSIONS: Reoperations after LASIK performed as re-lifts appear to be effective and reasonably safe when using the technique described and respecting a residual stromal thickness of 280 microns.

Comorbidity↗

[Asphericity of the cornea and astigmatism].

BACKGROUND: Regarding astigmatism of the cornea, curvature as well as asphericity depend on the meridional axis. Their functional dependence and relation to the quality of the retinal image are still unclear. METHODS: The astigmatic eye was modelled using a biconoid anterior corneal surface by means of a commercially available optical designer programme (Zemax EE, Zemax). The influence of asphericity and astigmatism on the quality of the retinal image was determined by means of ray tracing. Thirty eyes with astigmatism of up to 5.3 D underwent corneal topography (Keratograph C, Oculus) which allowed a numerical evaluation of the cylindric power as well as the asphericity in the main meridians. RESULTS: The quality of the retinal image of an eye with corneal astigmatism can be improved by a factor of 2.28 if the asphericity is optimised. Correction of the central astigmatism only (without considering asphericity) yields only a rather marginal improvement. The average difference of the asphericity in the main meridians is close to zero, however, the individual difference ranges from - 0.372 to + 0.444 which is definitely clinically relevant. CONCLUSIONS: Anisotropic asphericity of the cornea may significantly enhance or compensate central corneal astigmatism. Clinically manifest astigmatism is an individually variable combination of asphericity and curvature difference in the two main meridians and is dependent on the pupil size. Laser correction of corneal astigmatism must take meridional asphericity into account.

Astigmatism↗

Air pollutants enhance rhinoconjunctivitis symptoms in pollen-allergic individuals.

BACKGROUND: Little is know about the relation of airborne pollen allergens to nasal and ocular symptoms in combination with air pollutants. OBJECTIVE: The hypothesis was that air pollutants exacerbate allergic symptoms of the nose and eyes during the pollen season. In addition, the use of allergen measurements instead of pollen counts should be tested. METHODS: Fifteen pollen-allergic, nonsmoking subjects with weak reactivity of the airways recorded rhinoconjunctival symptoms and medication every morning and evening throughout the pollen season. Symptoms were compared with air pollutants (nitrogen oxide [NOx], particulate matter smaller than 10 microm, and ozone) and birch and grass pollen counts or, alternatively, to airborne birch and grass allergens determined using ELISA-techniques. A multiple linear regression model was used which controlled for autocorrelation of the residuals of the time series (Cochrane-Orcutt approach). This model was applied to each subject individually, followed by calculations of summary scores for the group. RESULTS: Air pollution levels were moderate, often meeting air quality standards. Effect estimates (increase of score with 10-fold increase of concentration) were NOx = 1.06, P < 0.01; ozone = 1.59, P < 0.01; and pollen = 0.48, P < 0.001. Using allergen concentrations instead of pollen counts resulted in similar effect estimates. Using particulate matter smaller than 10 microm instead of NOx gave comparable but less consistent results. CONCLUSIONS: Symptoms were related to moderate levels of pollutants, suggesting that rhinoconjunctival tissue is very sensitive to irritant stimuli during an ongoing allergic inflammation, and that susceptibility toward allergens might be increased in areas with increased levels of air pollutants. Allergen measurements seem equally usable as pollen counts to investigate rhinoconjunctivitis.

Adult↗

Acute sensory responses of nonsmokers at very low environmental tobacco smoke concentrations in controlled laboratory settings.

The objective of this study was to provide a basis for effectively protecting nonsmokers from acute sensory impacts and for preventing deterioration of indoor air quality caused by environmental tobacco smoke (ETS) emissions. With an olfactory experiment we determined odor detection thresholds (OT) of sidestream ETS (sETS), and with a full-body exposure experiment we investigated sensory symptoms at very low sETS exposure concentrations. OT concentrations for sETS are three and more orders of magnitude lower than ETS concentrations measured in field settings and correspond to a fresh air dilution volume of > 19,000 m(3) per cigarette, over 100 times more than had previously been suggested for acceptable indoor air conditions. Eye and nasal irritations were observed at one order of magnitude lower sETS concentrations than previously reported, corresponding to a fresh air dilution volume of > 3,000 m(3) per cigarette. These findings have great practical implications for defining indoor air quality standards in indoor compartments where ETS emissions occur. Our study strongly supports the implementation and control of smoking policies such as segregating smoking areas from areas where smoking is not permitted or instituting smoking bans in public buildings.

Adolescent↗

An assessment of indoor air contaminants in buildings with recreational activity.

Indoor air quality measurements were carried out during three concerts and one ice hockey game in three different halls. Gas phase components consisted of CO2, CO, and NO whereas for particulate indicators, measurements of particle mass distributions (0.05-9 microm), particle number distributions (0.75-10 microm), and particle bound polycyclic aromatic hydrocarbons (pPAH) were carried out. The calculated ventilation rates did not meet the ventilation requirements for rooms with occupants who smoke to be perceived as acceptable by 80% of the occupants. Average PM9 (mass of particulate matter with an aerodynamic diameter < 9 microm) concentrations throughout the events ranged from 318 to 2000 microg m(-3). Particle concentrations in the size range < 0.4 microm measured 203-696 microg m(-3), the majority of it being attributed to environmental tobacco smoke (ETS). For particle numbers > 0.75 microm concentrations ranged from 2 x 10(4) to 1.9 x 10(5) particles per l while for pPAH, concentrations from 336 to 990 ng m(-3) were observed. The average event concentrations for the gaseous component CO2 ranged from 1110 to 1700 ppm, for CO 2-3.1 ppm and for NOx 237 ppb. The event to baseline concentration ratios for gaseous components ranged from 1.1 to 4.3 while for particulate indicators generally much greater ratios between 0.7 and 140 were found. Possible health effects inflicted by an exposure based on the measured concentrations of the various parameters are discussed.

Air Pollutants↗

Differences in size selective aerosol sampling for pollen allergen detection using high-volume cascade impactors.

BACKGROUND: Assessment of the allergen content of airborne particles small enough to reach the bronchiolar airways is important for a better understanding of allergic asthma. OBJECTIVE: In order to test the performance of a high-volume cascade impactor for size-selective sampling of airborne particles, the characteristics of pollen deposition, and the particle size-dependent allergen distribution, were re-examined. METHODS: Two cascade impactors with rectangular slots were run in parallel, one with glass fibre filters on all stages, the other with silicone grease on stage 2 (collection of particles of size 4.2-10.2 micrometer) instead. Pollen was counted using light microscopy and allergens were measured using ELISA techniques. RESULTS: In the impactor without the greased stage 2, a heavy bounce and blow-off for pollen was found. Bounced pollen was deposited mainly on the back-up filter, the sampling stage for particles smaller than 1.4 micrometer. However, if stage 2 was coated with silicone grease, less than 1% of total pollen was found in the lower stages. On the first stage of the sampler (50% cut-point, 10.2 micrometer) where all pollen should impact, pollen had a deposition efficiency of only 24-47%, depending on the abundant pollen species. Much less allergen was found in fine particle fractions than in previous studies in which particles were sampled with similar samplers but without grease as a pollen trap. CONCLUSIONS: The observed bounce and blow-off of pollen without a greased stage 2 leads to serious mistakes when assessing the allergen content of the fractions collecting particles smaller than intact pollen, i.e., below 10.2 micrometer. Pollen allergen concentrations in respirable particle fractions are much lower than in the pollen size fraction. This is of great importance both for symptoms of sensitized allergic asthmatics and for research of asthma-related mechanisms.

Aerosols↗

Membrane formation in the chamber angle after failure of argon laser trabeculoplasty: analysis of risk factors.

AIM: Membrane formation in the chamber angle induced by argon laser trabeculoplasty (ALT) can be a cause of treatment failure. Identification of risk factors for membrane formation was the primary aim of this retrospective study. METHODS: Semithin sections of trabeculectomy specimens obtained in a 2 year period were examined by light microscopy. 122 eyes which were treated with one or more ALTs before trabeculectomy were identified. In 46 eyes, a sufficient amount of trabecular meshwork was obtained to permit morphological analysis. RESULTS: Eyes treated with ALT had a significantly higher incidence of membrane formation (p=0.001). In 23/46 specimens a cellular and collagenous membrane was observed covering the entire trabecular meshwork. In 14/23 specimens (61%), this membrane was readily visible at low power magnification (x40). Comparison of these eyes with those without membrane formation revealed a significant difference in the number of ALTs (mean 2.07 (SD 0.73) v 1.48 (0.59); p=0.026) and in preoperative IOP (32.0 (9. 7) v 26.2 (8.4) mm Hg; p=0.04). CONCLUSIONS: Membrane formation in the chamber angle is a frequent cause of ALT failure. The major risk factor is the number of ALTs performed.

Aged↗

Asymmetry of Dam remethylation on the leading and lagging arms of plasmid replicative intermediates.

In Escherichia coli, adenine methylation at the sequence GATC allows coupling of cellular processes to chromosome replication and the cell cycle. The transient presence of hemimethylated DNA after replication facilitates post-replicative mismatch repair, induces transcription of some genes and allows transposition of mobile elements. We were interested in estimating the half-life of hemimethylated DNA behind the replication fork in plasmid molecules and in determining whether Dam methyltransferase restores N6 adenine methylation simultaneously on both replicative arms. We show that remethylation takes place asynchronously on the leading and lagging daughter strands shortly after replication. On the leading arm the fully methylated adenine is restored approximately 2000 bp (corresponding to 2 s) behind the replication fork, while remethylation takes twice as long (at 3500-4000 bp or approximately 3.5-4 s) on the lagging replicative arm. This observation suggests that Dam remethylation of the lagging arm requires ligated Okazaki fragments.

Cell Cycle↗

Primary DNA damage but not mutagenicity correlates with ciprofloxacin concentrations in German hospital wastewaters.

Recently, we showed for the wastewater of a large Swiss university hospital that primary DNA damage, assessed by a bacterial SOS repair assay (umuC test), could be largely assigned to a specific class of antibiotics, the fluoroquinolones (FQs) (Hartmann et al. [1998] Environ Toxicol Chem 17:377-382). In an attempt to confirm the significance of FQs for the bacterial DNA damaging effects in native hospital wastewaters, 25 samples from five German clinics were screened in this study by the umuC test. The results were compared to HPLC-derived concentrations of ciprofloxacin, an important member of the FQs. Ten samples (40%) were umuC-positive and ciprofloxacin concentrations ranged from 0.7 to 124.5 microg/L (n = 24). Primary DNA damage, as indicated by the umuC test, correlated strongly with ciprofloxacin concentrations in a logistic, dose-dependent manner (r2 = 0.896), almost irrespective of the use of S9 metabolic activation. The lowest observed effect concentration (LOEC) for ciprofloxacin was 5.2 microg/L (+S9) and 5.9 microg/L (-S9). Similar to our previous findings, these results indicate that positive umuC results in hospital wastewater are strongly dependent on the presence of fluoroquinolone antibiotics. In a second part of the study, previously generated Ames and V79 chromosomal aberration data of the same samples (Gartiser and Brinker [1995] in Umweltbundesamt Texte 74/95) were compared with the newly generated results. Neither the mutagenic effects detected by the Ames assay (8%, n = 25) nor the positive V79 results (46% n = 13) seemed to be caused by ciprofloxacin. Therefore, the Ames and V79 results suggest the presence of additional mutagens that are yet to be identified.

Animals↗

Transcriptional activity and chromatin structure of enhancer-deleted rRNA genes in Saccharomyces cerevisiae.

We used the psoralen gel retardation assay and Northern blot analysis in an in vivo yeast system to analyze effects of rDNA enhancer deletions on the chromatin structure and the transcription of tagged rDNA units. We found that upon deletion of a single enhancer element, transcription of the upstream and downstream rRNA gene was reduced by about 50%. Although removing both flanking enhancers of an rRNA gene led to a further reduction in transcription levels, a significant amount of transcriptional activity remained, either resulting from the influence of more distantly located enhancer elements or reflecting the basal activity of the polymerase I promoter within the nucleolus. Despite the reduction of transcriptional activity upon enhancer deletion, the activation frequency (proportion of nonnucleosomal to nucleosomal gene copies in a given cell culture) of the tagged rRNA genes was not significantly altered, as determined by the psoralen gel retardation assay. This is a strong indication that, within the nucleolus, the yeast rDNA enhancer functions by increasing transcription rates of active rRNA genes and not by activating silent transcription units.

Chromatin↗

Geometry and physics of catenanes applied to the study of DNA replication.

The concept of ideal geometric configurations was recently applied to the classification and characterization of various knots. Different knots in their ideal form (i.e., the one requiring the shortest length of a constant-diameter tube to form a given knot) were shown to have an overall compactness proportional to the time-averaged compactness of thermally agitated knotted polymers forming corresponding knots. This was useful for predicting the relative speed of electrophoretic migration of different DNA knots. Here we characterize the ideal geometric configurations of catenanes (called links by mathematicians), i.e., closed curves in space that are topologically linked to each other. We demonstrate that the ideal configurations of different catenanes show interrelations very similar to those observed in the ideal configurations of knots. By analyzing literature data on electrophoretic separations of the torus-type of DNA catenanes with increasing complexity, we observed that their electrophoretic migration is roughly proportional to the overall compactness of ideal representations of the corresponding catenanes. This correlation does not apply, however, to electrophoretic migration of certain replication intermediates, believed up to now to represent the simplest torus-type catenanes. We propose, therefore, that freshly replicated circular DNA molecules, in addition to forming regular catenanes, may also form hemicatenanes.

Biophysical Phenomena↗

Three-dimensional multi-scale line filter for segmentation and visualization of curvilinear structures in medical images.

This paper describes a method for the enhancement of curvilinear structures such as vessels and bronchi in three-dimensional (3-D) medical images. A 3-D line enhancement filter is developed with the aim of discriminating line structures from other structures and recovering line structures of various widths. The 3-D line filter is based on a combination of the eigenvalues of the 3-D Hessian matrix. Multi-scale integration is formulated by taking the maximum among single-scale filter responses, and its characteristics are examined to derive criteria for the selection of parameters in the formulation. The resultant multi-scale line-filtered images provide significantly improved segmentation and visualization of curvilinear structures. The usefulness of the method is demonstrated by the segmentation and visualization of brain vessels from magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), bronchi from a chest CT, and liver vessels (portal veins) from an abdominal CT.

Bronchography↗

Chromatin structure and methylation of rat rRNA genes studied by formaldehyde fixation and psoralen cross-linking.

By using formaldehyde cross-linking of histones to DNA and gel retardation assays we show that formaldehyde fixation, similar to previously established psoralen photocross-linking, discriminates between nucleosome- packed (inactive) and nucleosome-free (active) fractions of ribosomal RNA genes. By both cross-linking techniques we were able to purify fragments from agarose gels, corresponding to coding, enhancer and promoter sequences of rRNA genes, which were further investigated with respect to DNA methylation. This approach allows us to analyse independently and in detail methylation patterns of active and inactive rRNA gene copies by the combination of Hpa II and Msp I restriction enzymes. We found CpG methylation mainly present in enhancer and promoter regions of inactive rRNA gene copies. The methylation of one single Hpa II site, located in the promoter region, showed particularly strong correlation with the transcriptional activity.

Animals↗

A plasmid rescue to investigate mutagenesis in transgenic D. melanogaster.

We present a plasmid rescue from transgenic Drosophila to study spontaneous and mutagen-induced mutations in vivo. Transgenic Drosophila lines were established by transformation with a shuttle vector containing the bacterial lacZ gene as a target for mutagenesis. The target gene can be recovered into bacteria by restriction endonuclease treatment of total genomic DNA, followed by ligation of the recircularized shuttle vectors. The resulting circular plasmids are then transformed back into E. coli lacZ- mutants, where the activity of the lacZ genes is scored on the induction substrate X-Gal. The number of inactivated versus intact lacZ genes directly indicates the mutation frequency. By the described target gene rescue procedure up to 5000 lacZ gene copies can be rescued from one fly routinely. Spontaneous background mutation rates using this system are 2.6 +/- 0.6 x 10(-4). Treatment of larvae with ethylnitrosourea (ENU) resulted in a dose-dependent increase of the mutation frequency to 4.8 +/- 0.6 x 10(-4) for 0.5 mM and 6.9 +/- 1.2 x 10(-4) for 1 mM ENU, respectively.

Animals↗

The stability of nucleosomes at the replication fork.

Purified simian virus (SV40) minichromosomes were photoreacted with psoralen under various conditions that moderately destabilize nucleosomes. This assay allows indirect distinction between stable nucleosomes, partially unravelled nucleosomes and nucleosomes containing (or lacking) histone H1. In replicating molecules the passage of the replication machinery destabilizes the nucleosomal organization of the chromatin fiber over a distance of 650 to 1100 bp. In front of the fork, an average of two nucleosomes are destabilized presumably by the dissociation of histone H1 and the advancing replication machinery. On daughter strands, the first nucleosome is detected at a distance of about 260 nucleotides from the elongation point. This nucleosome is interpreted to contain no histone H1, while no stepwise association of (H3-H4)2 tetramers with H2A/H2B dimers on nascent DNA can be detected in vivo. The second nucleosome after the replication fork appears to contain histone H1. The prolonged nuclease sensitivity of newly replicated chromatin described in the literature therefore may not be due to a slow reassociation of histone H1.

Animals↗

[Risk factors for development of argon laser trabeculoplasty failure producing membrane in the chamber angle].

INTRODUCTION: The major cause of ALT failure is membrane formation in the chamber angle. The aim of this retrospective study was to identify possible risk factors. MATERIAL AND METHODS: We studied sections from the surgical specimens from all trabeculectomies at our department within 2 years. We identified 122 eyes with at least one preoperative ALT. In 46 specimens enough trabecular meshwork for morphological analysis was present. RESULTS: Half of the patients showed a membrane covering the trabecular meshwork. In 14 of 23 eyes we could see this membrane even at low-power magnification (40 x). Various possible risk factors were evaluated, but none showed a significant correlation. When we compared only these eyes with membranes visible at low-power magnification with eyes without, however, we found a significant difference in the number of ALTs (mean +/- SD 2.07 +/- 0.73 vs 1.48 +/- 0.59; P = 0.026) and preoperative intraocular pressure (32.0 +/- 9.7 mmHg vs 26.2 +/- 8.4 mmHg; P = 0.04). CONCLUSION: We found no distinct risk factor for membrane formation, but it becomes more frequent with every additional laser treatment.

Adult↗

Detection of genotoxic activity in native hospital waste water by the umuC test.

The genotoxic potential of the waste water of a hospital was evaluated by the umuC test. Within 2 years over 800 native waste water samples were analysed. Genotoxic activity was found in 13% of the samples. The highest genotoxic activity occurred in the morning hours, but genotoxic samples were detected also during the day and at night. 96% of the genotoxic waste water samples revealed a genotoxic potential without growth inhibition of test bacteria monitored as OD600, in the same way as antineoplastic drugs like mitomycin C or cisplatin. 4% of the genotoxic waste water samples showed combined cytotoxic and genotoxic activities as seen in control experiments using glutaraldehyde containing disinfectants and certain antibiotics.

Bacterial Proteins↗

Transcription in the yeast rRNA gene locus: distribution of the active gene copies and chromatin structure of their flanking regulatory sequences.

In growing yeast cells, about half of the 150 tandemly repeated rRNA genes are transcriptionally active and devoid of nucleosomes. By using the intercalating drug psoralen as a tool to mark accessible sites along chromatin DNA in vivo, we found that the active rRNA gene copies are rather randomly distributed along the ribosomal rRNA gene locus. Moreover, results from the analysis of a single, tagged transcription unit in the tandem array are not consistent with the presence of a specific subset of active genes that is stably maintained throughout cell divisions. In the rRNA intergenic spacers of yeast cells, an enhancer is located at the 3' end of each transcription unit, 2 kb upstream of the next promoter. Analysis of the chromatin structure along the tandem array revealed a structural link between transcription units and adjacent, 3' flanking enhancer sequences: each transcriptionally active gene is flanked by a nonnucleosomal enhancer, whereas inactive, nucleosome-packed gene copies are followed by enhancers regularly packaged in nucleosomes. From the fact that nucleosome-free enhancers were also detected in an RNA polymerase I mutant strain, we interpret these open chromatin structures as being the result of specific protein-DNA interactions that can occur before the onset of transcription. In contrast, in this mutant strain, all of the rRNA coding sequences are packaged in nucleosomal arrays. This finding indicates that the establishment of the open chromatin conformation on the activated gene copies requires elongating RNA polymerase I molecules advancing through the template.

Cell Division↗