PubMed Health⌕ Search

Biomedical subjects

C Frei

Publications and source records attributed to C Frei.

12 recordsLinked to original sources

[Investigation about the clinical use of brushite- and hydroxylapatite-cement in sheep].

For future clinical use as synthetic bone replacement, an injectable brushite-(chronOS-Inject) and hydroxylapatite-(Biobon) cement were compared in a drill hole model in 10 sheep over time at 2, 4, 6, 8, 16 and 24 weeks. Results were compared regarding their practical use, biocompatibiliy, resorption mechanism and subsequent new bone formation. The cements were filled into drill holes (psi 8 x 13mm) of the proximal and distal humerus, and femur and the samples evaluated macroscopically, radiologically and microscopically including histomorphometrical quantification of percentages of new bone, fibrous tissue and remnants of cements. The cement area decreased continuously from 2 to 24 weeks with chronOS-Inject, as well as the area of granules. Inversely, the subsequent new bone formation increased from 2-24 weeks accordingly. With Biobon the cement area decreased slower between 2 and 24 weeks, and the new bone formation was less. Both cements were well integrated into the bone in long bones. chronOS-Inject demonstrated good biocompatibility and was almost completely replaced through bone within 24 weeks. Biobon was resorbed considerably slower and initially a slight inflammatory reaction including bone resorption was observed within the adjacent host bone.

Absorbable Implants↗

Compositional changes of a dicalcium phosphate dihydrate cement after implantation in sheep.

A hydraulic calcium phosphate cement having dicalcium phosphate dihydrate (DCPD) as end-product of the setting reaction was implanted in a cylindrical defect in the diaphysis of sheep for up to 6 months. The composition of the cement was investigated as a function of time. After setting, the cement composition consisted essentially of a mixture of DCPD and beta-tricalcium phosphate (beta-TCP). In the first few weeks of implantation, the edges of the cement samples became depleted in DCPD, suggesting a selective dissolution of DCPD, possibly due to low pH conditions. The cement resorption at this stage was high. After 8 weeks, the resorption rate slowed down. Simultaneously, a change of the color and density of the cement center was observed. These changes were due to the conversion of DCPD into a poorly crystalline apatite. Precipitation started after 6-8 weeks and progressed rapidly. At 9 weeks, the colored central zone reached its maximal size. The fraction of beta-TCP in the cement was constant at all time. Therefore, this study demonstrates that the resorption rate of DCPD cement is more pronounced as long as DCPD is not transformed in vivo.

Animals↗

Calibration processes in desert ant navigation: vector courses and systematic search.

This study investigates the ability of desert ants to adapt their path integration system to an "open-jaw" training paradigm, in which the point of arrival (from the nest) does not coincide with the point of departure (to the nest). Upon departure the ants first run off their home vector and then start a systematic search for the nest. Even if they are subjected to this training-around-a-circuit procedure for more than 50 times in succession, they never adopt straight homeward courses towards the nest. Their path integration vector gets slightly recalibrated (pointing a bit closer to the nest), and their search pattern gets asymmetric (with its search density peak shifted towards the nest), but the bipartite structure of the inbound trajectory invariably remains. These results suggest (1). that the ants cannot learn separate inbound and outbound vectors (i.e. vectors that are not 180 degrees reversals of each other), (2). that the recalibrated vector is dominated by the ant's outbound course, (3). that the recalibration of the vector and the modification of the search geometry are fast and flexible processes occurring whenever the ant experiences a mismatch between the stored and actual states of its path integrator.

Animals↗

Analysis of etoposide binding to subdomains of human DNA topoisomerase II alpha in the absence of DNA.

Epipodophyllotoxins are effective anti-tumor drugs that inhibit eukaryotic DNA topoisomerase II by trapping the enzyme in a covalent complex with DNA. We show that both the recombinant N-terminal ATPase domain and the B'A' core domain of human topoisomerase IIalpha (htopoIIalpha) bind radiolabeled etoposide specifically, even in the absence of DNA. The addition of ATP impairs etoposide binding to the holoenzyme and the N-terminal domain, but not to the core domain. To see if this interference resembles that between novobiocin and ATP in the bacterial GyrB subunit, we modeled the structure of the N-terminal domain of htopoIIalpha and performed molecular docking analysis with etoposide. Mutagenesis of critical amino acids, predicted to stabilize the drug within the N-terminal domain, reveals a less efficient binding of etoposide to the mutated proteins as monitored by direct drug binding assays, although the binding of ATP is not affected.

Adenosine Triphosphate↗

The yeast Sgs1p helicase acts upstream of Rad53p in the DNA replication checkpoint and colocalizes with Rad53p in S-phase-specific foci.

We have examined the cellular function of Sgs1p, a nonessential yeast DNA helicase, homologs of which are implicated in two highly debilitating hereditary human diseases (Werner's and Bloom's syndromes). We show that Sgs1p is an integral component of the S-phase checkpoint response in yeast, which arrests cells due to DNA damage or blocked fork progression during DNA replication. DNA polepsilon and Sgs1p are found in the same epistasis group and act upstream of Rad53p to signal cell cycle arrest when DNA replication is perturbed. Sgs1p is tightly regulated through the cell cycle, accumulates in S phase and colocalizes with Rad53p in S-phase-specific foci, even in the absence of fork arrest. The association of Rad53p with a chromatin subfraction is Sgs1p dependent, suggesting an important role for the helicase in the signal-transducing pathway that monitors replication fork progression.

Cell Cycle Proteins↗

RecQ-like helicases: the DNA replication checkpoint connection.

The eukaryotic homologues of the Escherichia coli RecQ DNA helicase play conserved roles in the maintenance of genome stability. Results obtained in yeast and mammalian systems are beginning to form a coherent picture about what these helicases do to ensure normal cell division and why humans who lack these enzymes are cancer prone. Recent data suggest that the yeast enzyme Sgs1p, as well as two human homologues, which are encoded by the Bloom's and Werner's syndrome genes, function during DNA replication and possibly in a replication checkpoint specific to S phase.

Adenosine Triphosphatases↗

Structural maintenance of chromosomes protein C-terminal domains bind preferentially to DNA with secondary structure.

Structural maintenance of chromosomes (SMC) proteins interact with DNA in chromosome condensation, sister chromatid cohesion, DNA recombination, and gene dosage compensation. How individual SMC proteins and their functional domains bind DNA has not been described. We demonstrate the ability of the C-terminal domains of Saccharomyces cerevisiae SMC1 and SMC2 proteins, representing two major subfamilies with different functions, to bind DNA in an ATP-independent manner. Three levels of DNA binding specificity were observed: 1) a >100-fold preference for double-stranded versus single-stranded DNA; 2) a high affinity for DNA fragments able to form secondary structures and for synthetic cruciform DNA molecules; and 3) a strong preference for AT-rich DNA fragments of particular types. These include fragments from the scaffold-associated regions, and an alternating poly(dA-dT)-poly(dT-dA) synthetic polymer, as opposed to a variety of other polymers. Reannealing of complementary DNA strands is also promoted primarily by the C-terminal domains. Consistent with their in vitro DNA binding activity, we show that overexpression of the SMC C termini increases plasmid loss without altering viability or cell cycle progression.

Base Composition↗

Chromosome dynamics: the SMC protein family.

Recent evidence suggests that members of the structural maintenance of chromosomes (SMC) protein family are involved in a much broader spectrum of chromosome and DNA metabolic reactions than was originally thought. Other than their role in chromosome condensation, SMC proteins are essential for sister chromatid cohesion and gene dosage compensation, and are involved in DNA recombination. This diversity of function is achieved both through the formation of different heterodimers and through their participation in higher-order protein complexes adapted to achieve specific ends.

Animals↗

The production system and disease incidence in a national random longitudinal study of Swiss dairy herds.

A prospective longitudinal observational study based on a stratified random sample of 113 Swiss dairy farms was conducted between April 1993 and July 1994 with the following objectives: (i) to provide statistically valid estimates of disease frequency in the Swiss dairy cow population, and (ii) to evaluate the feasibility and quality of an intensive farm-based data recording system. During the 15-month study period, farmers were asked to record every health and management event related to their cattle herd. This information was mailed back to the study centre at fortnightly intervals. Additionally, farms were visited regularly to verify received data and to discuss specific problems. During these farm visits, management data were recorded using questionnaires. A complete data set of individual animal events with a total observation time of about 1740 cow-years and 275 calf-years was collected and disease-incidence measures were calculated. The most frequent events were reproductive disorders and udder diseases, followed by lameness and metabolic disorders. Experience with the data collection technique used in this study suggests that a farm-based system is effective and reliable, as long as good contact with the farmers is maintained, and incentives to stimulate their motivation are provided.

Animal Husbandry↗

[Value of scanning laser ophthalmoscopy and polarimetry compared with perimetry in evaluating glaucomatous changes in the optic papilla and nerve fiber layer].

The aim of the study was to establish quantitative correlations between morphological changes at the optic nerve head (ONH) and the retinal nerve fiber layer (NFL) and functional abnormalities i.e. visual field alterations in glaucoma. A cross-sectional study of open-angle glaucoma patients of various stages was performed. Scanning laser tomographic (TopSS) assessment of the ONH and scanning laser polarimetric (Nerve Fiber Analyzer) measurements of the peripapillary NFL thickness (NFLT) were compared to results of computerized static perimetry (Octopus G-1). One eye from each of 157 glaucoma suspects (n = 58) and patients with established open-angle glaucoma (n = 99) was assessed. The parameter "modulation" (difference between maximum and minimum of NFLT) gave the best correlation (r2 = 0.23) to the visual field index for mean sensitivity. Tomography gave the best correlation between the neuroretinal rim area at the inferior and superior pole of the ONH and the visual field index loss variance (r2 = 0.20). Conventional planimetric data of the ONH and clinical assessment of the NFL yielded slightly better correlations to the visual field data than the scanning laser tomography or polarimetry. Although NFL parameters are more complicated to obtain, they yield better correlations to diffuse visual field loss than parameters of the ONH. The new scanning laser techniques do not improve these correlations between morphology and function; however, they allow objective assessment of ONH and NFL parameters without mydriasis.

Adolescent↗

PIK1, an essential phosphatidylinositol 4-kinase associated with the yeast nucleus.

Transmission of mitogenic and developmental signals to intracellular targets is often mediated by inositol derivatives. Here we present the cloning and characterization of a gene from Saccharomyces cerevisiae, PIK1, encoding the enzyme that catalyses the first committed step in the production of the second messenger inositol-1,4,5-trisphosphate. PIK1 encodes a phosphatidylinositol 4-kinase (PI 4-kinase) essential for growth. Cells carrying PIK1 on a multicopy vector overexpress PI 4-kinase activity exclusively in a nuclear fraction, suggesting that PIK1 is part of a nuclear phosphoinositide cycle. Temperature-sensitive mutations, but not a null mutation, can be suppressed by high osmolarity or an elevated concentration of Ca2+. Conditional mutants have a cytokinesis defect as indicated by a uniform terminal phenotype of cells with large buds and fully divided nuclei. We suggest that PIK1 controls cytokinesis through the actin cytoskeleton.

1-Phosphatidylinositol 4-Kinase↗