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P Schütz

Publications and source records attributed to P Schütz.

At least 19 recordsLinked to original sources
PubMed2000

Induced micronucleus frequencies in peripheral lymphocytes as a screening test for carriers of a BRCA1 mutation in breast cancer families.

Enhanced sensitivity to the chromosome-damaging effects of ionizing radiation is a feature of many cancer-predisposing conditions. It has been suggested that women with breast cancer are deficient in the repair of radiation-induced DNA damage. We have now investigated whether mutagen sensitivity is related to mutations in the breast cancer gene BRCA1. We studied the induction and repair of DNA damage in lymphocytes of women from families with familial breast cancer and breast and ovarian cancer. The mutagens used were gamma-irradiation and hydrogen peroxide and the DNA effects were determined with the micronucleus test and the comet assay. Women with a BRCA1 mutation (n = 12) and relatives without the familial mutation (n = 10) were compared to controls (i.e., healthy women without family history of breast or ovarian cancer; n = 17). Our results indicate a close relationship between the presence of a BRCA1 mutation and sensitivity for the induction of micronuclei. Compared to a concurrent control, 10 of 11 women with a BRCA1 mutation showed elevated radiation sensitivity. Of the 10 related women without the familial mutation, only 2 had clearly enhanced micronucleus frequencies. In addition to the sensitivity toward gamma-irradiation, hypersensitivity toward hydrogen peroxide was also observed, indicating that the mutagen sensitivity is not solely due to a defect in the repair of DNA double strand breaks. In contrast to the results with the micronucleus assay, we found no significant difference between women with and without a BRCA1 mutation with respect to the induction and repair of DNA damage in the comet assay. This finding suggests a normal rate of damage removal and points to a disturbed fidelity of DNA repair as a direct or indirect consequence of a BRCA1 mutation. Our results support the usefulness of induced micronucleus frequencies as a biomarker for cancer predisposition and suggest its application as a screening test for carriers of a BRCA1 mutation in breast cancer families.

Adult↗
PubMed2000

Induction and repair of formaldehyde-induced DNA-protein crosslinks in repair-deficient human cell lines.

We have previously shown that the alkaline Comet assay (single cell gel electrophoresis) in a modified version is a sensitive test for the detection of formaldehyde-induced DNA-protein crosslinks (DPC). Our results also indicated that formaldehyde-induced DPC are related to the formation of chromosomal effects such as micronuclei and sister chromatid exchanges. To better understand the genetic consequences of formaldehyde-induced DPC we have now investigated the induction and removal of DPC in relationship to the formation of micronuclei in normal and repair-deficient human cell lines. We did not find significant differences between normal cells, a xeroderma pigmentosum (XP) cell line and a Fanconi anaemia (FA) cell line with respect to the induction and removal of DPC. However, the induction of micronuclei was enhanced in both repair-deficient cell lines, particularly in XP cells, under the same treatment conditions. Comparative investigations with the DNA-DNA crosslinker mitomycin C (MMC) revealed a delayed removal of crosslinks and enhanced induction of micronuclei in both repair-deficient cell lines. FA cells were found to be particularly hypersensitive to micronucleus induction by MMC. In contrast to the results with formaldehyde, induction of micronuclei by MMC occurred at much lower concentrations than the effects in the Comet assay. Our results suggest that more than one repair pathway can be involved in the repair of crosslinks and that disturbed excision repair has more severe consequences with regard to the formation of chromosomal aberrations after formaldehyde treatment than has disturbed crosslink repair.

Cell Line↗
PubMed2000

Mutagen sensitivity of human lymphoblastoid cells with a BRCA1 mutation in comparison to ataxia telangiectasia heterozygote cells.

Our previous results indicated a close relationship between the presence of a BRCA1 mutation in lymphocytes and hypersensitivity for the induction of micronuclei by gamma irradiation and hydrogen peroxide (H(2)O(2)). Comparative investigations with the comet assay (single-cell gel electrophoresis) suggested a normal rate of damage removal and pointed to a disturbed fidelity of DNA repair as a direct or indirect consequence of a BRCA1 mutation. We now wanted to see whether similar results could be obtained with lymphoblastoid cell lines (LCLs) and whether such permanent cells are suitable as a model for the investigation of mechanisms involved in mutagen sensitivity. Our results show that LCLs with a BRCA1 mutation are also hypersensitive to the chromosome-damaging effects of gamma irradiation or H(2)O(2), as revealed by the micronucleus test. Interestingly, LCLs heterozygous for an ataxia telangiectasia (AT) mutation have similar characteristics as BRCA1 cells with respect to the induction and repair of DNA damage induced by either gamma irradiation or H(2)O(2). However, caffeine enhanced the induction of micronuclei by gamma irradiation only in normal and heterozygous AT cells but not in BRCA1 cells, thus indicating a difference in the pathways leading to mutagen sensitivity in cells with a BRCA1 or an AT mutation. Our results suggest that caffeine could be useful in discriminating AT heterozygotes from carriers of a BRCA1 mutation, as well as BRCA1 mutation carriers from normal individuals.

Ataxia Telangiectasia↗
PubMed1999

The influence of temperature during alkaline treatment and electrophoresis on results obtained with the comet assay.

The alkaline comet assay (single-cell gel electrophoresis) is becoming established as a genotoxicity test with many fold applications in vitro and in vivo. While the underlying principles are identical, various modifications of the method are in use which clearly affect the sensitivity and resolving power of the assay. One variable of potential importance that has been disregarded until now is temperature during alkaline treatment and electrophoresis. We therefore performed comet assay experiments with human blood and V79 Chinese hamster cells using two different temperatures (4 and 20 degrees C, i.e. room temperature) during alkaline treatment and electrophoresis. DNA damage was induced by the two standard mutagens gamma irradiation and methyl methanesulfonate (MMS). The results clearly indicate significant differences in the detection of background and mutagen-induced DNA damage at these two temperatures. Under otherwise identical test conditions (including the duration of alkaline treatment and electrophoresis), increased temperature during alkaline treatment and electrophoresis strongly enhances DNA migration. Our findings suggest that the comet assay should be performed under strictly controlled and reproducible temperature conditions. In any case the temperature during alkaline treatment and electrophoresis should be stated in a publication to allow for a critical evaluation of results obtained with the comet assay.

Alkalies↗
PubMed1999

Comparative evaluation of the genotoxic properties of potassium bromate and potassium superoxide in V79 Chinese hamster cells.

The genotoxic potential of two oxidizing compounds, potassium bromate and potassium superoxide, was comparatively tested in various genotoxicity tests with V79 Chinese hamster cells. Both substances clearly induced cytotoxicity, chromosome aberrations and increased DNA migration in the alkaline comet assay. Using a modified comet assay protocol with FPG protein, a DNA repair enzyme which specifically nicks DNA at sites of 8-oxoguanines and formamidopyrimidines, we detected oxidative DNA base damage only after potassium bromate treatment. HPLC analysis also revealed significantly increased levels of 8-oxodeoxyguanosine after potassium bromate treatment but not after potassium superoxide treatment. Furthermore, potassium bromate clearly induced gene mutations at the HPRT locus while potassium superoxide only had a small effect on HPRT mutant frequencies. Molecular analysis of potassium bromate-induced mutations indicated a high portion of deletion mutations. Three out of four point mutations were G to T transversions which typically arise after replication of 8-oxoguanine. Our results suggest that the two oxidizing compounds induce specific patterns of genotoxic effects that reflect the types of DNA alterations induced by different reactive oxygen species (ROS).

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

[Perioperative monitoring of hemoglobin fractions in homozygous sickle cell disease].

This case report presents the perioperative management of double-sided hip arthroplasty in a patient (female, 25 years old) homozygous for sickle cell anemia (SS). The fraction of sickle hemoglobin (Hb S) to total hemoglobin was monitored with an automated cation exchange microcolumn chromatography. The main purpose of ion exchange chromatography is to measure glycated hemoglobin A (HbA1c) in diabetic patients. Furthermore, as a by-product, this test enables the quantitative assessment of aberrant hemoglobin molecules such as sickle cell hemoglobin Hb S with sufficient precision and selectivity. The standard method, hemoglobin-electrophoresis is more complicated and not generally available. For the perioperative estimation of the risk for sickle cell related complications and as a guide for transfusion therapy, knowledge of preoperative Hb S level is essential. In this case report, the clinical use of a rapid laboratory test at low costs with common equipment in a patient with known homozygous sickle cell anemia is demonstrated.

Adult↗
PubMed1999

[Management of case fees and special charges by using the coding system "do it"].

INTRODUCTION: With the German health care restructuring legislation ("Gesundheitsstrukturgesetz") the coding of diagnoses and operations according to ICD-9 and ICPM (OPS-301) was introduced for budget assignment ("Fallpauschalen/Sonderentgelte"). METHODS: Application of the structured coding system "do it" in orthopedics and traumatology in combination with a surgical documentation system. Results of 8,664 documented operative cases within three years. RESULTS: In total, 11,854 ICD-9 or ICD-10 and 20,178 ICPM (OPS-301) were coded. 2,914 "Fallpauschalen" and/or 3,456 "Sonderentgelte" were found. The System achieved high acceptance due to its userfriendliness and simple functionality. DISCUSSION: In comparison with text- or thesaurus-based coding systems the "do it" coding system does not require any knowledge of the ICD or ICPM (OPS-301). It can be adapted to individual clinical requirements by implementing frequent diagnoses and individual therapy concepts. In combination with a medical information system the coding system can be integrated seamlessly into routine documentation.

Documentation↗
PubMed1992

[Langerhans-cell histiocytosis in children].

Histiocytosis from Langerhans cells is a new term for a group of diseases formerly called histiocytosis X. In The Faculty Hospital Motol the authors treated between July 1974 and December 1980 84 children with this disease. Twenty one suffered from the malignant form (formerly Letterer-Siwe and Hand-Schüller-Christian disease) and in 63 patients the diagnosis of eosinophil granuloma was established. In 21 children with unequivocally malignant disease the authors started chemotherapy immediately after establishment of the diagnosis and in six they indicated in addition radiotherapy. Of these 21 children 16 are in complete remission and 5 children died from progression of the disease during treatment. In the group of 63 children with eosinophil granuloma in 44 only excochleation of the focus was performed. Chemotherapy was administered to 12 children, incl. 5 where it was combined with radiotherapy. A relapse of the disease was recorded in 8 children. At present all patients suffering from the disease are in complete remission.

Adolescent↗
PubMed1991

Alterations in Krebs cycle enzyme activities and carbohydrate catabolism in two strains of Trypanosoma brucei during in vitro differentiation of their bloodstream to procyclic stages.

A rapid switch from a fermentative to a primarily oxidative type of glucose utilization was observed during in vitro differentiation of Trypanosoma brucei STIB348 and EATRO1244 bloodstream to procyclic trypomastigotes. In accordance with previously published reports bloodstream populations produced pyruvate as the major end product of glucose catabolism, together with very small amounts of CO2, succinate and glycerol. During differentiation pyruvate excretion decreased within 48 h to the low levels produced by 28-day procyclic stages. Concomitant with the decline in pyruvate formation, acetate appeared as a new product and the rates of respiratory CO2 increased considerably. The amount of carbon released with these compounds could account for nearly all of the glucose carbon consumed. Rates of glucose utilization and formation of acetate and CO2 in cells differentiated for 48 h were essentially the same as those found in 28-day procyclics. Succinate and glycerol excretion remained low during the entire transformation process, and no significant difference in the pattern and quantities of end products were found between the two trypanosome strains. During trypanosome differentiation the changes in metabolism were associated with marked alterations in enzyme activity levels. Activities of the tricarboxylic acid (TCA) cycle enzymes citrate synthase, isocitrate dehydrogenase (NAD+), succinate dehydrogenase and fumarase were not detectable in bloodstream trypomastigotes but appeared upon differentiation for 24 h. An exception was citrate synthase whose activity was not demonstrable until 48 h postinoculation into culture. After 48 h the majority of the TCA cycle enzyme activities continued to increase steadily until day 28. Pyruvate kinase activity decreased in differentiating cells after 48 h to about 25% of the level found in bloodstream trypomastigotes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aconitic Acid↗
PubMed1990

[Injuries of the facial skeleton in children].

An analysis of a group of patients hospitalized in 1985-1989 at the Dental Clinic for Children on account of facial injuries revealed a higher incidence of injuries in boys, as compared with girls, the ratio being approximately 1.8:1. The highest incidence was recorded in the group aged 9-10 years. Among skeletal injuries isolated mandibular fractures predominated followed by isolated fractures of the alveolar processes (19%) and isolated fractures of the middle portion of the face (12%). The most frequent fracture was that of the articular process of the mandible. 20% of the injuries patients had associated injuries, mostly of the CNS. In the aetiology of facial skeletal fractures falls from a bicycle held an important place (28%). From the therapeutics aspects 68% of the cases were treated by conservative methods, 25% were operated and 7% were left without treatment.

Accidental Falls↗