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Biomedical subjects

J Heil

Publications and source records attributed to J Heil.

At least 19 recordsLinked to original sources

Validation of the SOS/umu test using test results of 486 chemicals and comparison with the Ames test and carcinogenicity data.

The present study gives a comprehensive update of all umu genotoxicity assay results published so far. The available data of 486 chemicals investigated with the umu test are compared with the Ames test (274 compounds) as well as rodent carcinogenicity data (179 compounds). On the whole, there is good agreement between the umu test and the Ames test results, with a concordance of about 90%. The umu test was able to detect 86% of the Ames mutagens, while the Ames test (using at least 5 strains) detected 97% of the umu positive compounds. The elimination of TA102 from the set of Ames tester strains reduced the percentage of detectable umu genotoxins from 97 to 86%. The agreement between carcinogenesis and umu response was 65%, which is comparable to earlier studies concerning rodent carcinogenesis and Salmonella mutagenesis. The present compilation of umu results provides a database that can be used for the comparison of the SOS-inducing activity of chemicals and their mutagenicity, respectively, carcinogenicity. The results presented here clearly demonstrate that a chemical which induces the expression of the umu operon can be regarded a rodent carcinogen with a high degree of certainty (93%).

Animals

Genotoxicity of dental materials.

This study was performed to characterize the (possible) DNA-damaging properties of dental materials and to identify specific compounds that contribute to this genotoxicity. For screening, three tests that assay for different aspects of genotoxicity (i) the bacterial umu-test; (ii) the eucaryotic DNA synthesis inhibition test; and (iii) the in vivo alkaline filter elution technique were chosen. This investigation gives several lines of evidence that most dental materials tested (14 chemical monosubstances present in dental devices and 7 extracts of dental materials) yield 'positive' results in at least one of the genotoxicity tests, however, with effects ranging from 'borderline' to 'strong positive'. The extracts of the widely used dental materials Vitrebond and AH26 elicited clear concentration-related genotoxic responses in all test systems. On the basis of these data and public concern, more attention has to be given to local or systemic complications which may be associated with the use of dental materials.

Animals

Skilled motor performance and working memory in rowers: body patterns and spatial positions.

Previous studies using unfamiliar laboratory tasks (e.g. Smyth & Pendleton, 1990) have shown that working memory for movements to targets external to the body (positional movements) is dissociable from working memory for movements made to recreate specific configurations of body parts (patterned movements). In Experiment 1 this dissociation is replicated using tasks that were adapted for use in Experiment 2. In Experiment 2 the timing of experienced rowers performance of patterned and positional elements of the rowing stroke was selectively disrupted by concurrent performance of patterned and positional memory tasks, respectively. These results suggest that patterned and positional elements of well-practised everyday motor tasks, which involve a complex interaction of the two types of movement, are controlled separately and place dissociable demands on working memory.

Adult

[Genotoxicity--causes and sequelae].

Genotoxicity is being increasingly focussed in both scientific and public discussions. This paper tries to point out the connections with mutagenicity and carcinogenicity and to show up several important medical aspects of DNA damage.

Carcinogenicity Tests

Detection of mammalian carcinogens with an immunological DNA synthesis-inhibition test.

There is a close relationship between genotoxicity, mutagenicity and carcinogenicity. But the controversy of which short-term test system best recognizes human carcinogens is still going on. Currently, the Salmonella gene mutation assay ('Ames test') is the most widely used test for the screening of mutagens. However, many in vitro tests hold unsatisfactory validity data, presumably because of the inability of present short-term tests to detect non-genotoxic carcinogens, which are increasingly being brought into focus in the discussions of genesis of cancer. One principle often neglected in this context is the property of genotoxic agents to inhibit replicative DNA synthesis in (proliferating) eukaryotic cells. We believe that this early response to DNA damage is important in the multistage process of carcinogenesis. Accordingly, we proposed that a DNA synthesis-inhibition test should be included in the test batteries for carcinogen screening. In this paper we report the development of an appropriate DNA synthesis-inhibition test based on immunological techniques.

Carcinogenicity Tests

Genotoxicity of the fungicide dichlofluanid in seven assays.

Seven different endpoints for detection of genotoxicity have been used to demonstrate the DNA-altering properties of Dichlofluanid, a fungicide commonly used in viticulture pest control. Each endpoint (DNA synthesis inhibition test, alkaline viscosimetry, umu-test, alkaline filter elution, FADU-test, 32P-postlabeling, and electron microscopy) shows clear evidence of genotoxicity. These data indicate that application of the fungicide dichlofluanid may be mutagenic and/or carcinogenic for exposed humans.

Aniline Compounds

Renal preservation after warm ischemia using oxygen free radical scavengers to prevent reperfusion injury.

Oxygen free radicals damage kidneys and accumulate during the period of preservation prior to transplantation. We hypothesized that a perfusate containing either an oxygen free radical scavenger such as ceruloplasmin, or an iron-chelating agent such as deferoxamine, would improve kidney preservation. Thirty-eight mongrel dogs underwent autotransplantation of the left kidney after 30 min of warm ischemia and 48 hr of machine perfusion (MOX-100, Water Instruments, Rochester, MN) at 5 degrees C and pH of 7.4. The right kidney was removed at the time of autotransplantation. Four blind code-labeled preservation solutions were tested. SGF-I was used for the control group (Group 1, n = 13), and the remaining animals were transplanted with kidneys preserved with one of three solutions modified from the basic SGF-I solution: Group 2, SGF-I plus deferoxamine (656 mg/liter), n = 8; Group 3, SGF-I ceruloplasmin enriched (72 mg/dl), n = 8; and Group 4, SGF-I ceruloplasmin reduced (3.4 mg/dl), n = 9. Serum creatinine levels were measured daily for 2 weeks and survival curves for each of the four groups were estimated by the Kaplan-Meier method. Peak mean serum creatinine levels +/- standard errors in Groups 1 through 4 were 12.6 +/- 1.97, 7.8 +/- 0.90, 7.1 +/- 1.26, and 8.2 +/- 1.09, respectively. Repeated measures analysis of variance showed statistically significant differences between the groups with respect to their serum creatinine profiles (Wald's test x2 with 3 df = 22.39, P value less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A microplate version of the SOS/umu-test for rapid detection of genotoxins and genotoxic potentials of environmental samples.

The umu-microtest is a miniaturized automated short-term test version proposed for screening of umuC-dependent mutagenic potentials of chemicals relevant to environmental pollution, river water and industrial waste water. The test is based on the SOS/umu-test and has been modified in order to allow extensive testing of environmental samples. Genetically engineered Salmonella typhimurium (TA1535/pSK1002) are incubated on a microplate rotor in a sloping position for 2 h with the test samples, followed by addition of fresh culture medium to reach a 10-fold dilution of the incubation medium. 2 h later, the activity of the beta-galactosidase, which reflects umuC induction, is determined colorimetrically. The incubation of the bacteria in the presence of the test compounds as well as the assessment of beta-galactosidase activity takes place in 96-well microplates, thus enabling simultaneous screening of large numbers of samples. Data of the genotoxic potentials are available within 8 h. Computer-controlled automation is possible by using a laboratory workstation.

Azides

A microplate version of the DNA-synthesis inhibition test for rapid detection of DNA-alteration potentials.

A microplate version of the DNA-synthesis inhibition test (DIT) for fast detection of DNA-alteration potentials has been developed. The DIT is based on the concept that DNA damage causes inhibition of DNA synthesis that becomes detectable some time after replicating cells have been in contact with genotoxic agents. In this test procedure human tissue culture cells (HeLa S3), prelabeled with [14C]thymidine, arfe exposed for 90 min to the substances in question. After the cells are rinsed, they are allowed to recover for 2 1/2 h in fresh culture medium, thereby unspecific interactions interfering with DNA replication are practically eliminated. Next, [3H]thymidine is added for 30 min, and then the cells are harvested and thoroughly rinsed. Finally, incorporated radioactivity is determined by liquid scintillation counting for measurement of the 3H/14C ratio. This allows for the evaluation of DNA synthesis during the 3H-labeling period and of the extent of genotoxic damage. This microplate version of the DIT can be carried out fully automated in a laboratory workstation. The test is compared to other tests for genotoxicity. Its advantages are discussed.

Autoanalysis

En bloc simultaneous pancreas and kidney allotransplantation in the pig.

The pig is a large animal suitable for experimental pancreas transplantation due to its anatomy and transplant immunology, both of which are similar to humans. We established a model of en bloc simultaneous pancreas and kidney transplantation that decreases preservation time, operation time, and clamp time. The donor aorta--with celiac axis, superior mesenteric artery, and left renal artery--is anastomosed en bloc to the recipient's aorta in a side-to-oblique fashion. The portal vein is anastomosed end-to-side to the distal vena cava, and the left renal vein end-to-side to the left common iliac vein. The donor duodenum is anastomosed to the bladder to allow monitoring of the urinary amylase for rejection. En bloc transplantation is preferable for separating pancreas and kidney anastomoses in pigs. This technique could be used in humans, especially in adult uremic diabetic patients who receive a combined pancreas/kidney transplant from a pediatric cadaver donor.

Anastomosis, Surgical