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Biomedical subjects

J Fuchs

Publications and source records attributed to J Fuchs.

At least 109 records · Page 6Linked to original sources
PubMed1995

Clastogenic factors in plasma of HIV-1 infected patients.

The objective of this study was to investigate the clastogenic activity of plasma ultrafiltrates from HIV-1 infected patients. Clastogenic factors are chromosome-damaging agents with low molecular weight (< 10,000 daltons) which cause chromosome aberrations, sister chromatid exchanges, DNA strand breakage, and gene mutation. They have first been described in the plasma of irradiated persons, but they are also found in hereditary breakage syndromes and chronic inflammatory diseases with autoimmune reactions. Their formation and their clastogenic effects are modulated by superoxide anion radicals. We analyzed a total of 22 HIV-1 positive patients in comparison to 20 reference plasma samples from healthy HIV negative blood donors of similar age. The plasma ultrafiltrates (filter cutoff 10,000 daltons) from patients induced a statistically significant increase in chromosomal breakage in the cytogenetic test system (20.5 +/- 6.8 aberrations per 100 cells), while no increase was observed in test cultures exposed to plasma ultrafiltrates from healthy blood donors (6.3 +/- 2.9 aberrations per 100 cells). The breakage values were slightly, but not significantly, lower in the 10 patients with more than 200 T-helper cells/ml (18 +/- 4 aberrations per 100 cells), than in the 12 patients with less than 200 T-helper cells/ml (22.3 +/- 7.9 aberrations per 100 cells). HIV patients with high clastogenic activity (induction of more than 20 aberrations per 100 cells, range 20 to 39) showed higher plasma levels for malondialdehyde than those with lower clastogenic activity (less than 20 aberrations per 100 cells, range 12 to 18). However, the difference was statistically not significant. Another lipid peroxidation product, 4-hydroxynonenal, was increased equally in both groups. There were no significant differences in water- and lipid-soluble plasma antioxidants between the low- and high-breakage group. In agreement with previous findings, the clastogenic effects of plasma ultrafiltrates in the test cultures were reduced by the antioxidant enzyme superoxide dismutase. The presence of clastogenic factors in the plasma of HIV patients is further evidence for a prooxidant state in these persons. Since clastogenic factor formation appears to occur at an early stage of the disease, it may be significant for virus release or activation, because of the superoxide anion stimulating effects of clastogenic factors. From a practical standpoint, clastogenic factors may be useful for evaluation of promising drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Ascorbic acid and urate in human seminal plasma: determination and interrelationships with chemiluminescence in washed semen.

Peroxidative damage induced by reactive oxygen species (ROS) has been proposed as one of the major causes of defective sperm function. The ROS detected in semen reflect an imbalance between ROS generation and degradation. The objective of the present study was to investigate the relationship between the oxidative and anti-oxidative potential in semen of infertile patients and healthy donors. Specimens were obtained from 28 patients and 18 healthy donors (controls). A conventional spermiogram, measurement of luminol-chemiluminescence (CL) in washed semen, and high performance liquid chromatography determination of ascorbic acid and urate concentrations in seminal plasma were performed. Oligozoospermic patients exhibited higher CL signals than controls (P < 0.001). Normozoospermic patients showed lower ascorbic acid (mean +/- SE: 491 +/- 46 microM, P < 0.04) and urate concentrations (320 +/- 22 microM, P < 0.009) than controls (612 +/- 35 and 426 +/- 26 microM respectively). Seminal plasma ascorbic acid was negatively correlated with the CL signals (P < 0.0006) and positively correlated with the percentage of spermatozoa with normal morphology (P < 0.006). This is the first report of a correlation between the anti-oxidant ascorbic acid in seminal plasma and ROS generation in human semen. Furthermore, the reduced ascorbic acid/urate concentrations found in semen of normozoospermic patients might be indicative of a reduced anti-oxidative protection.

Adult↗
PubMed1995

Detection of primary DNA damage: applicability to biomonitoring of genotoxic occupational exposure and in clinical therapy.

The biological effect of putative genotoxic chemicals in the work place environment was monitored in peripheral mononuclear blood cells of exposed workers. DNA strand breaks, alkali-labile sites of DNA and DNA cross-links were measured using the alkaline filter elution method. A dose dependent increase in DNA damage was found in sterilization workers exposed to ethylene oxide and metal workers with exposure towards N-nitrosodiethanolamine. Two subpopulations with different response to the external exposure were found in nonsmoking sterilization workers. Nurses handling antineo-plastic agents without adequate safety provisions showed a statistically significantly higher rate of DNA strand breaks compared to other nurses handling cytostatic drugs with recommended safety equipment and also compared to not exposed controls. Also in several other occupational groups such as fire fighters possibly exposed to several genotoxic chemicals after an accident in a chemical plant, roofers and petrol pump attendants a significantly higher amount of DNA damage was found compared to controls. No statistically significant differences in the amount of DNA strand breaks were found in cabinet makers and car mechanics compared to controls. In peripheral mononuclear blood cells of ovarial carcinoma patients as well as of patients with Morbus Hodgkin an increased DNA strand break rate was found after application of cytostatic drugs. The individual patients showed a very different response after drug intake. The increase in DNA damage after drug application is possibly related to the success of the chemotherapy.

Animals↗
PubMed1995

Extramedullary hematopoiesis and intratumoral production of cytokines in childhood hepatoblastoma.

Extramedullary hematopoiesis is a characteristic feature of hepatoblastoma (HB). We investigated 15 HB to characterize intratumoral hematopoietic foci and to find clues to the pathophysiology of their formation. By conventional histology and immunohistochemistry, we found erythroblasts in all and megakaryocytes in 10 of the HB, whereas granulocyte and monocyte precursor cells could not be identified in hematopoietic foci of any tumor. Only a minority of erythropoietic cells in these foci contained fetal Hb (HbF). We recently found that HB cells produce IL-1 beta and thus stimulate stromal cells to secrete IL-6. We therefore searched for other hematopoietic cytokines in HB. Supernatants of primary HB cultures were subjected to ELISA, bioassayed, and immunoblotted. We detected erythropoietin (EPO) in 11 of 15, stem cell factor (SCF) in 7 of 11, granulocyte colony-stimulating factor (G-CSF) in 4 of 15, granulocyte/macrophage colony-stimulating factor (GM-CSF) in 6 of 15, IL-3 in 1 of 12, leukemia inhibitory factor (LIF) in 1 of 9, and macrophage colony-stimulating factor (M-CSF) in 1 of 8 conditioned media. With immunoenzymatic labeling we localized EPO and SCF to the cytoplasm of epithelial HB cells, whereas stromal cells and cells of immature fibrous tissue of mixed HB expressed SCF, G-CSF, GM-CSF, LIF, and M-CSF. EPO and SCF could also be detected in extracts of epithelial HB cells. We conclude that, in HB, erythropoiesis and megakaryopoiesis but not the granulocyte-macrophage lineage is induced by fetal and embryonal tumor cells in cooperation with stromal cells by locally secreted cytokines.

Carcinoma, Hepatocellular↗
PubMed1995

Single-strand breaks in deoxyribonucleic acid in fire fighters accidentally exposed to o-nitroanisole and other chemicals.

OBJECTIVES: The aim of the study was to detect single-strand breaks in deoxyribonucleic acid (DNA) in mononuclear blood cells of fire fighters exposed to o-nitroanisole and other substances released into the environment during an accident in a chemical plant. METHODS: The level of DNA single-strand breaks in mononuclear blood cells was detected by alkaline elution. The results were compared for 16 fire fighters who worked in a contaminated area for about 8 h and two reference groups (one of fire fighters who had not worked in the contaminated area, group I, and one of persons without any apparent occupational exposure to genotoxic substances, group II). RESULTS: The mean normalized elution rate (nER) 19 d after the accident was slightly but statistically significantly (P < 0.05) higher for the exposed fire fighters [mean 1.48 +/- 95% confidence interval (95% CI) 0.21] than for reference group I (mean 1.21 +/- 95% CI 0.21) or reference group II (mean 1.17 +/- 95% CI 0.18). No statistically significant difference was found between reference groups I and II. Another analysis was performed three months after the first. The level of DNA single-strand breaks (mean nER 1.12 +/- 95% CI 0.11) was no longer increased in comparison with the levels of the reference groups. CONCLUSIONS: DNA single-strand breaks were increased in fire fighters exposed to o-nitroanisole and other substances. In comparison with the extent of DNA strand breaks found in other occupational groups the increase was only moderate. The observed decrease in DNA single-strand breaks to the reference level in exposed fire fighters three months later suggests a DNA repair mechanism for DNA single-strand breaks caused by o-nitroanisole.

Accidents↗
PubMed1995

[Management of disabled patients in private households 1991--empirical analysis with data by the socioeconomic panel].

Domestic care can be provided by relatives, the social net or professional care givers. Even before the new German Care Insurance starts paying, the part of the family in care giving is immense. The readiness for care-giving exists in general, but depends on local and temporal possibilities. This is even clearer by differentiating between care-getting persons in single- and non-single households, irrespective of the degree of illness, are mainly looked after by relatives. The care for people living in single households is mostly provided by professionals.

Adolescent↗
PubMed1995

[Does income effect health? Analysis with data by the socioeconomic panel].

To determine the influence of income on health, the per capita weighted income is computed for every respondent of the German Socio-economic Panel. The effect of this income variable on health satisfaction and utilisation of medical services is examined via cross-sectional analysis, considering age and gender and taking the life circumstances under account (operationalized via professional activity level of qualification, partner and parenthood). Analysis of variance and regression show that health satisfaction grows with increasing income, while there is no evidence for similar effects of income on the utilisation of medical services.

Adolescent↗
PubMed1994

Glycolaldehyde causes DNA-protein crosslinks: a new aspect of ethylene oxide genotoxicity.

After in vitro incubation of human peripheral mononuclear blood cells with glycolaldehyde (a putative metabolite of ethylene oxide) for 2 h at 37 degrees C, a dose-dependent increase in DNA crosslinks was observed in a dose range between 1 and 10 mM using the alkaline filter elution technique. The elution rate of mononuclear blood cells after treatment with ionizing radiation (600 cGy) was reduced more than 5-fold if cells were incubated with 10 mM glycolaldehyde for 2 h. After treatment with proteinase K DNA crosslinks were no longer detected in cells incubated with glycolaldehyde. Therefore the crosslinks produced by glycolaldehyde could clearly be identified as DNA-protein crosslinks. Additionally glycolaldehyde induced DNA single-strand breaks in a dose range between 1 and 10 mM. The elution rate of mononuclear blood cells was increased about 18-fold if cells were incubated with 5 mM glycolaldehyde for 2 h using an elution procedure with proteinase K. In vitro incubation of mononuclear cells with ethylene oxide for 2 h at 37 degrees resulted in a dose-dependent increase in DNA single-strand breaks between 0.5 and 10 mM ethylene oxide. Moreover, a time-dependent increase in DNA single-strand breaks after incubation with 1.5 mM ethylene oxide was observed with an increased number of single-strand breaks already detectable after 15 min and a maximum level which was detected after 2 h of incubation. However, no DNA-DNA or DNA-protein crosslinks could be detected although a wide concentration range and many different incubation times were tested. Therefore DNA crosslinks, for which evidence was found in mononuclear blood cells of humans occupationally exposed to ethylene oxide, are possibly generated by glycolaldehyde, a putative intermediate in the metabolism of ethylene oxide to glycolic acid.

Acetaldehyde↗
PubMed1994

Lifespan of immunosuppressed NMRI-mice is increased by deprenyl.

Immunosuppressed NMRI-mice (nu/nu) were raised and kept under germ-reduced conditions and fed with a germ-reduced diet (14 animals = controls). For another 14 mice 4 mg of selegiline were admixed to 10 kg of the diet. The 50% survival rate of the latter group was 160% from birth or 220% from the beginning of the study. The survival rate in weeks finally reached 350%, and the area under the curve 250%. The last mouse in the control group died at the age of 5 months, 2.5 months after the study was started; the last mouse in the selegiline group died at the age of 14.5 months, 1 year after the beginning of the study.

Animals↗
PubMed1994

Utility of DNA amplified by degenerate oligonucleotide-primed PCR (DOP-PCR) from the total genome and defined chromosomal regions of field bean.

Degenerate oligonucleotide primed (DOP)-PCR has emerged as a simple and rapid method for representative amplification of highly complex genomic DNA from humans, mice and Drosophila. The present paper describes the adaptation of this method for use on a plant species, Vicia faba, with a large genome (2C = 30 pg). Specific low-copy-number sequences as well as highly repeated sequences were detectable among DOP-PCR products obtained from small samples of purified genomic DNA (100 pg), DNA from 10 prophase nuclei, 10 flow-sorted chromosomes or 15 microdissected chromosome segments (satellites) following reamplification with sequence-specific primers and/or Southern hybridization. Biotinylated chromosome-specific DOP-PCR products were used for fluorescent in situ hybridization. All chromosomes showed hybridization signals, with the exception of regions containing Fok elements which are not present in the chromosomal DNA targeted by DOP-PCR.

Base Sequence↗
PubMed1994

Differentiation of field bean heterochromatin by in situ hybridization with a repeated FokI sequence.

The chromosomes of a field bean line with a reconstructed karyotype (ACB) were hybridized in situ with biotinylated probes of a repetitive Fok I sequence, of DOP-PCR (degenerate oligonucleotide primed polymerase chain reaction) amplified DNA from a chromosome that does not contain this sequence, and with probes containing dispersed repetitive sequences. The results were compared with Giemsa banding, DNA late replication and Fok I in situ digestion patterns. This allowed further differentiation between the chromatin types of this species. Centromeric and NOR-associated heterochromatin as well as euchromatin were shown to be free of Fok I sequence repeats. Among the interstitial late replicating Giemsa bands, subdivided into 'marker' and 'additional' bands, most of the marker bands located at mid-arm positions were composed mainly or exclusively of tandemly arranged Fok I repeats. Some of the marker bands and nearly all of the additional bands located in the vicinity of centromeres were free of FokI sequence repeats, of Fok I recognition sites, and possibly also of dispersed repetitive sequences. They are probably composed of specific, not yet defined, repetitive sequences.

Base Sequence↗
PubMed1994

Genotoxic risk for humans due to work place exposure to ethylene oxide: remarkable individual differences in susceptibility.

Single strand breaks of DNA of peripheral mononuclear blood cells from 97 male and female workers occupationally exposed to ethylene oxide were analysed by the alkaline elution method. These individuals were occupied with the sterilization of medical devices in hospitals and in commercial plants. Ethylene oxide in the air of the working areas was detected up to a maximal concentration of 16.5 mg/m3 calculated as 4-h time-weighted average (4h TWA). Mean value was 1.47 +/- 0.52 mg/m3 (1 mg/m3 = 0.55 ppm). Compared to the mean elution rate of the DNA from non-smoking workers exposed to air concentrations of ethylene oxide below the detection limit of 0.1 mg/m3 (4h TWA) the non-smokers working in rooms with a concentration of ethylene oxide between 0.5 mg/m3 and 2 mg/m3 showed a statistically significant (P < 0.05) 119% higher mean elution rate and even for the non-smokers exposed to 0.1-0.5 mg/m3 of ethylene oxide a statistically significant (P < 0.05) 53% higher mean elution rate was observed. For smokers a similar tendency was found but the increase in elution rates in response to the external exposure was smaller than in non-smokers and no statistical significance was obtained. According to their sensitivity to ethylene oxide the non-smoking workers could be classified into two subpopulations. In the majority of the non-smokers (67%) approximately 5-fold more DNA strand breaks were induced by ethylene oxide than in the other non-smokers. A lowest detectable effect level could only be specified for non-smokers. (ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants, Occupational↗
PubMed1994

Cigarette smoking protects mononuclear blood cells of carcinogen exposed workers from additional work exposure-induced DNA single strand breaks.

DNA single-strand breaks in mononuclear blood cells (MNC) of taxi drivers, painters, ethylene oxide-exposed sterilization workers, metal workers, and car mechanics were detected by alkaline filter elution and compared to smoking and non-smoking control persons. Cigarette smoking caused a small but statistically significant increase in control persons (13.5%). In all occupationally exposed groups except the car mechanics, statistically significant increases of DNA single-strand breaks were detected in non-smokers compared to non-smoking controls or comparing groups with high and low exposure. For non-smoking workers the increase in DNA single-strand breaks was found to be 22% for taxi drivers, 60% for painters, 70% for ethylene oxide-exposed workers, and 69% for metal workers compared to control persons. For smokers, however, the increase in DNA single-strand breaks caused by additional occupational exposure was smaller and did not reach statistical significance in any of the occupational groups investigated in this study. Since a high level of glutathione may help to detoxify electrophilic DNA-damaging agents we measured the concentration of total glutathione in MNC of smoking and non-smoking control persons. The glutathione concentration was 13% higher in smokers, but statistical significance was weak (p < 0.05; t-test). Thus cigarette smoking, which represents a highly significant risk factor in carcinogenesis by itself, protects on the other hand against some additional genotoxic insults.

Carcinogens↗
PubMed1994

Sequence organization and the mechanism of interstitial deletion clustering in a plant genome (Vicia faba).

Intercalary deletions and duplication-deletions are types of chromatid aberrations typical of the aberration spectrum observed in the first mitosis of plant cells after mutagen treatment. They are the results of error-prone recombination repair and arise when reunion is not prevented by inhibition of DNA synthesis. Both types of aberrations are nearly exclusively located in chromosome regions composed of tandemly arranged highly repetitive DNA sequences (e.g. FokI elements). The data discussed in the present paper make it possible to arrive at a simple mechanistic interpretation of the origin of these aberration types.

Chromatids↗
PubMed1994

Antioxidant inhibition of skin inflammation induced by reactive oxidants: evaluation of the redox couple dihydrolipoate/lipoate.

Reactive oxygen species play an important role in mediating skin inflammation, and antioxidants may provide protection. We investigated the anti-inflammatory activity of natural antioxidants, such as superoxide dismutase, catalase, trolox (a water-soluble tocopherol analog) and the redox couple dihydrolipoate/lipoate in skin. Furthermore we compared the anti-inflammatory potency of natural R and racemic dihydrolipoate, as well as R and S lipoate. Skin inflammation in hairless mice was induced by intradermal injection of the hydrogen peroxide producing enzyme glucose oxidase (GOD) or by topical application of the prooxidant drug anthralin. Intradermal injection of the antioxidants inhibited skin inflammation caused by GOD (catalase, dihydrolipoate) and anthralin (trolox, superoxide dismutase, dihydrolipoate). There was no statistically significant difference between the anti-inflammatory activity of the natural R and racemic dihydrolipoate. R or S lipoate did not inhibit skin inflammation when injected intradermally. In feeding experiments, however, R lipoate significantly inhibited GOD-mediated skin inflammation, while S lipoate was only marginally protective. We conclude that (1) several natural antioxidants such as catalase, superoxide dismutase and dihydrolipoate have anti-inflammatory properties in dermatitis induced by reactive oxidants, (2) lipoate (oxidized dihydrolipoate) has skin anti-inflammatory activity when administered orally and (3) naturally occurring R lipoate is a more potent anti-inflammatory agent than the non-physiological S lipoate.

Animals↗
PubMed1994

Penetration of spin-labeled dihydrolipoate into the skin of hairless mice. Modification of epidermal and dermal polarity.

Electron paramagnetic resonance (EPR) imaging with the modulated field gradient technique is a novel method to investigate skin biophysical and biochemical properties employing specific nitroxide spin probes. Using this method, a distinct increase in polarity from epidermis towards lower dermis is observed with the spin label dit-butylnitroxide (DTBN). With proxylmaleimide a considerable increase in mobility is found, when epidermis is compared with dermal compartments. The effect of the natural antioxidant dihydrolipoate on skin membrane polarity was studied. Skin penetration of spin labeled dihydrolipoate was investigated by EPR imaging. The results indicate that dihydrolipoate also increases membrane polarity. The biophysical and biochemical changes in the epidermis and dermis as revealed by spatial imaging, provide indirect evidence for skin penetration of dihydrolipoate. This conclusion was supported by the finding that spin labeled derivatives of dihydrolipoate and lipoate were detected inside epidermis and dermis by EPR imaging. This study demonstrates the feasibility of EPR imaging to investigate pharmacodynamic and pharmacokinetic properties of spin labeled drugs in skin.

Animals↗