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A Hartwig

Publications and source records attributed to A Hartwig.

At least 55 records · Page 3Linked to original sources
PubMed1993

Cellular damage by ferric nitrilotriacetate and ferric citrate in V79 cells: interrelationship between lipid peroxidation, DNA strand breaks and sister chromatid exchanges.

Ferric nitrilotriacetate (Fe-NTA) and ferric citrate (Fe-citrate) were used to study the cellular damage mediated by iron overload with respect to cytotoxicity, lipid peroxidation, DNA strand breaks and sister chromatid exchanges (SCE). At non-toxic concentrations, Fe-NTA induced lipid peroxidation, DNA strand breaks and SCE in a dose- and time-dependent manner. Comparing the time courses of the different events, the increase in lipid peroxidation seems to be associated with the generation of DNA strand breaks, since both types of cellular damage were observed after 1-3 h of incubation. In contrast, the induction of SCE was low after 24 h and increased after 48 and 72 h treatment, indicating the requirement of other types of DNA damage. Fe-citrate was inactive in the induction of lipid peroxidation and SCE, and no significant number of DNA strand breaks were generated, as determined by the alkaline unwinding method. Our results suggest that the induction of lipid peroxidation and DNA strand breaks by iron overload depend on special features of the iron complex applied, while the chromosomal and genetic effects require site specific DNA damage dependent on intracellular iron metabolism. It is concluded that iron overload is able to induce genetic damage in intact cells provided that iron is present in a bioavailable form.

Animals↗
PubMed1993

Toward a nosology of human aggressive behavior.

General attempts have been made to catalog or categorize research literature on aggressive behavior. In the animal literature this category has been delineated by clearly observed and described patterns of behavior. These include offensive and defensive expressions in animals and the characterization of attack behaviors by typography into defensive and offensive. The human literature is considerably deficient in the description and categorization of human aggressive behavior. Current nosologies offer no utilitarian schema for characterizing violent behavior in clinical populations regarding the typography of the violence, its prediction, or guidance as to its treatment. The generation of databased nosologies may provide a mechanism for the development of research and clinically relevant nosologies based upon cluster analyses of treatment outcomes and behavioral characteristics. This strategy may provide a more effective approach for further research concerning clinical aggressive or destructive behaviors.

Aggression↗
PubMed1992

Mechanisms of cobalt(II) uptake into V79 Chinese hamster cells.

V79 Chinese hamster cells were used as a model for the characterization of the Co(II) uptake into mammalian cells as well as the mechanisms involved. Co(II) was taken up in a dose and time dependent manner. The uptake was exponential without saturation in the tested concentration range up to 400 microM CoCl2. Furthermore, there was a high intracellular cobalt accumulation at elevated extracellular Co(II) doses (up to 16 fold at 200 microM). The time course of Co(II) uptake showed a maximum after about 8-12 h with no further change after the longest tested incubation time (24 h). The uptake of Co(II) into V79 cells seems to be mediated by multiple mechanisms: active, energy consuming transport like ion pumps and endocytosis, since the Co(II) uptake was significantly reduced by ouabain (an inhibitor of the Na+/K+ATPase), N-ethylmaleinimide (an inhibitor of the Ca2+/Mg2+ATPase and the Na+/K+ATPase), chlorpromazine (a calmodulin antagonist and inhibitor of the Ca2+/Mg2+ ATPase) as well as by the endocytosis inhibitor chloroquine. Furthermore, the two agents iodoacetate and potassium cyanide, which produce ATP depletion, resulted in a diminution of the intracellular cobalt concentration. An uptake through anion channels could be excluded, since 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid was not inhibitory.

Animals↗
PubMed1992

The genetic toxicology of cobalt.

Genetic and related effects of cobalt compounds are reviewed and discussed with respect to mechanisms. In prokaryotic assays, Co(II) salts generally are nonmutagenic. In Saccharomyces cerevisiae, CoCl2 is mutagenic to mitochondrial genes and weakly mutagenic or nonmutagenic to chromosomal genes. In plants, Co(II) salts induced gene mutations and chromosomal aberrations. In mammalian cells in vitro, Co(II) compounds caused DNA strand breaks, sister-chromatid exchanges and aneuploidy, but not chromosomal aberrations. In two cell lines, CoCl2 was weakly mutagenic. Interestingly, the poorly soluble compound CoS caused DNA strand breaks and morphological transformation of mammalian cell lines. In contrast to its weak clastogenic and mutagenic properties, cobalt(II) exerts pronounced antimutagenicity in bacteria and mostly comutagenic effects in mammalian cells. In Escherichia coli CoCl2 lowered the frequency of mutations induced by MNNG, uv or X rays. In Chinese hamster V79 cells, CoCl2 enhanced the mutagenicity and clastogenicity of uv light but not of gamma rays. Regarding direct genotoxic mechanisms, Co(II) induces the formation of reactive oxygen species when combined with hydrogen peroxide in cell-free systems. At high (i.e., millimolar) concentrations, Co(II) also decreases the fidelity of DNA synthesis. Regarding anti- and co-mutagenic mechanisms, evidence for the interference of Co(II) with DNA repair processes is discussed. These mechanisms are regarded as relevant for the risk assessment of human exposure to cobalt in combination with other agents.

Animals↗
PubMed1991

Modulation by Co(II) of UV-induced DNA repair, mutagenesis and sister-chromatid exchanges in mammalian cells.

In bacterial test systems, Co(II) has been shown to be antimutagenic in combination with several chemical and physical agents. To investigate whether such modulations also apply to mammalian cells, the effect of Co(II) on UV-induced mutagenesis, sister-chromatid exchanges as well as DNA damage and its removal was determined. Co(II) itself is weakly mutagenic at the HPRT locus and increases the frequency of sister-chromatid exchanges. Additionally, at both endpoints the metal ions enhance the genotoxicity of UV light. To discriminate between an enhancement of DNA damage and an interference with repair processes, the number of pyrimidine cyclobutane dimers was determined by HPLC. While the induction of these DNA lesions is not affected by Co(II), their removal is inhibited at concentrations of 75 microM Co(II) and higher. Analysis of the kinetics of strand-break induction and closure after UV irradiation by nucleoid sedimentation reveals an accumulation of strand breaks in the presence of Co(II). This indicates that either the polymerization or the ligation step in excision repair is affected. Since similar interactions with the processing of UV-induced DNA damage have been observed with other carcinogenic and/or mutagenic metal ions, this appears to be a common mechanism of metal genotoxicity.

Animals↗
PubMed1990

Indirect mechanism of lead-induced genotoxicity in cultured mammalian cells.

The data concerning the mutagenic, clastogenic and carcinogenic properties of inorganic lead compounds have been conflicting. To investigate whether the genotoxicity of lead is due to indirect effects such as interference with DNA-repair processes, the induction of mutations, sister-chromatid exchanges and strand breaks by lead ions alone as well as in combination with UV light as a standard mutagen were determined. Lead acetate alone does not induce DNA-strand breaks in HeLa cells or mutations at the HPRT locus and sister-chromatid exchanges in V79 Chinese hamster cells. However, at all endpoints tested, lead ions interfere with the processing of UV-induced DNA damage. They inhibit the closing of DNA-strand breaks after UV irradiation and enhance the number of UV-induced mutations and sister-chromatid exchanges, indicating an inhibition of DNA repair. These data point out the necessity to consider such indirect effects when assessing the genotoxicity of metal compounds. As possible mechanisms of repair inhibition we suggest either the interaction with repair enzymes such as polymerase or ligase or else the interaction with calcium-regulated processes, for example with calmodulin.

Animals↗
PubMed1990

The Carolina Nosology of Destructive Behavior (CNDB).

This article sets forth a multiaxial system for cataloging individuals who manifest destructive behavior toward themselves, others, or property. An initial codification to describe the characteristics of the destructive behavior of the individual is presented, followed by a description of a quaternary axial system which catalogs in a clinically relevant manner, individuals engaging in destructive behavior. The four axes presented and developed are Axis A--a medical diagnosis axis, Axis B--an axis of psychological correlates, Axis C--an axis of biological correlates, and Axis D--an axis of moral/cultural correlates. This nosology is proposed in order to standardize the coding of human destructive behavior. It is intended to be used by members of the clinical and research communities in order to compare patient types and their relationship to treatment interventions.

Aggression↗
PubMed1990

Ethical issues in selecting patients for treatment with clozapine: a commentary.

Three ethical constructs of distributive justice--utilitarianism, Marxism, and the theories of John Rawls--are applied to selection of patients for treatment with clozapine. Elements of an ethical selection process include a means of monitoring the clinical effectiveness of the drug so that it is not wasted and procedures for ensuring that patients' rights to advocacy and due process are met. The authors suggest that a disproportionate number of patients with tardive dyskinesia may receive clozapine because clinicians and hospitals risk litigation if these patients continue to receive standard neuroleptics and experience worsening side effects.

Chronic Disease↗
PubMed1989

Enhancement of UV-induced mutagenesis and sister-chromatid exchanges by nickel ions in V79 cells: evidence for inhibition of DNA repair.

With regard to contradictory results concerning the mutagenicity of nickel compounds in short-term assays, especially in bacterial test systems, Chinese hamster V79 cells were used to measure mutagenicity, comutagenicity and the induction of sister-chromatid exchanges (SCEs) by NiCl2. We confirmed the induction of mutations at the HGPRT locus as well as SCEs. In addition, NiCl2 shows a pronounced comutagenic effect towards UV. When using confluent cultures or resting cells due to serum deprivation, where more time is given for repair processes, the comutagenic effect is higher compared to logarithmically growing cells (10 and 4 times, respectively, compared to twice). Hence, we attribute this enhancement in mutagenicity to inhibition of DNA repair. Also the increase in induced SCEs after combined treatment with UV and NiCl2 supports this thesis. Furthermore, NiCl2 enhances the cyto-toxicity of cis-DDP about 12-fold. Since no comutagenic effect is observed in combination with MMS, we suggest that the inhibition of DNA repair by Ni(II) applies to all DNA changes that are repaired by the 'long-patch' excision repair system. This inhibition may occur via replacement of other divalent metal ions essential in repair and regulation processes.

Cell Line↗
PubMed1988

Genetic toxicology of lead compounds.

We have investigated the activity of insoluble and soluble lead compounds in inducing mutagenesis, cell transformation and sister chromatid exchange in mammalian cells. Insoluble lead sulfide, readily phagocytized, was more than four times as toxic to V79 cells on a microM basis, than two moderately soluble lead compounds although the exposure time for the soluble salts was five times longer. These findings demonstrate the importance of different cellular mechanism(s) of metal uptake and bioavailability. Both insoluble lead sulfide and more soluble lead nitrate were mutagenic at the HPRT locus in V79 cells. Although less mutagenic at the higher concentrations, lead nitrate at a concentration of 500 microM enhanced the mutation frequency greater than 6-fold above background following a 5-day exposure. Although the mechanism(s) by which lead induces mutations is unknown, failure of both compounds to induce SCE and DNA single-strand breaks, detectable by alkaline elution, suggests that lead-induced mutations may not be a result of direct damage to DNA but may occur via indirect mechanisms including disturbances in enzyme functions important in DNA synthesis and/or repair, or in DNA-helical structure. Lead acetate also transformed SHE cells in a dose-response fashion following a 48-h exposure. Our results indicate that lead compounds may be genotoxic by an indirect mechanism, and lend support to the view that lead is a carcinogen.

Animals↗
PubMed1984

Ethics and psychiatric research: problems and justification.

The discussion of ethics in psychiatry continues to increase. Research in psychiatry, like all medical research, is of ethical concern because it often involves risks to subjects so that others may benefit. It also involves the allocation of monetary and human resources. In recent years these concerns have been brought to the forefront of professional and public attention. The authors consider the problem of justifying resource allocations and the risks involved in psychiatry research, survey some of the special problems faced by researchers in this field, and give a brief account of present government regulations that pertain to research ethics in psychiatry.

Behavioral Research↗
PubMed1982

[Erythrocyte creatine concentration in infants and children with congenital heart disease and left-to-right shunts (author's transl)].

The creatine concentration of red blood cells was determined in 58 children with congenital acyanotic malformations of the heart at the age of 3 weeks to 3 1/2 years. It was correlated to the severity of the hemodynamic changes, the physical development of the children and number of reticulocytes. The average creatine concentration in the red cells of all patients was 12.8 +/- 4.80 mg/100 ml cells, i.e. twice as high as that of the control group (6.61 +/- 1.19 mg/100 ml cells). Particularly high creatine values were found in children, who died in consequence of their heart disease without previous operation (18.49 +/- 4.25 mg/100 ml cells, n = 11) and those children who had to be operated on as a life-saving measure (17.88 +/- 3.43 mg/100 ml cells, n = 10). The highest creatine concentration was found in a 4 weeks-old infant with hypoplastic left heart syndrome (25.3 mg/100 ml cells). In children with a systolic pressure in the pulmonary artery of greater than 50 torr the creatine concentration was significantly higher than in those with pressures less than 50 torr. Increased creatine values correlated well with the poor physical development and increased reticulocyte numbers of the children. There was no correlation found between capillary pO2 and creatine concentration. It is concluded that the determination of erythrocyte creatine in children with congenital heart disease of the left-right shunt type furnishes additional objective information on the general condition of the organism and its adaptation capacities to hypoxia. It may serve as a valuable diagnostic and prognostic measure.

Blood Cell Count↗
PubMed1982

[Varrosis].

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Animals↗
PubMed1981

Creatine in density-fractionated red cells, a useful indicator of erythropoietic dynamics and of hypoxia past and present.

Creatine in density-fractionated red cells is not only a useful criterion of cell age but also an excellent indicator of erythropoietic dynamics particularly under the influence of present and past hypoxia. This is documented on patients with cardiac hypoxia. A histogram is proposed which permits the simultaneous evaluation of four parameters: (1) the creatine concentration of each separate fraction, (2) the absolute density of a given cell fraction, (3) the percentage distribution of cells over the whole gradient and within the different fractions and (4) the general position of the red cell population with respect to its median density, which serves to characterize the overall age of a red cell population. Creatine histograms on fractionated red cells are shown to be useful aids for diagnosis and prognosis in hypoxic clinical states. They may also give retrograde information on past stimulation of erythropoiesis.

Adult↗