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Biomedical subjects

M Faust

Publications and source records attributed to M Faust.

At least 37 records · Page 2Linked to original sources
PubMed2003

Water quality objectives for mixtures of toxic chemicals: problems and perspectives.

The need to develop water quality objectives not only for single substances but also for mixtures of chemicals seems evident. For that purpose, the conceptual basis could be the use of the two existing biometric models: concentration addition (CA) and independent action (IA), which is also called response addition. Both may allow calculation of the toxicity of mixtures of chemicals with similar modes of action (CA) or dissimilar modes of action (IA), respectively. The joint research project Prediction and Assessment of the Aquatic Toxicity of Mixtures of Chemicals (PREDICT) within the framework of the IVth Environment and Climate Programme of the European Commission, provided the opportunity to address (a) chemometric and QSAR criteria to classify substances as supposedly similarly or dissimilarly acting; (b) the predictive values of both models for the toxicity of mixtures at low, statistically nonsignificant effect concentrations of the individual components; and (c) the predictability of mixture toxicity at higher levels of biological complexity. In this article, the general outline, methodological approach, and some preliminary findings of PREDICT are presented. A procedure for classifying chemicals in relation to their structural and toxicological similarities has been developed. The predictive capabilities of CA and IA models have been demonstrated for single species and, to some extent, for multispecies testing. The role of very low effect concentrations in multiple mixtures has been evaluated. Problems and perspectives concerning the development of water quality objectives for mixtures are discussed.

Animals↗
PubMed2002

Specific localization of the catalytic subunits of protein kinase CK2 at the centrosomes.

The protein kinase CK2 holoenzyme is composed of two regulatory beta subunits and two catalytic alpha or alpha' subunits. Although experimental evidence for involvement of the enzyme in the regulation of cell proliferation is accumulating, the exact mechanism of its action is still unclear. The subcellular localization of the enzyme may be a key to its function. We have recently shown that the CK2 holoenzyme is tightly associated with the Golgi complex and the endoplasmic reticulum. Centrosomes, which organize spindle formation during the cell cycle and microtubule cytoskeleton formation and, thereby, the location and orientation of different organelles in the cell, are in close vicinity to the Golgi complex. Because several kinases and phosphatases have been described to regulate the functions of the centrosome, we analysed the association of CK2 with these organelles. Using biochemical cell fractionation and coimmunoprecipitation, we never found the holoenzyme but only the catalytic alpha subunits associated with the centrosome. These data were confirmed by immunoelectron microscopy. Thus, the present data point to a particular role of the catalytic alpha and alpha' subunit of protein kinase CK2, which may be different from their roles in the holoenzyme.

Animals↗
PubMed2001

Predicting the joint algal toxicity of multi-component s-triazine mixtures at low-effect concentrations of individual toxicants.

Herbicidal s-triazines are widespread contaminants of surface waters. They are highly toxic to algae and other primary producers in aquatic systems. This results from their specific interference with photosynthetic electron transport. Risk assessment for aquatic biota has to consider situations of simultaneous exposure to various of these toxicants. In tests with freshwater algae we predicted and determined the toxicity of multiple mixtures of 18 different s-triazines. The toxicity parameter was the inhibition of reproduction of Scenedesmus vacuolatus. Concentration-response analyses were performed for single toxicants and for mixtures containing all 18 s-triazines in two different concentration ratios. Experiments were designed to allow a valid statistical description of the entire concentration-response relationships, including the low concentration range down to EC1. Observed effects and effect concentrations of mixtures were compared to predictions of mixture toxicity. Predictions were calculated from the concentration-response functions of individual s-triazines by applying the concepts of concentration addition and independent action (response addition) alternatively. Predictions based on independent action tend to underestimate the overall toxicity of s-triazine mixtures. In contrast, the concept of concentration addition provides highly accurate predictions of s-triazine mixture toxicity, irrespective of the effect level under consideration and the concentration ratio of the mixture components. This also holds true when the mixture components are present in concentrations below their individual NOEC values. Concentrations statistically estimated to elicit non-significant effects of only 1% still contribute to the overall toxicity. When present in a multi-component mixture they can co-operate to give a severe joint effect. Applicability of the findings obtained with s-triazines to mixtures of other contaminants in aquatic systems and consequences for risk assessment procedures are discussed.

Chlorophyta↗
PubMed2001

Global public goods and health: taking the agenda forward.

We examined recent special health initiatives to control HIV/AIDS, malaria, and tuberculosis, and make four policy recommendations for improving the sustainability of such initiatives. First, international cooperation on health should be seen as an issue of global public goods that concerns both poor and rich countries. Second, national health and other sector budgets should be tapped to ensure that global health concerns are fully and reliably funded; industrialized countries should lead the way. Third, a global research council should be established to foster more efficient health-related knowledge management. Fourth, managers for specific disease issues should be appointed, to facilitate policy partnerships. Policy changes in these areas have already begun and can provide a basis for further reform.

Communicable Disease Control↗
PubMed2001

Wild-type p53 inhibits protein kinase CK2 activity.

The growth suppressor protein p53 and the protein kinase CK2 are both implicated in cellular growth regulation. We previously found that p53 binds to protein kinase CK2 via its regulatory beta-subunit. In the present study, we analyzed the consequences of the binding of p53 to CK2 for the enzymatic activity of CK2 in vitro and in vivo. We found that the carboxy-terminus of p53 which is a potent transforming agent stimulated CK2 activity whereas full length wild-type p53 which is a growth suppressor inhibited the activity of protein kinase CK2. Inhibition of protein kinase CK2 by p53 was dose-dependent and was seen for various CK2 substrates. Experiments with heat-denatured p53 and the conformational mutant p53(R175H) revealed that an intact conformation of p53 seemed to be necessary. Transfection of wild-type and of mutant p53 into p53-/- cells showed that the inhibition of p53 on CK2 activity was also detectable in intact cells and specific for wild-type p53 indicating that the growth suppressing function of p53 might at least be partially achieved by down-regulation of protein kinase CK2.

Amino Acid Sequence↗
PubMed2001

Analysis of standard and non-standard visual word format in the two hemispheres.

A dual-route model for the recognition of written words is hypothesised. The model postulates that the two cerebral hemispheres differ in their sensitivity to the visual format of verbal stimuli. Such stimuli may be 'standard', that is in Standard Visual Format (SVF), or "non-standard", i.e. in non-standard Visual Format (NSVF). In the left hemisphere (LH), SVF words are routed directly to the lexicon, while NSVF words must go through an additional encoding phase prior to lexicon access. In the right hemisphere (RH) all words (SVF and NSVF) must proceed to an additional encoding phase prior to accessing the lexicon. Two lateralized lexical decision experiments are reported. In Section 2, angle of orientation was used to define SVF and NSVF. In Section 3, presentation of verbal stimuli was preceded by a cue indicating whether the coming lexical stimulus was in SVF or NSVF, while SVF was defined as in Section 2. The results showed that the difference in RT, favouring RVF stimulation was found for orientations up to 30 degrees. Greater angles of presentation significantly reduced RVF superiority. The largest differences between responses to stimuli presented to the two visual fields was found when word stimuli were in SVF (up to 30 degrees ) and presented after a priming cue. The results are discussed in terms of the model, but alternative explanations are suggested.

Adult↗
PubMed2001

Bihemispheric sensitivity to sentence anomaly.

This study investigated cerebral asymmetries in sensitivity to sentence-level semantic anomaly. To separate the effects of anomalous message processing from those attributable to low sentence constraint, low-constraint sentence-fragment primes were followed by target words presented to the left or right visual fields. When completed by the target word, the sentences represented either normal or anomalous messages; in addition, one-half of the sentence primes contained a word strongly related to the target. Targets presented to both the left and right visual fields were advantaged by the presence of a related word, and disadvantaged by the presence of a semantically anomalous message. Contrary to some previous claims, this result implies that the right hemisphere can construct some message-level interpretations from sentences, such that semantic anomaly is registered, even if finer gradations of sentence constraint are not. This rudimentary integration of word meanings in sentences may provide a scaffolding for right hemisphere discourse processing. In light of these findings, we propose a revised view of left/right hemisphere differences in the processes used to interpret sentence meaning.

Adult↗
PubMed2001

QSAR approach for the selection of congeneric compounds with a similar toxicological mode of action.

The selection of compounds with a similar toxicological mode of action is a key problem in the study of chemical mixtures. In this paper, an approach for the selection of chemicals with similar mode of action, based on the analysis of structural similarities by means of QSAR and chemometric methods, is described. As a first step, a complete representation of chemical structures for examined chemicals (phenylureas and triazines) by different sets of molecular descriptors allows a preliminary exploration of similarity using multi-dimensional scaling (MDS). The use of genetic algorithm (GA) to select the most relevant molecular descriptors in modeling toxicity data makes it possible to develop predictive toxicity models. The final step is a similarity analysis, based again on MDS, using selected molecular descriptors, really relevant in describing the toxicological effect.

Humans↗
PubMed2001

Evidence from sentence priming for an atypical language organisation in the brain of dyslexic males.

The present study used an experimental paradigm that combined sentence priming, lexical decision, and visual hemifield stimulation to investigate the relationship between dyslexia and linguistic processing by the two hemispheres. It was predicted that left hemisphere (LH) superiority for word recognition in a constraining versus a neutral sentence context would be reduced, or even reversed in dyslexic as compared to normal participants. Because both dyslexia and LH superiority for language processing are considered to be more prevalent for males than for females, it was further expected that this decrease, or reversal, in LH superiority for word recognition in a sentence context would be more pronounced for males with dyslexia than for females with dyslexia. A total of 88 children, half of whom were females, participated in the study: 44 children were diagnosed as dyslexic and 44 were normal readers. The results generally confirmed the hypothesis and provided strong support for a reversal in hemispheric asymmetry in males with dyslexia. Implications for sentence processing of the excessive involvement of the right hemisphere (RH) in the dyslexia of males are discussed and the lexical-decision-sentence-priming paradigm is recommended as a promising means of exploring the issues related to these implications.

Journal Article↗
PubMed2001

A general best-fit method for concentration-response curves and the estimation of low-effect concentrations.

Risk assessments of toxic chemicals currently rely heavily on the use of no-observed-effect concentrations (NOECs). Due to several crucial flaws in this concept, however, discussion of replacing NOECs with statistically estimated low-effect concentrations continues. This paper describes a general best-fit method for the estimation of effects and effect concentrations by the use of a pool of 10 different sigmoidal regression functions for continuous toxicity data. Due to heterogeneous variabilities in replicated data (i.e., heteroscedasticity), the concept of generalized least squares is used for the estimation of the model parameters, whereas a nonparametric variance model based on smoothing spline functions is used to describe the heteroscedasticity. To protect the estimates against outliers, the generalized least-squares method is improved by winsorization. On the basis of statistical selection criteria, the best-fit model is chosen individually for each set of data. Furthermore, the bootstrap methodology is applied for constructing confidence intervals for the estimated effect concentrations. The best-fit method for the estimation of low-effect concentrations is validated by a simulation study, and its applicability is demonstrated with toxicity data for 64 chemicals tested in an algal and a bacterial bioassay. In comparison with common methods of concentration-response analysis, a clear improvement is achieved.

Data Interpretation, Statistical↗
PubMed2001

Localization of individual subunits of protein kinase CK2 to the endoplasmic reticulum and to the Golgi apparatus.

The protein kinase CK2 is composed of two catalytic alpha- or alpha'- and two regulatory beta-subunits. In mammalian cells there is ample evidence for the presence of individual CK2 subunits beside the holoenzyme. By immunofluorescence studies using peptide antibodies which allow us to detect the CK2alpha-, alpha'- and beta-subunits we found all three subunits to be co-localized with a 58 KDa Golgi protein which is specific for the Golgi complex. Subfractionation studies using dog pancreas cells revealed the presence of all three subunits of CK2 at the smooth endoplasmic reticulum (sER)/Golgi fraction whereas the rough endoplasmic reticulum (rER) harboured only the catalytic alpha- and alpha'-subunits. We found that the microsomal preparation from dog pancreas cells contained CK2 which phosphorylated a CK2 specific synthetic peptide and which was heparin sensitive. Furthermore, we could immunoprecipitate the CK2alpha-subunit that exhibited a kinase activity which phosphorylated a CK2 specific substrate and which was heparin sensitive. Protease digestion experiments revealed that the CK2 subunits were located on the cytosolic side of the rER and the sER/Golgi complex. Thus, we could demonstrate an asymmetric distribution of the CK2 subunits at the rER and sER/Golgi complex. Since the CK2alpha- and alpha'-subunits exhibit a substrate specificity which is different from the CK2 holoenzyme one might speculate that the asymmetric distribution of the CK2 holoenzyme and the CK2 catalytic subunits may have regulatory functions.

Animals↗
PubMed2000

[Coronary heart disease prevention. Are there differences in cholesterol synthesis inhibitors?].

All statins have been shown to reduce plasma cholesterol concentrations significantly. Cardioprotective effects of these drugs appear to be mainly due to cholesterol lowering. It remains unclear whether pharmacokinetic differences of statins are of clinical relevance. The clinical studies with statins performed on more than 30,000 individuals demonstrate that lipid lowering drug therapy not only reduces cardiovascular complications but also is a safe and well tolerated long-term therapy. However, the majority of patients who should be treated according to appropriate guidelines, still do not receive any cholesterol lowering therapy. Therefore, it is a main goal that at least high-risk patients (e.g. with coronary heart disease or diabetes mellitus type 2) should be treated with statins.

Anticholesteremic Agents↗
PubMed2000

Sentence and word outline shape as co-primes for target words presented to the two visual hemifields.

A lexical decision experiment tested visual field stimulation of word targets after priming the central visual field by the target word outline shape and/or an incomplete sentence. In general, RT was shorter and accuracy better for target words presented to the RVF. Responses were quicker and more accurate to target words presented to either visual hemifield after priming by either a congruent incomplete sentence or a congruent word outline shape (WOS). However, the joint effect of WOS and an incomplete sentence as co-primes was different when the succeeding word target appeared in the RVF than when it appeared in the LVF. While a congruent WOS and incomplete sentence acting as co-primes reduced RT to LVF targets orthogonally. the two variables operated interactively as co-primes on target words presented to the RVF.

Adult↗
PubMed2000

Subcellular localization of protein kinase CK2. A key to its function?

More than 46 years ago, Burnett and Kennedy first described protein kinase CK2 (formerly known as casein kinase 2) in liver extracts. Since then, protein kinase CK2 has been investigated in many organisms from yeast to man. It is now well established that protein kinase CK2 is a pleiotropic and ubiquitous serine or threonine kinase, which is highly conserved during evolution. A great number of studies deal with substrates of CK2, but the fact that over 160 substrates exist is more confusing than elucidatory. The holoenzyme is composed of two regulatory beta-subunits and two catalytic alpha- or alpha'-subunits. There is now increasing evidence for individual functions of the subunits that are different from their functions in the holoenzyme. Furthermore, more and more studies describe interacting partners of the kinase that may be decisive in the regulation of this enzyme. A big step forward has been the determination of the crystal structure of the two subunits of protein kinase CK2. Now the interactions of the catalytic subunit of CK2 with ATP as well as GTP and the interaction between the regulatory subunits can be explained. However, cellular functions of protein kinase CK2 still remain unclear. In the present review we will focus our interest on the subcellular localization of protein kinase CK2. Protein kinase CK2 is found in many organisms and tissues and nearly every subcellular compartment. There is ample evidence that protein kinase CK2 has different functions in these compartments and that the subcellular localization of protein kinase CK2 is tightly regulated. Therefore studying the subcellular localization of protein kinase CK2 may be a key to its function.

Animals↗
PubMed2000

The effect of immigration and welfare reform legislation on immigrants' access to health care, Cuyahoga, and Lorain Counties.

This study examined the effect of the passage of the Personal Responsibility and Work Opportunity Reconciliation Act of 1996 and the Illegal Immigration Reform and Immigrant Responsibility Act of 1996 on immigrants' ability to access health care in two counties in Northeastern Ohio. Semistructured interviews were conducted with 251 individuals of varying immigration status and ethnicity. Data collected included type of recent illness, type and location of care received, type of health insurance, if any, and problems encountered. Significant associations were found between birth in a former Soviet-controlled area and use of public insurance. We did not detect an adverse effect of the welfare and immigration reform laws on ability to access care, most likely because a large proportion of respondents were permanent residents or asylees and were eligible for publicly funded medical care under the reform laws. The most common problems in obtaining medical care included lack of insurance and/or money, transportation, language, dissatisfaction with the doctor's care, and long waits. Individuals born in former Soviet-controlled areas as well as those who spoke Spanish or Slavic languages at home or work reported more difficulties in accessing care. Many undocumented individuals indicated that they would delay or refrain from seeking care due to fear of immigration consequences.

Journal Article↗
PubMed2000

Determining needs and setting priorities for HIV-affected and HIV-infected persons: northeast Ohio and San Diego.

The Ryan White Comprehensive AIDS Resources Emergency (CARE) Act of 1991 requires that communities receiving Title I funding engage in a needs assessment and priority process to guide the allocation of those funds to various services within the local community. This paper reports on the process and results of the needs assessments in northeast Ohio and San Diego County for 1996-1997 and 1998. Data from northeast Ohio's 1998 needs assessment indicated significant differences between whites and nonwhites in the utilization of HIV specialist care, HIV-related prescription medications such as antiretrovirals, and health insurance. A need for additional dental care, complementary therapies, housing, and assistance with utility payments was found in both geographic areas. Consumer participation in San Diego's health department-based needs assessment process was more extensive than in northeast Ohio's academic-based approach but was also related to increased community-borne expense.

Adult↗
PubMed2000

Five cases with central diabetes insipidus and hypogonadism as first presentation of neurosarcoidosis.

OBJECTIVES: We retrospectively reviewed 5 patients with neurosarcoidosis, who all presented with central diabetes insipidus and hypogonadism. DESIGN: This was a single-centre, retrospective analysis of 5 cases with a minimum follow-up of 2 years. METHODS: Case analysis included clinical, biochemical, and endocrinological evaluation and frequent CT/MRI scans of involved organs as primary evaluation and in response to immunosuppressive therapy. RESULT: Neurosarcoidosis was diagnosed in all patients. Two patients had no proven extracerebral manifestation and had a stable disease over 3 and 5 years. One patient showed deterioration with corticosteroids alone but partial remission after additional cyclophosphamide. Pituitary dysfunction remained unchanged in all patients, despite total clinical and radiological remission in two patients. However, one of these patients died of acute granulomatous meningoencephalitis after two years of follow-up. CONCLUSION: Although the presenting symptoms of neurosarcoidosis may vary, the occurrence of central diabetes insipidus associated with typical radiological features is suggestive of neurosarcoidosis. However, there is an increasing number of case reports on lymphocytic hypophysitis. Without the bioptic diagnosis, the differentiation between potentially lethal isolated neurosarcoidosis and lymphocytic hypophysitis is difficult. These cases demonstrate the difficulties in diagnosing neurosarcoidosis and reflect experiences with follow-up parameters.

Adult↗