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T Höfer

Publications and source records attributed to T Höfer.

8 recordsLinked to original sources
PubMed2001

Intercellular Ca2+ wave propagation through gap-junctional Ca2+ diffusion: a theoretical study.

Intercellular regenerative calcium waves in systems such as the liver and the blowfly salivary gland have been hypothesized to spread through calcium-induced calcium release (CICR) and gap-junctional calcium diffusion. A simple mathematical model of this mechanism is developed. It includes CICR and calcium removal from the cytoplasm, cytoplasmic and gap-junctional calcium diffusion, and calcium buffering. For a piecewise linear approximation of the calcium kinetics, expressions in terms of the cellular parameters are derived for 1) the condition for the propagation of intercellular waves, and 2) the characteristic time of the delay of a wave encountered at the gap junctions. Intercellular propagation relies on the local excitation of CICR in the perijunctional space by gap-junctional calcium influx. This mechanism is compatible with low effective calcium diffusivity, and necessitates that CICR can be excited in every cell along the path of a wave. The gap-junctional calcium permeability required for intercellular waves in the model falls in the range of reported gap-junctional permeability values. The concentration of diffusive cytoplasmic calcium buffers and the maximal rate of CICR, in the case of inositol 1,4,5-trisphosphate (IP3) receptor calcium release channels set by the IP(3) concentration, are shown to be further determinants of wave behavior.

Animals↗
PubMed2000

Use of health hazard criteria for estimating the hazard potential of chemicals to water in case of a spill.

Accidental spills resulting in severe pollution can occur during transportation or handling of large volumes of chemicals. To address this problem, chemicals are classified according to the level of hazard to man and the environment in order to then define graduated technical standards. Three regulatory examples (enforced or drafted for transport and industrial installations in Europe) covering aspects of limnic as well as sea water are discussed in regard to health aspects of pollution. Whereas for the safety of seagoing tankships an exposure orientated combination of health and environmental aspects is used, for industrial plants in Germany a scoring system based on the European Union's Risk Phrase system is applied. The health-related parameters primarily used for hazard classification are repeated-dose toxicity and acute oral and dermal toxicity. Acute oral toxicity is most widely used because of the ready availability of data. Carcinogenicity is treated as the most important hazard. The report discusses the importance of dermal exposure, aspiration, and endocrine disruption as parameters as well as the importance of health criteria for the protection of aquatic organisms.

Animals↗
PubMed1999

Evaluating the hazards of harmful substances carried by ships: the role of GESAMP and its EHS working group.

GESAMP's EHS working group, evaluation of the hazards of harmful substances carried by ships, contributed in the early 1970s to the chemical carriage provisions (Annexes II and III) of the MARPOL Convention, and after formal setup in 1974 under IMCO/IMO, has evaluated the hazards of approximately 2200 chemical substances transported worldwide by shipping. Hazard ratings for chemicals based on five criteria: bioaccumulation in marine organisms and tainting of seafood; damage to marine life defined by aquatic toxicity thresholds; acute hazard to human health, defined by oral intake; hazard to human health on the basis of skin or eye contact; and reduction of amenities, have been assigned by the working group experts (30 scientists from 11 countries overall). The ratings are used by IMO committes to assign marine pollution categories under MARPOL 73/78, ensuring that shipping of chemicals in bulk or as packaged goods is conducted with due consideration for ship type, guidelines for discharges from tank cleaning and deballasting operations, packaging and labeling and response during accidents or loss. Since 1995, the working group has reviewed and revised its hazard criteria, and largely harmonized them with OECD. This will ensure compatibility of criteria and approaches across transport sectors. The criteria now include two measures of bioaccumulation, biodegradation, chronic toxicity to aquatic organisms, additional human health endpoints, and effects on marine wildlife and benthic habitats. The working group maintains a composite list of evaluations of hazards of harmful substances at IMO, London.

Animals↗
PubMed1999

Model of intercellular calcium oscillations in hepatocytes: synchronization of heterogeneous cells.

Hepatocytes respond with repetitive cytosolic calcium spikes to stimulation by vasopressin and noradrenalin. In the intact liver, calcium oscillations occur in a synchronized fashion as periodic waves across whole liver lobules, but the mechanism of intercellular coupling remains unclear. Recently, it has been shown that individual hepatocytes can have very different intrinsic oscillation frequencies but become phase-locked when coupled by gap junctions. We investigate the gap junction hypothesis for intercellular synchronization by means of a mathematical model. It is shown that junctional calcium fluxes are effective in synchronizing calcium oscillations in coupled hepatocytes. An experimentally testable estimate is given for the junctional coupling coefficient required; it mainly depends on the degree of heterogeneity between cells. Intercellular synchronization by junctional calcium diffusion may occur also in other cell types exhibiting calcium-activated calcium release through InsP(3) receptors, if the gap junctional coupling is strong enough and the InsP(3) receptors are sufficiently sensitized by InsP(3).

Animals↗
PubMed1995

Dictyostelium discoideum: cellular self-organization in an excitable biological medium.

The dynamics which govern the establishment of pattern and form in multicellular organisms remain a key problem of developmental biology. We study this question in the case of morphogenesis during aggregation of the slime mould Dictyostelium discoideum. Here detailed experimental information allows the formulation of a mechanistic model in which the central element is the coupling of the previously much-studied intracellular cyclic AMP signalling with the chemotactic cell response in cyclic AMP gradients. Numerical simulations of the model show quantitatively how signal relay, chemotactic movement and adaptation orchestrate the collective modes of cell signalling and migration in the aggregating cell layer. The interaction of chemotaxis with the cyclic AMP excitation waves causes the initially homogeneous cell layer to become unstable towards the formation of a branching cell stream pattern with close cell-cell contacts as observed in situ. The evolving cell morphology in turn leads to a pattern of non-homogeneous excitability of the medium and thus feeds back into the cAMP dynamics. This feedback can explain the decrease in signalling period and propagation speed with time, as well as observations on the structure of the spiral wave core in this self-organized excitable medium.

Animals↗
PubMed1993

A second-order approach to metabolic control analysis.

In the mathematical formalism of metabolic control analysis the changes in metabolite concentrations and fluxes have been related to the underlying parameter perturbations by a linear approximation, thus restricting the analysis to very small parameter perturbations. Obviously, the response of the system variables to larger parameter perturbations can be described more accurately if, in addition to the linear terms, the second-order terms are considered. The basic equations of this approach are derived. The second-order effects can be expressed (i) by the second-order elasticity coefficients of the reaction rates with respect to the kinetic parameters and/or metabolite concentrations, and (ii) by the control coefficients and pi-elasticities of the linear theory. Parameter-independent second-order control coefficients can be defined if the reaction rates depend linearly on the perturbation parameters. These coefficients satisfy summation theorems similar to those of the linear theory. The formalism is applied to an unbranched chain of monomolecular reactions and to a skeleton model of glycolysis. The second-order approximation turns out to be more accurate for a relatively wide range of rate perturbations. However, the use of the second- and higher-order expansions for tackling practical problems seems limited since the required higher-order elasticity coefficients may be hard, if not impossible, to obtain experimentally. These difficulties, as well as the general limitations of the local approach of metabolic control analysis, may be compensated for by a combination with kinetic modelling.

Animals↗
PubMed1982

Selenium in the testis of the rat: studies on its regulation and its importance for the organism.

In male rats, fed for 10 weeks on a Torula yeast-based, low selenium and low vitamin E diet, the selenium level and the glutathione peroxidase activity in the blood and in several tissues decreased by 50 to 98% compared with animals that received the same basal diet supplemented with 0.25 mg Se/kg sodium selenite. In the testes, however, the selenium content did not differ from that of the control animals. Despite the low selenium levels in the extragonadal tissues and their increased requirement of this element due to the low vitamin E status, the selenium from an intravenously injected dose of sodium selenite was retained above all in the testes. After the removal of the pituitary gland, because of the decrease in the testicular mass and in the selenium content in the remaining testicular tissue, the amount of selenium in the testes was greatly reduced. After administration of pregnant mare's serum gonadotropin (PMS), due to the regeneration of the tissue and the simultaneous restoration of the selenium content, a relatively large amount of this element was shifted to the testes even though the selenium status in the other tissues was low. The results of these studies show that the selenium level in the male gonads is maintained by regulation mechanisms and that the supply of sufficient amounts of selenium to the testes has priority over the supply to other tissues.

Animals↗