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I Zimmermann

Publications and source records attributed to I Zimmermann.

At least 19 recordsLinked to original sources
PubMed2005

Development of a long-acting therapeutic system: Part I: A method to produce silicon rubbers with well-defined microstructures.

Based on the free-volume theory of diffusion in rubbers it is shown that the diffusion coefficient D of a permeating drug can be written as the product of two probabilities D approximately w(1)w(2). The polymer chains in a rubber are subject to thermal vibrations. Hence collisions between vibrating polymer segments and permeating drug molecules can occur. w(1) describes the probability that by such a collision a drug molecule experiences an energy exchange which is large enough to overcome its interactions with its neighborhood. w(2) describes the probability that a permeating drug molecule will find in its immediate neighborhood a free volume being equal or larger than its own volume. Diffusion takes place if the drug molecule experiences a sufficiently large exchange of momentum and finds at the same time a sufficiently large free volume. As both events are independent their overall probability is given by the product of the two probabilities. For a given rubber and a given species of drug molecules in a first approximation w(1) can be considered as constant. This means the diffusion coefficient is mainly determined by w(2). This probability, however, is strongly determined by the microstructure of the rubber. In this study a procedure is developed allowing for a straightforward synthesis of silicone rubbers with defined network density.

Delayed-Action Preparations↗
PubMed2004

The Arabidopsis GNARLED gene encodes the NAP125 homolog and controls several actin-based cell shape changes.

In plants many aspects of cell shape regulation are controlled by actin-dependent processes. The ARP2/3 complex has been recognized as a regulator of actin organization. Mutations in genes encoding components of the ARP2/3 complex lead to cell shape defects in several cell types, including trichomes, epidermal pavement cells and hypocotyl cells. We show here that mutations in the GNARLED (GRL) gene cause a similar range of phenotypes. The GRL gene encodes the Arabidopsis homolog of NAP125, which in animals is known to act as one regulator of the ARP2/3-regulating complex WAVE-HSPC300. As an HSPC300 homolog is present in the Arabidopsis genome but no WAVE homolog has yet been found, the existence of a related regulation pathway was doubtful. Our finding that GRL encodes a putative regulator of the WAVE-HSPC300 complex, NAP125, combined with the phenotypic similarity between arp2/3 and grl mutants, provides evidence that the ARP2/3 complex is indeed regulated by the above mentioned pathway in Arabidopsis.

Actins↗
PubMed2001

[General AL-amyloidosis: a rare complication in Waldenstrom macroglobulinemia].

Waldenström's macroglobulinemia (W.M.) is a paraproteinemic disorder similar to multiple myeloma expressing a monoclonal IgM paraprotein. The course of W.M. is milder and the occurrence of renal disease is less frequent than in multiple myeloma. Amyloidosis occurs in less than 5% of patients with monoclonal IgM. We report a 65 year old patient with an asymptomatic long-term survival whose W.M. remained without any therapy. Amyloidosis developed twenty-one years after the initial diagnosis presenting with the nephrotic syndrome, renal and heart failure. W.M. combined with amyloidosis is a rare association. The deposition of amyloid causes progressive organ damage and indicates a bad prognosis. Most commonly nephrotic syndrome or heart failure are signs of amyloidosis. The development of amyloidosis does not seem to be influenced by the duration of W.M. disease or the paraprotein level. It is not known whether the amyloidosis can be prevented by an early chemotherapy.

Aged↗
PubMed2001

Early functional apoptotic responses of thymocytes induced by Tri-n-butyltin.

BACKGROUND: Programmed cell death, also termed apoptosis, is the main focus of interest in a variety of scientific and clinical areas. For a better understanding of the mechanisms of apoptosis, from the onset of the cellular death program to the late stages of apoptosis or apoptotic necrosis, very early functional events have to be quantified because they might be involved in temporal and causal relationships between apoptosis-related key processes. METHODS: We have established a flow cytometric technique to quantify time-dependent signals simultaneously with high temporal resolution (Deltat = 1 s) in living cells. With this technique, the response of cells to apoptosis-stimulating agents can be analyzed over 15 min. For this purpose, a thermostatted sample tube holder for repeatable interruption-free injection of substances into the cell suspension was developed. Early detectable fluorescence and scatter parameters were related to intracellular free Ca2+ concentration, [Ca2+]i (Indo-1 fluorometry), membrane permeability (propidium iodide [PI] influx), and cell volume (forward scatter). RESULTS: A T-cell line (Jurkat) served as a model system. Apoptosis was induced by the biozid Tri-n-butyltin (TBT). Dependent on the TBT concentration (0.3-10 microM), the mean free [Ca2+]i increased by a factor of 1.2-6 during a short time interval of just 2 min. Especially after low TBT concentrations (< 0.5 microM), this [Ca2+]i increase was nearly transient during the observation time of 15 min. Higher TBT concentrations (0.5-10 microM), however, induced a transient increase of [Ca2+]i (Ca-TR) only in a fraction of the cells; in another subpopulation, a steady-state Ca2+ signal (Ca-SST) was observed. The analysis of the simultaneously registered PI signals of the Ca-SST cells showed a shift to increasing PI fluorescence (by a factor of about 4) with increasing Ca2+ concentrations. In Ca-TR cells, the PI fluorescence remained nearly unchanged. These apoptosis-related changes (increase in [Ca(2+)]i and membrane permeability) could be confirmed by the additional observation of a TBT concentration-dependent decrease in cell volume measured during the same early time period. CONCLUSIONS: The simultaneously analyzed parameters (i.e., [Ca2+]i, membrane permeability, and cell volume) suggested that, in our model system of Jurkat T-cells treated with TBT, an apoptotic cell fate was indicated very early (within 15 min) by the steady-state [Ca2+]i level.

Apoptosis↗
PubMed2000

[Herpes zoster].

Explore the source record for details and available documents.

Aged↗
PubMed2000

Simultaneous recording of calcium transients and reactive oxygen intermediates of human polymorphonuclear granulocytes in response to formyl-Met-Leu-Phe and the environmental agent sulfite.

BACKGROUND: Human polymorphonuclear granulocytes (PMN) are an essential component in the immunological defense network against a variety of harmful pathogens. We have studied the effects of the airborne pollutant sulfite on the calcium metabolism and respiratory burst of these cells simultaneously. METHODS: A flow cytometric method was developed using the fluochromes Indo-1 and DHR-123. This method allowed us to investigate the real-time kinetics of intracellular free calcium and reactive oxygen intermediates in viable cells with a temporal resolution of 1 s over a time course of 17 min. An additional feature was the possibility to discriminate between reacting and nonreacting cells after treatment with defined stimuli, thus gaining additional insight into the behavior of cell subpopulations. RESULTS: We analyzed the effects of sulfite on PMN before and after stimulation with formyl-Met-Leu-Phe (FMLP). Treatment with sulfite alone (0.001-1 mM) caused a small, nontransient increase in intracellular calcium. Preincubation with sulfite reduced the maximal calcium response elicited by FMLP. A significant increase in steady-state calcium levels after stimulation with FMLP was observed after treatment with sulfite in concentrations of 10 and 100 mM. Regarding the respiratory burst, treatment with sulfite alone in concentrations of 0.001-1 mM induced a significant increase in DHR-123-derived fluorescence, whereas concentrations of 5 and 10 mM caused a significant depression of this fluorescence below baseline values. Sulfite caused a maximal twofold increase of DHR-123-derived fluorescence compared with the FMLP response. Similar results were obtained after preincubation with sulfite before treatment with FMLP, showing that the effect of sulfite on the respiratory burst was additive to the FMLP response. Regarding the fractions of responding cells, treatment with sulfite up to 1 mM induced a concentration-dependent increase of burst-reactive PMN, whereas preincubation before stimulation with FMLP showed no correlation between sulfite concentration and fraction of burst-reacting cells. CONCLUSIONS: By simultaneous registration of [Ca(2+)](i) and [H(2)O(2)](i) of PMN after treatment with FMLP and sulfite, the essential responses were already observed within a short time interval (15 min). Striking differences were found in the response of calcium as second messenger and respiratory burst in PMN treated with sulfite. Until a critical concentration (0. 5-1 mM), sulfite caused a concentration-dependent increase of [H(2)O(2)](i), in addition to the FMLP-induced response. The [Ca(2+)](i) changes induced by sulfite alone, however, were found to be small and showed no correlation with the respiratory burst response.

Air Pollutants↗
PubMed2000

Characterization of dimethyldiacyloxysilanes by differential scanning calorimetry, Raman scattering and X-ray diffraction.

The phase behaviour of diacyloxydimethylsilanes (DMS Cn; n = 10, 12, 14, 16, 18, 20, 22) was investigated by differential scanning calorimetry, X-ray diffraction and Raman spectroscopy. All DMS Cn melt from a crystalline phase to an isotropic liquid with a single sharp transition. On cooling, the homologous DMS C16 up to DMS C22 show a characteristic monotropic phase (L beta'H). In contrast to the calorimetrical investigations, it was not possible to analyse the monotropic phase of DMS C16 by X-ray diffraction. This behaviour is due to a two-phase region (gel phase--crystalline phase). The Raman spectra of all DMS are very similar. Only in the low frequency range we find different bands of the longitudinal acoustic modes. The Raman measurements demonstrate undoubtedly that in the solid state the alkyl chains are in all-trans conformation. The factor group splitting of the CH2 scissoring Raman mode show that the DMS Cn are arranged in a subcell packing with two molecules per unit cell. The highly ordered all-trans structure of the alkyl chains is present up to the melting transition. On melting there are changes in different regions of the Raman spectra: C-H stretching, CH2 scissoring mode, C-C skeletal stretching, CH3 rocking and longitudinal acoustic modes. On cooling DMS C18 and DMS C20 from the melt to the crystalline state, the gel phase is also proved by Raman scattering. Based on the results of the Raman and X-ray data the gel phase is characterized by a hexagonal subcell packing and by an ordered structure of the alkyl chain residues.

Calorimetry, Differential Scanning↗
PubMed1999

Differential response of non-transferrin bound iron uptake in rat liver cells on long-term and short-term treatment with iron.

BACKGROUND: Uptake of non-transferrin-bound iron by the liver is important as a clearance mechanism in iron overload. In contrast to physiological uptake via receptor-mediated endocytosis of transferrin, no regulatory mechanisms for this process are known. This study compares the influence of long-term and short-term depletion and loading of hepatocytes with iron on the uptake of non-transferrin bound iron, its affinity, specificity and the interaction with the transferrin-mediated pathways. METHODS: Rats were fed iron-deficient, normal and 3,5,5-trimethylhexanoyl-ferrocene-containing diets to obtain livers with the corresponding desired status and the hepatocytes from these livers were used for transport studies. Hepatocytes from normal rats were depleted or loaded with iron by short-term treatment with desferrioxamine or ferric ammonium citrate, respectively. Uptake of non-transferrin bound iron was assayed from ferric citrate and from ferric diethylene triammine pentaacetate. RESULTS: Uptake of non-transferrin-bound iron in hepatocytes could be seen as consisting of a high-affinity (Km=600 nM) and a low-affinity component. Whereas in normal and in iron-starved rats the high-affinity component was more prominent, it disappeared altogether in hepatocytes from rats with iron overload resulting from prolonged feeding with TMH-ferrocene-enriched diet. Overloading also led to loss of inhibition by diferric transferrin, which occured in starved as well as normal cells. In contrast, short-term iron-depletion of isolated hepatocytes with desferrioxamine had only a weak stimulatory effect, whereas treatment with ferric ammonium citrate strongly increased the uptake rates. However, the inhibition by diferric transferrin also disappeared. In both cases, uptake of non-transferrin bound iron was inhibited by apotransferrin. CONCLUSIONS: Non-transferrin bound iron uptake in liver cells is apparently regulated by the iron status of the liver. The mode of response to iron loading depends on the method of loading in terms of time course and the form of iron used. It cannot be explained by the behavior of the iron regulatory protein, and it is complex, seeming to involve more than one transport system.

Animal Feed↗
PubMed1999

Isolation of ethyl methanesulfonate-induced gametophytic mutants in Arabidopsis thaliana by a segregation distortion assay using the multimarker chromosome 1.

The life cycle of plants comprises two alternating generations, the diploid sporophyte (spore-bearing plant) and the haploid gametophyte (gamete-bearing plant). In contrast to animals, the postmeiotic cells give rise to haploid organisms whose function is to produce the gametes and to mediate fertilization. Analysis of gametophyte development and function has been hampered by the difficulty of identifying haplo-phase-specific mutants in conventional mutagenesis screens. Here we use a genetic strategy that is based on segregation distortion of nearby visible markers to screen for EMS-induced gametophytic mutants in Arabidopsis thaliana. Using the multiple marker chromosome mm1 we have isolated seven lines that displayed an altered segregation of markers. Reciprocal backcrosses of these lines showed a marked reduction of the transmission of the male and/or female gametes. Phenotypic analysis revealed that different aspects of either gametophytic development or function were affected. Three male gametophytic lines showed specific arrests during pollen development. One male gametophytic line was specifically defective in pollen tube elongation. Three gametophytic lines showed variable defects in both male and female gametophytic development.

Arabidopsis↗
PubMed1998

Physicochemical characterisation of human stratum corneum lipid liposomes.

Liposomes were prepared from an extract of all human stratum corneum lipids (hSCL) and characterised in terms of temperature and the presence of Ca2+ by different physicochemical methods. Vesicle aggregation and lateral phase separation were induced by divalent cations with Ca2+ being more efficient than Mg2+. At 24.1 degrees C, i.e. well below physiological temperatures the suspensions consisted of a lamellar phase and crystalline cholesterol. At and above 37 degrees C, this cholesterol surplus was dissolved in the hSCL membranes. However, melting of the hSCL was not completed up to 60 degrees C. The presence of Ca2+ (> or = 9 mM) induced lateral phase separation and fusion of vesicles into extended multilamellar lipid sheets (MLLS) at and above 32.5 degrees C. Upon a subsequent cooling cycle recrystallisation of cholesterol occurred within the MLLS. Finally, membrane mixing of hSCL liposomes with vesicles made of synthetic lipids was investigated. No mixing was observed between either of DPPE/oleic acid, DPPC/DPPE, DPPC/lyso-PC and hSCL liposomes. Mixtures of DPPC/cholesterol hemisuccinate showed a temperature-dependent membrane mixing behaviour, whilst hSCL liposomes and phosphatidylserine liposomes fused temperature-independently with hSCL liposomes.

Calcium↗
PubMed1998

Determination of the optimum mixing time for a mixture of lactose and colloidal silicon dioxide.

The homogeneity of a mixture of colloidal silicon dioxide (CSD) and lactose is examined by quantifying the dependence of the CSD content on the mixing time. CSD concentration is determined photometrically as a blue silica-molybdic complex. Its deviation from the expected content is taken to characterize the mixture quality and the optimum mixing time. The conformity of this result with the flow properties of the same mixture is studied by measuring the dependence of the angle of repose on the mixing time.

Colloids↗
PubMed1998

A combined calorimetric and semiempirical quantum chemical approach to describe the solution thermodynamics of drugs.

A combined calorimetric-semiempirical quantum chemical approach is presented to calculate the energy changes for the solution process of drugs. The aim of the presented approach is to understand the elementary steps of the solution process and to propose strategies for an improvement of solubility of drugs. On the basis of the Hess theorem, an alternative route for the solution process via sublimation of the solute, creation of a cavity for the solute in the solvent, transfer into this cavity, and the reorganization of the dipoles of the solute and the solvent can be taken. This approach allows the calculation of all energies describing the direct solution process as well as the alternative route. The approach was tested on 11 substances of different molecular structure by calculating the standard free energy of the specific phase transition. A general way to calculate the energy changes of all phase transitions is given. The complete cycle with DeltaG, DeltaH, and DeltaS was calculated exemplary for the nonsteroidal analgesic ibuprofen. The low solubility of ibuprofen was shown to be due to its high standard free energy of sublimation. Therefore the preparation of solid dispersions could be considered.

Calorimetry↗
PubMed1997

The STUD gene is required for male-specific cytokinesis after telophase II of meiosis in Arabidopsis thaliana.

During male meiosis in wild-type Arabidopsis the pollen mother cell (PMC) undergoes two meiotic nuclear divisions in the absence of cell division. Only after telophase II is a wall formed which partitions the PMC into four microspores. Each microspore undergoes two subsequent mitotic divisions to produce one vegetative cell and two sperm cells in the mature pollen grain. In this paper we describe the isolation and the phenotypic characterization of mutations in the STUD (STD) gene, which is specifically required for male-specific cytokinesis after telophase II of meiosis. Although the male meiotic nuclear divisions are normal in std mutant plants, no walls are formed resulting in a tetranucleate microspore. Despite the absence of cell division in the PMC, postmeiotic development in the coenocytic microspore proceeds relatively normally, resulting in the formation of large pollen grains which contain four vegetative nuclei and up to eight sperm cells. Interestingly, these enlarged pollen grains which contain multiple vegetative nuclei and extra sperm cells behave as single male gametophytes, producing only single pollen tubes and resulting in partial male fertility in std mutant plants. Characterization of the process of pollen development and pollen function in std mutants thus reveals two different types of developmental regulation. Each of the four nuclei found in a std microspore following meiosis is capable of independently undergoing the complete mitotic cell division (including cytokinesis) which the single nucleus of a wild-type microspore would normally undertake. The ability of the four meiotic products to independently continue through mitosis does not depend on their division into separate cells, but is controlled by some subcellular component found within the coenocytic microspore. By contrast, the mature std pollen grain functions as a unit and produces only a single pollen tube despite the presence of multiple nuclei within the vegetative cell, suggesting that this process is controlled at the cellular level independently of the extra subcellular components.

Arabidopsis↗