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Biomedical subjects

E Storch

Publications and source records attributed to E Storch.

At least 19 recordsLinked to original sources
PubMed1996

The menopause: women's psychology and health care.

Menopause has often been described as a time of loss and decay in the lay and medical literature. The present research aims at defining women's perception of themselves and their health care needs in this period of life. Through a community-based sample of women, participative assessments were performed and their conclusions contrasted with the opinions of male and female gynecologists. Though both groups coincided concerning the relevance of loneliness, partnership, beauty and the "empty nest" syndrome, several items showed a marked difference between both groups. Gynecologists tended to perceive women as much more striving for an active sex-life, depressed, lacking projects for the future and worried about their health care than they actually were. Women, instead, stressed the relevance of menopause as a life crisis laden with opportunities for self-accomplishment and positive changes in life-style towards greater autonomy.

Attitude of Health Personnel↗
PubMed1996

Formation of (R)-8-hydroxywarfarin in human liver microsomes. A new metabolic marker for the (S)-mephenytoin hydroxylase, P4502C19.

Kinetic studies demonstrate that two forms of human liver cytochrome P450 are responsible for the formation of (R)-8-hydroxywarfarin: a low-affinity enzyme (KM approximately 1.5 mM), previously identified as P4501A2; and a high-affinity enzyme (KM = 330 microM), now identified as P4502C19 on the basis of the following evidence. In crossover inhibition studies with P4501A2-depleted human liver microsomes between (R)-warfarin and (S)-mephenytoin, reciprocal competitive inhibition was observed. Apparent KM values for (S)-mephenytoin-4'-hydroxylation (52-67 microM) were similar to the determined Ki values (58-62 microM) for (S)-mephenytoin inhibition of (R)-8-hydroxywarfarin formation. Similarly, the apparent KM for (R)-warfarin 8-hydroxylation in furafylline-pretreated microsomes (KM = 289-395 microM) was comparable with the Ki values (280-360 microM) for (R)-warfarin inhibition of (S)-4'-hydroxymephenytoin formation. Inhibition studies with tranylcypromine, a known inhibitor of (S)-mephenytoin hydroxylase activity, and either substrate in three different microsomal preparations yielded nearly identical inhibitory constants: Ki = 8.7 +/- 1.6 microM for inhibition of (S)-4'-hydroxymephenytoin formation and 8.8 +/- 2.5 microM for inhibition of (R)-8-hydroxywarfarin formation. In addition, fluconazole, a potent inhibitor of (R)-warfarin 8-hydroxylation, Ki = 2 microM, was found to inhibit (S)-mephenytoin hydroxylation with an identical Ki (2 microM). Finally, a strong correlation between (S)-mephenytoin 4-hydroxylation and (R)-warfarin 8-hydroxylation activities in furafylline-pretreated microsomes was demonstrated in 14 human liver microsomal preparations (r2 = 0.97).

Aryl Hydrocarbon Hydroxylases↗
PubMed1995

Alterations of cardiac contractile function are related to changes in membrane calcium transport in spontaneously hypertensive rats.

OBJECTIVE: Transport activities of cardiac sodium-calcium exchange and sarcoplasmic reticulum calcium ATPase were measured biochemically in spontaneously hypertensive rats (SHR) with hypertrophied myocardium and in normotensive Wistar-Kyoto (WKY) rats and it was tested whether possible differences have consequences for the contractile properties of papillary muscle. METHODS: Sarcolemmal sodium-dependent calcium transport via sodium-calcium exchange and oxalate-supported sarcoplasmic reticulum calcium uptake were measured in left ventricular membranes of 22-week-old rats. Postextrastimulatory potentiated contractions, postrest potentiated contractions, the twitch-to-twitch decay of those potentiations and the response to increasing stimulation frequency of left ventricular papillary muscles were analysed. RESULTS: Compared with WKY rats we found in SHR: a significant increase in sodium-calcium exchange (65%) and in sarcoplasmic reticulum calcium uptake (24%); a steeper twitch-to-twitch decay in postextrastimulatory potentiated contractions and postrest potentiated contractions, suggesting a lower calcium fraction recirculating between myofilaments and sarcoplasmic reticulum and, consequently, a relatively higher calcium efflux via sodium-calcium exchange; a stronger rest-dependent decrease in recirculating calcium fraction in postrest potentiated contractions accompanied by accelerated relaxation, suggesting an increasing driving force for calcium extrusion via sodium-calcium exchange, probably caused by decreasing intracellular sodium during rest; a greater transient decrease in peak force of subsequent twitches after postrest potentiated contractions below pre-interventional level, indicating higher cellular calcium loss; and a smaller negative inotropic effect in response to doubling of stimulation rate as a manoeuvre to increase the intracellular sodium level. CONCLUSION: In SHR, the contractile properties suggest an increased contribution of sodium-calcium exchange to cellular calcium removal, which is strongly supported by the enhanced sodium-calcium exchange activity in cardiac membrane vesicles.

Animals↗
PubMed1994

Interpretation of the inotropic effect of 2,3-butanedione monoxime on the isometric twitch of guinea-pig papillary muscle.

The negative inotropic effect of 2,3-butanedione monoxime (BDM) on the isometric twitch of guinea-pig papillary muscle was analysed by parameters characterizing the time course of the mechanogram. BDM at concentrations of up to 4 mmol/l produced a clear negative inotropic effect, whereas the Ca transient measured in isolated cardiomyocytes was only slightly affected. Peak force was more reduced than dF/dtmax and dF/dtmin. This led to an earlier, more narrow peak and a shortening of twitch duration. Based on a reaction scheme for the cross-bridge cycle, a mathematical model using a Ca transient and mechanograms as input data has been developed. The kinetic parameters were estimated by fitting the model to various time courses of force obtained at rising concentrations of BDM. BDM decreased the ratio of rate constants for cross-bridge attachment and detachment in a concentration-dependent manner: the formation of cross-bridges became inhibited, whereas dissociation was promoted. Above 4 mmol/l BDM the more marked alterations of the parameters of the mechanogram indicated an additional suppressing effect on intracellular Ca supply. The computer analysis suggests how the cellular mechanism(s) of the BDM-induced negative inotropic effect are reflected in the time course of the mechanogram.

Animals↗
PubMed1989

The isometric twitch of rabbit papillary muscle: reflection of the cellular calcium movements?

The cycling of the activator-Ca of the myocardium is mediated by the sarcolemma (SL) and the sarcoplasmic reticulum (SR). Both the extent and the time course of the release as well as of the removal of the activator-Ca by the SL differ from that by the SR. The visualization of these differences in the isometric myograms of isolated myocardium (Bogdanov et al. 1979; Günther et al. 1986; King and Bose 1983; Malecot et al. 1986) prompted the conclusion that distinct cellular Ca movements determine distinct parts of the isometric contraction-relaxation cycle. To test this hypothesis the effects of Ca, isoprenaline and ouabain on the isometric contraction-relaxation cycle of rabbit papillary muscles were re-evaluated. The similarities and differences in the effects of the interventions on the twitch measures could be explained by their effects on the cellular Ca movements.

Animals↗
PubMed1989

Postrest contractions as an example for the regulation of the course of isometric twitch.

Postrest contractions (PRC) of isometrically contracting rabbit papillary muscles are used to analyse how the shape of the twitch can be explained by existing models for the accompanying Ca-regulation. By the change of the extracellular Ca concentration (Cae) potentiated or depressed PRC were produced. The course of the twitch is separated by mechanical indices commonly used. The results fit some biochemical and electro-physiological findings, as the regulatory role of the sarcoplasmic reticulum and the Na-Ca exchange, but do not reflect others. The sharp separation between an early and late phase of the contraction and relaxation, respectively, is limited by the overlapping of different Ca regulating processes.

Animals↗
PubMed1989

The feeding with unsaturated fatty acids modifies the course of the isometric contraction of rabbit papillary muscle in hypoxia.

Alterations of cardiac membrane functions can be induced by lipid rich diets. As to this the influence of the admixture of cholesterol (group Ch) and rape oil (group R) to standard food during 12 weeks on the course of the isometric twitch of rabbit papillary muscles in normoxia and hypoxia was studied. In group R the rate of contraction and relaxation is enhanced. This points to alterations in the role of the sarcoplasmic reticulum (SR), most probably due to the incorporation of unsaturated fatty acids. During hypoxia at 4 mM Ca concentration the force is more decreased in group R than in the control group C, but the rate of the contraction remains higher. The relaxation is more impaired especially in the early phase. The load-length relation is shifted to the left. The influence of hypoxia in group Ch was similar to group C. The results are hints for the Ca overload of the cells, preferentially in group R. The SR function seems to be more damaged, f.i. by radicals reacting with unsaturated fatty acids and by Ca activated lipolyses.

Animals↗
PubMed1987

Activation of cytotoxic activity in cultures of bone marrow-derived macrophages by indomethacin.

Indomethacin was tested for its ability to augment the cytotoxic capacity of cultured bone marrow-derived macrophages (M phi) against P815 and YAC-1 tumor cells. M phi were obtained from the bone marrow of C57BL/6 mice precultured for 10-14 days and were virtually 100 percent pure. By addition of indomethacin these cells were activated to kill tumor cells in a 4-h and 18-h Cr-release assay. Since indomethacin is a potent inhibitor of the cyclooxygenase system, M phi were treated with prostaglandin E2. This treatment partially reversed indomethacin-induced cytotoxicity. Addition of other cyclooxygenase inhibitors such as acetyl-salicylic-acid, diclofenac or carprofen also induced cytotoxicity in bone marrow-derived M phi. In all experiments we failed to detect any production of interferon. Addition of anti-interferon did not alter the cytolytic capacities demonstrating that endogenously induced interferon was not relevant in this mechanism. Our data show that cyclooxygenase inhibitors induce cytolytic activity of murine M phi not only against a M phi target but also against YAC-1 cells usually considered to be targets for natural killer cells.

Animals↗
PubMed1986

Prolongation of survival of mice bearing the Eb and ESb lymphoma by treatment with interferon inducers alone or in combination with Corynebacterium parvum.

The objective of this study was to evaluate if pretreatment with Corynebacterium parvum (C. parvum) augments the effects of interferon (IFN) inducers on survival of DBA/2 mice transplanted with two syngeneic lymphoma variants, the low metastatic Eb and the high metastatic ESb tumor. The involvement of IFN in the treatment effects was investigated. As inducers of IFN-alpha/beta Newcastle disease virus (NDV), polyinosinic-polycytidylic acid (polyI:polyC), and 10-carboxymethyl-9-acridanone (CMA) were injected i.p. at the site of tumor transplantation. The Eb tumor was found to be sensitive to the antiproliferative action of IFN-alpha/beta in vitro. In vivo single injections of each of the inducers retarded growth of the Eb tumor. In C. parvum-pretreated mice the effects of the inducers on survival were markedly increased. There was a correlation between prolonged survival and local IFN levels in response to polyI:polyC or CMA but not upon NDV. Injections of each of the inducers increased cytotoxicity of peritoneal exudate cells against the Eb tumor cells in vitro especially when mice were pretreated with C. parvum. Although other mechanisms cannot be excluded IFN-mediated activation of host defence and also direct antiproliferative effects of endogenously produced IFN seem to be involved in the antitumor effects by these IFN inducers in the Eb model. In the ESb tumor model irrespective of additional pretreatment with C. parvum survival was only slightly prolonged by the treatments and endogenous IFN induction did not result in any real benefit for the animals. When compared with Eb cells the ESb cells were less sensitive to the antiproliferative action of IFN-alpha/beta in vitro and less sensitive to in vitro cytotoxicity by the host cells. Although other mechanisms may additionally be active in vivo the different susceptibility of the Eb and ESb tumor cells to the direct and indirect actions of IFN seems to contribute to the different responsiveness of these tumor cell lines to the treatments with IFN inducers.

Acridines↗
PubMed1986

Local interferon induction by bacterial lipopolysaccharide in mice after pretreatment with Corynebacterium parvum.

C57BL/6 mice were injected intraperitoneally (i.p.) with Corynebacterium parvum and subsequently, after an interval of 7-10 days, i.p. with lipopolysaccharide (LPS). The peritoneal wash-fluid was recovered at various times after injection of LPS. Marked interferon (IFN) titers were observed between 2 and 10 h after injection of LPS, whereas no IFN was detected in mice injected with either C. parvum or LPS alone. Very low doses of LPS (0.1 microgram/mouse) were sufficient to cause IFN production in the double-stimulation protocol. The IFN produced was neutralized by an antibody against IFN-alpha/beta. In additional experiments, mice were treated by C. parvum alone; the peritoneal exudate cells (PEC) were recovered and stimulated in vitro by LPS. Again substantial titers of IFN were induced by small concentrations of LPS, whereas untreated PEC did not produce IFN. The cell producing IFN in these cultures was not a T lymphocyte, as experiments with a monoclonal anti-thy 1.2 antibody showed.

Animals↗
PubMed1986

Enhancement by carprofen or indomethacin of interferon induction by 10-carboxymethyl-9-acridanone in murine cell cultures.

Non-steroidal anti-inflammatory drugs such as carprofen or indomethacin enhanced interferon (IFN) production induced by suboptimal concentrations of 10-carboxymethyl-9-acridanone (CMA) in murine cell cultures. This effect was observed in fibroblasts and in different populations of leukocytes as in peritoneal exudate and spleen cells, and was most pronounced in bone marrow-derived macrophages. Carprofen was the most effective compound causing an up to 500-fold increase of CMA-induced IFN production in pure bone marrow-derived macrophages. In these macrophage cultures the potentiating effect on CMA-induced IFN production by carprofen and indomethacin did not depend on inhibition of cyclooxygenase.

Acridines↗
PubMed1986

Production of interferon-beta by murine T-cell lines induced by 10-carboxymethyl-9-acridanone.

Besides the established T-cell property of producing gamma interferon (IFN-gamma), murine T cells additionally possess the ability to produce IFN-alpha and IFN-beta when appropriate inducers such as 10-carboxymethyl-9-acridanone (CMA) or Newcastle disease virus (NDV) are used. Interleukin 2 (IL-2)-dependent murine T-cell lines, but not purified resting splenic T cells, responded to CMA and NDV with production of IFN-alpha, beta. The IFN production by these T cells was not restricted to a special subset, since T cells expressing the Lyt 1+2- and the Lyt 1-2+ phenotype responded to these inducers with IFN production. After prolonged passaging of the T-cell lines in IL-2-containing medium, the ability to respond to CMA with production of antiviral activity was sustained longer than the ability for concanavalin A-induced IFN-gamma production. Whereas the NDV-induced T-cell supernates contained both IFN-alpha and IFN-beta, the induction with CMA resulted exclusively in the synthesis of IFN-beta by the T-cell lines.

Acridines↗
PubMed1986

Characterization of interferon induced in murine macrophage cultures by 10-carboxymethyl-9-acridanone.

Pure murine macrophages were induced by 10-carboxymethyl-9-acridanone to produce interferon. The supernatants were partially purified by a three-column procedure including a DEAE-Biogel A, a CM-Biogel A, and a CH-Sepharose 4B column. The specific activity achieved was about 10(5) IU/mg. Two different activities were detected after the third step and designated activity 1 and activity 2. The determination of the molecular weight was in the range of 24,000-27,000 dalton for activity 1 and in the range of 32,000-34,000 dalton for activity 2. Both were neutralized by antibodies against mouse interferon-beta, indicating that two different moieties were produced both representing interferon-beta. When macrophages were induced in the presence of tunicamycin, only one activity of a molecular weight of about 19,000 dalton was found which again was neutralized by anti-interferon-beta.

Acridines↗
PubMed1986

Induction of natural killer cell activity in mice by injection of indomethacin.

The natural killer (NK) cell system of mice in the peritoneal cavity is of very low to undetectable activity, and testing peritoneal NK cells is a useful model to study the influence of activating substances upon local injection. Injection of indomethacin at doses of 100-400 micrograms/mouse caused a marked activation of NK cell activity which was maximal at 3 days and lasted for a total of 6 days. A similar albeit less marked effect was observed with other cyclooxygenase inhibitors such as aspirin. Prostaglandin E2 reversed the activation of NK cells induced by injection of indomethacin. The cellular count of the peritoneal population was 2-fold elevated after indomethacin injection but the percentage of macrophages in the washed-out cell population was decreased from 60% (controls) to around 20%. The NK cell nature of the effector cells activated by indomethacin was substantiated by the finding that previous injection of anti-asialo GM1 antibody prevented activation. Interferon could not be detected in the peritoneal wash fluid after injection of indomethacin, suggesting interferon-independent activation. However, the possibility of small interferon quantities being locally produced could not be excluded. In further experiments we found after intraperitoneal injection of indomethacin not only cells that killed YAC-1 targets in a 4-hour assay but also killer cells that were insensitive to anti-asialo GM1 and killed P815 cells in an 18-hour assay. We assumed that these were macrophages and have done further experiments with in vitro grown bone-marrow-derived macrophages. These could be activated for killing of P815 targets by the addition of indomethacin, but (to a lesser degree) also for killing of YAC-1 lymphoma cells.

Animals↗
PubMed1986

Modification of relaxation of isometrically contracting rabbit papillary muscle by calcium, isoprenaline, ouabain and amiloride.

The influence of isoprenaline, ouabain, amiloride, as well as enhanced extracellular Ca on the time course of relaxation of the isometrically contracting papillary muscle was investigated. Under the experimental conditions used the relaxation rate shows different phases, which are modified characteristically. It is concluded that this reflects the different involvement of the Ca transport mechanisms for the relaxation.

Amiloride↗
PubMed1986

Stimulation pattern dependent contractions of myocardial preparations after lipid diets.

Lipid diets modify the electro-mechanical coupling. To characterize the regulation of the supply of Ca for the activation of the contraction the influence of the stimulation pattern on the development of tension was investigated after diets containing cholesterol (Ch), rape oil (RO) and cholesterol-oil (ChO). The sequence of increasing inotropic states produced was compared with a control group (C). In ChO high resting potentiation, low postextrastimulatory potentiation (PEP) and a delayed Ca supply for interpolated extra contractions (EC) are typical features. The positive inotropic effect of rising extracellular Ca grows parallel to the sequence of the inotropic states. The maximum rate of contraction and relaxation correlates linearly with the tension development. Some of the results are similar in RO. In both groups a more pronounced involvement of the sarcoplasmic reticulum in the Ca regulation should be responsible for the effects. Especially in C the Ca loading effect of paired stimulation shortens the latent period and increases the rate of contraction and relaxation. In Ch the highest values of PEP are reached. These results reflect the involvement of a high sarcolemmal fraction of Ca in the activation.

Animals↗
PubMed1985

Interferon inducibility in mice treated with Corynebacterium parvum.

Mice were given single intraperitoneal (i.p.) injections of Corynebacterium parvum, followed, after different time intervals, by i.p. injections of the interferon inducers polyinosinic-polycytidylic acid (poly-I:poly-C), 10-carboxymethyl-9-acridanone (CMA) or herpes simplex virus. With all three inducers production of interferon in the peritoneal cavity was enhanced in C. parvum-pretreated mice. Production of circulating interferon in C. parvum-pretreated mice was enhanced with CMA and depressed with poly-I:poly-C as inducers. This modulation of the interferon response was prominent for at least 10 weeks after C. parvum injection and then gradually reverted. The increased local interferon production seemed to be caused by macrophages still activated several weeks after treatment with C. parvum.

Animals↗