Biomedical subjects

H Zimmer

Publications and source records attributed to H Zimmer.

At least 19 recordsLinked to original sources

PubMed2000

Comitogenic effect of catecholamines on rat cardiac fibroblasts in culture.

OBJECTIVE: We studied the ability of norepinephrine and of other catecholamines to affect the proliferation of cardiac fibroblasts isolated from adult rat hearts. Furthermore, we investigated the possible adrenergic receptor involved in this process. METHODS: Norepinephrine (NE), phenylephrine (PE), isoproterenol (ISO), forskolin (FO), epidermal growth factor (EGF), platelet-derived growth factor AA (PDGF-AA) and specific inhibitors of the alpha(1)-, alpha(2)-, beta(1)- and beta(2)-adrenoceptors and of the protein kinase A (PKA) were applied to cardiac fibroblasts in culture. Cell number was measured by use of a Coulter Counter. Activation of the cAMP response element binding protein (CREB) was measured by Western blotting and subsequent use of a phospho-specific antibody. Activation of the p42- and the p44-mitogen activated protein kinase (p42/p44(MAPK)) was assessed by detection of phosphorylation shifts and by incorporation of 32P-labelled phosphate into myelin basic protein. RESULTS: Fibroblasts isolated from hearts of adult rats were grown in 10% serum-containing media which induced an increase in cell number by 94%. After 48 h, treatment with 10 microM NE caused an even greater increase in cell number by 222%, i.e. another 128% (comitogenic effect). In contrast, NE alone had no effect on the growth of serum-deprived cells. EGF and PDGF-AA did not replace serum as the basic mitogen. After addition of NE to proliferating cells under serum conditions, there was a rapid, time-dependent significant activation of the p42/p44(MAPK) and of CREB for up to 60 and 120 min, respectively. In both cases, the maximum of activation was reached after 5 min. Application of FO (0.1-20 microM) caused a strong activation of CREB, while no increase in the phosphorylation of the p42/p44(MAPK) was detected. Treatment with 20 microM FO led to an identical increase in cell number as application of NE. Specific blockade of PKA with RpcAMPS prevented the activation of CREB and also the comitogenic effect of FO as well as of NE. The alpha- and beta-adrenergic receptor blocker carvedilol (10 microM) normalized all NE-induced effects. Prazosin and yohimbine, inhibitors of alpha(1)- and alpha(2)-adrenoceptor activation, respectively, did not influence the NE-evoked increase in cell number. In contrast, the non-selective beta-adrenoceptor blocker propranolol (1 microM) completely suppressed the comitogenic effect of NE. A similar effect was obtained with the specific beta(2)-adrenoceptor blocker ICI 118,551 (5 microM), while the beta(1)-adrenoceptor blocker metoprolol did not influence the increase in cell number. CONCLUSIONS: NE elicits a comitogenic effect on cultured rat cardiac fibroblasts which is prevented by beta(2)-adrenergic blockade. The activation of CREB contributes to the increase in proliferation. The p42/p44(MAPK) which was also found to be activated by NE might as well be involved in the regulation of the comitogenic effect.

Adrenergic beta-Antagonists↗

PubMed2000

Habituation and laterality of orienting processes as reflected by slow negative waves.

The study is concerned with the question of whether the orienting wave (O-wave), a slow potential shift of the event-related brain potential, is a component of the orienting response (OR). As habituation is supposed to be the most important characteristic of the OR, we focussed particularly on any habituating aspect of the O-wave. Results suggest that its bilateral distribution over midfrontal areas might constitute such a link relating the O-wave to orienting activity. Hemispheric asymmetry linearly decreased its right-sided predominance in response to repeated presentations of an initially novel auditory stimulus. A similar, concomitant diminution of the skin conductance response (SCR) occurred. Both, the O-wave and the SCR varied, moreover, with signal value and electrodermal lability which are known to relate to the OR. Therefore we suggest the O-wave comprise features typical of a component of the OR. A hypothesis is put forward according to which the O-wave and its laterality are dependent on the ascending noradrenergic locus coeruleus system.

Adolescent↗

PubMed2000

[Frequency and mean amplitude of spontaneous electrodermal fluctuations are not interchangeable indicators of psychological processes].

The study was concerned with the question of whether the frequency and the mean amplitude of spontaneous electrodermal fluctuations convey the same information about mental processes. In order to examine this, the content and the personal relevance of induced imaginations was varied experimentally. The experimental manipulations followed a 2 x 2 factorial design for independent groups (content of cells: 24 subjects each). Changes in electrodermal activity were measured as differences between the imagination and a resting phase. Results revealed that the two variables are not exchangeable indicators of mental processes. Although the two variables correlated significantly, they responded differently to the experimental manipulations. The imagination of death-related contents increased the frequency of spontaneous electrodermal fluctuations more than the imagination of neutral contents. High personal relevance enhanced the mean amplitude of these spontaneous fluctuations regardless of the imagined content. Therefore it was concluded that the two variables have something in common but, on the whole, do not depend on identical factors. Frequency of spontaneous electrodermal fluctuations seems to be a reflection of covert orienting processes, whereas their mean amplitude seems to reflect the activity of an appraisal system incorporating goals and past experiences. However, both variables, seem to be, in the same way, dependent on a kind of basal activation or vigilance.

Arousal↗

PubMed1999

Determination of ethyl glucuronide, a minor metabolite of ethanol, in human serum by liquid chromatography-electrospray ionization mass spectrometry.

A rapid and sensitive determination procedure using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) has been developed for the determination of ethyl glucuronide (EtG) in human serum. Samples were precipitated with methanol, centrifuged and the supernatant was evaporated to dryness followed by reconstitution with distilled water. As mobile phase 30 mM ammonium acetate-acetonitrile (30:70, v/v) was utilized. The base peak observed at m/z 221 was the [M-H]- ion of EtG, which was detectable in satisfactory sense. The detection limit was 0.03 microg/ml in the selected ion monitoring mode. A calibration graph constructed for EtG in serum gave good linearity over the range from 0.1 to 25 microg/ml. This paper also presents the application of this LC-ESI-MS procedure to the analysis of authentic serum samples.

Alcohol Drinking↗

PubMed1998

Effect of ribose on cardiac adenine nucleotides in a donor model for heart transplantation.

Preservation time of explanted hearts is short. Cardiac function after transplantation declines dramatically in hearts that have been preserved for more than 4 to 6 hours. This has been linked to a critical decrease in high energy phosphates (HEP) after explantation. Ribose has previously been shown to stimulate HEP synthesis and to improve cardiac function. In this study, ribose was infused into 20 rats for 24 hours continuously before explantation (donor treatment) and also added to the solutions used for preservation. Saline was used in the control group. Myocardial tissue biopsies were taken after 24h of infusion and after 4h of preservation. High energy phosphates were determined by HPLC. Adenosine triphosphate content (ATP), energy charge and total adenine nucleotides (TAN) were significantly lower after 4h of preservation in both the ribose-treated and the control group compared to hearts before preservation. The difference in mean ATP concentrations between the 4 hours preserved ribose group and the control group was not significant. Single case analysis however revealed a minimum ATP level of 12.3 micromol/g dry weight in 10 ribose treated hearts whereas 2 out of 11 control hearts showed ATP levels below 10 micromol/g dry weight. - This study supports the hypothesis that ribose treatment is capable of maintaining ATP at a higher level in preserved rat hearts. Donor treatment and metabolic support with ribose during organ preservation may be suitable to prolong preservation time of donor hearts.

Adenine Nucleotides↗

PubMed1995

Poly(binaphthyl-20-crown-6) as receptor based molecular selective potentiometric electrodes for catecholamines and other 1,2-dihydroxybenzene derivatives.

A novel type of poly(crown ether) electrode that is capable of selectively determining some 1,2-dihydroxybenzenes has been developed. A lipophilic macrocyclic crown ether, binaphthyl-20-crown-6, is electrochemically deposited on a platinum disc electrode. The film obtained is used as a sensory element for a potentiometric electrode for the determination of some neurotransmitters, namely, catecholamines. The new electrode is also capable of discriminating the steric shapes of 1,2-dihydroxybenzene moieties. The response of the new electrode is based on the principle of 'host-guest' chemistry. The potentiometric response is dependent on the pH of the solution and the nature of the buffer medium. The new sensor electrode has a useful analytical range of 1.5 x 10(-8) M-2 x 10(-5) M with a linear dynamic range between about 1 x 10(-7) M-5 x 10(-4) M with a 'super-Nernstian' slope of 110-130 mV/decade. The detection limit in phosphate buffer (0.1 M, pH 9.4) is ca. 3 x 10(-8) M for catecholamine. The sensor electrode is virtually insensitive towards interference from most inorganic ions and circumvents the interference from ascorbic acid, which is often found using amperometric methods in biological samples. A partial response mechanism of the present electrode is discussed, supported by results of electron dispersive analysis by x-rays (EDAX).

Animals↗

PubMed1993

Study of procainamide hapten-specific antibodies in rabbits and humans.

Procainamide (PA) is the drug most commonly associated with the induction of autoantibodies and drug-related lupus (DRL). While the majority of these patients express autoantibodies, antibodies to the parent drug and metabolites, PA-hydroxylamine (PAHA) or nitroso-PA (NOPA), have not been reported in humans. Hapten-carrier conjugates were prepared using human hemoglobin (HgB) or autologous rabbit erythrocytes with PAHA or NOPA. PA was conjugated to rabbit serum albumin (RSA) or egg albumin (OVA) via diazotization and condensation methods. Rabbits were immunized with hapten conjugates in Freund's adjuvant. These hapten-carrier compounds (5-10 micrograms/ml) were used as test antigens for antibodies in sera from the rabbits and 40 patients on chronic PA treatment. 10 SLE patients, 33 elderly and 20 young normal controls by ELISA. Type I and II collagens were also used as test antigens for human sera. Sera from rabbits immunized with the PA compounds had elevated IgG antibody values to PA, PAHA and NOPA, but no autoantibodies. Absorption of the rabbit sera with the PA compounds reduced the antibody levels; ssDNA and histones failed to inhibit the total binding values. Mean binding to PA-OVA was 0.95 +/- 0.41 for PA patients and 1.37 +/- 0.26 standard error of means (S.E.M.) in the SLE patients compared to 0.37 +/- 0.14 S.E.M. in the normal sera (P < or = 0.05); similar binding values to PAHA-HgB and NOPA-HgB were also observed. Sixty-eight percent of the PA patients had antibodies to type II collagen. Elevated binding values to PA compounds were inhibited by absorption of human sera with ssDNA or total histones; absorption with PA or PAHA had no significant effect. These findings suggest that sera from PA patients containing high titers of autoantibodies cross-react in vitro with unrelated antigens.

Adult↗

PubMed1993

[Methods for quantifying phasic skin conductance amplitudes: threats to validity?].

Two methods of determining the event-related skin conductance response (SCR) amplitude are in common use. In one of these, the difference in conductance between the point of onset and the peak level of a single wave is measured (method 1). The second approach is to determine the difference between two measures, one characterizing the prestimulus level, the other the highest conductance point of the SCR reached within a fixed period following the stimulus (method 2). A problem with quantifying the SCR amplitude occurs when a SCR is elicited before an immediately preceding response has had time to recover, because in this case the two methods lead to quite different values. If the amplitude of each response is measured from its own individual deflection point, the measurable amplitude of the second response will be smaller when it occurs immediately after or in the ascending limb of the first response. The problem is most evident in situations with a high probability of response superimposition, such as when a large number of nonspecific responses occur at the same time as the SCRs. This is found in individuals with a high degree of electrodermal lability. Electrodermal lability refers to a psychophysiological construct that is operationally defined by the frequency of spontaneous electrodermal fluctuations. In the present study, we therefore systematically investigated the effects of the two score methods on SCR amplitude in relation to lability by analyzing electrodermal data from two habituation studies. As expected, several method-specific effects which were related to lability emerged. Results and questions concerning the relevance of the findings are discussed, with special emphasis on the validity of psychophysiological investigations.

Adult↗

PubMed1992

Stimulus rise time, intensity and the elicitation of unconditioned cardiac and electrodermal responses.

In recent discussions on the differentiation of orienting, startle and defense responses, the importance of stimulus rise time for the elicitation of different cardiac response patterns was re-emphasized. Especially, it has been claimed that phasic accelerative heart rate (HR) responses-interpreted as indicators of startle-might not only be evoked by auditory stimuli with instantaneous rise times and high intensities, but also by low to moderate stimulus intensities with sudden onsets. The present study examined this question by manipulating rise time (instantaneous vs. 50 ms) and intensity (60 vs. 95 dB). Subjects (N = 120) were randomly assigned to one of the four independent groups. They performed a habituation experiment in which 12 tones of 1000 Hz with a constant interstimulus interval of 90 s were presented. On trial 13, a change in rise time was introduced by reversing the rise time condition in each group (i.e., from instantaneous to 50 ms and vice versa). Examination of HR changes across 4 poststimulus seconds, of maximal HR deceleration and acceleration, as well as examination of magnitude of skin conductance responses (SCRs) indicated clear intensity effects. Rise time, on the other hand, had no effects on HR and SC that could be interpreted as indicative of startle. Thus, it could neither be observed that instantaneous rise time led to stronger accelerative HR responses nor that the combination of instantaneous rise time and high intensity elicited anything but a dominant accelerative response pattern. These findings were also obtained when the first four trials were analyzed separately. As a consequence of stimulus change, larger SCRs as well as larger decelerative HR responses were observed without, however, being affected by the direction of the change in rise time. In sum, the present study suggests that the role attributed to rise time with respect to eliciting qualitatively different cardiac response patterns has been exaggerated. The consequences for the differentiation of different unconditioned responses are briefly addressed.

Acoustic Stimulation↗

PubMed1992

[Change in the event-related skin conductivity: an indicator of the immediate importance of elaborate information processing?].

In recent psychophysiological conceptualizations of the orienting response (OR) within the framework of information processing, the OR is increasingly considered a "call for processing resources", something which is especially inferred from variations in the event-related skin conductance response (SCR). The present study, therefore, was concerned with certain implications arising from this framework or perspective, particularly in regard to the question of whether stimuli eliciting skin conductance responses obligatorily receive/evoke processing priority or not. In order to examine whether these electrodermal responses denote a capturing of attention or merely a call for processing resources, short (1 s) pure sine tones of 65 dB with sudden onset (commonly used as orienting stimuli) were inserted in a reaction time paradigm with an additional memory load. This demand was primarily given because memory processes play a key role in theories of orienting and habituation. The task was run under two different conditions of complexity, factorially combined with a novelty variation of the added auditory stimuli. The results revealed a substantial deterioration of task performance subsequent to the occurrence of the tones, which, however, was dependent on task complexity and on novelty of the tones. The task impairment is particularly remarkable as subjects were asked to avoid distractions by paying attention to the task and as the tones were introduced as subsidiary and task-irrelevant. Together with the missing effects of task complexity on phasic and tonic electrodermal activity, results suggest that information-processing conceptualizations of the OR can only be a meaningful heuristic contribution to theoretical developments about human orienting and its habituation if the setting of processing priority, its conditions, as well as its implications are adequately taken into account. In addition, it seems to be promising to consider the strength of the SCR as an index of urgency of elaborate, attention-demanding processing and not as a peripheral physiological manifestation of the OR, or, respectively, of a call for unspecific processing resources. Such a view would also do justice to the aspect of prioritization. The sufficient conditions for an OR's occurrence could, in this context, be equated with, among others, some of those which activate a mechanism subserving selective attention and, as a possible result, which lead to further and more elaborate processing of potentially important information.

Adult↗

PubMed1991

Electrochemistry and detection of some organic and biological molecules at conducting poly(3-methylthiophene) electrodes.

Electrodes modified by the electrodeposition of poly(3-methylthiophene) were used as chemical sensors for some organic and biological molecules of industrial and medicinal interest. The electrochemical behaviors of ferri/ferrocyanide, catechol, ascorbic acid, hydroquinone, dopamine epinephrine, acetaminophen, p-aminophenol and NADH were examined by cyclic voltammetry. The results showed that the proposed modified surface catalyzes the oxidation of these compounds. Differential pulse and square wave techniques were used for the analysis of binary mixture of ascorbic acid with catechol, NADH, dopamine and p-aminophenol. Voltammetric peak resolution was also demonstrated for a ternary mixture of ascorbic acid, catechol and p-aminophenol. Polymer coated electrode was also used in an amperometric detector for flow injection analysis of most of the aforementioned compounds. The responses of the polymer electrode were 4-10 times larger as compared to those of platinum. The modified electrode displayed excellent response stability for successive injections and detection limits were 10 ppb for catechol, dopamine, epinephrine, NADH and p-aminophenol, 1 ppb for acetaminophen and 100 ppb for ascorbic acid. Voltammetric peak positions were affected by the nature of the electrolyte and its pH. Also, film thicknesses were shown to be a factor affecting both the current magnitudes and oxidation peak potential of NADH.

Acetaminophen↗

PubMed1991

[Significance of heart rate deceleration in pattern recognition tasks].

As strength of foreperiod heart rate (HR) deceleration in reaction time paradigms with a fixed foreperiod has been discussed in terms of activities related to differences in regulations of attentional processes, the present study was concerned with the question of whether this variable also accounts for the variance in the latency of response in two attention-demanding pattern recognition tasks, one of which involved mental rotation. Subjects were required to determine as quickly and as correctly as possible whether a two-dimensional asymmetrical shape was intrinsically identical to a previously presented visual pattern or not, regardless of its rotational position within the picture plane. The first stimulus was always in normal upright position, whereas the probe stimulus could either be rotated or presented in an upright position. The findings of the study are indicative of a reliable relation between anticipatory HR deceleration and reaction time. It was not restricted to detection and response requirements but also held true in the case of additional mental rotation requirements. Strength of anticipatory HR deceleration is therefore interpreted as an indicator of regulations of attentional processes mustered in order to facilitate or to support stimulus detection and response elicitation as well as to prime or to set up the mental structures required in mental rotation. Additional support for this assumption could be found in the analyses of HR changes at the beginning of the response interval.

Adult↗

PubMed1991

[Marker identification and mental rotation in automatic conditions].

A basic finding of mental rotation research is that the time required to discriminate an asymmetrical visual stimulus from its reflected or backward version typically varies systematically with the angular departure of the probe stimulus from its normal upright (or expected) position within the picture plane. This regular dependence of reaction time (RT) on the rotational position (orientation) of the probe stimulus was interpreted by assuming an internal process working as a kind of mental analog of an external physical rotation and being carried out to bring the internal representations of the stimuli into congruence with each other before a decision is made. The present study was designed to investigate whether the dependence of RT on orientation also holds true in the case of a probe that can be identified on the basis of a single distinctive feature. In addition, it was examined whether the efficiency of the underlying processes could be improved by training. Results showed that the dependence of RT on orientation (RT function) does not occur if the presented visual probes differ with regard to a simple feature as, for example, an easily detectable angular difference. A change of the RT function, which would have indicated a change in the speed of the underlying processes, did not occur despite an "automatization" training.

Adult↗

PubMed1990

Individual differences in resting heart rate and spontaneous electrodermal activity as predictors of attentional processes: effects on anticipatory heart rate deceleration and task performance.

The present study was concerned with the question of whether tonic resting heart rate (HR) and resting spontaneous electrodermal activity account for the association between anticipatory HR deceleration and task performance in a choice reaction time (RT) task with a fixed foreperiod. The task employed (a varied mapping paradigm) differed from simple RT tasks especially with regard to processing and attention demands. Subjects were required to determine as quickly and accurately as possible whether a 'complex' probe, presented for 80 ms, was identical or not to one of two distinct memory items, presented at the onset of each trial. Reaction times as well as accuracy of responses were determined. Additionally, reaction time and error data were synthesized to obtain a joint measure of response behaviour. The results of the present study were indicative of a reliable anticipatory HR deceleration extended over the last seconds preceding the probe stimulus. In agreement with previous findings, the HR deceleration grew stronger over blocks of trials and was sensitive to detection requirements, i.e. probe complexity. Furthermore, HR deceleration was related to task performance. Subjects with stronger decelerations (below the median on mean deceleration) exhibited a more impulsive (fast-inaccurate) and subjects above the median a more reflective (slow-accurate) response style. The effect was mainly due to a significant difference in RT. Further results indicated that the relationship between anticipatory deceleration and RT performance was especially due to the response behaviour of one group of subjects. Subjects above the median of resting HR and resting spontaneous electrodermal activity behaved in a prominent reflective manner and also displayed the lowest foreperiod deceleration. Results were discussed in terms of differences in the regulation or control of attentional processes.

Adult↗

PubMed1990

Psychometric properties of non-specific electrodermal response frequency for a sample of male students.

In the present study data on the frequency of non-specific electrodermal responses (NSRs) are presented for a large and, with regard to sex, age and educational level, homogeneous sample of male students (n = 590). These data were obtained in 9 independent experiments in which NSRs were recorded under equivalent conditions. NSRs were scored as skin conductance changes greater than 0.02 muSiemens. A recording period of 5 min prior to experimental manipulations was chosen. A systematic comparison between the 9 studies, the distribution of NSRs for the total sample, as well as descriptive data for stabile and labile subgroups are presented. For 213 subjects NSR-frequency was recorded twice, with a retest interval of one day. For these subjects retest analyses and data on the degree of stability of the classification into stabile and labile groups are also presented. In the discussion the necessity to develop standardized scoring criteria for NSRs is emphasized.

Adult↗

PubMed1990

Electrochemical investigations of immunologically reactive procainamide metabolites.

As a result of the implication of N-oxidized procainamide metabolites in drug-related lupus (DRL), the electrochemical behaviour of these compounds was investigated and a coulometric synthesis of the nitroso derivative developed using a previously described carbon packed bed bulk electrolysis flow cell. The electrochemical characterization of the parent p-substituted aromatic amine and the N-oxidized derivatives was achieved through systematic comparison with previously well described aromatic amine and nitro systems using cyclic voltammetry and liquid chromatography with electrochemical detection (LC-EC). Chromatographically assisted hydrodynamic voltammetry indicated current limiting plateau potentials of 0.45 and -0.2 V versus Ag/AgCl, respectively, for synthetically prepared procainamide hydroxylamine and electrolytically prepared nitrosoprocainamide. Reaction characterization and binding behaviour is described for each of the procainamide metabolites following in vitro incubations with cysteine, glutathione, ascorbic acid and mouse haemoglobin.

Chromatography, High Pressure Liquid↗

PubMed1989

Procainamide hydroxylamine lymphocyte toxicity--I. Evidence for participation by hemoglobin.

A number of lines of evidence suggest that the lupus-like symptoms associated with procainamide therapy may be caused by products of metabolic N-oxidation. In the present study, the perfusion of the isolated rat liver with a hemoglobin-free solution containing procainamide (100 microM) resulted in the rapid appearance of the N-oxidation metabolite procainamide hydroxylamine in the perfusate. Addition of procainamide hydroxylamine in vitro to whole rat blood (1-40 microM) resulted in a concentration-dependent loss of proliferative response among mononuclear cells isolated from the treated blood and cultured with mitogens (phytohemagglutinin, PHA-P: concanavalin A, Con A; and pokeweed mitogen, PWM), as well as a loss of viability. Similar effects on lymphocyte mitogen responsiveness were observed when procainamide hydroxylamine (1-40 microM) was added to rat whole splenic cell populations. Carbon monoxide or ascorbic acid pretreatment inhibited the toxicity of procainamide hydroxylamine to lymphocytes in whole blood, but only carbon monoxide pretreatment inhibited procainamide hydroxylamine-induced methemoglobin formation. These observations are consistent with the participation of hemoglobin in a redox cycle with procainamide hydroxylamine, generating products which are primarily responsible for its cytotoxicity in blood.

Acecainide↗

PubMed1989

[Anticipatory and event related changes in heart rate as indicators of attention processes].

The present study was concerned with the question of whether phasic event-related heart rate (HR) changes under easy intake conditions account for the association between anticipatory HR deceleration and task performance in a choice reaction time (RT) task with a fixed foreperiod. The task employed differed from simple RT tasks especially with regard to processing and attention demands. Subjects were required to determine as quickly and accurately as possible whether a probe, presented for 80 ms, was identical or not to one of two distinct memory items, presented at the onset of each trial. Reaction times as well as accuracy of responses were determined. The results of the present study were indicative of a reliable anticipatory HR deceleration which was related to latency of responses to the probe stimulus. Subjects with stronger decelerations reacted faster than subjects with diminished or missing decelerations. Furthermore a relation was found between this association and the heart rate changes to repeated presentations of a non-signal auditory stimulus under habituation conditions. Results were discussed in terms of differences in the regulation or control of attentional processes.

Adult↗