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Biomedical subjects

A Hoffmann

Publications and source records attributed to A Hoffmann.

At least 145 records · Page 8Linked to original sources
PubMed1998

Rapid modulation of L-type calcium current by acutely applied oestrogens in isolated cardiac myocytes from human, guinea-pig and rat.

Gender-based differences in cardiovascular mortality may be due to a cardio-protective effect of oestrogens on the myocardium. However, mRNA expression of oestrogen receptors in myocardial tissue of the adult heart has yet to be demonstrated. Furthermore, a calcium antagonistic action of 17beta-oestradiol on myocardial tissue has been discussed. Therefore, two subjects were investigated in atrial myocytes of the human, and ventricular myocytes of guinea-pig and rat in this study. (1) Are oestrogen receptors expressed in adult myocardial cells? (2) Is there an influence of oestrogens on the L-type calcium current of cardiac myocytes? Expression of oestrogen receptors was investigated by reverse polymerase chain reaction. L-type calcium current was usually measured by the patch-clamp technique in whole-cell recording mode under selective recording conditions, i.e. overlapping currents were blocked. One series of experiments was performed in perforated patch configuration to avoid internal perfusion. 17beta-oestradiol inhibited L-type calcium current reversibly in all three species. At 10(-5) M, the inhibition was 15-20%. This inhibition was independent of the sex and the species. A full concentration response curve of 17beta-oestradiol on basal L-type current was recorded from female guinea-pig myocytes. The inhibition increased from 2% at 10(-7) M to about 30% at 10(-4) M 17beta-oestradiol. The values could be fitted by a sum of two sigmoidal functions with log EC50 values of -6.5 and -4.9 M and Hill slopes of 2.5 for both. The specificity of the 17beta-oestradiol action was tested by recording the L-type current in the presence of 17alpha-oestradiol and oestrone. 17alpha-oestradiol also inhibited the current, but with a maximal inhibition of only 17%. The concentration-response curve could be fitted by a single sigmoidal function (log EC50 -6-3 M; Hill slope 0.55). Oestrone did not influence the current at all. The decrease in L-type current after the application of 17beta-oestradiol via a rapid perfusion system developed with a time constant of 3-4 s, which was in the same range as that for the influence of isoprenaline. The isoprenaline-stimulated L-type current was much more susceptible to the inhibition by 17beta-oestradiol, i.e. in pre-stimulated cells (1) the inhibitory effect is significantly higher (e.g. at 10(-5) M, inhibition was 36.3% compared with 11.2% in untreated cells) and (2) an inhibitory effect can be seen with oestradiol concentrations as low as 10(-9) M. Although the concentrations needed to gain a calcium antagonistic influence on the basal current were much too high to explain a cardio-protective influence of oestrogens, the presence of oestrogen receptors in cardiac myocytes of all three species, together with the shift in concentration dependence following pre-stimulation by isoprenaline, suggest that myocytes are a potential target for oestrogen.

Animals↗
PubMed1998

Intergeneric transfer of conjugative and mobilizable plasmids harbored by Escherichia coli in the gut of the soil microarthropod Folsomia candida (Collembola).

The gut of the soil microarthropod Folsomia candida provides a habitat for a high density of bacterial cells (T. Thimm, A. Hoffmann, H. Borkott, J. C. Munch, and C. C. Tebbe, Appl. Environ. Microbiol. 64:2660-2669, 1998). We investigated whether these gut bacteria act as recipients for plasmids from Escherichia coli. Filter mating with E. coli donor cells and collected feces of F. candida revealed that the broad-host-range conjugative plasmid pRP4-luc (pRP4 with a luciferase marker gene) transferred to fecal bacteria at estimated frequencies of 5.4 x 10(-1) transconjugants per donor. The mobilizable plasmid pSUP104-luc was transferred from the IncQ mobilizing strain E. coli S17-1 and less efficiently from the IncF1 mobilizing strain NM522 but not from the nonmobilizing strain HB101. When S17-1 donor strains were fed to F. candida, transconjugants of pRP4-luc and pSUP104-luc were isolated from feces. Additionally, the narrow-host-range plasmid pSUP202-luc was transferred to indigenous bacteria, which, however, could not maintain this plasmid. Inhibition experiments with nalidixic acid indicated that pRP4-luc plasmid transfer took place in the gut rather than in the feces. A remarkable diversity of transconjugants was isolated in this study: from a total of 264 transconjugants, 15 strains belonging to the alpha, beta, or gamma subclass of the class Proteobacteria were identified by DNA sequencing of the PCR-amplified 16S rRNA genes and substrate utilization assays (Biolog). Except for Alcaligenes faecalis, which was identified by the Biolog assay, none of the isolates was identical to reference strains from data banks. This study indicates the importance of the microarthropod gut for enhanced conjugative gene transfer in soil microbial communities.

Animals↗
PubMed1998

The gut of the soil microarthropod Folsomia candida (Collembola) is a frequently changeable but selective habitat and a vector for microorganisms.

Interaction potentials between soil microarthropods and microorganisms were investigated with Folsomia candida (Insecta, Collembola) in microcosm laboratory experiments. Microscopic analysis revealed that the volumes of the simple, rod-shaped guts of adult specimens varied with their feeding activity, from 0.7 to 11.2 nl. A dense layer of bacterial cells, associated with the peritrophic membrane, was detected in the midgut by scanning electron microscopy. Depending on the molting stage, which occurred at intervals of approximately 4 days, numbers of heterotrophic, aerobic gut bacteria changed from 4.9 x 10(2) to 2.3 x 10(6) CFU per specimen. A total of 11 different taxonomic bacterial groups and the filamentous fungus Acremonium charticola were isolated from the guts of five F. candida specimens. The most abundant isolate was related to Erwinia amylovora (96.2% DNA sequence similarity to its 16S rRNA gene). F. candida preferred to feed on Pseudomonas putida and three indigenous gut isolates rather than eight different type culture strains. When luciferase reporter gene-tagged bacterial strains were pulse fed to F. candida, gut isolates were continuously shed for 8 days to several weeks but Escherichia coli HB101 was shed for only 1 day. Ratios of ingested to released bacterial cells demonstrated that populations of nonindigenous gut bacteria like Sinorhizobium meliloti L33 and E. coli HB101 were reduced by more than 4 orders of magnitude but that the population of gut isolate Alcaligenes faecalis HR4 was reduced only 500-fold. This work demonstrates that F. candida represents a frequently changeable but selective habitat for bacteria in terrestrial environments and that microarthropods have to be considered factors that modify soil microbial communities.

Animals↗
PubMed1998

Nuclear localization of IkappaB alpha is mediated by the second ankyrin repeat: the IkappaB alpha ankyrin repeats define a novel class of cis-acting nuclear import sequences.

The ability of the IkappaB alpha protein to sequester dimeric NF-kappaB/Rel proteins in the cytoplasm provides an effective mechanism for regulating the potent transcriptional activation properties of NF-kappaB/Rel family members. IkappaB alpha can also act in the nucleus as a postinduction repressor of NF-kappaB/Rel proteins. The mechanism by which IkappaB alpha enters the nucleus is not known, as IkappaB alpha lacks a discernible classical nuclear localization sequence (NLS). We now report that nuclear localization of IkappaB alpha is mediated by a novel nuclear import sequence within the second ankyrin repeat. Deletion of the second ankyrin repeat or alanine substitution of hydrophobic residues within the second ankyrin repeat disrupts nuclear localization of IkappaB alpha. Furthermore, a region encompassing the second ankyrin repeat of IkappaB alpha is able to function as a discrete nuclear import sequence. The presence of a discrete nuclear import sequence in IkappaB alpha suggests that cytoplasmic sequestration of the NF-kappaB/Rel-IkappaB alpha complex is a consequence of the mutual masking of the NLS within NF-kappaB/Rel proteins and the import sequence within IkappaB alpha. Nuclear import may be a conserved property of ankyrin repeat domains (ARDs), as the ARDs from two other ARD-containing proteins, 53BP2 and GABPbeta, are also able to function as nuclear import sequences. We propose that the IkappaB alpha ankyrin repeats define a novel class of cis-acting nuclear import sequences.

Ankyrins↗
PubMed1998

Afferent and efferent connections of the dorsocentral telencephalon in an electrosensory teleost, Gymnotus carapo.

Biotinylated dextran amine was injected unilaterally into dorsal regions of the telencephalon of the weakly electric fish Gymnotus carapo in order to study the afferent and efferent connections of specific dorsal regions with ventral regions of the telencephalon and with other regions of the central nervous system. Efferent pathways from the dorsolateral area of the telencephalon project ipsilaterally to the anterior hypothalamic nucleus, the ventral thalamus and magnocellular tegmental nucleus, whose axons reach the spinal cord. Anterograde labeling showed that the central division of the dorsal telencephalon sends efferent projections through the lateral forebrain bundle towards the ipsilateral lateral and medial preglomerular nucleus, the pretectal nucleus, the optic tectum and the dorsal torus semicircularis, regions that are all involved in the processing of electrosensory and/or multisensory information. In addition, when biotinylated dextran amine was injected into the dorsal torus semicircularis, retrogradely labeled neurons were observed in the dorsocentral area of the telencephalon. The dorsocentral area is also a target of the extra-telencephalic afferents originating from rostral, lateral and medial regions of preglomerular complex. Within the telencephalon, neurons of many ventral subdivisions project ipsilaterally to the dorsocentral area. The dorsocentral, dorsolateral and dorsomedial areas are connected ipsilaterally and reciprocally. The dorsocentral area is reciprocally connected with its contralateral homologue through the anterior commissure.

Afferent Pathways↗
PubMed1998

[Computer-based determination of stereopsis].

AIM: A computer-based approach to assess stereopsis for screening purposes is described. This approach is based on random-dot stereograms (RDS). METHOD: The TNO test is a common method to assess stereopsis based on red/green anaglyphs and the use of RDS. This technique was transferred to a computer-based platform. To investigate the validity of the computer-based approach, 25 subjects were tested with both the TNO test and the computer-based approach. RESULTS: With regard to the spectral emission of the monitor screen, accurate separation of red and green for RDS generation was not possible. However, adaptation of the RDS to the colour filters used permitted the best-possible separation. The resolution of the monitor required a viewing distance of 2 m. The results obtained showed no significant differences between the two methods. CONCLUSIONS: For the computer-based screening, RDS and anaglyphs can be employed. The influence of the spectral emission of the monitor screen and its resolution can be reduced by adapting the RDS colours to the filters used and modifying the viewing distance.

Depth Perception↗
PubMed1998

[Computer-based determination of red/green color vision defects].

A commonly used method of investigating colour vision, that is, the ability of the human visual system to discriminate colours, is based on the use of isochromatic colour plates, such as those used in the Ishihara test. The present paper describes a new computer-based method of determining red/green colour vision deficiencies. The method involves the presentation of Ishihara colour plates on a computer monitor. It has been verified experimentally that, despite the differences between the spectral emission of the computer screen and the daylight reflected by the Ishihara plates, the method is capable of distinguishing between subjects with from those without colour vision deficiencies. For screening purposes, the use of a reduced number of plates is suggested. This suggestion makes use of nine instead of 14 plates, and the criterion of two incorrectly recognized plates to determine a colour vision deficiency.

Adult↗
PubMed1998

Keratinocyte growth inhibition by streptococcal proteins.

M proteins are receptor proteins and one of the virulence factors of streptococci. M proteins seem to play a role in inflammatory skin disorders such as psoriasis. It is however unknown whether M proteins have a direct influence on proliferative activity of human keratinocytes. In the present study human HaCaT keratinocytes were exposed to M proteins (M1, M3, M5, M12) and the proliferative and proinflammatory response was analyzed. We found a dose-dependent inhibition of keratinocyte proliferation with crude extract of strain M3 4/55. Following affinity chromatography we found inhibitory activity for keratinocyte proliferation with a maximum of 80% at 10-8 M in the M protein. Additionally tested M1 protein preparation showed an inhibitory activity of 55% whereas other M preparations (5 and 12) did not show any effect. In supernatants from HaCaT cultures IL-1alpha, IL-1beta, IL-6, IL-8, TNFalpha and ICAM-1 were measured by ELISA. The levels of IL-8 were high and TNFalpha was upregulated, whereas ICAM-1 was decreased from around 20 ng/ml to almost zero. In contrast to the streptococcal-derived M3 protein preparation the recombinant M3 did not interfere with the proliferation of HaCaT cells. Because neither recombinant M3 protein nor M3 protein purified by ion exchange chromatography on a Q-resource column had any antiproliferative activity on keratinocytes we suggest, that a component different from M3 protein was responsible.

Antigens, Bacterial↗
PubMed1998

Vasoactive intestinal peptide and epidermal growth factor: co-mitogens or inhibitors of keratinocyte proliferation in vitro?

Vasoactive intestinal peptide (VIP) is a neuropeptide with a broad range of biological activities in various tissues. Interactions of VIP and epidermal growth factor (EGF) are of particular interest for dermatology. They may be either co-mitogenic or inhibitory. HaCaT keratinocytes cultivated under serum-free conditions in vitro have been used to investigate the interactions of VIP and EGF. EGF was found to induce cell growth, whereas preincubation with VIP inhibited EGF-induced proliferation in a dose-dependent manner. Maximum growth inhibition was 46% (p < 0.01) at a VIP concentration of 10(-7) M. EGF-induced growth is mediated by tyrosine kinase (TK). Therefore we studied the effect of VIP on TK activity. Cells were incubated with VIP (10(-13)-10(-7) M) for 48 h and stimulated with EGF at a final concentration of 500 ng/ml. SDS-PAGE and Western blot with the antibody RC20H against TK were performed. We found a dose dependent decrease of EGF receptor TK activity. At VIP concentration of 10(-7) M a residual TK activity of 65% was detected. To investigate the possibly involved signal transduction pathways, we performed inhibition experiments with wortmannin, pertussis toxin, 2'5'diacylglycerol and adenosine-3':5'-mono-phosphorothioate. However, none of the inhibitors was effective in abolishing growth inhibition by VIP. VIP was shown to be growth inhibitory for human keratinocytes. The data suggest that EGF receptor TK is involved in signal transduction of VIP. Thus TK activity is a possible common target of both EGF- and VIP-induced cellular responses.

Androstadienes↗
PubMed1998

In vitro investigations of drug release and penetration--enhancing effect of ultrasound on transmembrane transport of flufenamic acid.

Although topical drugs are usually applied at a convenient site, the target for the drug interaction may be systemic. Phonophoresis is the use of ultrasound to enhance the delivery of topical applied drugs. The purposes of our study were to investigate the in vitro penetration and the in vivo transport of flufenamic acid in dependence of ultrasound. Percutaneous absorption studies are performed in various in vitro models to determine the rate of drug absorption via the skin. We designed a phonophoretic drug delivery system to investigate the influence of ultrasound on transmembrane transport of different drugs. We investigated the absorption of flufenamic acid in a buffer medium in dependence of ultrasound energy and application time. For evaluating membrane penetration of flufenamic acid, the concentration range of buffer solution was measured. Ultrasound energy was supplied for between 5 and 30 min at a range of intensities up to 1.5 W/cm2, energy levels commonly used for therapeutic purpose. The pronounced effect of ultrasound on the transmembrane absorption of the drug was observed at all ultrasound energy levels studied. The time of application was found to play an important role in delivery and transport of drug. Dependent on time, we observed a rise of temperature up to 4.5 degrees C. It appears that there was no difference between an intensity of 0.3 and 1.5 W/cm2 and the measured drug concentrations in solution. The highest penetration was observed at an intensity of 1.0 W/cm2 after 30 min. These results were not significantly different from concentration measurements after 30 min and 0.5 and 1.5 W/cm2. It seems that the arise of drug concentration is caused by effects of temperature and by variation of membrane delivery in dependence of temperature. Using this in vitro model we note it is possible to compare the transdermal penetration and absorption of commercial flufenamic ointment in volunteers.

Administration, Topical↗
PubMed1998

Comparison of skin atrophy and vasoconstriction due to mometasone furoate, methylprednisolone and hydrocortisone.

BACKGROUND/AIMS: Topical glucocorticoids with improved benefit/risk ratio are of great interest in dermatology, but there are very few trials directly comparing the efficacy and side-effects of these new preparations. In our study the vasoconstrictor effect and side-effects of two of these new glucocorticoids were evaluated and blanching effect was determined by two-dimensional laser scanning. METHODS: In a randomised, double blind intra-individual comparative trial, 10 subjects were treated with various glucocorticoids or drug-free vehicle. The test drugs were mometasone furoate (MF), methylprednisolone aceponate (MP) and hydrocortisone (OH-C). The preparations were tested for a period of 3 weeks with occlusion on the flexor side of the forearm. Skin thickness and vasoconstriction were determined using 20 MHz ultrasound scanning, laser Doppler scanning (LDS) and chromometry. RESULTS: No adverse effects were observed during the observation period. Only partial vasoconstriction occurred in most cases during the observation period. MP and MF produced maximal blanching between days 3 and 5 of treatment, while with OH-C clinically visible blanching did not occur. Ultrasound evaluation of skin thickness showed similar behaviour for all three steroids tested: there were no signs of skin atrophy in any of the cases. LDS evidenced hypoperfusion of a test area on the perfusion image in only a few patients and there were no significant differences between the steroids tested. On evaluation of vasoconstriction caused by the steroids tested using chromometry there was a significant difference between MF and OH-C on the L*a*b* scale (P < 0.005). Only at day 3 was a blanching effect caused by MP and MF demonstrable (a-value, P < 0.05). CONCLUSION: In summary, the synthetic steroids MF and MP presented side-effects similar to those of OH-C but much greater vasoconstrictor effect; after an application period of over 5 days under occlusion a blanching effect in our model was not demonstrable by means of chromometry. Two-dimensional laser scanning offers no advantage in the evaluation of the blanching effect in comparison to one-dimensional laser fluxmetry (LDF).

Administration, Topical↗
PubMed1998

[Evaluation of the circulatory system in workers in the cellulose-paper industry].

The effect of occupational exposure on the circulatory system disorders was evaluated in 802 workers (675 men and 127 women). Occupational histories were analysed, as well as physical and X-ray examinations, laboratory tests (fasting blood cholesterol, triglycerides and glucose) and ECGs were performed. In doubtful cases echocardiography and stress tests on an ergonometer were carried out. Ischaemic heart disease was diagnosed in 1.37% and symptoms suggesting this disease in 6.48% of workers. The incidence of hypertension, anginal pain and dysrhythmias reported were significantly related to workers' age and duration of employment. Smoking, obesity, hypercholesterolaemia and positive family history were found to be most frequent risk factors. Arterial hypertension was diagnosed in 9.48% of workers. Non-occupational factors seem to be mainly responsible for the circulatory system disorders, however, the effects of occupational factors occurring in the cellulose and paper industry which may accelerate the development of ischaemic heart disease, arterial hypertension and dysrhythmias cannot be excluded.

Adult↗
PubMed1998

Evaluation of an oral pulsatile delivery system for melatonin in humans.

Using melatonin (MT) as a circadian synchroniser in humans to treat a variety of rhythm disorders, it is desirable to develop controlled-release dosage forms that deliver MT in accordance with its endogenous secretory pattern as well as preparations that release MT in a pulsatile way. In this paper we describe two oral pulsatile dosage forms containing 10 mg MT each (capsules B and C) and a fast-release form containing 5 mg MT (capsule A) studied in a randomised single-dose, threefold cross-over study in 15 healthy male volunteers. The concentrations of both MT in serum and its main metabolite 6-sulfatoxymelatonin (aMT6s) in urine were analysed by means of specific radioimmunoassays up to 10 h p.a. of the MT preparations. Mean peak concentrations of MT in serum were reached between 0.5 h and 0.75 h (Cmax[1] pmol/ml): 20.7 (A), 16.4 (B), 9.7 (C). The capsules B and C released a second MT pulse after about 3.5 h with Cmax[2] of 13.0 and 17.5 pmol/ml, respectively. Dose proportionality for the MT preparations studied was calculated by determining the AUC0-infinity (pmol/ml.h): 18.4 (A), 36.1 (B), 42.4 (C). The terminal serum half-lives of MT ranged between 0.64 and 0.84 h. The time course of the renally excreted aMT6s correlated with that of changes in MT serum concentrations.

Adult↗
PubMed1998

CYP2E1 genotyping in renal cell/urothelial cancer patients in comparison with control populations.

OBJECTIVE: Genetic polymorphisms in enzymes involved in carcinogen metabolism have been found to influence susceptibility to cancer. Ethanol-inducible CYP2E1 is an enzyme of major toxicological interest because it metabolizes several drugs, precarcinogens, and solvents to reactive metabolites. In the present investigation, we studied the cytochrome P450 2E1 genetic polymorphism in renal cell/urothelial cancer patients in comparison with healthy control populations in the regions of Jena and Halle in Germany. PATIENTS AND MATERIAL: DNA of peripheral white blood cells was isolated both from 273 renal cell/urothelial cancer patients and 298 controls from the regions of Jena and Halle. METHOD: We focused on polymorphisms in the promoter region and intron 6 of the CYP2E1 gene. The polymorphims were identified as restriction fragment length polymorphisms (RFLPs) by polymerase chain reaction (PCR) and subsequently applying the restriction enzymes PstI/RsaI and DraI. RESULTS: In the region of Jena as well as of Halle, the frequency distributions of the PstI/RsaI, DraI, and combined DraI + PstI/RsaI genotypes showed no significant differences between controls and renal cell/urothelial cancer patients. We did not find significant differences between Jena and Halle. 86.7% of all subjects with a homozygote PstI/RsaI genotype also carried a homozygote DraI genotype, whereas 5.2% of all subjects with a heterozygote PstI/RsaI genotype also carried a heterozygote DraI genotype. The heterozygote genotype of PstI/RsaI polymorphism always determines the heterozygote genotype of DraI polymorphism. Our results failed to demonstrate any differences in the distribution of CYP2E1 polymorphisms between renal cell/urothelial cancer patients and controls. CONCLUSION: Summing up, our results show that CYP2E1 genotype cannot predict risk for renal cell/urothelial cancer in the population from 2 different regions in Germany. The results demonstrate a lack of association between CYP2E1 genetic polymorphism and renal cell cancer/urothelial cancer.

Carcinoma, Renal Cell↗
PubMed1998

[Do patients with changes in the vertebral arteries have an increased risk in carotid artery obliteration?].

There was no difference between the groups investigated in terms of the preoperative neurological stages. In patients with VA involvement, both the 30-day mortality rate (p < 0.01) and the long-term survival rate (p < 0.01) were significantly poorer. In the study group, the incidence of shunt procedures was three times as high as in the control group (p < 0.01).

Carotid Artery, Internal↗
PubMed1997

The lateral hypothalamus in the modulation of tonic immobility in guinea pigs.

The lateral hypothalamus has been reported to be involved in the organization of aggression and predatory attack but not in behavioral inhibition responses such as tonic immobility (TI). TI may be defined as an inborn behavioral inhibition characterized by profound physical inactivity and relative lack of responsiveness to the environment, triggered by an intense sensation of fear generated during prey-predator confrontation. Our study indicates that cholinergic stimulation of anterior regions of the lateral hypothalamus of guinea pigs potentiates the duration of TI episodes, while stimulation of medial and posterior regions of this structure promotes a decrease in TI duration, suggesting that the lateral hypothalamus modulates the duration of TI episodes in a differentiated manner.

Animals↗
PubMed1997

[Stress as cardiovascular risk factor].

With appropriate assessment, stress has been shown to be an important variable for the development and course of cardiovascular diseases. Elements of stress include life events, inadequate coping strategies, deficient social support and a combination of heavy demands/ low rewards at work as well as in other situations. Dealing with stress therefore is important in cardiac rehabilitation and secondary prevention, as well as in the primary prevention of cardiovascular disease. The issue was discussed controversially at a workshop at the Annual meeting of the Swiss Society of Cardiology in 1996. The opposing views are presented.

Combined Modality Therapy↗