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Biomedical subjects

F Hofmann

Publications and source records attributed to F Hofmann.

At least 37 records · Page 2Linked to original sources
PubMed2002

Occupational risk for hepatitis A and hepatitis E among health care professionals?

BACKGROUND: Since transmission routes of hepatitis E virus (HEV) and hepatitis A virus (HAV) are believed to be similar, comparable risk factors and a correlation between the two seroprevalence rates may be assumed. MATERIALS AND METHODS: Anti-HAV and anti-HEV serology was assessed in 511 German subjects from nursing, pediatric nursing and administration groups, none of whom had been vaccinated against HAV. At the same time a standardized questionnaire on occupational and individual parameters was completed. RESULTS: Overall seroprevalence for anti-HEV was 3.9%, for anti-HAV 28%. Multivariate analysis revealed that anti-HEV seroprevalence was significantLy higher in persons working in emergency admission or in surgery, while persons working in children's psychiatry were more likely to be anti-HAV positive. Comparing the two serological resulLts, no contingency difference was found (chi2 = 0.42 (df = 1), p > 0.05). CONCLUSION: Specific departments of health care show higher prevalence of anti-HAV or anti-HEV. In the case of HEV further studies in the exposed working field are needed. Since no connection between the two serological results was found, transmission mechanisms might be (partly) different.

Adult↗
PubMed2002

[In vitro imaging of magnetite particles].

PURPOSE: To find an optimal imaging modality for the assessment of magnetite agglomerations used as the heating sources during magnetic thermoablation of tumors. METHODS: 1 to 107 mg of coated (starch) magnetite particles were directly administered to an in vitro tumor model (swine lymph nodes) and investigated immediately (radiography) or after being embedded within a 4 % agar-phantom (sonography). T1-weighted MR images (TR = 400 ms, TE = 14 ms) were acquired from lymph nodes containing 0.5 to 25 mg magnetite. RESULTS: All investigated magnetite masses were qualitatively detectable by radiography. Sonographically, only mass agglomerations containing 107 mg magnetite were appropriately discernible. MRT images revealed distinct susceptibility artifacts. CONCLUSIONS: Based on the investigated imaging modalities, radiography is the method of choice for assessment of magnetite agglomerations using relevant dosages for magnetic thermoablation of tumors.

Animals↗
PubMed2002

[Needle stick injuries in health care - frequency, causes und preventive strategies].

Healthcare workers (HCW) are at risk for infections with blood-borne pathogens - especially hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) - resulting from occupational blood-exposure trough injuries with sharp instruments and needle sticks. Results of a study on the epidemiology of needle stick injuries (NSI) among HCW in two German hospitals indicate that 500,000 NSI occur annually in Germany. Most of these injuries occur during disposal of used syringes and "recapping". Administration of the post-exposure prophylaxis is recommended for HCW who are occupationally exposed to HBV (vaccine/immunoglobulin) and HIV (antiretroviral drugs) i.e. the immediately reporting of blood exposure is very important. Comprehensive programmes to prevent NSI - e.g. avoiding of recapping, use of disposal containers, surgical gloves and in particular safety devices - minimize a high cost of NSI due to the administration of PEP, developing of chronic hepatitis, cirrhosis and liver cancer.

Blood-Borne Pathogens↗
PubMed2001

Attitudes of homoeopathic physicians towards vaccination.

Vaccinations are one of the most effective preventive procedures in modern medicine. However, earlier studies have indicated that homoeopathic physicians do not recommend or apply vaccinations as frequently as their allopathic colleagues. Few studies have been undertaken to clarify this question and most of these have not distinguished between medically and non-medically qualified homoeopathic practitioners. Therefore, misunderstandings have arisen concerning this question. In the study presented only medically qualified colleagues were included. In the course of this study, 219 medically qualified homoeopathic and 281 non-homoeopathic physicians in Germany (response rate 30.4%) returned a questionnaire about the application and recommendation of 17 different vaccinations in their practices. The answers show that the responding homoeopathic physicians do not generally refuse vaccines but rather view them with a specific hierarchy. The 'classical' vaccines against tetanus, diphtheria and poliomyelitis are applied to nearly the same degree as by non-homoeopathic colleagues. Vaccines against childhood diseases, risk group vaccinations and vaccinations judged as ineffective are applied and accepted with more restraint by homoeopathic physicians.

Adult↗
PubMed2001

Aspartate residues of the Glu-Glu-Asp-Asp (EEDD) pore locus control selectivity and permeation of the T-type Ca(2+) channel alpha(1G).

The structural determinant of the permeation and selectivity properties of high voltage-activated (HVA) Ca(2+) channels is a locus formed by four glutamate residues (EEEE), one in each P-region of the domains I-IV of the alpha(1) subunit. We tested whether the divergent aspartate residues of the EEDD locus of low voltage-activated (LVA or T-type) Ca(2+) channels account for the distinctive permeation and selectivity features of these channels. Using the whole-cell patch-clamp technique in the HEK293 expression system, we studied the properties of the alpha(1G) T-type, the alpha(1C) L-type Ca(2+) channel subunits, and alpha(1G) pore mutants, containing aspartate-to-glutamate conversions in domain III, domain IV, or both. Three characteristic features of HVA Ca(2+) channel permeation, i.e. (a) Ba(2+) over Ca(2+) permeability, (b) Ca(2+)/Ba(2+) anomalous mole fraction effect (AMFE), and (c) high Cd(2+) sensitivity, were conferred on the domain III mutant (EEED) of alpha(1G). In contrast, the relative Ca(2+)/Ba(2+) permeability and the lack of AMFE of the alpha(1G) wild type channel were retained in the domain IV mutant (EEDE). The double mutant (EEEE) displayed AMFE and a Cd(2+) sensitivity similar to that of alpha(1C), but currents were larger in Ca(2+)- than in Ba(2+)-containing solutions. The mutation in domain III, but not that in domain IV, consistently displayed outward fluxes of monovalent cations. H(+) blocked Ca(2+) currents in all mutants more efficiently than in alpha(1G). In addition, activation curves of all mutants were displaced to more positive voltages and had a larger slope factor than in alpha(1G) wild type. We conclude that the aspartate residues of the EEDD locus of the alpha(1G) Ca(2+) channel subunit not only control its permeation properties, but also affect its activation curve. The mutation of both divergent aspartates only partially confers HVA channel permeation properties to the alpha(1G) Ca(2+) channel subunit.

Aspartic Acid↗
PubMed2001

Molecular determinants of the interaction between the inositol 1,4,5-trisphosphate receptor-associated cGMP kinase substrate (IRAG) and cGMP kinase Ibeta.

Cyclic GMP-dependent protein kinase I (cGKI) affects the inositol 1,4,5-trisphosphate (InsP(3))-dependent release of intracellular calcium by phosphorylation of IRAG (inositol 1,4,5-trisphophate receptor-associated cGMP kinase substrate). IRAG is present in a macromolecular complex with the InsP(3) receptor type I (InsP(3)RI) and cGKIbeta. The specificity of the interaction between these three proteins was investigated by using the yeast two-hybrid system and by co-precipitation of expressed proteins. The amino-terminal region containing the leucine zipper (amino acids 1-53) of cGKIbeta but not that of cGKIalpha or cGKII interacted with the sequence between amino acids 152 and 184 of IRAG in vitro and in vivo most likely through electrostatic interaction. cGKIbeta did not interact with the InsP(3)RI, but co-precipitated the InsP(3)RI in the presence of IRAG indicating that IRAG bound to the InsP(3)RI and to cGKIbeta. cGKIbeta phosphorylated up to four serines in IRAG. Mutation of these four serines to alanine showed that cGKIbeta-dependent phosphorylation of Ser(696) is necessary to decrease calcium release from InsP(3)-sensitive stores. These results show that cGMP induced reduction of cytosolic calcium concentrations requires cGKIbeta and phosphorylation of Ser(696) of IRAG.

Animals↗
PubMed2001

Delivery of proteins into living cells by reversible membrane permeabilization with streptolysin-O.

The pore-forming toxin streptolysin O (SLO) can be used to reversibly permeabilize adherent and nonadherent cells, allowing delivery of molecules with up to 100 kDa mass to the cytosol. Using FITC-labeled albumin, 10(5)-10(6) molecules were estimated to be entrapped per cell. Repair of toxin lesions depended on Ca(2+)-calmodulin and on intact microtubules, but was not sensitive to actin disruption or to inhibition of protein synthesis. Resealed cells were viable for days and retained the capacity to endocytose and to proliferate. The active domains of large clostridial toxins were introduced into three different cell lines. The domains were derived from Clostridium difficile B-toxin and Clostridium sordelli lethal toxin, which glycosylate small G-proteins, and from Clostridium botulinum C2 toxin, which ADP-ribosylates actin. After delivery with SLO, all three toxins disrupted the actin cytoskeleton to cause rounding up of the cells. Glucosylation assays demonstrated that G-proteins Rho and Ras were retained in the permeabilized cells and were modified by the respective toxins. Inactivation of these G-proteins resulted in reduced stimulus-dependent granule secretion, whereas ADP-ribosylation of actin by the C. botulinum C2-toxin resulted in enhanced secretion in cells. The presented method for introducing proteins into living cells should find multifaceted application in cell biology.

Albumins↗
PubMed2001

Long-pulse improved central electron confinement in the TCV tokamak with electron cyclotron heating and current drive.

Current profile tailoring by electron cyclotron heating (ECH) and current drive (ECCD) is used to improve central electron energy confinement in the TCV tokamak. Counter-ECCD on axis alone achieves this goal in a transient manner only. A stable scenario is obtained by a two-step sequence of off-axis ECH, which stabilizes magnetohydrodynamics modes, and on-axis counter-ECCD, which generates a flat or inverted current profile. This high-confinement regime, with central temperatures up to 9 keV (at a normalized beta(N) approximately 0.6), has been sustained for the entire duration of the heating pulse, or over 200 electron energy confinement times and 5 current redistribution times.

Journal Article↗
PubMed2001

An inhibitory role of Rho in the vasopressin-mediated translocation of aquaporin-2 into cell membranes of renal principal cells.

Vasopressin regulates water reabsorption in renal collecting duct principal cells by a cAMP-dependent translocation of the water channel aquaporin-2 (AQP2) from intracellular vesicles into the cell membrane. In the present work primary cultured inner medullary collecting duct cells were used to study the role of the proteins of the Rho family in the translocation of AQP2. Clostridium difficile toxin B, which inhibits all members of the Rho family, Clostridium limosum C3 toxin, which inactivates only Rho, and the Rho kinase inhibitor, Y-27632, induced both depolymerization of actin stress fibers and AQP2 translocation in the absence of vasopressin. The data suggest an inhibitory role of Rho in this process, whereby constitutive membrane localization is prevented in resting cells. Expression of constitutively active RhoA induced formation of actin stress fibers and abolished AQP2 translocation in response to elevation of intracellular cAMP, confirming the inhibitory role of Rho. Cytochalasin D induced both depolymerization of the F-actin cytoskeleton and AQP2 translocation, indicating that depolymerization of F-actin is sufficient to induce AQP2 translocation. Thus Rho is likely to control the intracellular localization of AQP2 via regulation of the F-actin cytoskeleton.

Amides↗
PubMed2001

Low pH-induced formation of ion channels by clostridium difficile toxin B in target cells.

Clostridium difficile toxin B (269 kDa), which is one of the causative agents of antibiotic-associated diarrhea and pseudomembranous colitis, inactivates Rho GTPases by glucosylation. Here we studied the uptake and membrane interaction of the toxin with eukaryotic target cells. Bafilomycin A1, which prevents acidification of endosomal compartments, blocked the cellular uptake of toxin B in Chinese hamster ovary cells cells. Extracellular acidification (pH </= 5.2) induced uptake of toxin B into the cytosol even in the presence of bafilomycin A1. Toxin B increased (86)Rb(+) release when preloaded Chinese hamster ovary cells were exposed to low pH (pH </= 5.6) for 5 min. Release of (86)Rb(+) depended on the concentration of toxin B and on the pH of the extracellular medium. An antibody directed against the holotoxin prevented channel formation, whereas an antibody against the N-terminal enzyme domain was without effect. The N-terminally truncated toxin B fragment consisting of amino acids 547-2366 increased (86)Rb(+) efflux when cells were exposed to low pH. Toxin B also induced pH-dependent channel formation in artificial lipid bilayer membranes. Clostridium sordellii lethal toxin, another member of the family of large clostridial cytotoxins, also induced increased (86)Rb(+) release at low pH. The results suggest that large clostridial cytotoxins including C. difficile toxin B and C. sordellii lethal toxin undergo structural changes at low pH of endosomes that are accompanied by membrane insertion and channel formation.

Animals↗
PubMed2001

The amino side of the C-terminus determines fast inactivation of the T-type calcium channel alpha1G.

We analysed the kinetic properties of the fast inactivating T-type calcium channel alpha1G in HEK 293 cells transfected with different alpha1G chimeras, containing the N-terminus, III-IV linker or various C-terminal regions of the slowly inactivating L-type alpha1C. A highly negatively charged region of 23 amino acids at the amino side of the intracellular carboxy terminus of alpha1G was found to be critical for fast inactivation. The N-terminus of alpha1G does not seem to be necessary for inactivation of the T-type calcium channel because replacement of the a1G N-terminus with the alpha1C N-terminus did not influence channel kinetics at all. Replacing the III-IV linker of alpha1G with that of a1C decreased the rate of inactivation at -20 mV from 15.8 +/- 1.8 to 8.5 +/- 1.1 ms, and shifted the potential for half-maximal inactivation from -69.6 +/- 0.8 to -54.0 +/- 1.7 mV. However, these parameters were not significantly different at other potentials. We suggest a putative 'ball-and-chain'-like mechanism for inactivation in which the negative charges function as an acceptor domain for a ball, hypothetically located at a different intracellular part of the channel. In addition, transferring the IQ motif and EF hand of alpha1C to alpha1G does not confer Ca2+-dependent inactivation on alpha1G, suggesting that other sequences besides the C-terminus are needed for Ca2+-dependent inactivation of alpha1C.

Algorithms↗
PubMed2001

Regulation by rho family GTPases of IL-1 receptor induced signaling: C3-like chimeric toxin and Clostridium difficile toxin B inhibit signaling pathways involved in IL-2 gene expression.

In this study the participation of Rho family GTPases in the regulation of IL-1-activated protein kinase cascades controlling IL-2 synthesis was investigated in murine EL-4 thymoma cells. The recombinant C3-like chimeric toxin, which consists of the C3 toxin of Clostridium limosum and the N-terminal part of Clostridium botulinum C2 toxin (C2IN-C3) interacting with the C2II binding subunit to facilitate uptake into cells, and selectively inactivates Rho A by ADP-ribosylation, prevented IL-1-stimulated activation of Jun-NH2-terminal-kinases (JNK) and p38 mitogen-activated-protein kinases (MAPK). UDP-monoglucosylation and concomitant inactivation of Rho A and of Rac-2 by Clostridium difficile toxin B also inhibited IL-1-induced activation of JNK and p38 MAPK, but additionally inhibited activation of the extracellular-regulated-kinase pathway and DNA binding of the transcription factor NFkappaB. Accordingly, pre-treatment of cells with C21N-C3 fusion toxin only decreased IL-1-stimulated IL-2 synthesis by 50%, while in C. difficile toxin B-treated cells IL-1-induced IL-2 secretion was reduced by 90%. These results imply that together with Rho A an additional member of the Rho family G proteins, i.e. Rac-2, is critically involved as an upstream regulator in IL-1-induced activation of different MAPK, stress-activated protein kinases, and in NFkappaB activation controlling IL-2 gene expression in response to IL-1, acting in close proximity to the IL-1-receptor complex.

Animals↗
PubMed2001

Task profile and risk of occupational hepatitis A infection in sewerage workers.

OBJECTIVE: The aim of the study was to assess to what extent parameters of task-related occupational exposure influence anti-hepatitis A virus (anti-HAV) seroprevalence in sewerage workers, using a new instrument for classification of exposure. METHODS: A new instrument for the assessment of work-related infection hazards was developed based on expert interviews, evaluation of literature and theoretical considerations. It was included in a questionnaire for collecting detailed information on occupational exposure, safety awareness, safety behaviour and socio-demography. Anti-HAV status was assessed for all (n = 343) (non-vaccinated) study participants. RESULTS: Marked differences in task profile and task-related exposure within the group of sewerage workers were found, underlining the necessity of a detailed exposure analysis. In a multivariate model three risk factors that were related significantly to anti-HAV positivity were identified: age, country of origin and task-related exposure. CONCLUSIONS: Since task profiles and occupational exposure differ strongly within the job category of sewerage workers. evaluation of endangerment has to reflect individual task-related exposure. The task-exposure matrix developed and presented in this study is a practicable and valid instrument for exposure assessment and may be used for the exposure analysis of further biological agents in this working environment. Besides the known risk parameters age and origin, our study demonstrates a dose-response relationship between the degree of occupational exposure and the anti-HAV seroprevalence. Therefore, an effective worksite HAV-prevention programme should consider all technical, structural and educational measures that help to reduce individual exposure.

Adult↗
PubMed2001

Differential and age-dependent expression of hyperpolarization-activated, cyclic nucleotide-gated cation channel isoforms 1-4 suggests evolving roles in the developing rat hippocampus.

Hyperpolarization-activated cation currents (I(h)) are found in several brain regions including thalamus and hippocampus. Important functions of these currents in promoting synchronized network activity and in determining neuronal membrane properties have been progressively recognized, but the molecular underpinnings of these currents are only emerging. I(h) currents are generated by hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCNs). These channel proteins are encoded by at least four HCN genes, that govern the kinetic and functional properties of the resulting channels. Because of the potential impact of I(h)-mediated coordinated neuronal activity on the maturation of the functional hippocampal network, this study focused on determining the expression of the four members of the HCN gene family throughout postnatal hippocampal development at both the regional and single cell level.The results of these experiments demonstrated that HCNs 1, 2 and 4 are differentially expressed in interneuronal and principal cell populations of the rat hippocampal formation. Expression profiles of each HCN isoform evolve during postnatal development, and patterns observed during early postnatal ages differ significantly from those in mature hippocampus. The onset of HCN expression in interneurons of the hippocampus proper precedes that in the dentate gyrus, suggesting that HCN-mediated pacing activity may be generated in hippocampal interneurons prior to those in the hilus. Taken together, these findings indicate an age-dependent spatiotemporal evolution of specific HCN expression in distinct hippocampal cell populations, and suggest that these channels serve differing and evolving functions in the maturation of coordinated hippocampal activity.

Aging↗
PubMed2001

Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4-/- mice.

Agonist-induced Ca2+ entry into cells by both store-operated channels and channels activated independently of Ca2+-store depletion has been described in various cell types. The molecular structures of these channels are unknown as is, in most cases, their impact on various cellular functions. Here we describe a store-operated Ca2+ current in vascular endothelium and show that endothelial cells of mice deficient in TRP4 (also known as CCE1) lack this current. As a consequence, agonist-induced Ca2+ entry and vasorelaxation is reduced markedly, showing that TRP4 is an indispensable component of store-operated channels in native endothelial cells and that these channels directly provide an Ca2+-entry pathway essentially contributing to the regulation of blood vessel tone.

Acetylcholine↗