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Biomedical subjects

E Krause

Publications and source records attributed to E Krause.

At least 19 recordsLinked to original sources
PubMed2007

[Oxcarbazepine in the treatment of epilepsy].

BACKGROUND: Oxcarbazepine (OXC; Timox) is a new antiepileptic drug (AED) chemically related to carbamazepine (CBZ), with comparable efficacy but superior safety according to controlled clinical trials. In a prospective, post-marketing surveillance (PMS) study the efficacy and tolerability of OXC were investigated under conditions of daily routine practice. METHODS: The treatment of 1385 male and female epilepsy patients aged between 1 month and 94 years, who were newly stabilized on OXC or changed over from another AED, was documented in 362 centers over a period of 8 weeks. Efficacy and tolerability were assessed by documenting the frequency of seizures and adverse drug reactions (ADRs) and by global efficacy and tolerability ratings obtained from the patients and investigators. RESULTS: Before the PMS study, 688/1335 patients (49.7 %) had received pre-treatment with CBZ, 342 (24.7 %) had received another AED and 335 (25.6 %) had had no AED pre-treatment (initial OXC monotherapy). In 161 patients pre-treated with CBZ (23,4 % of 688) an immediate (overnight) switch to OXC was performed while most others were switched during a titration phase. Of the patients with CBZ pre-treatment 21 % were switched to OXC at the recommended dose ratio of 1 : 1.4 - 1 : 1.6 (CBZ : OXC) while roughly 60 % were changed to OXC with a lower ratio. In the total sample the median OXC maintenance dose was 900 mg/day. During treatment with OXC the frequency of seizures per 4 weeks decreased by an average of 76 % in comparison to a retrospective pre-phase. 74 % of the patients showed an improved seizure situation, and 40.5 % became seizure-free under OXC (patients with initial monotherapy became seizure-free in 62 % of the cases). 71 % of the patients showed a reduction of their seizure frequency versus baseline by > or = 50 %. ADRs were reported in 10,8 % of the participants (incidence: 1 in 459 days of exposition to OXC; overnight switching from CBZ to OXC: 1 event in 1284 days). Only 2.5 % of the patients terminated OXC administration due to ADRs while 92 % continued treatment with OXC beyond the end of the study. CONCLUSIONS: The results underline the high antiepileptic efficacy and good tolerability of OXC previously demonstrated in controlled clinical trials. When changing from CBZ to OXC, immediate (overnight) switching showed particularly favorable results.

Adolescent↗
PubMed2006

Proteomic analysis of Entamoeba histolytica.

In this study, the proteome of axenically grown Entamoeba histolytica parasites was explored by two-dimensional gel electrophoresis (2-DE), employing a practical and effective procedure for the solubilization of E. histolytica proteins. Approximately 900 protein species in the pH range between 4 and 7 were detected by Coomassie Blue staining. Ninety-five spots were excised, trypsinated and subjected to mass spectrometry. The resultant data from peptide mass fingerprints were compared with those available in the E. histolytica genome and the (non-redundant) National Center for Biotechnology Information (NCBI) databases for the identification and categorization of proteins. Sixty-three of the proteins identified were predicted to relate to the cytoskeleton, surface, glycolysis, RNA/DNA metabolism, the ubiquitin-proteasome system, vesicular trafficking and signal transduction. The present study demonstrates, for the first time, that corresponding genes are indeed expressed in E. histolytica and provides a foundation for further proteomic studies of this parasite.

Animals↗
PubMed2006

[Treatment of hearing impairment in children].

The prerequisite for normal speech development is the ability to hear normally. Our objective here is the detection of a hearing deficit with a relevant impact on the acquisition of speech before the child is three months old. Such a hearing impairment due to sensorineural deafness requires the provision of a hearing aid, which needs to be done before the child is six months old. If the provision of a hearing aid fails to provide the desired results, or if they may no longer be expected, a cochlear implant is indicated. In the event of tympanic effusion persistence, an adenotomy with paracentesis, and possibly the insertion of an ear tube, is indicated. This intervention can be done before the child is one year old. Permanent sound-conduction deafness may be due to auditory canal atresia or middle ear anomalies. In such cases, it is important to establish whether surgical reconstruction, for example of the sound conduction system, can restore good hearing over the long term. Prior to surgery at the age of about five, the child must be provided with a hearing aid.

Child↗
PubMed2006

On the self-association potential of transmembrane tight junction proteins.

Tight junctions seal intercellular clefts via membrane-related strands, hence, maintaining important organ functions. We investigated the self-association of strand-forming transmembrane tight junction proteins. The regulatory tight junction protein occludin was differently tagged and cotransfected in eucaryotic cells. These occludins colocalized within the plasma membrane of the same cell, coprecipitated and exhibited fluorescence resonance energy transfer. Differently tagged strand-forming claudin-5 also colocalized in the plasma membrane of the same cell and showed fluorescence resonance energy transfer. This demonstrates self-association in intact cells both of occludin and claudin-5 in one plasma membrane. In search of dimerizing regions of occludin, dimerization of its cytosolic C-terminal coiledcoil domain was identified. In claudin-5, the second extracellular loop was detected as a dimer. Since the transmembrane junctional adhesion molecule also is known to dimerize, the assumption that homodimerization of transmembrane tight junction proteins may serve as a common structural feature in tight junction assembly is supported.

Animals↗
PubMed2005

[Uterine gas gangrene through clostridium perfringens sepsis after uterus rupture postpartum].

Anaerobic infections with Clostridium perfringens (CP) occur rarely but are associated with considerable maternal mortality. We report the case of a patient who developed uterine gas gangrene postpartum and discuss the management of this infection. A 28-year-old patient, GII, PII with history of Caesarean in 2002, delivered a healthy girl per vacuum extraction. Postpartally she presented with an acute abdomen and a laparotomy was performed. The uterotomy suture was intact but a parametrane tear had to be resutured. 36 hours later the patient's condition worsened quickly. Cellulitis was diagnosed and after receiving the results of the wound swabs (CP positive) from the uterus and haematoma, tazobactam and clindamycin were administered. Her condition continued to deteriorate and gaseous gangrene was seen with unilateral extension to the abdomen reaching as far as the axilla cranially and to the thigh caudally. Due to the extensive infection it was necessary to perform a hysterectomy, necrosis removal and splitting of the fascia followed by several debridements and leaving the wound open in order to avoid anaerobic conditions. The patient was discharged after 21 days. She developed a post-traumatic syndrome with severe depression. Clostridium perfringens is ubiquitous and is found vaginally in ca. 1 - 10 % of healthy women and usually does not cause a serious infection. Under the right conditions it can cause an endometritis leading to sepsis. Early recognition and interdisciplinary treatment are of extreme importance. In this case the surgical treatment through hysterectomy combined with targeted antibiotic therapy, ultimately saved the patient's life.

Adult↗
PubMed2001

Protein kinase C regulates the phosphorylation and cellular localization of occludin.

Occludin is an integral membrane phosphoprotein specifically associated with tight junctions, contributing to the structure and function of this intercellular seal. Occludin function is thought to be regulated by phosphorylation, but no information is available on the molecular pathways involved. In the present study, the involvement of the protein kinase C pathway in the regulation of the phosphorylation and cellular distribution of occludin has been investigated. Phorbol 12-myristate 13-acetate and 1,2-dioctanoylglycerol induced the rapid phosphorylation of occludin in Madin-Darby canine kidney cells cultured in low extracellular calcium medium with a concomitant translocation of occludin to the regions of cell-cell contact. The extent of occludin phosphorylation as well as its incorporation into tight junctions induced by protein kinase C activators or calcium switch were markedly decreased by the protein kinase C inhibitor GF-109203X. In addition, in vitro experiments showed that the recombinant COOH-terminal domain of murine occludin could be phosphorylated by purified protein kinase C. Ser(338) of occludin was identified as an in vitro protein kinase C phosphorylation site using peptide mass fingerprint analysis and electrospray ionization tandem mass spectroscopy. These findings indicate that protein kinase C is involved in the regulation of occludin function at tight junctions.

Alkaline Phosphatase↗
PubMed2001

An FGF-binding protein (FGF-BP) exerts its biological function by parallel paracrine stimulation of tumor cell and endothelial cell proliferation through FGF-2 release.

Fibroblast growth factors FGF-1 (aFGF) and FGF-2 (bFGF) are found in most embryonic and adult normal and tumor tissues, where they are immobilized in the extracellular matrix (ECM). Mobilization of these FGFs is part of a tightly controlled process resulting in the activation of high-affinity FGF receptors. Recently, we have shown that a secreted FGF-binding protein (FGF-BP) binds non-covalently to FGF-2 and is able to release it from the ECM. This process of growth factor bioactivation seems to play a pivotal role in the growth of squamous cell carcinomas, especially through induction of tumor angiogenesis. Since previous studies provided only indirect evidence for the proposed mechanism of FGF-BP-mediated FGF-2 release, we decided to use recombinant purified FGF-BP to study further the underlying mechanism of FGF-BP action. Here we show that FGF-BP is able to bind directly to FGF-2 without additional cofactors and to exhibit bioactivity. The purified recombinant FGF-BP stimulates tumor cell growth as well as endothelial cell growth and chemotaxis, indicating a dual growth-supporting role of FGF-BP in tumors. We show that this paracrine FGF-BP effect is dependent on endogenously expressed FGF-2, since it can be completely blocked by anti-FGF-2 antibodies. In tumor xenografts and in tumor cells, we detected a pattern of specific FGF-BP-immunoreactive high molecular weight forms, which presumably represent stable covalent complexes of FGF-BP and show marked differences in their occurrence in different tumors and in their heparin binding affinity. By providing further insight into the mechanism of FGF-BP action, our results emphasize the relevance of FGF-BP and of FGF-2 in tumor growth.

Adrenal Gland Neoplasms↗
PubMed2001

Study of the conformational transition of A beta(1-42) using D-amino acid replacement analogues.

A critical event in Alzheimer's disease is the transition of Abeta peptides from their soluble forms into disease-associated beta-sheet-rich conformers. Structural analysis of a complete D-amino acid replacement set of Abeta(1-42) enabled us to localize in the full-length 42-mer peptide the region responsible for the conformational switch into a beta-sheet structure. Although NMR spectroscopy of trifluoroethanol-stabilized monomeric Abeta(1-42) delineated two separated helical domains, only the destabilization of helix I, comprising residues 11-24, caused a transition to a beta-sheet structure. This conformational alpha-to-beta switch was directly accompanied by an aggregation process leading to the formation of amyloid fibrils.

Amino Acid Sequence↗
PubMed2001

Role of helix formation for the retention of peptides in reversed-phase high-performance liquid chromatography.

In order to get insight into the role of helix formation for retention in reversed-phase HPLC, we have studied the isocratic retention behavior of amphipathic and non-amphipathic potentially helical model peptides. Plots of the logarithmic capacity factor in absence of organic solvent (ln k0) versus l/T were used to derive the enthalpy, deltaH0, the free energy, deltaG0, the entropy of interaction, deltaS0, and the heat capacity change, deltaCp. Retention of all peptides was accompanied by negative deltaCp revealing that hydrophobic interactions play a large role independent of peptide sequence and secondary structure. deltaH0 was negative for the amphipathic analogs and was attributed mainly to helix formation of these peptides upon interaction with the stationary phase. In contrast, deltaH0 was considerably less exothermic or even endothermic for the non-amphipathic analogs. The differences in helix formation between the individual analogs were quantified on the basis of thermodynamic data of helix formation previously derived for peptides in a hydrophobic environment. Correlation of the helicity with the free energy of stationary phase interaction revealed that helix formation accounts for approximately 40-70% of deltaG0, and is hence in addition to the hydrophobic effect a major driving force of retention.

Chromatography, High Pressure Liquid↗
PubMed2001

Identification and characterization of neutral endopeptidase (EC 3. 4. 24. 11) from human prostasomes--localization in prostatic tissue and cell lines.

BACKGROUND: An antibody directed against a 100 kDa protein was immunoselected from a polyvalent antiserum against human prostasomes. The antibody as well as biochemical characteristics of the respective antigen were used to study the structural relationship of the latter with prostate membrane specific antigen (PMSA), another 100 kDa membrane protein of the prostate. METHODS: The isolated purified 100 kDa protein was characterized by tryptic degradation, aminoacid-sequencing and mass spectroscopy peptide-fingerprinting as well as mono-saccharide analysis and lectin binding and identified as a prostasomal neutral endopeptidase (NEP, EC 3.4.24.11). Immunohistochemistry, immunoelectron microscopy, in situ hybridization, and RT-PCR were performed to analyze the expression and distribution of the protein in normal and malignant human prostatic tissues and cell lines. RESULTS: Prostatic NEP, which has no relationship with PMSA, is a glycosylated, integral membrane protein type II. The prevalent glycosyl residues are NeuNAc, GlcNAc, GalNAc, Gal, Man, Fuc. NEP-mRNA is expressed in human prostatic epithelial and some stromal cells. NEP-immunoreactivity is strong in normal prostatic epithelium and confined to the apical plasma membrane. During apocrine secretion, the enzyme is released from the secretory cells, contributing to the formation of prostasomes. In prostate cancer specimens, immunoreactivity of apical plasma membranes is lost, while generalized cytoplasmic immunoreactivity develops. CONCLUSIONS: Prostatic secretory cells contain a membrane-bound, highly glycosylated neutral endopeptidase which is restricted to the apical plasma membrane. The enzyme is released from the cells in an apocrine fashion and contributes to the formation of prostasomes. In prostate cancer cells a preferential cytoplasmic localization is observed, pointing to alterations in intracellular targeting.

Amino Acid Sequence↗
PubMed2001

Phosphopeptide analysis by positive and negative ion matrix-assisted laser desorption/ionization mass spectrometry.

This article describes a simple procedure for the detection of phosphorylated peptides by comparable positive and negative ion mode matrix-assisted laser desorption/ionization mass spectrometry measurements. Based on studies with phosphorylated peptides (EAIXAAPFAK, X = pS, pT, pY) and their corresponding non-phosphorylated analogs, it was found that phosphopeptides, which are characterized by a low ionization efficiency in the positive ion mode, exhibit drastically increased signal intensities in the negative ion mode compared to their non-phosphorylated analogs. The effect was successfully used to identify phosphorylated sequences of the commonly used phosphoprotein standards, protein kinase A and beta-casein, by peptide mass fingerprint analyses of the corresponding Lys C and trypsin digests using both (positive and negative) ion modes. The comparison of positive and negative ion spectra of a given protein digest (relative intensity([M - H]-)/relative intensity([M + H]+)) can be used to identify any phosphopeptides present which may then be separated and analyzed further.

Caseins↗
PubMed2001

Toxicokinetics of atrazine in embryos of the zebrafish (Danio rerio).

Atrazine (2-chloro-4-ethylamino-6-isopropylamine-s-triazine) is a widely used selective herbicide. Due to its persistence, it is present in many surface waters, contaminating nontarget organisms such as fish. Teratogeny of atrazine was examined during the first 48 h of zebrafish development (embryo test) and correlated to effects on the microsomal and soluble glutathione S-transferases (m-/sGST; EC 2.5.1.18). Atrazine at 4 mg/L disturbed the normal development to long pec stage, at concentrations between 10 and 20 mg/L it caused retardations in organogenesis, a slowdown of movements, and functional disturbances of heart and circulatory system. m- and sGST activities were affected by atrazine in all investigated developmental stages. Atrazine elevated the mGST activity dose dependently up to a concentration of 5 mg/L, and the sGST up to 1 mg/L. Higher atrazine concentrations caused a decrease of GST activity, especially of the sGST of the younger stages, 32 cells and 75% epiboly. This might indicate that the detoxication system itself is affected, which then gives rise to morphological abnormalities during fish development. In vitro tests were performed to purify and characterize GST-formed atrazine metabolites by the use of ESI--HPLC--MS. mGST showed higher conversion rates compared to sGST.

Abnormalities, Drug-Induced↗
PubMed2001

Anti-inflammatory planar chiral [2.2]paracyclophaneacetic acid enantiomers.

OBJECTIVE AND DESIGN: To elucidate if the planar chiral paracyclophane moiety conveys pharmacological activity to arylacetic acid analogs in two animal models. MATERIAL OR SUBJECTS: Female NMRI mice (6 mice/group); female Wistar rats (8 rats/group); thrombocytes from human blood. TREATMENT: The enantiomers of [2.2]paracyclophaneacetic acid were applied locally (10(-7) and 10(-6) mol/ear) and orally (10-100 mg/kg). METHODS: (a) Phorbol myristyl acetate model of acute inflammation of the inner auricle. (b) Oxazolone model of allergic contact dermatitis. (c) Carrageenan model of acute inflammation. (d) Inhibition of cyclooxygenase-1 and 12-lipoxygenase (in vitro). RESULTS: (a) PMA model: pR-(-)-[2.2]paracyclophaneacetic acid (10(-6) mmol/ear): 58% inhibition after 24 h (p < 0.05). (b) Oxazolone model: pR-(-)-[2.2]paracyclophaneacetic acid (10(-6) mmol/ear): 42% inhibition after 24 h (p < 0.05). (c) Carrageenan model: pR-(-)-[2.2]paracyclophaneacetic acid (10 mg/kg): 31.4% inhibition (paw volume 0.48 +/- 0.13 ml). (d) Cyclooxygenase-1 and 12-lipoxygenase: no inhibition at concentrations up to 10 microM. CONCLUSIONS: The easily accessible [2.2]paracyclophane moiety should find its use in medicinal chemistry as it is a pharmacophoric substituent with the interesting feature of planar chirality.

Acetates↗
PubMed2001

Application of MS and NMR to the structure elucidation of complex sugar moieties of natural products: exemplified by the steroidal saponin from Yucca filamentosa L.

An approach, using well characterized procedures, is presented that should be of general applicability for the structural elucidation of complex sugar moieties of natural products. The methods used are exemplified by the structure elucidation of a new gitogenin-based steroidal saponin that has a strong leishmanicidal activity similar to preparations used in clinical practice and has been isolated by bioactivity-guided fractionation of the ethanolic extract of Yucca filamentosa L. leaves. The saponin has been characterized as 3-O-((beta-D-glucopyranosyl-(1-->3)- beta-D-glucopyranosy-(1-->2))(alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3))-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranosyl)-25R,5alpha-spirostan-2alpha,3beta-diol.

Biological Products↗