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Biomedical subjects

E Müller

Publications and source records attributed to E Müller.

At least 91 records · Page 5Linked to original sources
PubMed1999

Estimation of wound age and VCAM-1 in human skin.

To estimate the age of skin wounds, the endothelial adhesion molecule VCAM-1 (CD 106) was detected in paraffin sections after autoclaving and using the ABC technique. The percentage of VCAM-1 positive blood vessels was determined after the blood vessels had been marked with PECAM-1 (CD 31). Low positive staining reactions were observed for VCAM-1 on endothelial cells of uninjured skin in 18% of the samples. In injured skin, 51% of the cases investigated showed a VCAM-1 expression. Strong positive staining reactions were observed 3 h at the earliest and 3.5 days at the latest after the time of injury. The immunohistochemical results for VCAM-1 differed significantly between the injured and uninjured skin (P < 0.01). In a few cases VCAM-1 was detected (n = 6) at low intensity in postmortem skin wounds and a moderate to strong expression of VCAM-1 is indicative of the vitality of the wound. The detection of VCAM-1 can be used for estimating the age of wounds in forensic applications if the degree of expression of further adhesion molecules, especially that of selectins, is taken into account.

Forensic Medicine↗
PubMed1999

Expression of aldose reductase, sorbitol dehydrogenase and Na+/myo-inositol and Na+/Cl-/betaine transporter mRNAs in individual cells of the kidney during changes in the diuretic state.

The effect of changes in medullary extracellular tonicity on mRNA expression for aldose reductase (AR), sorbitol dehydrogenase (SDH), Na+/Cl-/betaine (BGT) and Na+/myo-inositol (SMIT) cotransporter in different kidney zones was studied using Northern blot analysis and non-radioactive in situ hybridization in four groups of rats: controls, acute diuresis (the loop diuretic furosemide was administered), chronic diuresis (5 days of diuresis), and antidiuresis [5 days of diuresis followed by 24 h deamino-Cys1, d-Arg8 vasopressin (dDAVP)]. Acute administration of the loop diuretic furosemide significantly reduced AR, SMIT and BGT gene expression in the inner and outer medulla compared with controls. Administration of dDAVP to chronically diuretic rats raised the expression of these three mRNAs in the inner but not the outer medulla compared with the chronically diuretic rats. None of these alterations in medullary tonicity significantly changed SDH expression. The in situ hybridization studies showed AR, BGT and SMIT mRNAs to be expressed in both epithelial and non-epithelial cells of the outer and inner medulla. The various cell types (epithelial, endothelial and interstitial cells) differed in their expression pattern and intensity of AR, SDH, BGT and SMIT mRNA, but the inner medullary cells responded uniformly to a decrease in extracellular tonicity with a reduction, and to an increase with enhancement of their AR, BGT and SMIT expression.

Aldehyde Reductase↗
PubMed1999

Inhibition of NaCl-induced heat shock protein 72 expression renders MDCK cells susceptible to high urea concentrations.

Exposure of Madin-Darby canine kidney (MDCK) cells to elevated extracellular NaCl concentrations is associated with increased heat shock protein 72 (HSP72) expression and improved survival of these pretreated cells upon exposure to an additional 600 mM urea in the medium. To establish a causal relationship between HSP72 expression and cell protection against high urea concentrations, two approaches to inhibit NaCl-induced HSP72 synthesis prior to exposure to 600 mM urea were employed. First, the highly specific p38 kinase inhibitor SB203580 was added (100 microM) to the hypertonic medium (600 mosm/kg H2O by NaCl addition, 2 days of exposure), which significantly reduced HSP72 mRNA abundance and HSP72 content. Survival of these cells after a 24-h urea treatment (600 mM) was markedly curtailed compared with appropriate controls. Second, a pcDNA3-based construct, containing 322 bases of the HSP72 open reading frame in antisense orientation and the geneticine resistance gene, was transfected into MDCK cells. Clones with strong inhibition of HSP72 synthesis and others which express the protein at normal levels (comparable to nontransfected MDCK cells) after heat shock treatment or hypertonic stress were established. When these transformants were subjected to hypertonic stress for 2 days prior to exposure to an additional 600 mM urea for 24 h, cell survival was significantly reduced in those clones in which HSP72 expression was strongly inhibited. These results provide further evidence for the protective function of HSP72 against high urea concentrations in renal epithelial cells.

Animals↗
PubMed1999

Influence of NaCl, urea, potassium and pH on HSP72 expression in MDCK cells.

The renal inner medulla is characterised by elevated extracellular concentrations of NaCl, urea, potassium and hydrogen ions, an environment that may affect cell viability negatively. High amounts of HSP72, a stress protein allowing cells to resist harmful situations, are also observed in this region. The present study examined HSP72 induction by various medullary stress factors, individually or in combination, in MDCK cells, a renal epithelial cell line expressing characteristics of the medullary collecting duct. MDCK cells were incubated for 3 days in media containing elevated concentrations of NaCl, urea, potassium and hydrogen ions individually or in combination. HSP72 mRNA and protein expression were determined by Northern and Western blot analyses, respectively. HSP72 expression was enhanced moderately by addition of 50 mM NaCl to normal medium at pH 7.4 but enhanced strongly when added at pH 6.5. The latter degree of HSP72 induction was comparable to that observed when 150 mM NaCl was added at pH 7.4. In normal medium (pH 7.4) containing 300 mM urea, MDCK HSP72 expression was not different from controls. In contrast, urea-induced HSP72 expression was clearly evident when medium pH was lowered to 6.5. Potassium at 20 or 40 mM induced HSP72 only slightly. These results indicate that expression of HSP72 in renal epithelial cells is regulated synergistically by NaCl, urea and pH. Since HSP72 is only slightly induced by increased potassium, this probably reflects the changes in medium osmolality rather than a specific effect of potassium. The high medullary HSP72 content observed even in diuresis may be due to co-operative effects of medullary solutes on HSP72 expression.

Animals↗
PubMed1999

Distribution of emerin during the cell cycle.

Human emerin is a nuclear membrane protein that is lost or altered in patients with Emery-Dreifuss muscular dystrophy (EMD). While the protein is expressed in the majority of human tissues analyzed, the pathology predominates in cardiac and skeletal muscles of patients with EMD. Our results show that emerin can be detected by immunocytochemistry and immunoblotting in the nuclear envelope of all vertebrates studied from man to Xenopus. Immunolocalizations and nuclear envelope extraction experiments confirm that emerin possesses properties characteristic for integral membrane proteins of the inner nuclear membrane. Some nuclear envelope proteins are localized also in annulate lamellae (AL), i.e. cytoplasmic flattened membrane cisternae penetrated by pore complexes. To verify whether emerin is contained in these membrane stacks, we have induced the formation of AL by exposure of rat cells (line RV-SMC) to sublethal doses of the antimitotic drug vinblastine sulfate and found that emerin is present in the nuclear envelope, but is absent from AL. In contrast to the homogeneous distribution of emerin in the nuclear envelope of interphase cells, this protein shows a focal accumulation in the nuclear membranes of late telophase cells. During early reassembly of the nuclear envelope at this mitotic stage emerin colocalizes with lamin A/C but not with lamin B and LAP2 proteins. Confocal laser scanning microscopy after double-labeling experiments with emerin and tubulin shows that emerin is concentrated in areas of the mitotic spindle and in the midbody of mitotic cells suggesting a close interaction of these proteins. Our data suggest that emerin participates in the reorganisation of the nuclear envelope at the end of mitosis.

Animals↗
PubMed1999

Periplakin and envoplakin are target antigens in canine and human paraneoplastic pemphigus.

BACKGROUND: On the basis of clinical and histopathologic similarities to human paraneoplastic pemphigus (PNP), we recently identified the first case of PNP in a nonhuman species, the dog. OBJECTIVE: To determine a similar pathogenesis in both species, the present study aimed to define whether common antigens are targeted in dog and man. METHODS: Canine and human PNP sera were used in parallel to immunoprecipitate 14C-labeled human keratinocyte antigens. The immunoreactive proteins were then identified by immunoprecipitation of canine keratinocyte extracts with specific antibodies to the antiplakin family members follwed by immunoblot analysis using canine and human PNP sera. RESULTS: Protein bands of 210, 190, 170, and 130 kd were identified in dogs and humans. In both species, envoplakin and periplakin were demonstrated as antigens. Anti-desmoglein 3 antibodies could not be demonstrated in canine PNP, but in human PNP. CONCLUSION: These results demonstrate that canine PNP closely correlates to the human counterpart and may therefore represent an excellent model for the human disease.

Animals↗
PubMed1999

The tyrosine kinase NPM-ALK, associated with anaplastic large cell lymphoma, binds the intracellular domain of the surface receptor CD30 but is not activated by CD30 stimulation.

The heterogenous group of anaplastic large cell lymphomas (ALCLs) is characterized by expression of the Ki-1/CD30 antigen, a member of the tumor necrosis factor receptor superfamily. About 40 to 50% of cases diagnosed as ALCL contain a specific chromosomal rearrangement, t(2;5)(p23;q35), resulting in expression of the chimeric tyrosine kinase NPM-ALK. As NPM-ALK-positive lymphomas define a distinct subtype within the group of ALCL, the chimeric protein might be responsible for certain pathogenetic and clinicopathologic characteristics. To better elucidate the function of NPM-ALK, we investigated a possible mechanism for regulation of its activity. We demonstrate that NPM-ALK specifically binds to the intracellular domain of the cytokine receptor CD30. In vitro binding assays revealed that the ALK portion of NPM-ALK mediates interaction of the two proteins. Stimulation of the CD30 receptor by cross-linking with immobilized anti-CD30 antibody results in complete growth inhibition of Karpas 299, an NPM-ALK-positive ALCL cell line, but does not alter proliferation of HDLM-2, a Hodgkin's lymphoma-derived cell line lacking t(2;5). Western blot analysis of coimmunoprecipitated CD30 and NPM-ALK proteins from stimulated Karpas 299 cells showed that the interaction of the proteins is not modified by stimulation. Activation of CD30 neither enhanced NPM-ALK activity measured by autophosphorylation of the chimeric tyrosine kinase nor phosphorylation of phospholipase C-gamma, an NPM-ALK substrate. We conclude that NPM-ALK is not stimulated by CD30 activation, but exists as a constitutively hyperactivated protein. Interaction with CD30 may extend the subcellular localization of NPM-ALK to the microenvironment of membrane-associated proteins.

Enzyme Activation↗
PubMed1999

Improvement of the acquisition of a large amount of MR images on a conventional whole body system.

Modern whole body MR systems are equipped with echo-planar-imaging capability, which allows the measurement of a single slice in a fraction of a second or of thousands of images in few minutes. A considerable restriction to the acquisition of series containing large amounts of images in patient examinations is the time-consuming data handling time of the images at conventional systems, which includes the time to insert the images into the systems database. We propose the arrangement of several images on a new image with a large matrix size like a mosaic. The handling time depends mostly on the number of images without consideration of their matrix size. Therefore, image handling is strongly reduced by the use of such mosaic images.

Data Collection↗
PubMed1999

[Nursing science and natural sciences. Critical notes on a difficult relationship as a starting point for its new definition].

This article deals with the question of how nursing, supported by its own science, can gain benefit from natural science disciplines, if it can be presupposed that such disciplines represent one of the most important bases of nursing science. In the context of this question it is necessary to ascertain the condition, which must be fulfilled by the natural sciences in order to be able to occupy the honorable position of a cognate discipline of nursing science. This position is elucidated on the background of following aspects: The fundamental relationship between nursing science and the natural science with regard to their traditional perspectives and scientific objectives is discussed and illuminated on the background of differing concepts of body and person. In a further elaboration of this theme the particular meaning of the concept of person for nursing action is taken up and on its bases an extension of nursing issues which should be further developed is devised. In conclusion some propositions are brought up for discussion.

Biological Science Disciplines↗
PubMed1999

Hypertonicity-induced accumulation of organic osmolytes in papillary interstitial cells.

BACKGROUND: Medullary cells of the concentrating kidney are exposed to high extracellular solute concentrations. It is well established that epithelial cells in this kidney region adapt osmotically to hypertonic stress by accumulating organic osmolytes. Little is known, however, of the adaptive mechanisms of a further medullary cell type, the papillary interstitial cell [renal papillary fibroblast (RPF)]. We therefore compared the responses of primary cultures of RPFs and papillary collecting duct (PCD) cells exposed to hypertonic medium. METHODS: In RPFs and PCD cells, organic osmolytes were determined by high-performance liquid chromatography; mRNA expression for organic osmolyte transporters [Na+/Cl(-)-dependent betaine transporter (BGT), Na(+)-dependent myo-inositol transporter (SMIT)], and the sorbitol synthetic and degrading enzymes [aldose reductase (AR) and sorbitol dehydrogenase (SDH), respectively] was determined by Northern blot analysis. RESULTS: Exposure to hypertonic medium (600 mOsm/kg by NaCl addition) caused intracellular contents of glycerophosphorylcholine, betaine, myo-inositol, and sorbitol, but not free amino acids, to increase significantly in both RPFs and PCD cells. The rise in intracellular contents of these organic osmolytes was accompanied by enhanced expression of mRNAs coding for BGT, SMIT, and AR in both RPFs and PCD cells. SDH mRNA abundance, however, was unchanged. Nonradioactive in situ hybridization studies on sections from formalin-fixed and paraffin-embedded, normally concentrating kidneys showed strong expression of BGT, SMIT, and AR mRNAs in interstitial and collecting duct cells of the papilla, whereas expression of SDH mRNA was much weaker in both cell types. CONCLUSIONS: These results suggest that both RPFs and PCD cells use similar strategies to adapt osmotically to the high interstitial NaCl concentrations characteristic for the inner medulla and papilla of the concentrating kidney.

Aldehyde Reductase↗
PubMed1999

Knee joint forces during downhill walking with hiking poles.

The aim of this study was to determine external and internal loads on the knee joint during downhill walking with and without hiking poles. Kinematic, kinetic and electromyographic data were collected from eight males during downhill walking on a ramp declined at 25 degrees. Planar knee joint moments and forces were calculated using a quasi-static knee model. The results were analysed for an entire pole-cycle as well as differentiated between single and double support phases and between each step of a pole-cycle. Significant differences between downhill walking with and without hiking poles were observed for peak and average magnitudes of ground reaction force, knee joint moment, and tibiofemoral compressive and shear forces (12-25%). Similar reductions were found in patellofemoral compressive force, the quadriceps tendon force and the activity of the vastus lateralis; however, because of a high variability, these differences were not significant. The reductions seen during downhill walking with hiking poles compared with unsupported downhill walking were caused primarily by the forces applied to the hiking poles and by a change in posture to a more forward leaning position of the upper body, with the effect of reducing the knee moment arm.

Adult↗
PubMed1999

Loss of invasiveness in squamous cell carcinoma cells overexpressing desmosomal cadherins.

The molecular and structural characteristics of intercellular adhesion were investigated in a squamous cell carcinoma (SCCA) cell line, originally derived from an oral tumor with an invasive growth pattern. The expression of adherens junction and desmosomal components were compared with that of cultured normal oral keratinocytes. Lack of membrane association in interdesmosomal areas, the disorganization of the actin cytoskeleton and the faster cell disassembly upon E-cadherin antibody binding in SCCA cells indicated decreased functional adherens junctions. These observations were supported by a significant reduction in E-, N-, and P-cadherin protein expression. In contrast, the level of desmosomal cadherin proteins, desmoglein 1/2 and desmocollin 2, were substantially upregulated and accompanied, ultrastructurally, by increased number and size of desmosomes. Since tumor invasion suppressor capacity has been proposed for desmosomal cadherins, we investigated the in vivo invasion potential of these SCCA cells by introducing them into SCID mice. Tumors developed, but with a benign phenotype. Based on these results, we hypothesize that the benign behavior of this SCCA cell line is a consequence of overexpressed desmosomal cadherins. This SCCA cell line, therefore, represents an excellent model system to further investigate the regulation and tumor invasion suppressor potential of desmosomal adhesion molecules.

Animals↗
PubMed1999

Cost of bacterial vaginosis in pregnancy. Decision analysis and cost evaluation of a clinical study in Germany.

OBJECTIVE: To estimate the economic impact of screening for and treatment of bacterial vaginosis during early pregnancy. STUDY DESIGN: Data from a clinical study that aligned two screening and treatment strategies and a no-screening or treatment strategy with three gynecologic practices in Berlin were used in decision tree analysis. Costs applied to the clinical outcomes were determined from standard German references and the charges from university clinics. RESULTS: Practices A and B screened all 600 patients in the early second trimester and treated the positive cases with clindamycin 2% vaginal cream (A) or a Lactobacillus preparation (B), which incurred lower total costs, $493,159 and $497,619, as compared to practice C (total costs, $534,926), which did not screen or treat for bacterial vaginosis. Including costs of screening and treatment, the net savings of practice A as compared to practice C was estimated to be $47,316. CONCLUSION: The presence of more preterm, premature and low-birth-weight infants added costs for practice C. The estimated cost savings lend support to the value of screening and treatment for bacterial vaginosis in early pregnancy.

Administration, Intravaginal↗
PubMed1998

Proprotein cleavage of E-cadherin by furin in baculovirus over-expression system: potential role of other convertases in mammalian cells.

Sequence analysis of the adhesion molecule E-cadherin had revealed a multibasic motif [4PArg-Gln-Lys-Arg1P], reminiscent of the minimal cleavage signal for furin, the prototype of the proprotein convertase family, and/or other members sharing similar sequence specificity. Mutation of this site was sufficient to abolish processing of E-cadherin in fibroblasts reinforcing the possibility that proprotein convertases are involved in the maturation of this adhesion molecule. Here we demonstrate that even though furin can efficiently and specifically cleave proE-cadherin in a baculovirus-based co-expression system, the furin-deficient LoVo cells were found to process endogenous E-cadherin as efficiently as normal cell lines. This suggests, for the first time, that E-cadherin is not only a substrate for furin but for other mammalian convertases sharing similar sequence specificity.

Amino Acid Sequence↗
PubMed1998

New Sesquiterpene Lactones from Illicium floridanum

In continuation of our phytochemical investigation of Illicium floridanum Ellis (American star anise, star bush), three new sesquiterpene lactones possessing the anisatin-type carbon skeleton (8,9-seco-prezizaane skeleton), 14-acetoxy-3-oxofloridanolide (1), 13-acetoxy-14-(n-butyryloxy)floridanolide (2), and 3beta-acetoxy-14-n-butyryloxy-10-deoxyfloridanolide (3), were isolated from fruits of this plant. Their structures were elucidated by 1D and 2D NMR measurements. The molecular structure of 1 was obtained by single crystal X-ray diffraction. The 11,3-delta-lactone structure of the compound previously described as debenzoyldunnianin in our previous communication, on grounds of NMR spectral evidence and X-ray crystallographic analysis is revised to a delta-lactone closed between C-11 and C-7 (compound 4). The neurotoxic sesquiterpene lactone anisatin (5) and its isomer 2alpha-hydroxyneoanisatin (3-deoxy-2alpha-hydroxyanisatin, 6) were also isolated and identified by spectroscopic means. The presence of the neurotoxin 5 in relatively high amounts in the fruits and leaves confirms and explains early reports on the toxicity of this plant.

Journal Article↗