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H Müller

Publications and source records attributed to H Müller.

At least 217 records · Page 12Linked to original sources
PubMed1997

[Molecules of regulated secretion are differentiation markers of neuroendocrine tumors].

Regulated secretory vesicles of neuroendocrine cells encompass two distinct types, i.e. hormone-storing large dense core vesicles (LDCV) and neuron-like small synaptic vesicles (SSVs). The membranes of the vesicles and the acceptor organelles contain proteins which are essential for targeted membrane fusion and protein transport (SNARE hypothesis). Membrane proteins of SSV analogues such as synaptophysin, synaptobrevin (v-SNARE) and synaptotagmin are key proteins of neurosecretion. The plasma membrane proteins syntaxin and SNAP25 (t-SNARE) are indispensible for this locking/fusion process. This study was done to identify the molecular components of LDCVs, SSV analogues and the SNARE-complex in neuroendocrine tumors. Immunohistochemical analysis using a panel of antibodies was done on file material from benign or low-grade malignant neuroendocrine tumors (n = 20) and high-grade malignant intermediate or small cell carcinomas (n = 27) of the gut, pancreas and lung. The statistical evaluation of our results indicate that the expression of all marker molecules of the regulated secretory pathway is significantly reduced in high-grade malignant carcinomas when compared to benign or low-grade malignant tumors. The reduction of the LDCV matrix protein chromogranin A and of the SSV membrane protein synaptobrevin is highly significant in high-grade malignant carcinomas, which may even loose these proteins. In contrast, the synthesis of synaptophysin and the t-SNARE-protein SNAP25 appears to be better maintained even in small cell carcinomas. We conclude that the immunohistochemical diagnosis of high-grade malignant neuroendocrine tumors should mainly be based on the identification of SSV- and SNARE-proteins, especially synaptophysin and SNAP25. These marker molecules of the regulated secretory pathway are valuable tools for the diagnosis and classification of neuroendocrine tumors and contribute to the understanding of cellular differentiation pathways.

Biomarkers↗
PubMed1996

Factors affecting the transfer of radiocaesium from soil to roe deer in forest ecosystems of southern Germany.

Since 1987, in Southern Germany, as a consequence of the Chernobyl accident, the 137Cs activity concentration in roe deer (Capreolus capreolus) has been intensively monitored. A large data set is now available with approximately 5000 samples, with information about the location of the animal, the time of slaughtering, soil characteristics and distance to intensively managed agricultural land. Both the roe deer 137Cs activity concentrations and aggregated transfer coefficients soil-roe deer (T(ag,r)) show a considerable variability with geometric mean and geometric standard deviation in meat of 270.3.5 +/- 1 Bq.kg-1 and 0.01.3.5 +/- 1 m2.kg-1, respectively. From 1987 to 1991, T(ag,r) values exhibited a decline with an ecological half-life of about 3 years. Since 1991, no further decrease of the roe deer contamination level was observed. This general trend is superimposed by an increase in T(ag,r) in autumn that has occurred in almost every year, which is probably due to consumption of mushrooms. This hypothesis is supported by a significant positive correlation between the precipitation during July and August, stimulating the fungi's growth and the height of the maximum in T(ag,r) in autumn. Animals are less contaminated when living in parts of the forest from where they have access to intensively managed agricultural land. A small, but significant correlation is observed between the T(ag,r) and soil parameters; the total potassium content of the soil and the pH of the organic soil layer. The highest transfer coefficients soil-roe deer were found on a peat bog, where most values ranged from 0.01-0.1 m2.kg-1, and neither a pronounced seasonal variation, nor a long-term decrease was observed. On sites with coniferous forests, most T(ag,r) values range from 0.005 to 0.05 m2.kg-1, on sites with a mixture of coniferous and deciduous trees, the transfer coefficients range mostly from 0.002 to 0.02 m2.kg-1. This is a further indication of the importance of the uppermost soil layers and the biological processes therein with respect to the bioavailability of caesium. On the two sites, the values at the lower boundary are more typical for animals that have access to agricultural areas, whereas the higher values were observed in autumn and for animals grazing distant from agricultural areas.

Animals↗
PubMed1996

Differential requirement for the mitochondrial Hsp70-Tim44 complex in unfolding and translocation of preproteins.

The mitochondrial heat shock protein Hsp70 is essential for import of nuclear-encoded proteins, involved in both unfolding and membrane translocation of preproteins. mtHsp70 interacts reversibly with Tim44 of the mitochondrial inner membrane, yet the role of this interaction is unknown. We analysed this role by using two yeast mutants of mtHsp70 that differentially influenced its interaction with Tim44. One mutant mtHsp70 (Ssc1-2p) efficiently bound preproteins, but did not show a detectable complex formation with Tim44; the mitochondria imported loosely folded preproteins with wild-type kinetics, yet were impaired in unfolding of preproteins. The other mutant Hsp70 (Ssc1-3p') bound both Tim44 and preproteins, but the mitochondria did not import folded polypeptides and were impaired in import of unfolded preproteins; Ssc1-3p' was defective in its ATPase domain and did not undergo a nucleotide-dependent conformational change, resulting in permanent binding to Tim44. The following conclusions are suggested. (i) The import of loosely folded polypeptides (translocase function of mtHsp70) does not depend on formation of a detectable Hsp70-Tim44 complex. Two explanations are possible: a trapping mechanism by soluble mtHsp70, or a weak/very transient interaction of Ssc1-2p with Tim44 that leads to a weak force generation sufficient for import of loosely folded, but not folded, polypeptides. (ii) Import of folded preproteins (unfoldase function of mtHsp70) involves a reversible nucleotide-dependent interaction of mtHsp70 with Tim44, including a conformational change in mtHsp70. This is consistent with a model that the dynamic interaction of mtHsp70 with Tim44 generates a pulling force on preproteins which supports unfolding during translocation.

Adenine Nucleotides↗
PubMed1996

Properties of the human arginine vasopressin V2 receptor after site-directed mutagenesis of its putative palmitoylation site.

Most G-protein-coupled receptors have conserved cysteine residues in their C-terminal cytoplasmic domain that appear to be generally palmitoylated. An example is the human arginine vasopressin V2 receptor with cysteine residues at positions 341 and 342. Site-directed mutagenesis of the putative palmitoylation site was used to study the significance of palmitoylation for the V2 receptor. A multifunctional expression plasmid was constructed by cloning the V2 receptor cDNA into the vector pCDNAI.Neo. The resulting plasmid allowed site-directed mutagenesis experiments without subcloning, and stable and transient expression of the V2 receptor in Ltk- and COS.M6 cells respectively. The conserved cysteine residues Cys-341 and Cys-342 were placed by serine residues, yielding the single mutants C-341S and C-342S and the double mutant C-341S/C-342S. Functional expression in stably transfected Ltk- cells showed that the affinity of the three mutant receptors for arginine vasopressin was not altered. In contrast with the activation of adenylate cyclase through beta 2 adrenergic receptors, arginine vasopressin stimulated adenylate cyclase to the same extent and with similar EC50 values in both wild-type and mutant receptors. Transient expression of the C-341S/C-342S mutant receptor in COS.M6 cells confirmed an unaltered affinity of the mutant receptor for arginine vasopressin. However, the number of arginine vasopressin-binding sites on the cell surface was reduced by 30%, suggesting that the transport of the mutant receptor to the cell surface was impaired. In addition, the decrease in detectable arginine vasopressin-binding sites on the cell surface following pre-exposure to hormone was reduced, indicating that the sequestration/internalization of the mutant receptor on the cell surface was affected. The present data indicate that palmitoylation of the V2 receptor is important for intracellular trafficking and/or sequestration/internalization but not for agonist binding or activation of the Gs/adenylate cyclase system.

Adenylyl Cyclases↗
PubMed1996

Definitions of cytomegalovirus disease after heart transplantation: antigenemia as a marker for antiviral therapy.

In this prospective study, cytomegalovirus (CMV) antigenemia was defined as the marker for initiation and episodes of antigenemia as the indicator for the duration of antiviral therapy (CMV hyperimmune globulin and ganciclovir). The CMV antigenemia assay and CMV-specific IgM and IgG antibody tests were used to monitor CMV infection in 22 heart transplant recipients who, between October 1992 and July 1994, were followed up for 6 months. A total of 178 out of 627 antigenemia assays tested positive. The highest number of positive cells was greater after primary infection than after either reactivation (43.3 vs 0.3; P < 0.01) or reinfection (43.3 vs 9.3; P = NS). Sixty episodes of antigenemia were observed. More episodes of antigenemia were seen after primary infection than after either reactivation (4.6 vs 0.2; P < 0.01) or reinfection (4.6 vs 2.2; P = NS). The detection of antigenemia indicated the initiation of antiviral therapy within 24 h after the blood sample was harvested. Therapy was stopped immediately after a subsequent negative result became available. Our experience indicates that antigenemia directed antiviral therapy prevents CMV disease after primary and secondary infection in heart transplant recipients.

Adolescent↗
PubMed1996

[Daily intake of carotenoids (carotenes and xanthophylls) from total diet and the carotenoid content of selected vegetables and fuit].

The recommended daily intake is currently either 2 mg of beta-carotene (recommended by DGE, Germany, in addition to 1.0 (0.8) mg retinol-equivalents for vitamin A requirement) or 5-6 mg of beta-carotene (recommended by NCI, USA). The present studies were carried out to investigate to what extent a balanced diet prepared using household or cafeteria methods contributes to achieve the desired intake. Beta-carotene and other carotenoids in the total daily diet samples were determined by RP-HPLC. In addition to beta-carotene, in decreasing quantity lutein, alpha-carotene, antheraxanthin, lycopene, zeaxanthin, neoxanthin, beta-cryptoxanthin, alpha-cryptoxanthin and violaxanthin were estimated. The intake of beta-carotene (carotenoids) ranged from 0.2 to 9.7 mg/d (0.7-16.5 mg/d) with mean values (median) of 1.1 mg/d for beta-carotene and 3.9 mg/d for carotenoids based on results from investigations of 39 total daily diet samples. The recommended daily intake can only be achieved by consuming (100-200 g/d) of vegetables und fruits with a particularly high carotenoid content. Kale (34.8), red peppers (27.4), parsley (25.7), spinach (17.3), lamb's lettuce (16.0), carrots (15.8) and tomatoes (12.7) headed the list of vegetables with more than 10 mg/100 g. In the case of fruit, papayas (3.8), grapefruits (3.6), nectarines (2.9) and apricots (2.6) were pre-eminent with more than 2 mg/ 100 g. The results distinguish between provitamin A and non-provitamin A carotenoids. In addition the contents of beta-carotene and lutein are shown.

Carotenoids↗
PubMed1996

Docosahexaenoic and arachidonic acid content of serum and red blood cell membrane phospholipids of preterm infants fed breast milk, standard formula or formula supplemented with n-3 and n-6 long-chain polyunsaturated fatty acids.

UNLABELLED: The contents of docosahexaenoic (DHA) and arachidonic acid (AA) of plasma and red blood cell membrane phospholipids were studied in 41 very low birth weight infants fed either breast milk (n = 18), a standard formula without long-chain polyunsaturated fatty acids with 20 or 22 carbon atoms (LCP) but with alpha-linolenic acid and linoleic acid (n = 11) or a formula additionally supplemented with n-3 and n-6 LCP in relations typical for human milk (n = 12) after 2, 6, and 10 weeks of feeding. The content of DHA and AA in plasma phospholipids declined in the infants fed the LCP-free formula but remained more or less constant during the whole feeding period in those infants fed breast milk as well as in those fed the LCP-supplemented formula. The differences between the group fed the LCP-free standard formula and the two groups fed LCP-containing diets became significant during the first 2 weeks of feeding. In contrast, there were no differences between the group fed breast milk and the group fed the supplemented formula during the study period. Similar effects could be observed regarding the composition of red blood cell membrane phospholipids, but the differences between the infants fed the LCP-free standard formula and the two other groups with LCP-containing diets were significant only for AA. The data indicate that very low birth weight infants are unable to synthesize LCP from alpha-linolenic acid and linoleic acid in sufficient amounts to prevent a decline of LCP in plasma and red blood cell phospholipids. Additionally, the data show, that supplementation of formulas with n-3 and n-6 LCP in amounts typical for human milk fat results in similar fatty acid profiles of plasma and red blood cell membrane phospholipids as found during breast milk feeding. CONCLUSION: Supplementation of formula with long-chain polyunsaturated fatty acids improves the LCP status of very low birth weight infants.

Arachidonic Acids↗
PubMed1996

[High resolution scanning electron microscopy of isolated outer hair cells].

Isolated hair cell preparations have gained wide acceptance as a model for studying physiological and molecular properties of the sensory cells involved in the hearing process. Ultrastructural details, such as stereocilia links, lateral membrane substructure or synaptic links are of crucial importance for normal sensory transduction. For this reason, we developed a high-resolution scanning electron microscopy (SEM) procedure to study the surface of isolated hair cells. Cells were mechanically and/or enzymatically separated, isolated and immobilized on cover slips by alcian blue and fixed by 2% glutardialdehyde or 1% OsO4. After dehydration, preparations were critical point-dried and sputter-coated with gold-palladium (2-4 nm). Up to 5 nm resolution was achieved. Optimal fixation kept the cells in their typical cylindrical forms. Preservation of the stereocilia and the apical plates of the outer hair cells depended strongly on the fixation process. Tip- and side-links were observed only sporadically because of the aggressive preparation procedure. The lateral plasma membranes of the cell bodies showed regular granular structures of 5-7 nm diameter at maximal magnification. The granular structure of the cell membrane seemed to correspond to putative transmembrane proteins believed to generate membrane-based motility. The remnants of the nerve endings and/or supporting cells usually covered the cell base. The preservation of the cells was better when enzymatic isolation was omitted. The technique used allowed for high resolution ultrastructural examination of isolated hair cells and, when combined with immunological labeling, may permit the identification of proteins at a molecular level.

Animals↗
PubMed1996

Amperometric detection of heavy metal ions in ion pair chromatography at an array of water/nitrobenzene micro interfaces.

A novel amperometric detector for heavy metal ions has been developed and successfully applied for ion pair chromatography. The detector is based on the electrochemical transfer of the metal ions across an array of water/nitrobenzene micro interfaces. The ion transfer is facilitated by the neutral ionophores methylenebis(diphenylphosphineoxide) and methylenebis(di- phenylphosphinesulfide). More than eight metals are separated in less than 15 min on an RP18 column using octyl sulfonate as ion pair reagent. For the heavy metals, the limits of decision are 19(Pb(2+)), 9(Zn(2+)), 9l (Co(2+)), 8(Cd(2+)) and 1.6(Mn(2+)) microg/L. The applicability of the new method for water samples is demonstrated.

Journal Article↗
PubMed1996

Radiation exposure from radionuclides in ground water: an uncertainty analysis for selected exposure scenarios.

The uncertainty of the potential radiation exposure of the general population has been estimated for a normalized contamination of ground water that is being used as drinking water for humans and animals, for irrigation of food and feed crops, and for fish production in freshwater bodies. The frequency distributions of annual effective dose equivalents were calculated assuming a normalized activity concentration in water of 1 Bq/l for each radionuclide considered. Estimated frequency distributions of the parameters were used as model input. This estimation is based on an exposure scenario which reflects the present radioecological conditions. Another important source for the uncertainty of the potential dose due to radionuclides released to the ground water is the uncertainty of the exposure scenario. Since such a contamination may not occur before some time in the far future, it is impossible to predict the exact boundary conditions. Therefore, scenarios were stimulated with modified consumption habits, more extensive farm management and different climatic conditions. The distributions of the potential doses cover in general about a factor of 10-20. The intake of drinking water, the root uptake and the contamination of fish are most important for the resulting potential radiation exposure. For nearly all radionuclides, the intake of drinking water dominates the potential exposure. In most cases radioactive daughter nuclides are of minor importance. In general, the influence of the exposure scenario on the dose is relatively small.

Animals↗
PubMed1996

Secretory phospholipase A2 does not appear to be associated with phenotypic variation in familial adenomatous polyposis.

Recent studies in mice have provided strong evidence for a modifier gene that is capable of effecting the expression of the mouse equivalent of familial adenomatous polyposis (FAP). A candidate gene has been proposed, namely secretory phospholipase A2 (sPLA2). Increased tumor number in mice was correlated with low levels of sPLA2 expression and the presence of truncating mutations within the sPLA2 gene. In an attempt to determine whether any genetic alterations in the sPLA2 gene were associated with the expression of FAP in man, we investigated the genetic structure of sPLA2 in 97 polyposis coli patients presenting with various disease phenotypes, and its expression in 8 FAP patients displaying markedly different disease characteristics. In the current study no inactivating mutations in the sPLA2 gene were identified, suggesting that human sPLA2 is not associated with phenotypic variation in FAP.

Adenomatous Polyposis Coli↗
PubMed1996

How to assess the onset of antidepressant effect: comparison of global ratings and findings based on depression scales.

The timing of clinical drug effects in depression can be estimated by a variety of methodological approaches, which might account for the heterogeneity of findings. We compared the patients' own ratings of the onset of antidepressant effect with onset estimations that were based on the intraindividual courses of depression as measured by the Hamilton Depression Rating Scale and a self-rating scale, the von Zerssen Adjective Mood Scale. The data of two control-group studies on brofaromine vs. imipramine were reanalyzed, the first, comprising 224 non-elderly and the second 195 elderly patients. In both studies the patients rated a significantly earlier onset of activity (means: days 12 and 16) than any other method. The means of the scale-based ratings varied between days 20 and 31 and showed a marked dependence on the response criteria selected: strict response criteria produced later onset estimations than less strict ones. Whereas the patient's own ratings indicated a significantly later onset of activity in the elderly patients, none of the scale-based measures supported this difference. The discussion focuses on the importance of methodological aspects.

Adult↗
PubMed1996

[Continuous intra- and postoperative peridural analgesia with combined low dose sufentanil, clonidine and bupivacaine].

OBJECTIVE: The purpose of this study was to investigate whether continuous epidural administration of combined low dose local anaesthetic, opioid and clonidine can provide sufficient postoperative analgesia after major abdominal surgery. METHODS: 45 patients (ASA I-III), scheduled for major abdominal surgery, were randomly divided into three groups. Prior to surgery all patients received an epidural catheter before induction of general anaesthesia. After 90 minutes a 10 ml bolus of the study solution was given via the epidural catheter followed by a continuous infusion of 5 ml/h until the end of surgery and further on 5-8 ml/h for 24 hours postoperatively. The solutions consisted of 50 micrograms sufentanil in 50 ml 0.125% bupivacaine (group 1), 150 micrograms clonidine in 50 ml 0.125% bupivacaine (group 2) and 50 micrograms sufentanil + 150 micrograms clonidine in 50 ml 0.125% bupivacaine (group 3). Measurements included the total dose of infused drug solution, pain at rest and on exercise by a visual analogue scale, cardiorespiratory data and side-effects within the first 24 hours postoperatively. A standardised interview on analgesia and side-effects was held two days after surgery. RESULTS: At rest excellent analgesia could be provided by all of the tested drug solutions. On exercise we evaluated lower pain scores in group 3 (1.9 +/- 1.1) compared to group 1 (2.8 +/- 1.6) or group 2 (3.8 +/- 2.1) (2 vs 3 p < 0.05). Severe side effects such as respiratory depression or drop of heart rate or blood pressure did not occur. CONCLUSIONS: Epidural administration of drug solutions containing a low dose local anaesthetic, opioid and alpha 2-agonist, provides excellent analgesia after major abdominal surgery. Patients at rest can be treated very effectively with both a combination of only two or with all of the tested drugs. On exercise the mixture containing all analgesics was more efficient than the solutions with only two of the tested drugs. Severe side effects such as respiratory depression or cardiovascular instability were not seen.

Abdomen↗
PubMed1996

Loss of antibody reactivity directed against the V3 domain of certain human immunodeficiency virus type 1 variants during disease progression.

We have previously shown that in AIDS patients a predominant species of infectious virus can be found which is not neutralized by homologous serum. The presence of the infectious virus was associated with the lack of type-specific antibody directed against the V3 domains of these virions. In contrast to this lack of V3-specific antibody, the other V3 domains of non-infectious virions were well recognized by antibody. To determine whether the lack of a V3-specific antibody response is due to a progressive loss of antibody during human immunodeficiency virus type 1 (HIV-1) infection, we monitored the anti-V3 antibody response in 90 patients over time. Anti-V3 antibodies were monitored by a V3-specific ELISA using 21 different V3 domains as a fusion with glutathione S-transferase (GST-V3) based upon sequences from 11 HIV-1 patient isolates and 10 sequences from an HIV-1 B subtype consensus-like GST-V3 expression library. This strictly heterologous screening showed a loss of V3-specific antibodies in 20 out of the 90 patients tested. To study the in vivo relevance of these findings we analysed V3 antibody loss in two patients. This strictly autologous antibody screening was performed based upon V3 sequences of the patients' cell-free virions. In both patients the loss of a V3-specific antibody could be detected in parallel to a decline of CD4+ T cells. Moreover, the escape of a distinct V3 variant was shown to correlate closely with the loss of the V3-specific antibody.

Amino Acid Sequence↗
PubMed1996

Susceptibility of chicken lymphoid cells to infectious bursal disease virus does not correlate with the presence of specific binding sites.

Pathogenic serotype 1 strains of infectious bursal disease virus (IBDV) replicate efficiently in lymphoid cells of the bursa of Fabricius of chicken. Lymphoid cells in other organs are not susceptible. Apathogenic serotype 2 strains do not replicate in lymphoid bursa cells or in other lymphoid cells. Chicken embryo fibroblasts (CEF), however, efficiently replicate strains of either serotype. Binding studies showed that strains of both IBDV serotypes bind to lymphoid cells isolated from the bursa, thymus or spleen, indicating that restriction of IBDV replication to lymphoid B cells is not determined by the presence of specific receptor sites. The specificity of binding was demonstrated by saturation and competition experiments. These revealed the presence of different receptors: CEF had receptors common to both serotypes and specific ones for each serotype. Receptor sites common to both serotypes were also present on lymphoid cells; however, additional serotype-specific sites were only demonstrated for the apathogenic serotype 2 strain. Strains of both serotypes specifically bound to proteins with molecular masses of 40 kDa and 46 kDa, exposed on the surface of CEF and lymphoid cells. Competition experiments indicated that these proteins might represent the common receptor sites of IBDV.

Animals↗