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Biomedical subjects

E Müller

Publications and source records attributed to E Müller.

At least 109 records · Page 6Linked to original sources
PubMed1998

Preparation of and optimal module housings for hollow fibre membrane ion exchangers.

Macroporous polyamide 6 hollow fibres can be polymer coated by a three-step procedure: first, reaction of the amino end groups with a bifunctional, double-bond-containing reagent; second, block polymerization with different monomers; and third, polymer analogue reactions with amines or sulphite salts to produce ion exchanger groups. The densities of double bonds are dependent on the amino densities and are in the range of 20-30 mumol/g polyamide 6. The ion exchanger fibres were packed in different types of module housings to get an optimal separation unit. The best housing seems to be a so-called single-dead-end arrangement of fibres. Three types of ion exchanger hollow fibres have been produced: a weak and a strong anion exchanger and a strong cation exchanger. The dynamic protein-binding capacities are in the range of 40 mg/ml membrane. Using these membrane modules, it is possible to separate proteins in the same way as with particle-based ion exchangers. Fast protein separations with low pressure drop are possible.

Animals↗
PubMed1998

Blockade of voltage-operated calcium channels, increase in spontaneous catecholamine release and elevation of intracellular calcium levels in bovine chromaffin cells by the plant alkaloid tetrandrine.

Experiments were performed in bovine chromaffin cells in short term primary culture. Tetrandrine is a plant alkaloid from the chinese medical herb Stefania tetrandra. The aim of the present study was to investigate the mechanisms by which tetrandrine interacts with calcium signalling and to provide a quantitative description of effects. Tetrandrine blocked voltage-operated calcium channel currents concentration-dependently as shown in whole cell patch-clamp recordings. The blockade of calcium channels reduced the potassium-stimulated catecholamine release. Besides, the drug increased the spontaneous (not stimulated) release of catecholamines in the presence of extracellular calcium. Measurements of intracellular calcium levels [Ca]i showed a calcium release from intracellular stores by tetrandrine. This tetrandrine-induced [Ca]i elevation was higher in calcium containing as compared to calcium free solution. Tetrandrine effects partially overlap with those of thapsigargin, but tetrandrine has additional targets, since it increased [Ca]i in cells pretreated with thapsigargin. We conclude that tetrandrine blocks voltage-operated calcium channels and increases [Ca]i by blocking endoplasmic and other calcium pumps.

Alkaloids↗
PubMed1998

[Early trans-sphenoid decompression in indirect traumatic optic neuropathy].

BACKGROUND: Indirect traumatic optic neuropathy represents a severe, potential vision-threatening disease process that requires close interdisciplinary cooperation for treatment. In general, any therapy has been discussed controversially in the literature. Based upon experiences with spinal cord trauma, high-dose steroid therapy is recommended initially to minimize secondary consequences following orbital trauma. The usefulness of surgical decompression of the optic nerve has been confirmed in several studies but is still not recommended in principle. PATIENTS AND METHOD: In nine consecutive patients with known indirect traumatic optic neuropathy and marked losses of vision, transsphenoidal optic decompressions were carried out with simultaneous systemic megadose steroid therapy. RESULTS: A postoperative increase in visual acuity from 1/35 to 10/20 occurred in five patients, while no improvement in visual acuity could be achieved in the other four patients. DISCUSSION AND CONCLUSION: Previous reports have indicated that some authors will not recommend surgical decompressions if a loss of sight or no light perception occurs directly after an accident. This situation was seen in seven of our patients. The visual acuity of four patients remained no light perception in spite of surgical treatment. In three other patients, an increase in visual acuity from amaurosis improved to 1/35, 4/20 and 8/20, respectively, following early decompression combined with steroids. This experience together with the positive results of other studies supports carrying out decompressions of the optic nerve, even when an amaurosis occurs directly after trauma.

Adolescent↗
PubMed1998

TNFa and b microsatellites in Germany.

Allele frequencies of TNFa and TNFb microsatellites were determined from 315 healthy unrelated Germans (mothers and putative fathers) by means of PCR. They were stably inherited and segregated in a Mendelian way. New mutations were not observed.

Alleles↗
PubMed1998

Enhanced expression of selectins in human skin wounds.

The aim of the study was to characterize the vitality and age of skin wounds by the detection of selectins. A prospective study was conducted for this purpose in which 197 vital human skin wounds (time since injury ranging from 3 min to 790 days) were investigated immunohistologically. Of the samples tested, 97 were taken from autopsy material and 100 from patient material from the department of surgery at the university hospital. The selectins were detected in paraffin sections after autoclaving and using the ABC technique. The intensity was rated by a semi-quantitative evaluation using a four-stage ordinal scale. Strong positive immunohistochemical reactions were observed for the P-selectin 3 min at the earliest and 7 h at the latest after the time of injury. For the E-selectin a positive staining was evident I h at the earliest and 17 days at the latest from the time the skin was injured. The staining intensity decreased significantly after an interval of 12 h from the time of injury (P < 0.05). The L-selectin was regularly detected on leukocytes in the samples of injured skin. The immunohistochemical results for the P- and E-selectins were significantly different between injured and uninjured skin (P < 0.01). The expression of the selectins is indicative of the vitality of the wound. P-selectin was detected in a few cases (n=4) at low intensity while E-selectin could not be found in the control samples (n=31) of postmortem skin wounds. The use of P- and E-selectins for forensic purposes can help to achieve better estimates of the age of wounds with short survival times.

Female↗
PubMed1998

Pretreatment with hypertonic NaCl protects MDCK cells against high urea concentrations.

In antidiuresis, the cells of the renal medulla are exposed to high extracellular concentrations of NaCl and urea. Since urea equilibrates with the intracellular compartment and is known to perturb intracellular macromolecules, high urea concentrations may well disturb the structure and function of cell proteins. Two types of organic substances are believed to counteract the adverse effects of high intracellular urea concentrations: specific organic osmolytes of the trimethylamine family [betaine and glycerophosphorylcholine (GPC)], which accumulate in renal medullary cells during prolonged periods of antidiuresis and cytoprotective heat shock proteins (HSPs), the tissue content of two of which (HSPs 27 and 72) is much higher in the inner medulla than in the iso-osmotic renal cortex. To evaluate the contribution of trimethylamines and HSPs to cytoprotection in the presence of high urea concentrations, the effect of HSP induction and osmolyte accumulation prior to exposure to high urea concentrations was examined in Madin-Darby canine kidney (MDCK) cells. Accumulation of organic osmolytes and synthesis of HSP27 and HSP72 was initiated by hypertonic stress (increasing the osmolality of the medium from 290 to 600 mosmol/kg H2O by NaCl addition). Control, non-conditioned cells remained in the isotonic medium for the same period. Upon subsequent exposure to an additional 600 mM urea in the medium for 24 h, 90% of the osmotically conditioned cells but only 15% of non-conditioned cells survived. The HSP72 and trimethylamine contents of the NaCl-conditioned MDCK cells, but not HSP27 content, correlated positively with cell survival. To separate the effects of organic osmolytes and HSP72, chronically NaCl-adapted MDCK cells were returned to isotonic medium for 1 or 2 days, so depleting them of trimethylamine osmolytes. HSP72, with its longer half life, remained elevated. Subsequent exposure of these cells to 600 mM urea in the medium resulted in about 80% survival. These results suggest that in MDCK cells and probably in the renal medulla, HSP72 and perhaps additional protective factors contribute substantially to the resistance against high urea concentrations.

Animals↗
PubMed1998

Effects of long-term changes in medullary osmolality on heat shock proteins HSp25, HSP60, HSP72 and HSP73 in the rat kidney.

The influence of diuresis and antidiuresis on the expression of heat shock proteins (HSP) 25, 60, 72 and 73 in the renal cortex and outer and inner medulla of Wistar rats was analysed. Medullary osmolality was reduced by long-term diuresis (3% sucrose in the drinking water for 3 weeks) and subsequently enhanced by transition to a concentrating state by giving normal drinking water again in combination with deamino-D-arginine vasopressin (dDAVP) for 5 days. Western blot analyses revealed that neither HSP73 nor HSP60 was influenced by any treatment. The HSP72 level in the medulla was markedly reduced (50%) when osmolality was lowered and increased when tonicity was high. RNAse protection assays showed that the effects on HSP72 are parallelled in general by changes in HSP72 mRNA. While levels of HSP25 were not influenced, isoelectric focusing revealed that the degree of phosphorylation of outer and inner medullary HSP25 increased following both treatments. It thus seems that HSP73 and HSP60 are not directly involved in the long-term adaptation to varying medullary osmolalities. The correlation between changes in osmolality and amounts of the major stress-inducible HSP72 in the medulla implies that medullary hypertonicity is stressful for kidney cells. Furthermore, adaptation to pronounced changes in the osmolality of the environment most likely involves phosphorylation of HSP25.

Animals↗
PubMed1998

Expression of Na+/Cl-/betaine and Na+/myo-inositol transporters, aldose reductase and sorbitol dehydrogenase in macula densa cells of the kidney.

It has been suggested that macula densa cells may be exposed to hyperosmotic stress. Since chronic exposure to hypertonic stress causes the amount of intracellular organic osmolytes to increase, the expression of transporters and enzymes that participate in the intracellular accumulation of organic osmolytes was examined using non-radioactive in situ hybridization in the macula densa region of control rats and furosemide-treated animals. Both the sodium- and chloride-dependent betaine transporter (BGT) and sodium-dependent myo-inositol transporter (SMIT) were expressed preferentially in macula densa cells and for both mRNAs the signal intensity was visibly reduced by furosemide. The enzymes aldose reductase (which mediates the conversion of glucose to sorbitol) and sorbitol dehydrogenase (which converts sorbitol into fructose) were expressed not only in macula densa cells but also in the surrounding tubular cells, and the expression was insensitive to furosemide. Thus it remains unclear whether the expression of BGT and SMIT is related to a putative hypertonic juxtaglomerular region.

Aldehyde Reductase↗
PubMed1998

Cellular response to osmotic stress in the renal medulla.

Cells of the renal medulla, which are exposed under normal physiological conditions to widely fluctuating extracellular solute concentrations, respond to hypertonic stress by accumulating the organic osmolytes glycerophosphorylcholine (GPC), betaine, myo-inositol, sorbitol and free amino acids. Increased intracellular contents of these osmolytes are achieved by a combination of increased uptake (myo-inositol and betaine) and synthesis (sorbitol, possibly GPC), decreased degradation (GPC) and reduced osmolyte release. In the medulla of the concentrating kidney, accumulation of organic osmolytes, which do not perturb cell function even at high concentrations, allows the maintenance of "normal" intracellular concentrations of inorganic electrolytes. Adaptation to decreasing extracellular solute concentrations, e.g. diuresis, is achieved primarily by activation of pathways allowing the efflux of organic osmolytes, and secondarily by inactivation of production (sorbitol) and uptake (betaine, myo-inositol) and stimulation of degradation (GPC). Apart from modulation of the osmolyte content, osmolality-dependent reorganization of the cytoskeleton and expression of specific stress proteins (heat shock proteins) may be further, as yet poorly characterized, components of the regulatory systems involved in the adaptation of medullary cells to osmotic stress.

Adaptation, Physiological↗
PubMed1998

Ultrastructural changes in fish gills as biomarker to assess small stream pollution.

In order to verify the principal suitability of gill ultrastructure as a biomarker, semi-field studies with two endigoneous fish, trout (Salmo trutta f. fario) and loach (Barbatula barbatula), were performed. The fish were exposed in flow-through systems to one heavily polluted (Körsch) and one lightly polluted small stream (Krähenbach) in South-West Germany. Ultrastructural responses in gills were correlated with limnological and chemical data recorded over a 2 year period in each stream. After 8 weeks of exposure to the heavily polluted stream, fish showed ultrastructural changes in the gills, such as cell proliferation, dilation of the endoplasmic reticulum, hyperplasia, hypersecretion, and epithelial lifting in chloride, epithelial, and mucus cells. The results of the study demonstrate that ultrastructural reactions in the gills of fish kept under semi-field conditions are potentially useful biomarkers indicating small stream pollution.

Animals↗
PubMed1998

Functional MRI of the motor cortex using a conventional gradient system: comparison of FLASH and EPI techniques.

Gradient echo (GE) and echo planar imaging (EPI) techniques are two different approaches to functional MRI (fMRI). In contrast to GE sequences, the ultra short EPI technique facilitates fMRI experiments with high spatial and temporal resolution or mapping of the whole brain. Although it has become the method of choice for fMRI, EPI is generally restricted to modern scanners with a strong gradient system. The aim of our study was to evaluate the applicability of EPI for fMRI of the motor cortex using a 1.5 T scanner with a conventional gradient system of 10 mT/m (rise time: 1 ms). Therefore, EPI was compared with a well-established high-resolution fast low-angle shot (FLASH) technique (matrix size 1282). The FLASH technique was applied additionally with a 64(2) matrix size to exclude influences caused by different spatial resolution, because the EPI sequence was restricted to a 64(2) matrix size. A total of 35 healthy volunteers were included in this study. The task consisted of clenching and spreading of the right hand. FLASH and EPI techniques were compared regarding geometric distortions as well as qualitative and quantitative fMRI criteria: Mean signal increase between activation and rest and the area of activation were measured within the contralateral, ipsilateral, and supplementary motor cortex. The quality of subtraction images between activation and rest, as well as the quality of z-maps and time course within activated regions of interest, was evaluated visually. EPI revealed significant distortions of the anterior and posterior brain margins; lateral distortions (relevant for the motor cortex) could be neglected in most cases. The mean signal increase was significantly higher using FLASH 1282 compared to FLASH 64(2) and EPI 64(2), whereas the activated areas proved to be smaller in FLASH 1282 functional images. Both results can be explained by well-documented partial volume effects, caused by different voxel size. Similar quality of the subtraction images and of the time courses in different regions of interest were found for all techniques under investigation, but slightly reduced quality of z-map in FLASH 1282. Within the limits of reproducibility and measurement accuracy, the location of contralateral activation was similar using FLASH and EPI sequences. In conclusion, EPI proved to be a reliable technique for fMRI of the motor cortex, even on an MR scanner with a conventional gradient system.

Adult↗
PubMed1998

Hexarelin exhibits protective activity against cardiac ischaemia in hearts from growth hormone-deficient rats.

Male rats were treated with growth hormone (GH)-releasing hormone antiserum to induce selective GH deficiency. The chronic administration of hexarelin to these GH-deficient rats had a pronounced protective effect against ischaemic and post-ischaemic ventricular dysfunction. Hexarelin prevented hyper-responsiveness of the coronary vascular bed to angiotensin II and also prevented the reduction in generation of 6-keto-prostaglandin F1alpha in perfused hearts from GH-deficient rats. The most plausible interpretation of these findings is that hexarelin acts via stimulation of specific cardiac and vascular receptors, triggering currently unknown cytoprotective mechanisms that are responsible for resistance to ischaemic insults and for the preservation of the integrity of the endothelial vasodilation function.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Long-chain polyunsaturated fatty acids in plasma and erythrocyte membrane lipids of children with phenylketonuria after controlled linoleic acid intake.

It has been reported that children with classical phenylketonuria (PKU) have reduced levels of arachidonic acid (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3) in plasma and membrane phospholipids compared to controls and may therefore require supplementation. However, it is not established that these changes are specific for PKU. They may as well be attributed to the specific composition of a largely vegetarian diet used for dietary PKU treatment. We therefore investigated the fatty acid composition of plasma phospholipids (PL), plasma cholesterol esters (CE), red blood cell phosphatidylcholine (PC), and red blood cell phosphatidylethanolamine (PE) in two groups of PKU patients including 8 children between 1 and 6 years (group A), 9 adolescents between 11 and 18 years (group B), and 20 age-matched healthy controls. Group A had good dietary control (median plasma phenylalanine 272 mumol/L during the last 6 months before phospholipid analysis) while median phenylalanine in group B was 714 mumol/L (p < 0.001). When compared to age-matched controls, group A showed significantly lower DHA levels in PE (4.21 vs 5.85 weight% (wt%), p < 0.01), in PC (1.02 vs 1.25 wt%, p < 0.05) and in CE (0.25 vs 0.54 wt%, p < 0.05). There was no significant difference of DHA between group B and controls. AA levels were similar in phospholipids of all groups. We conclude that reduced levels of long-chain polyunsaturated fatty acids in PKU patients occur only in those patients with strict dietary therapy with respect to n-3 fatty acids, most probably caused by reduced intake of n-3 fatty acids.

Adolescent↗
PubMed1998

Diagnosis and management of glutaric aciduria type I.

Glutaric aciduria type I (GA1) is a preventable cause of acute brain damage in early childhood, leading to a severe dystonic-dyskinetic disorder that is similar to cerebral palsy and ranges from extreme hypotonia to choreoathetosis to rigidity with spasticity. Degeneration of the putamen and caudate typically occurs between 6 and 18 months of age and is probably linked to changes in metabolic demand caused by normal maturational changes and superimposed catabolic stress. Recognition of this biochemical disorder before the brain has been injured is essential to outcome. Diagnosis depends upon the recognition of relatively non-specific physical findings such as hypotonia, irritability and macrocephaly, and on performance of urine organic acid quantification by gas chromatography--mass spectrometry or selective searches of urine or blood specimens by tandem mass spectrometry for glutarylcarnitine. The diagnosis may also be suggested by characteristic findings on neuroimaging. In selected patients diagnosis can only be reached by enzyme assay. Specific current management by the authors of this paper includes pharmacological doses of L-carnitine, as well as dietary protein restriction. Metabolic decompensation must be treated aggressively to avoid permanent brain damage. Multicentre studies are needed to establish best methods of diagnosis and optimal therapy of this disorder.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Cationic amino acid transporter mRNA expression in rat kidney and liver.

Expression of rat cationic amino acid transporter 2 (r-CAT-2) mRNA was studied in kidney and liver using Northern blot analysis and nonradioactive in situ hybridization with a probe identifying both the r-CAT-2alpha and -2beta splice variants. Expression of r-CAT-2 mRNA was higher in the liver than in the kidney. Within the kidney, r-CAT-2 mRNA was more abundant in the outer and inner medulla than in the cortex. In the liver lobule, the intensity of the hybridization signal in hepatocytes decreased between the portal area and the central vein. In the kidney, hybridization signals were detected in parietal cells of Bowman's capsule, various tubule cells of outer and inner medulla, in endothelial and interstitial cells of inner medulla, and in papillary epithelial cells.

Amino Acid Transport Systems, Basic↗
PubMed1998

Influence of osmotic stress on heat shock proteins 25 and 72 in mouse mesangial cells.

Previous studies have shown intense staining for heat shock protein 25 (HSP25) in the extraglomerular mesangium (EGM). Because relationships are believed to exist between osmotic stress, expression of HSP25, and protection against stress and because the EGM may be exposed to high local tonicity, we examined the expression of HSP25 and the major stress-inducible and cytoprotective HSP72 in mouse mesangial cells and embryonic lung fibroblasts (3T3) after exposure to hypertonic stress (addition of 150 mM NaCl to the medium for two to seven days). Mesangial, but not 3T3, cells expressed high levels of HSP25 already under control conditions, whereas neither cell line contained HSP72. Hypertonic treatment neither enhanced (mesangial cells) or induced (3T3 cells) HSP25 expression. HSP72, however, was induced strongly in 3T3 cells, but only minimally in mesangial cells. The high level of HSP25 in mesangial cells thus seems not to be a consequence of high tonicity in the EGM because cultured mesangial cells express HSP25 already under control conditions, and osmotic stress did not induce HSP25 in either cell line. Furthermore, high amounts of HSP25 seem to reduce the requirement for HSP72 after stress exposure, suggesting that, in mesangial cells, HSP25 might assume some functions of HSP72.

3T3 Cells↗
PubMed1998

Hypertonicity affects heat shock protein 27 and F-actin localization in Madin-Darby canine kidney cells.

High concentrations of NaCl are known to perturb the cytoskeleton. In this study, expression and intracellular localization of actin, an important component of the cytoskeleton and of heat shock protein (HSP)27, which promotes the assembly of F-actin, were examined in Madin-Darby canine kidney (MDCK) cells grown chronically in hypertonic medium. HSP27 mRNA abundance was increased twofold compared with wild-type MDCK cells. Chronic hypertonic stress led to enrichment of HSP27 in the insoluble component of the cell lysate and colocalization with cortical F-actin. These results support the notion that HSP27 participates in the modulation of actin dynamics following hypertonic stress.

Actins↗