Search PubMed⌕ Search

Biomedical subjects

B Friedrich

Publications and source records attributed to B Friedrich.

At least 19 recordsLinked to original sources
PubMed2006

Acute effects of hemodialysis on cytokine transcription profiles: evidence for C-reactive protein-dependency of mediator induction.

Chronic microinflammation increases cardiovascular morbidity in chronic hemodialysis (HD) patients. Previously published studies are controversial with respect to acute effects of HD treatment on up- or downregulation of cytokine protein levels. Twenty-nine chronic HD patients were hemodialysed for 4 h with a 4008 dialyser using high-flux membranes. Patients were separated into a low (up to 1 mg/dl) and a high (1.1 to 5.5 mg/dl) C-reactive protein (CRP) group. Blood was drawn before HD and 240 min after initiation of HD. Acute changes of transcript levels encoding pro- and anti-inflammatory mediators were analyzed in RNA stabilized immediately from blood leukocytes using microarray analysis (n=1) and quantitative real-time polymerase chain reaction (PCR) (Light Cycler) (n=29). In both patient groups, HD treatment significantly increased the transcript levels of several pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin-8 (IL-8), and chemokine receptors such as C-X-C chemokine receptor type 4, C-C chemokine receptor type 7, and the fractakine receptor CX3C chemokine receptor 1. In the low CRP group, the increase of transcript levels for anti-inflammatory IL-1-receptor antagonist and of the receptor for the anti-inflammatory cytokines IL-10 and interferon gamma was significantly more pronounced than in the high CRP group. Subgroup analysis revealed no difference between diabetic vs non-diabetic patients. These observations point towards a marked influence of a routine hemodialysis treatment on transcription in leukocytes of pro- and anti-inflammatory cytokines and receptors relevant for microinflammation. Diminished upregulation of receptors for anti-inflammatory factors in HD patients with high CRP levels could contribute to enhanced microinflammation in those patients.

Aged↗
PubMed2006

[Involuntary patient admission and treatment against patient's will by emergency physicians].

INTRODUCTION: The treatment of acutely ill patients who presumably lack the insight or judgement to determine their need for medical treatment, is a difficult challenge for emergency physicians. We have carried out a study to assess the frequency and relevance of involuntary treatment and procedures in medical emergency services. METHODS: Retrospective chart analysis for a 1-year period was performed for all treatment protocols of a medical emergency service unit and for all court-ordered treatments of a guardianship court. Cases of involuntary treatment by emergency physicians were identified and analysed. RESULTS: In 10.4% of all emergency calls analysed a relevant and acute psychiatric condition was found. In 0.3% of the cases or 4.8% of the psychiatric cases, involuntary inpatient commitment was chosen by the emergency physician. DISCUSSION: Involuntary inpatient commitment by emergency physicians was only necessary in relatively few cases. Nevertheless, in order to be able to correctly consider treatment and management options, emergency physicians should be aware of the basic conditions for treatment without a patient's consent.

Adolescent↗
PubMed2006

Cell volume regulatory mechanisms.

Prerequisites for cell survival include avoidance of excessive alterations of cell volume. Cells counterbalance the osmolarity due to cellular accumulation of organic substances by uneven distribution of inorganic ions. They extrude Na(+) in exchange for K(+) by the Na(+) /K(+) ATPase. The cell membrane is less permeable to Na(+) than to K(+) . The K(+) exit generates a cell-negative potential difference across the cell membrane which drives the exit of anions such as Cl(-) thus decreasing intracellular osmolarity. Upon cell swelling, cells release ions through activation of K(+) channels and/or anion channels, KCl-cotransport, or parallel activation of K(+) /H(+) exchange and Cl(-) /HCO-3 exchange. Upon cell shrinkage, cells accumulate ions through activation of Na(+) , K(+) , 2Cl(-) cotransport, Na(+) /H(+) exchange in parallel to Cl(-) /HCO3- exchange, or Na(+) channels. Na(+) taken up is extruded by the Na(+) /K(+) ATPase in exchange for K(+) . Shrunken cells further accumulate organic osmolytes. They generate sorbitol and glycerophosphorylcholine and monomeric amino acids by altered metabolism and take up myoinositol (inositol), betaine, taurine and amino acids by Na(+) coupled transport. They release osmolytes during cell swelling.

Biological Transport↗
PubMed2005

A hydrogen-sensing multiprotein complex controls aerobic hydrogen metabolism in Ralstonia eutropha.

H(2) is an attractive energy source for many microorganisms and is mostly consumed before it enters oxic habitats. Thus aerobic H(2)-oxidizing organisms receive H(2) only occasionally and in limited amounts. Metabolic adaptation requires a robust oxygen-tolerant hydrogenase enzyme system and special regulatory devices that enable the organism to respond rapidly to a changing supply of H(2). The proteobacterium Ralstonia eutropha strain H16 that harbours three [NiFe] hydrogenases perfectly meets these demands. The unusual biochemical and structural properties of the hydrogenases are described, including the strategies that confer O(2) tolerance to the NAD-reducing soluble hydrogenase and the H(2)-sensing regulatory hydrogenase. The regulatory hydrogenase that forms a complex with a histidine protein kinase recognizes H(2) in the environment and transmits the signal to a response regulator, which in turn controls transcription of the hydrogenase genes.

Aerobiosis↗
PubMed2005

Transcriptional regulation of nitric oxide reduction in Ralstonia eutropha H16.

Nitric oxide reduction in Ralstonia eutropha H16 is catalysed by the quinol-dependent NO reductase NorB. norB and the adjacent norA form an operon that is controlled by the sigma(54)-dependent transcriptional activator NorR in response to NO. A NorR derivative containing MalE in place of the N-terminal domain binds to a 73 bp region upstream of norA that includes three copies of the putative upstream activator sequence GGT-(N(7))-ACC. Mutations altering individual bases of this sequence resulted in an 80-90% decrease in transcriptional activation by wild-type NorR. Similar motifs are present in several proteobacteria upstream of genes encoding proteins of NO metabolism. The N-terminal domain of NorR contains a GAF module and is hypothesized to interact with a signal molecule. A NorR derivative lacking this domain activates the norAB promoter constitutively. Amino acid exchanges within the GAF module identified a cysteine residue that is essential for promoter activation by NorR. Signal sensing by NorR is negatively modulated by the iron-containing protein NorA.

Catalysis↗
PubMed2003

The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel alpha,beta,gamma-ENaC.

The serum- and glucocorticoid-inducible kinase 1 (SGK1) has been identified as a signalling molecule up-regulated by aldosterone, which stimulates the renal epithelial Na(+) channel ENaC. It is therefore thought to participate in the antinatriuretic action of this hormone. More recently, two isoforms, SGK2 and SGK3, have been cloned. The present study was performed to establish whether SGK2 and SGK3 influence ENaC activity similarly to SGK1. Dual-electrode voltage-clamp experiments in Xenopus laevis oocytes expressing alpha,ss,gamma-ENaC with or without SGK1, SGK2 or SGK3 revealed a stimulatory effect of all three kinases on the amiloride-sensitive current (I(Na)). To establish whether the SGK isoforms exert their effects through direct phosphorylation, we replaced the serine at the SGK consensus site of alphaENaC (alpha(S622A)ENaC) by site-directed mutagenesis. alpha(S622A),beta,gamma-ENaC was up-regulated similar to wild-type ENaC, suggesting that SGK isoforms do not act via direct phosphorylation of the transport proteins. In conclusion, SGK2 and SGK3 mimic the function of SGK1 and are likely to participate in the regulation of ENaC activity.

Animals↗
PubMed2002

K+ channel activation by all three isoforms of serum- and glucocorticoid-dependent protein kinase SGK.

The serum- and glucocorticoid-dependent kinase SGK1 was originally identified as a glucocorticoid-sensitive gene. Subsequently, the two homologous kinases SGK2 and SGK3 have been cloned, being products of distinct genes, which are differentially expressed and share 80% identity in amino acid sequence in their catalytic domains. While SGK1 has been shown to activate ion channels, including K(+) channels, the functions of SGK2 and SGK3 have not been examined. The present study was therefore performed to elucidate the effect of SGK1, SGK2, and SGK3 on electrical properties of renal epithelial cells. To this end human embryonic kidney (HEK293) cells were transfected with the kinases and ion-channel activity determined using the patch-clamp technique. In non-transfected cells and in cells transfected with the empty GFP construct a voltage-gated K(+) current was observed amounting to 303+/-19 pA ( n=13) and 299+/-29 pA ( n=23), respectively. Transfection with SGK1, SGK2 or SGK3 increased the voltage-gated K(+) current to 1056+/-152 pA ( n=17), 555+/-47 pA ( n=17), and 775+/-98 pA ( n=16), respectively. The K(+) current was fully blocked by 3 mM tetraethylammonium chloride and inhibited 45% by the Kv1 channel blocker margatoxin (10 nM). In dual electrode voltage-clamp experiments SGK isoforms up-regulated Kv1 voltage-gated K(+)channels expressed in Xenopus laevis oocytes. The present observations thus reveal a powerful stimulating effect of all three isoforms of SGK on K(+) channels. Those effects may participate in regulation of epithelial transport, cell proliferation, and neuromuscular excitability.

Animals↗
PubMed2002

Up-regulation of the human serum and glucocorticoid-dependent kinase 1 in glomerulonephritis.

Glomerulonephritis is paralleled by excessive formation of transforming growth factor-beta (TGF-beta), which participates in the pathophysiology of the disease. Recently, a novel downstream target of TGF-beta has been identified, i.e. the human serum and glucocorticoid-dependent kinase 1 (hSGK1), a serine/threonine kinase participating in the regulation of Na(+) transport. The present study was performed to elucidate transcriptional regulation of hSGK1 in glomerulonephritis. To this end, in situ hybridization was performed in biopsies from patients with clinical diagnosis of glomerulonephritis. hSGK1 transcript levels were moderately enhanced in 5 out of 9 patients and strongly enhanced in 4 out of 9 patients. Distal nephron epithelial cell hSGK1 transcript levels were low or absent in 7 of the 9 patients but markedly enhanced in 2 of the 9 patients. In conclusion, glomerulonephritis leads to glomerular and in some cases to epithelial up-regulation of hSGK1 transcription.

Adult↗
PubMed2001

Cerebral localization and regulation of the cell volume-sensitive serum- and glucocorticoid-dependent kinase SGK1.

The serum- and glucocorticoid-dependent kinase SGK1 is regulated by alterations of cell volume, whereby cell shrinkage increases and cell swelling decreases the transcription, expression and activity of SGK1. The kinase is expressed in all human tissues studied including the brain. The present study was performed to localize the sites of SGK1 transcription in the brain, to elucidate the influence of the hydration status on SGK1 transcription and to explore the functional significance of altered SGK1 expression. Northern blot analysis of human brain showed SGK1 to be expressed in all cerebral structures examined: amygdala, caudate nucleus, corpus callosum, hippocampus, substantia nigra, subthalamic nucleus and thalamus. In situ hybridization and immunohistochemistry in the rat revealed increased expression of SGK1 in neurons of the hippocampal area CA3 after dehydration, compared with similar slices from brains of euvolaemic rats. Additionally, several oligodendrocytes, a few microglial cells, but no astrocytes, were positive for SGK1. The abundance of SGK1 mRNA in the temporal lobe, including hippocampus, was increased by dehydration and SGK1 transcription in neuroblastoma cells was stimulated by an increase of extracellular osmolarity. Co-expression studies in Xenopus laevis oocytes revealed that SGK1 markedly increased the activity of the neuronal K+ channel Kv1.3. As activation of K+ channels modifies excitation of neuronal cells, SGK1 may participate in the regulation of neuronal excitability.

Animals↗
PubMed2001

A physical map of the megaplasmid pHG1, one of three genomic replicons in Ralstonia eutropha H16.

We have used pulsed field gel electrophoresis and megabase DNA techniques to investigate the basic genomic organization of Ralstonia eutropha H16, and to construct a physical map of its indigenous megaplasmid pHG1. This Gram-negative, soil-dwelling bacterium is a facultative chemolithoautotroph and a denitrifier. In the absence of organic substrates it can grow on H2 as its sole energy source and CO2 as its sole source of carbon. Under anaerobic conditions it can utilize nitrate as a terminal electron acceptor, whereby dinitrogen is released. Essential genetic determinants of the enzyme systems responsible for these metabolic processes are linked to the 0.44-Mb conjugative megaplasmid pHG1. Aside from pHG1, the genome of R. eutropha H16 is comprised of two circular chromosomes measuring 4.1 and 2.9 Mb, adding up to a total genome size of 7.1 Mb. An estimated five copies of rDNA are distributed on the two chromosomes. A macrorestriction map of pHG1 was derived for the endonucleases DraI and XbaI. Hybridization studies showed that genes for anaerobic metabolism are located on all three genomic replicons.

Anaerobiosis↗
PubMed2001

Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains.

Heterodimeric amino acid transporters are comprised of a type-II membrane protein named the heavy chain (4F2hc or rBAT) that may associate with a number of different polytopic membrane proteins, called light chains. It is thought that the heavy chain is mainly involved in the trafficking of the complex to the plasma membrane, whereas the transport process itself is catalysed by the light chain. The 4F2 heavy chain (4F2hc) associates with at least six different light chains to induce distinct amino acid-transport activites. To test if the light chains are specifically recognized and to identify domains involved in the recognition of light chains, C-terminally truncated mutants of 4F2hc were constructed and co-expressed with the light chains LAT1, LAT2 and y(+)LAT2. The truncated isoform T1, comprised of only 133 amino acids that form the cytosolic N-terminus and the transmembrane helix, displayed only a slight reduction in its ability to promote LAT1 expression at the membrane surface compared with the 529 amino acid wild-type 4F2hc protein. Co-expression of increasingly larger 4F2hc mutants caused a delayed translocation of LAT1. In contrast to the weak effects of 4F2hc truncations on LAT1 expression, surface expression of LAT2 and y(+)LAT2 was almost completely lost with all truncated heavy chains. Co-expression of LAT1 together with the other light chains did not result in displacement of LAT2 and y(+)LAT2. The results suggest that extracellular domains of the heavy chain are responsible mainly for recognition of light chains other than LAT1 and that the extracellular domain ensures proper translocation to the plasma membrane.

Amino Acid Transport Systems↗
PubMed2001

The H2 sensor of Ralstonia eutropha. Biochemical characteristics, spectroscopic properties, and its interaction with a histidine protein kinase.

Previous genetic studies have revealed a multicomponent signal transduction chain, consisting of an H(2) sensor, a histidine protein kinase, and a response regulator, which controls hydrogenase gene transcription in the proteobacterium Ralstonia eutropha. In this study, we isolated the H(2) sensor and demonstrated that the purified protein forms a complex with the histidine protein kinase. Biochemical and spectroscopic analysis revealed that the H(2) sensor is a cytoplasmic [NiFe]-hydrogenase with unique features. The H(2)-oxidizing activity was 2 orders of magnitude lower than that of standard hydrogenases and insensitive to oxygen, carbon monoxide, and acetylene. Interestingly, only H(2) production but no HD formation was detected in the D(2)/H(+) exchange assay. Fourier transform infrared data showed an active site similar to that of standard [NiFe]-hydrogenases. It is suggested that the protein environment accounts for a restricted gas diffusion and for the typical kinetic parameters of the H(2) sensor. EPR analysis demonstrated that the [4Fe-4S] clusters within the small subunit were not reduced under hydrogen even in the presence of dithionite. Optical spectra revealed the presence of a novel, redox-active, n = 2 chromophore that is reduced by H(2). The possible involvement of this chromophore in signal transduction is discussed.

Chromatography, Ion Exchange↗
PubMed2001

Time-dependent alignment and orientation of molecules in combined electrostatic and pulsed nonresonant laser fields.

We examine the time evolution of states created by the nonadiabatic interaction of a polar molecule with combined electrostatic and pulsed nonresonant laser fields and show that the orientation due to the electrostatic field alone can be greatly enhanced by restricting the angular amplitude of the molecule by the pulsed laser field. An analytic model indicates that in the short-pulse limit the interaction is governed by an impulsive transfer of action from the radiative field to the molecule.

Journal Article↗
PubMed2001

Protein and mRNA expression of serum and glucocorticoid-dependent kinase 1 in metanephrogenesis.

Abstract Expression of serum and glucocorticoid-dependent kinase 1 (SGK1) during development in mouse kidney (embryonic day [E] 14 to postnatal day [P] 1) was studied by in situ hybridization and immunofluorescence. In whole embryos, SGK1 mRNA was highly abundant in the developing metanephros, where SGK1 mRNA was expressed in the ureteric buds of the branching collecting duct system and in the mesenchymal blastema-derived comma- and s-shaped bodies. In E14 kidneys, SGK1 protein was below detection level, whereas at day E16, ureteric buds, s-shaped bodies and outgrowing loops of Henle expressed detectable amounts of SGK1 protein. SGK1 protein was also expressed in E16 primary tubules of the collecting duct system. In P1 kidneys, no or only faint SGK1 protein expression was apparent in comma- and s-shaped bodies, whereas SGK1 was continuously expressed by medullary collecting ducts. In conclusion, SGK1 is developmentally expressed in metanephrogenesis. High expression in developing collecting duct and in blastema-derived comma- and s-shaped bodies suggests a dual function of SGK1 in maturation of the reabsorbing collecting duct epithelium and in epithelial transition of the blastema cells.

Animals↗
PubMed2001

Synovial chondromatosis of the glenohumeral joint: a rare condition.

The case of a 22-year-old man with synovial chondromatosis (SC) of the shoulder joint is described. A literature review confirmed that SC of the glenohumeral joint is very rare and that the etiology of the disease is still unknown. The diagnosis is often delayed, and the preferred form of management remains controversial. We consider magnetic resonance imaging (MRI) a valuable tool in detecting SC at an early phase and estimating the intrasynovial extent of the disease. Shoulder arthroscopy today represents an elegant treatment option for removing the chondromas and performing a partial synovectomy. It might, however, be insufficent in cases of involvement of the bicipital tendon sheath and other recesses of the joint.

Adult↗
PubMed2001

Serum- and glucocorticoid-dependent kinase, cell volume, and the regulation of epithelial transport.

Ample pharmacological evidence points to a role of kinases in the regulation of cell volume. Given the limited selectivity of most inhibitors, however, the specific molecules involved have remained largely elusive. The search for cell volume regulated genes in liver HepG2 cells led to the discovery of the human serum- and glucocorticoid-dependent serine/threonine kinase hsgk1. Transcription and expression of hsgk1 is markedly and rapidly upregulated by osmotic and isotonic cell shrinkage. The effect of osmotic cell shrinkage on hsgk1 is mediated by p38 kinase. Further stimuli of hsgk1 transcription include glucocorticoids, aldosterone, TGF-beta1, serum, increase of intracellular Ca2+ and phorbolesters, whereas cAMP downregulates hsgk1 transcription. The hsgk1 protein is expressed in several epithelial tissues including human pancreas, intestine, kidney, and shark rectal gland. Co-expression of hsgk1 with the renal epithelial Na+-channel ENaC or the Na+/K+/2Cl(-)-cotransporter NKCC2 (BSC1) in Xenopus oocytes, accelerates insertion of the transport proteins into the cell membrane and thus, stimulates channel or transport activity. Thus, hsgk1 participates in the regulation of transport by steroids and secretagogues increasing intracellular Ca2+-activity. The stimulation of hsgk1 transcription by TGF-beta1 may further bear pathophysiological relevance.

Animals↗
PubMed2001

Staying power.

First-line managers influence nurses' job satisfaction and decrease nurses' interest in union activity.

Burnout, Professional↗