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C Hermann

Publications and source records attributed to C Hermann.

At least 19 recordsLinked to original sources
PubMed2005

Chronic periodontal disease is associated with single-nucleotide polymorphisms of the human TLR-4 gene.

Periodontitis is an inflammatory disease affecting the connective tissue surrounding the teeth leading to tooth loss. Pathogens associated with periodontitis interact with Toll-like receptors (TLRs) to induce cytokines causing and aggravating disease. We screened 197 individuals suffering from generalized periodontitis for the presence of Asp299Gly and Thr399Ile of TLR-4 as well as Arg753Gln of TLR-2 in comparison to matched controls. Single-nucleotide polymorphisms (SNPs) of TLR-4 were elevated among patients (odd's ratio 3.650, 95% CI 1.573-8.467, P < or = 0.0001), while no difference was observed for TLR-2. TLR-4 SNPs were correlated with chronic periodontitis (odd's ratio 5.562, 95% CI 2.199-14.04, P < or = 0.0001), but not with aggressive periodontitis. This observation was confirmed employing a group of periodontally healthy probands over 60 years of age. These data demonstrate that genetic variants of TLR-4 may act as risk factors for the development of generalized chronic periodontitis in humans.

Adult↗
PubMed2001

The generation of both T killer and Th cell clones specific for the tumor-associated antigen HER2 using retrovirally transduced dendritic cells.

Induction of antitumor immunity involves the presence of both CD8(+) CTLs and CD4(+) Th cells specific for tumor-associated Ags. Attempts to eradicate cancer by adoptive T cell transfer have been limited due to the difficulty of generating T cells with defined Ag specificity. The current study focuses on the generation of CTL and Th cells against the tumor-associated Ag HER2 using autologous dendritic cells (DC) derived from CD34(+) hematopoietic progenitor cells which have been retrovirally transduced with the human epidermal growth factor receptor 2 (HER2) gene. HER2-transduced DC elicited HER2-specific CD8(+) CTL that lyse HER2-overexpressing tumor cells in context of distinct HLA class I alleles. The induction of both HLA-A2 and -A3-restricted HER2-specific CTL was verified on a clonal level. In addition, retrovirally transduced DC induced CD4(+) Th1 cells recognizing HER2 in context with HLA class II. HLA-DR-restricted CD4(+) T cells were cloned that released IFN-gamma upon stimulation with DC pulsed with the recombinant protein of the extracellular domain of HER2. These data indicate that retrovirally transduced DC expressing the HER2 molecule present multiple peptide epitopes and subsequently elicit HER2-specific CTL and Th1 cells. The method of stimulating HER2-specific CD8(+) and CD4(+) T cells with retrovirally transduced DC was successfully implemented for generating HER2-specific CTL and Th1 clones from a patient with HER2-overexpressing breast cancer. The ability to generate and expand HER2-specific, HLA-restricted CTL and Th1 clones in vitro facilitates the development of immunotherapy regimens, in particular the adoptive transfer of both autologous HER2-specific T cell clones in patients with HER2-overexpressing tumors without the requirement of defining immunogenic peptides.

Alleles↗
PubMed2001

Oxidized LDL inhibits vascular endothelial growth factor-induced endothelial cell migration by an inhibitory effect on the Akt/endothelial nitric oxide synthase pathway.

BACKGROUND: Oxidized LDL (oxLDL) inhibits endothelial cell (EC) migration. Stimulating ECs with vascular endothelial growth factor (VEGF) leads to the activation of Akt/protein kinase B, which in turn activates endothelial nitric oxide synthase (eNOS) by phosphorylation on serine 1177. VEGF-induced cell migration is dependent on the generation of nitric oxide (NO). Therefore, we investigated whether oxLDL affects EC migration by an inhibitory effect on the Akt/eNOS pathway. METHODS AND RESULTS: During an in vitro "scratched wound assay," oxLDL dose-dependently inhibited the VEGF-induced migration of human umbilical vein endothelial cells. Western blot analysis revealed that oxLDL dose- and time-dependently led to dephosphorylation and thus deactivation of Akt. Moreover, oxLDL inhibited the VEGF-induced generation of NO, as detected and quantified using a fluorescent NO indicator, 4,5-diaminofluorescein diacetate. Overexpression of a constitutively active Akt construct (Akt T308D/S473D) or a phosphomimetic eNOS construct (eNOS S1177D) almost completely reversed the inhibitory effect of oxLDL on VEGF-induced EC migration and NO generation. CONCLUSIONS: Our data indicate that oxLDL-induced dephosphorylation of Akt, followed by impaired eNOS activation, reduces the intracellular level of NO and thereby inhibits VEGF-induced EC migration.

Amino Acid Substitution↗
PubMed2001

An experimental and theoretical study of the basicity of tetra-tert-butyltetrahedrane.

The gas-phase basicity (GB) of tetra-tert-butyltetrahedrane (tBu4THD) was determined by FT-ICR mass spectrometry and comparison with reference compounds of known basicity. Its GB, 1035+/-10 kJ x mol(-1), makes tetra-tert-butyltetrahedrane one of the strongest bases reported so far. Ab initio calculations [B3LYP/6-31G(d) and B3LYP/6-311 + G(d,p)//6-31G(d)] have been carried out in order to compare the high experimental basicity of tBu4THD with that estimated theoretically. Both B3LYP/6-31G(d) and QCISD(T) calculations were used to determine the reaction path which connects the initial tetrahedrane-ammonium complex with the final products, protonated cyclobutadiene (CBDH+) and ammonia.

Journal Article↗
PubMed2000

Differential RNA cleavage and polyadenylation of the glutamate transporter EAAT2 in the human brain.

We cloned four novel transcripts of the excitatory amino acid transporter 2, named EAAT2/3UT1-4, resulting from differential cleavage and polyadenylation. Tandem poly (A) sites were found to be functional at 72, 654, 973 nucleotides and more than 2 kb downstream of the stop codon. A tissue-specific expression was identified for 3'-variants of the EAAT2 RNA, most prominently for EAAT2/3UT4 (hippocampus>cortex>>cerebellum>thalamus) as demonstrated by Northern blot analysis and quantitative PCR. We conclude, that alternative poly (A) selection may contribute to the reported differential EAAT2 protein expression under normal and diseased conditions.

Base Sequence↗
PubMed2000

Nitric oxide down-regulates MKP-3 mRNA levels: involvement in endothelial cell protection from apoptosis.

MAP kinase-dependent phosphorylation processes have been shown to interfere with the degradation of the antiapoptotic protein Bcl-2. The cytosolic MAP kinase phosphatase MAP kinase phosphatase-3 (MKP-3) induces apoptosis of endothelial cells in response to tumor necrosis factor alpha (TNFalpha) via dephosphorylation of the MAP kinase ERK1/2, leading to Bcl-2 proteolysis. Here we report that the endothelial cell survival factor nitric oxide (NO) down-regulated MKP-3 by destabilization of MKP-3 mRNA. This effect of NO was paralleled by a decrease in MKP-3 protein levels. Moreover, ERK1/2 was found to be protected against TNFalpha-induced dephosphorylation by coincubation of endothelial cells with the NO donor. Subsequently, both the decrease in Bcl-2 protein levels and the mitochondrial release of cytochrome c in response to TNFalpha were largely prevented by exogenous NO. In cells overexpressing MKP-3, no differences in phosphatase activity in the presence or absence of NO were found, excluding potential posttranslational modifications of MKP-3 protein by NO. These data demonstrate that upstream of the S-nitrosylation of caspase-3, NO exerts additional antiapoptotic effects in endothelial cells, which rely on the down-regulation of MKP-3 mRNA.

Animals↗
PubMed2000

Pavlovian aversive and appetitive odor conditioning in humans: subjective, peripheral, and electrocortical changes.

Differential Pavlovian conditioning of aversive and appetitive odors was examined in 30 male healthy subjects. The appetitive conditioning group (n=15) received a pleasant odor (vanilla), the aversive conditioning group (n=15) an unpleasant odor (fermented yeast) as unconditioned stimulus. Slides of two different neutral faces that were easy to discriminate served as conditioned stimuli (CS). An EEG was recorded from nine electrodes. Electromyographic activity was measured bilaterally from the m. corrugator supercilii and m. zygomaticus. The startle response was obtained from the m. orbicularis oculi. Finally, heart rate and skin conductance response were assessed. The subjective data and the skin conductance response revealed successful differential aversive conditioning. By contrast, the pleasant odor failed to produce appetitive odor conditioning. The conditioned and unconditioned response of the corrugator muscles confirm previous reports on the m. corrugator being strongly involved in the expression of negative affect. Contrary to previous findings, magnitude of the startle reflex was not found to be modulated depending on the valence of the CS. Central psychophysiological parameters showed little change during differential conditioning. The presence of subjective-evaluative conditioning and contingency awareness without significant changes in cortical and cardiovascular correlates might be due to extremely localized cortical processing of conditioned olfactory cues or primarily subcortical processing. The latter interpretation is strengthened by the presence of differential conditioning in non-voluntary responses such as the corrugator muscles.

Adolescent↗
PubMed2000

Phosphorylation and activation of the endothelial nitric oxide synthase by fluid shear stress.

Fluid shear stress activates the endothelial nitric oxide (NO) synthase (eNOS) by a mechanism which does not require an increase in the intracellular concentration of free Ca2+ ([Ca2+]i), and is sensitive to several kinase inhibitors. Although phosphorylation of eNOS has been suggested to regulate enzyme activity, the mechanism of eNOS activation is still unclear. Here we demonstrate that fluid shear stress elicits the phosphorylation of eNOS on tyrosine and serine residues. Inhibition of phosphatidylinositol 3-kinase (PI3K), using wortmannin or a dominant negative mutant of its downstream target, Akt (protein kinase B), prevented the maintained serine phosphorylation and activation of eNOS. Enhancing eNOS phosphorylation by inhibiting serine/threonine phosphatases, increased eNOS activity by approximately twofold, as assessed by the accumulation of intracellular cyclic GMP, without increasing the intracellular concentration of free Ca2+. These data suggest that shear stress activates a pathway involving PI3K and the serine/threonine kinase Akt, which phosphorylates eNOS. This phosphorylation directly increases eNOS activity at resting [Ca2+]i, thus rendering the shear stress-induced activation of eNOS apparently Ca2+-independent.

Amino Acid Sequence↗
PubMed2000

N-3 polyunsaturated fatty acids do not affect cytokine response to strenuous exercise.

The aim of the present study was to investigate whether fish oil supplementation was able to modulate the acute-phase response to strenuous exercise. Twenty male runners were randomized to receive supplementation (n = 10) with 6.0 g fish oil daily, containing 3.6 g n-3 polyunsaturated fatty acids (PUFA), for 6 wk or to receive no supplementation (n = 10) before participating in The Copenhagen Marathon 1998. Blood samples were collected before the race, immediately after, and 1.5 and 3 h postexercise. The fatty acid composition in blood mononuclear cells (BMNC) differed between the fish oil-supplemented and the control group, showing incorporation of n-3 PUFA and less arachidonic acid in BMNC in the supplemented group. The plasma levels of tumor necrosis factor-alpha, interleukin-6, and transforming growth factor-beta(1) peaked immediately after the run, the increase being 3-, 92-, and 1.1-fold, respectively, compared with resting samples. The level of interleukin-1 receptor antagonist peaked 1.5 h after exercise, with the increase being 87-fold. However, the cytokine levels did not differ among the two groups. Furthermore, supplementation with fish oil did not influence exercise-induced increases in leucocytes and creatine kinase. In conclusion, 6 wk of fish oil supplementation had no influence on the acute-phase response to strenuous exercise.

Adult↗
PubMed2000

Insulin-mediated stimulation of protein kinase Akt: A potent survival signaling cascade for endothelial cells.

Insulin exerts potent antiapoptotic effects in neuronal cells and has been suggested to promote angiogenesis. Therefore, we investigated whether insulin inhibits tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Because insulin has been shown to stimulate the protein kinase Akt, we investigated whether activation of Akt contributes to the apoptosis-suppressive effect of insulin and characterized the downstream signaling pathway. Incubation with insulin dose-dependently prevented apoptosis induced by TNF-alpha (50 ng/mL). The extent of apoptosis suppression by insulin was similar to the effect of vascular endothelial growth factor. Pharmacological inhibition of Akt activation or overexpression of a dominant-negative Akt mutant prevented the antiapoptotic effect of insulin. Furthermore, we investigated the effect of TNF-alpha on Akt phosphorylation by Western blot analysis with the use of a phosphospecific Akt antibody. Incubation of HUVECs with TNF-alpha induced a marked dephosphorylation of Akt. Insulin counteracted this TNF-alpha-induced dephosphorylation of Akt. Furthermore, we investigated the downstream signaling events. Akt has been shown to mediate its apoptosis-suppressive effects via phosphorylation of Bad or caspase-9. However, incubation with insulin did not lead to enhanced phosphorylation of Bad at Ser 136 or Ser 112. In contrast, insulin inhibited caspase-9 activity and prevented caspase-9-induced apoptosis. Mutation of the Akt site within caspase-9 significantly reduced the apoptosis-suppressive effect of insulin. The present study demonstrates an important role for insulin-mediated Akt activation in the prevention of endothelial cell apoptosis, which may importantly contribute to cell homeostasis and the integrity of the endothelium. In endothelial cells, Akt seems to mediate its antiapoptotic effect, at least in part, via phosphorylation of caspase-9 rather than Bad.

Apoptosis↗
PubMed2000

Effect of chronic excess of tumour necrosis factor-alpha on contractile proteins in rat skeletal muscle.

The effect of chronic tumour necrosis factor-alpha (TNF-alpha) treatment on the synthesis of specific myofibrillar proteins such as heavy chain myosin, light chain myosin and G-actin in rat diaphragm were evaluated. Muscles (diaphragm) from control and experimental groups (TNF-alpha i.v. at 50 microg/kg body wt for 5 days) were incubated in the presence of 35S-methionine for 2 h. Myofibrillar protein extracts were prepared and protein was electrophoresed on sodium dodecyl sulphate-polyacrylamide gels. Heavy chain myosin, light chain myosin and G-actin were identified by Western blot analysis using specific monoclonal antibodies. Polyacrylamide gel electrophoresis (PAGE) followed by Western blot analysis revealed two types of heavy chain myosin (206 and 212 kD), all four types of light chain myosin (15, 16.5, 18 and 20 kD) and a single type of G-actin (42 kD). Chronic TNF-alpha treatment produced a significant decline in the synthesis of all types of myofibrillar proteins, namely heavy chain myosin, light chain myosin and G-actin. TNF-alpha impaired peptide-chain initiation in diaphragm muscle which was reversed by the branched-chain amino acids (BCAA) therapy of TNF-alpha treated rats. These findings indicate a significant role for TNF-alpha in the translational regulation of protein synthesis in skeletal muscle.

Actins↗
PubMed1999

Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation.

Nitric oxide (NO) produced by the endothelial NO synthase (eNOS) is a fundamental determinant of cardiovascular homesotasis: it regulates systemic blood pressure, vascular remodelling and angiogenesis. Physiologically, the most important stimulus for the continuous formation of NO is the viscous drag (shear stress) generated by the streaming blood on the endothelial layer. Although shear-stress-mediated phosphorylation of eNOS is thought to regulate enzyme activity, the mechanism of activation of eNOS is not yet known. Here we demonstrate that the serine/threonine protein kinase Akt/PKB mediates the activation of eNOS, leading to increased NO production. Inhibition of the phosphatidylinositol-3-OH kinase/Akt pathway or mutation of the Akt site on eNOS protein (at serine 1177) attenuates the serine phosphorylation and prevents the activation of eNOS. Mimicking the phosphorylation of Ser 1177 directly enhances enzyme activity and alters the sensitivity of the enzyme to Ca2+, rendering its activity maximal at sub-physiological concentrations of Ca2+. Thus, phosphorylation of eNOS by Akt represents a novel Ca2+-independent regulatory mechanism for activation of eNOS.

Androstadienes↗
PubMed1999

Comparison of transarterial and multiple nerve stimulation techniques for axillary block using a high dose of mepivacaine with adrenaline.

BACKGROUND: High-dose transarterial (TA) technique results in high effectiveness of the axillary block. The technique is fast and simple, but does not produce a satisfactory success rate when using the manufacturer's recommended dose of mepivacaine. The multiple nerve stimulation (MNS) technique requires more time and experience. This double-blind study compared effectiveness, safety and the time used to obtain an effective analgesia in 101 patients, having an axillary block by either TA or MNS techniques. METHODS: Mepivacaine with adrenaline (MEPA), 850 mg, was used for the initial block. Five millilitres of 1% solution was injected subcutaneously. In the TA group, 20 mL of 2% solution was injected deep to, and 20 mL superficial to the axillary artery. In the MNS group, four terminal motor nerves were electrolocated in the axilla, and injected with 10 mL each. Analgesia was assessed every 10 min and, when needed, supplemented after 30 min. The block was effective when analgesia was present in all sensory nerve areas distal to the elbow. RESULTS: The MNS group required median 11 min for block performance compared with 8 min for the TA group (P < 0.001). Latency of the initial block was shorter and the frequency of supplemental analgesia lower in the MNS group (median 10 min and 6%) than in the TA group (30 min and 36%, respectively), P < 0.001. All incomplete blocks were successfully supplemented. However, the total time to obtain an effective block was shorter in the MNS group (23 min) than in the TA group (37 min), P < 0.001. Two patients in each group had signs and symptoms of systemic toxicity, the most serious being atrial fibrillation and temporary loss of consciousness in a cardiovascularly medicated patient. The local adverse effects (intravascular injections and haematomas) were fewer in the MNS group, P < 0.001. CONCLUSION: The MNS technique of axillary block by four injections of 10 mL of 2% MEPA produces faster and more extensive block than the TA technique by two injections of 20 mL. Therefore, the MNS technique requires fewer supplementary blocks and results in faster patient readiness for surgery. However, high doses of MEPA may result in dangerous systemic toxic reactions.

Adolescent↗
PubMed1999

Bacterial flora accompanying Candida yeasts in clinical specimens.

From 1986 to 1988, in the prefluconazole era, 67,765 clinical specimens from the Göttingen University Hospital were investigated for bacteria and fungi in our institution. Oral and throat swabs, respiratory secretions, gastric juices, faeces, urine, genital swabs, blood, wound secretions and skin swabs were analysed for yeast-like fungi, and opportunistic or pathogenic bacteria. A total of 5195 specimens (7.7%) yielded Candida spp. alone or in combination with bacteria (fungal (F-) group) and 62,570 specimens yielded bacteria only or remained sterile (non-fungal group, N-group). Elevated rates of accompanying bacteria were detected with Candida spp. colonizing blood, urine, and skin. Among the dominant bacterial isolates, the distribution of staphylococci and enterococci did not reflect a distinct association pattern. Among the enterobacterial isolates from patients in intensive care, colonization patterns of the throat, gastric juices, and faeces reflected the use of a selective decontamination of the digestive tract (SDD). A statistically significant association between Candida and enterobacteria of the genus Enterobacter which was unaffected by SDD, was observed throughout this study. Such an association pattern was also observed, to a lesser extent, with the related genera Klebsiella and Serratia, but not with Escherichia coli.

Bacteria↗
PubMed1999

Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions.

Twenty-four healthy male volunteers received either placebo or 75, 150, or 300 microg filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) for 12 days to study effects on monocytes and lymphocytes. In all filgrastim-treated groups, tumor necrosis factor alpha (TNF-alpha), interleukin-12 (IL-12), and interferon gamma (IFN-gamma) release by whole blood in response to endotoxin (lipopolysaccharide) was reduced. IL-12 added in vitro to lipopolysaccharide-stimulated blood of filgrastim-treated donors restored IFN-gamma and TNF-alpha release, suggesting that the anti-inflammatory effect of granulocyte colony-stimulating factor is exercised through IL-12 suppression. Phytohemagglutinin- or anti-CD3 antibody-induced lymphocyte proliferation ex vivo was reduced by 60% from day 5 to day 15, after a 50% increase at day 2 with concomitant doubled IL-2 release. In vivo, filgrastim induced doubling of all T-cell populations by day 8. Filgrastim decreased proinflammatory cytokine production and lymphocyte proliferation ex vivo throughout prolonged treatment at all doses. This indicates that endogenous granulocyte colony-stimulating factor may counterregulate the inflammatory cytokine cascade and implies a potential indication for filgrastim in chronic inflammatory conditions.

Adult↗
PubMed1999

Upregulation of superoxide dismutase and nitric oxide synthase mediates the apoptosis-suppressive effects of shear stress on endothelial cells.

Physiological levels of laminar shear stress completely abrogate apoptosis of human endothelial cells in response to a variety of stimuli and might therefore importantly contribute to endothelial integrity. We show here that the apoptosis-suppressive effects of shear stress are mediated by upregulation of Cu/Zn SOD and NO synthase. Shear stress-mediated inhibition of endothelial cell apoptosis in response to exogenous oxygen radicals, oxidized LDL, and tumor necrosis factor-alpha was associated with complete inhibition of caspase-3-like activity, the central effector arm executing the apoptotic cell death program in endothelial cells. Shear stress-dependent upregulation of Cu/Zn SOD and NO synthase blocks activation of the caspase cascade in response to apoptosis-inducing stimuli. These findings establish the upregulation of Cu/Zn SOD and NO synthase by shear stress as a central protective cellular mechanism to preserve the integrity of the endothelium after proapoptotic stimulation.

Antisense Elements (Genetics)↗
PubMed1999

[Lower leg compartment syndrome after prolonged gynecologic surgeries in lithotomy position].

OBJECTIVE: How to prevent severe complications of lower leg compartment syndrome following gynecologic operations in the lithotomy position? MATERIAL AND METHODS: Two cases of lower leg compartment syndrome following long lasting gynecologic operations are presented. RESULTS: Early diagnosis by clinical signs, measurement of compartment pressure and creatine kinase activity and undelayed surgical intervention can avoid acute renal failure due to rhabdomyolysis and damage of neuromuscular function. CONCLUSIONS: Early diagnosis and undelayed surgical intervention can prevent severe complications of lower leg compartment syndrome following gynecologic operations in the lithotomy position.

Adult↗