Search PubMed⌕ Search

Biomedical subjects

C Schott

Publications and source records attributed to C Schott.

At least 19 recordsLinked to original sources
PubMed2000

Vascular bed heterogeneity in age-related endothelial dysfunction with respect to NO and eicosanoids.

1. Endothelial dysfunction has been described with ageing but the mechanisms responsible have not been clearly elucidated and might be different from one vessel to the other. This study assesses the relative contribution of endothelial nitric oxide (NO) and cyclo-oxygenase (COX) metabolites in relaxation to acetylcholine with ageing in the aorta and the small mesenteric artery of the rat. 2. In the aorta and branch II or III of superior mesenteric artery (SMA), endothelium-dependent relaxation to acetylcholine was not different between 12 - 14 (adult) and 32-week-old rats whereas it was reduced at 70 - 100 (old) weeks of age. 3. Despite an increased endothelial NO-synthase protein expression, the NO-synthase inhibitor, N(G)-nitro-L-arginine-sensitive component of relaxation decreased with ageing. 4. In old rats, exposure to the COX inhibitor, indomethacin, but not the selective COX-2 inhibitor, NS-398, potentiated response to acetylcholine. The thromboxane A(2)/prostaglandin H(2) receptor antagonist, GR 32191B enhanced relaxation to acetylcholine in aorta but it had no effect in SMA. Furthermore, acetylcholine increased thromboxane B(2) production (enzymeimmunoassay) in aorta but not in SMA. Finally, Western blot analysis showed enhanced expression of COX-1 and 2 in the two arteries with ageing. 5. These results suggest that the decrease in acetylcholine-induced relaxation with ageing involves reduced NO-mediated dilatation and increased generation of vasoconstrictor prostanoids most likely from COX-1. They also point out vascular bed heterogeneity related to the nature of prostanoids involved between the aorta (i.e., thromboxane A(2)) and the SMA (unidentified) arteries even though increased expression of COX occurs in both vessels.

Acetylcholine↗
PubMed2000

Immunomodulatory effects of acupuncture in the treatment of allergic asthma: a randomized controlled study.

OBJECTIVE: According to Traditional Chinese Medicine (TCM) acupuncture is a suitable treatment for complex chronic diseases such as bronchial asthma. In a randomized, controlled study we investigated immunologic effects of Chinese acupuncture on patients with allergic asthma. PATIENTS AND METHODS: The effects of acupuncture treatment given according to the principles of TCM (TCM group, n = 20) were compared with those of acupuncture treatment using points not specific for asthma (control group, n = 18). All patients were treated 12 times for 30 minutes over a time period of 4 weeks. Patients' general well-being and several peripheral blood parameters (eosinophils, lymphocyte subpopulations, cytokines, in vitro lymphocyte proliferation) were determined before and after acupuncture treatment. RESULTS: In the TCM group, significantly more patients indicated an improvement in general well-being (79% in the TCM group versus 47% in the control group; p = 0.049) after acupuncture treatment. The following changes were found in the TCM group: within the lymphocyte subpopulations the CD3+ cells (p = 0.005) and CD4+ cells (p = 0.014) increased significantly. There were also significant changes in cytokine concentrations: interleukin (IL)-6 (p = 0.026) and IL-10 (p = 0.001) decreased whereas IL-8 (p = 0.050) rose significantly. Additionally, the in vitro lymphocyte proliferation rate increased significantly (p = 0.035) while the number of eosinophils decreased from 4.4% to 3.3% after acupuncture (p > 0.05). The control group, however, showed no significant changes apart from an increase in the CD4+ cells (p = 0.012). CONCLUSION: The results imply that asthma patients benefit from acupuncture treatment given in addition to conventional therapy. Furthermore, acupuncture performed in accordance with the principles of TCM showed significant immune-modulating effects.

Acupuncture Therapy↗
PubMed2000

Age-related endothelial dysfunction with respect to nitric oxide, endothelium-derived hyperpolarizing factor and cyclooxygenase products.

Vascular aging is associated with both structural and functional changes that can take place at the level of the endothelium, vascular smooth muscle cells and the extracellular matrix of blood vessels. With regard to the endothelium, reduced vasodilatation in response to agonists occurs in large conduit arteries as well as in resistance arteries with aging. Reviews concerning the different hypotheses that may account for this endothelial dysfunction have pointed out alterations in the equilibrium between endothelium-derived relaxing and constricting factors. Thus, a decreased vasorelaxation due to nitric oxide and, in some arteries, endothelium-derived hyperpolarizing factor as well as an increased vasoconstriction mediated by cyclooxygenase products such as thromboxane A2 are likely to occur in age-induced impairment of endothelial vasodilatation. Furthermore, enhanced oxidative stress plays a critical role in the deleterious effect of aging on the endothelium by means of nitric oxide breakdown due to reactive oxygen species. The relative contribution of the above phenomenon in age-related endothelial dysfunction is highly dependent on the species and type of vascular bed.

Acetylcholine↗
PubMed1999

Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility.

A major function of the cell-to-cell adhesion molecule E-cadherin is the maintenance of cell adhesion and tissue integrity. E-cadherin deficiency in tumours leads to changes in cell morphology and motility, so that E-cadherin is considered to be a suppressor of invasion. In this study we investigated the functional consequences of three tumour-associated gene mutations that affect the extracellular portion of E-cadherin: in-frame deletions of exons 8 or 9 and a point mutation in exon 8, as they were found in human gastric carcinomas. Human MDA-MB-435S breast carcinoma cells and mouse L fibroblasts were stably transfected with the wild-type and mutant cDNAs, and the resulting changes in localization of E-cadherin, cell morphology, strength of calcium-dependent aggregation as well as cell motility and actin cytoskeleton organization were studied. We found that cells transfected with wild-type E-cadherin showed an epitheloid morphology, while all cell lines expressing mutant E-cadherin exhibited more irregular cell shapes. Cells expressing E-cadherin mutated in exon 8 showed the most scattered appearance, whereas cells with deletion of exon 9 had an intermediate state. Mutant E-cadherins were localized to the lateral regions of cell-to-cell contact sites. Additionally, both exon 8-mutated E-cadherins showed apical and perinuclear localization, and actin filaments were drastically reduced. MDA-MB-435S cells with initial calcium-dependent cell aggregation exhibited decreased aggregation and, remarkably, increased cell motility, when mutant E-cadherin was expressed. Therefore, we conclude that these E-cadherin mutations may not simply affect cell adhesion but may act in a trans-dominant-active manner, i.e. lead to increased cell motility. Our study suggests that E-cadherin mutations affecting exons 8 or 9 are the cause of multiple morphological and functional disorders and could induce the scattered morphology and the invasive behaviour of diffuse type-gastric carcinomas.

Actins↗
PubMed1999

Induction of nitric oxide synthase and dual effects of nitric oxide and cyclooxygenase products in regulation of arterial contraction in human septic shock.

BACKGROUND: The role of endogenous nitric oxide (NO) and cyclooxygenase metabolites was investigated in contractile responses of small omental arteries from patients with hyperdynamic septic shock. METHODS AND RESULTS: Expression of inducible NO synthase (immunostaining) and a high but variable level of NO production (NO spin trapping) was detected in arteries from patients with septic shock. In these vessels, ex vivo contractile responses to the thromboxane A2 analogue U46619 and to low concentrations of norepinephrine (NE) (up to 10 micromol/L) were not significantly different from controls. However, higher concentrations of NE caused pronounced fading of contraction in septic but not in nonseptic arteries. Exposure to either the NO synthase inhibitor NG-nitro-L-arginine methyl ester or the cyclooxygenase inhibitor indomethacin had no effect in control vessels. However, both inhibitors increased the response to the contractile effects of the 2 agonists only in patients with septic shock. In contrast to NG-nitro-L-arginine methyl ester, which decreased the threshold concentration of the fading effect of NE, indomethacin abolished this effect in arteries from septic patients. CONCLUSIONS: These results provide direct evidence for the induction of NO synthase in small arteries from patients with septic shock. They suggest that in these arteries, increased production of NO, in conjunction with vasodilatory cyclooxygenase metabolites, contributes to counteract hyperreactivity to agonists and decreases the cyclooxygenase product-mediated pronounced fading of contraction caused by a high concentration of NE.

Adult↗
PubMed1999

Identification of eleven novel tumor-associated E-cadherin mutations. Mutations in brief no. 215. Online.

The cell adhesion molecule E-cadherin (CDH1; MIM# 192090) has been implicated in numerous cellular functions, ranging from controlling morphogenesis to suppressing tumor invasion. We describe 11 previously unreported somatic E-cadherin mutations in two subgroups of gastric and breast cancer showing markedly reduced homophilic cell-to-cell interactions. Using reverse transcription-polymerase chain reaction (RT-PCR) and direct sequencing of the entire coding region 5 mutations were detected in diffuse-type gastric cancer specimens. The sequence alterations include 3 missense mutations affecting exons 3, 10, and 12. Furthermore, two in-frame deletions were identified removing 63 and 9 base pairs from exon 4 and 5, respectively. In invasive Lobular breast cancer 6 E-cadherin mutations were detected after RT-PCR amplification and direct sequencing or using single strand conformation polymorphism (SSCP) analysis followed by sequencing. In addition to two nonsense mutations affecting exon 2, four out-of-frame deletions removing 115 base pairs (entire exon 2), 224 base pairs (entire exon 3), 8 base pairs from exon 12 or 1 base pair from exon 13 were seen. Our report confirms the general principle that in diffuse-type gastric cancer E-cadherin mutations result in structurally altered proteins with possible reduced adhesive functions whereas in invasive lobular breast carcinomas complete loss-of-function mutations are characteristic.

Breast Neoplasms↗
PubMed1999

[Modification of bacterial growth by alloplastic bone substitutes].

BACKGROUND: To determine the applicability of alloplastic materials as bone substitutes it is now standard procedure to test materials for possible toxic effects and to study their behavior in animal models and cell cultures. This is especially important with respect to middle ear implants that can be put at risk by recurrent infections and require additional testing in a bacterially contaminated environment. MATERIALS AND METHODS: In the present study ionomeric cement (V-O CEM), bioactive glass ceramic and hydroxyapatite were subjected to contamination with S. aureus, E. coli, Pr. mirabilis, Ps. aeruginosa and Enterococci using agar diffusion and microbial suspension tests and examined for their antibacterial activity. A special feature of V-O CEM that had to be considered was that it could be implanted in two physical states (as a viscous substance and a fully hardened material). RESULTS: The agar diffusion test showed that an antibacterial effect of freshly mixed V-O CEM was demonstrable for up to 60 min. In the microbial suspension test growth of E. coli was found to be promoted after 48-h incubation by V-O CEM set for 1 h. S. aureus exhibited a depressed growth, while Pseudomonas cultures demonstrated cell death after 48 h. V-O CEM set for 24 h and 7 days, respectively, exerted a similar though less pronounced effect. Using the microbial suspension test, a comparison was also made of the antibacterial activities of 24-h V-O CEM, bioactive glass ceramic and hydroxyapatite against cultures of S. aureus, Pseudomonas and E. coli. The inhibitory effect of hydroxyapatite on the growth of S. aureus was found to persist beyond the 48-h incubation period. There was slight growth of E. coli in the presence of bioactive glass ceramic after 48 h, whereas hydroxyapatite produced inhibition of microbial growth. V-O CEM inhibited the growth of Pseudomonas, unlike bioactive glass ceramic and hydroxyapatite, which transiently promoted bacterial growth. DISCUSSION AND CONCLUSIONS: Our findings showed that V-O CEM, bioactive glass ceramic and hydroxyapatite exhibited material-dependent bacterial colonization and thus resembled polymeric bone substitutes (susceptible to invasion by S. epidermidis) and metals (sensitive to S. aureus). In general, users of bone substitutes should conduct preclinical tests in order to obtain advance information on the properties of possible replacement material. Since there can be varying interactions between the materials studied and bacterial growth, material-specific effects on bacterial growth should be investigated. While it is recognized that in vitro studies are an inadequate simulation of the clinical situation, they still provide some insight into the likely behavior of a bone substitutes in human sites.

Bacteriological Techniques↗
PubMed1998

Role of adventitial nitric oxide in vascular hyporeactivity induced by lipopolysaccharide in rat aorta.

This study was designed to elucidate the role of the adventitia in NO-mediated vascular effects of lipopolysaccharide (LPS). After incubation of rat aorta with LPS, the adventitia generated 3.5 times more nitrite plus nitrate than a corresponding segment of media. Control media covered by adventitia from LPS-treated aortic rings exhibited a 4 fold elevated level of cyclic GMP. Medial layers from LPS-treated aortic rings (like LPS-treated adventitia-intact rings) exhibited a decrease in sensitivity to noradrenaline (NA) that was reversed by 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (1 microM) or N omega-nitro-L-arginine methylester (0.3 mM). However, in contrast to LPS-treated adventitia-intact rings, medial layers showed no reduction in maximal contraction to NA and virtually no relaxation to L-arginine. These data indicate that in blood vessels exposed to LPS, the adventitia is a more powerful source of NO than the media. The adventitia-derived NO can reach soluble guanylyl cyclase in the medial layer and contribute greatly to vascular hyporeactivity and L-arginine-induced relaxation observed in blood vessels exposed to LPS.

Animals↗
PubMed1995

Increase in serum NG-hydroxy-L-arginine in rats treated with bacterial lipopolysaccharide.

Aortic rings isolated from rats 4 h after an injection i.p. of 30 mg/kg Escherichia coli lipopolysaccharide showed a marked hyporeactivity to noradrenaline. This effect was paralleled by an increase in the level of nitrite/nitrate in the serum of lipopolysaccharide-treated rats, indicative of an enhanced nitric oxide (NO) synthase activity. Most important, however, the serum concentration of the NO synthase intermediate, NG-hydroxy-L-arginine, was also markedly elevated from 3.7 to 15.8 microM. Circulating NG-hydroxy-L-arginine may thus represent a sensitive and specific marker of NO synthase activity in vivo.

Amino Acid Oxidoreductases↗
PubMed1995

Effects of losartan on contractile responses of conductance and resistance arteries from rats.

We investigated the selectivity of losartan as an angiotensin II (ANG II) antagonist in contractile experiments using segments of small mesenteric arteries and rings of aorta from rat. The concentration-effect curve of ANG II was not different in mesenteric arteries with an without endothelium. In both resistance and conductance vessels, it was shifted toward larger concentrations by losartan (3 nM) with similar apparent inhibition constant (KB) values: 4.1 +/- 1.8 nM (n = 6) in small mesenteric arteries and 1.9 nM (n = 6) in aorta. These values agree with the known affinity of losartan for AT1 receptors. At 1 microM, the AT2-selective ligand CGP 42112A had no effect on contractile responses induced by norepinephrine (NE), serotonin, or neuropeptide Y (NPY). However, it inhibited vasoconstriction elicited by prostaglandin F2 alpha (PGF2 alpha). This latter effect was also noted in the aorta. Similarly, losartan also competitively antagonized aortic contractile responses elicited by U 46619, a thromboxane A2 analogue (TXA2), with a pA2 value of 5.7. Two losartan analogues, DuP 532 and EXP 3174 (a metabolite of losartan), < or = 30 microM, did not antagonize U 46619, showing structural requirements for this antagonistic action of losartan. We conclude that in both rat resistance and conductance vessels, ANG II induces vasoconstriction through activation of AT1 receptors which are selectively blocked by losartan at nanomolar concentrations and that at micromolar concentrations, losartan may also block the vascular TXA2/PGF2 alpha (TP) receptor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Temporal relationships between levels of circulating NO derivatives, vascular NO production and hyporeactivity to noradrenaline induced by endotoxin in rats.

OBJECTIVE: Lipopolysaccharide (LPS) induces early (within 1 h) and delayed (after several hours) impairment of vascular reactivity to catecholamines whose mechanisms are different, although they probably both involve nitric oxide (NO). Temporal and quantitative relationships between hyporeactivity to noradrenaline and NO production were investigated in a rat model of endotoxaemia allowing to clearly distinguish the two phases of hyporeactivity. METHODS: Anaesthetised rats were infused with LPS (14 mg kg-1 h-1) for 1 h. Pressure responses to noradrenaline (NA) and circulating NO derivatives (nitrosyl haemoglobin, NO2-, NO3-) were monitored for 5 h after the onset of infusion. Reactivity to NA and tissue cyclic GMP level were also assessed ex vivo, in aortic rings taken at different experimental times. RESULTS: LPS-induced early hyporeactivity to NA was associated with a moderate but significant increase in plasma NO3- level, without any significant change in concentration of the other circulating NO derivatives. Neither reactivity ex vivo nor cyclic GMP content were modified in aortae taken after 1 h of LPS infusion. By contrast, delayed hyporeactivity (5 h after the onset of LPS infusion) was associated with a large increase in all circulating NO derivatives (up to 2.5 fold), enhanced aortic cyclic GMP level and aortic hyporeactivity ex vivo. Pre-treatment of rats with NG-nitro-L-arginine methyl ester (1 mg kg-1 i.v.) entirely prevented early hyporeactivity and rise in NO3- concentration. In addition it attenuated in comparable proportion both delayed hyporeactivity to NA in vivo and circulating levels of NO derivatives. CONCLUSION: The results confirm the involvement of NO in the two phases of hyporeactivity to NA induced by LPS. They strongly support the view that a circulating factor is involved in triggering endothelial NO release during the early phase, whereas the delayed phase is associated with a high production of NO in vascular smooth muscle resulting from the induction of NO synthase.

Animals↗
PubMed1994

Effect of bacterial lipopolysaccharide on function of rat small femoral arteries.

The effects of endotoxin on endothelial and smooth muscle function were investigated in small femoral arteries removed from rats 4 h after intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS; 20 mg/kg) or solvent. In the absence of L-arginine in the organ bath, the sensitivity of the arteries to norepinephrine (NE) was decreased only slightly, and the relaxing effects of neither 3-morpholinosydonimine-N-ethyl-carbamide (SIN-1), a nitric oxide (NO) donor, nor acetylcholine (ACh) were modified by LPS treatment despite morphological damage to the endothelium seen with scanning electron microscopy. However, L-arginine (30 microM to 1 mM), which had no effect on control vessels, caused a rapid and stereospecific relaxation of arteries from LPS-treated rats that was abolished by both NG-nitro-L-arginine methyl ester (1 mM), a NO synthase inhibitor, and methylene blue, an inhibitor of the activation of guanylyl cyclase by NO. The relaxing effect of L-arginine was observed in the absence of endothelium, although it was significantly greater in its presence. In addition, a 30-min exposure to extracellular L-arginine (100 microM) moderately but significantly decreased the sensitivity to ACh and SIN-1 of vessels from LPS-treated but not from control rats. These results indicate that LPS treatment induced a NO synthase activity in smooth muscle cells of rat small femoral arteries and that the resulting relaxation was dependent on extracellular L-arginine in these resistance vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

ANG II receptor expression and function during phenotypic modulation of rat aortic smooth muscle cells.

Angiotensin II (ANG II) receptors were investigated in primary cultured rat aortic smooth muscle cells (SMC) that expressed either a proliferative phenotype (during the growth phase) or a contractile phenotype (at postconfluence). For each phenotype, alpha-smooth muscle actin expression, 125I-labeled ANG II specific binding, D-myo-inositol 1,4,5-triphosphate [Ins(1,4,5)P3] production, and ANG II-mediated increases in intracellular calcium (Cai2+) were studied. In both phenotypes, 1) ANG II-specific high-affinity binding (KD 0.5 +/- 0.1 nM and Bmax 196 +/- 106 pmol/mg protein in proliferative state, KD 1.5 +/- 0.3 nM and Bmax 560 +/- 299 pmol/mg protein in postconfluent state) was entirely inhibited by the selective AT1-antagonist losartan as well as by [Sar1,Ala8]ANG II and ANG III; 2) the AT2-antagonist CGP 42112A was ineffective, except at very high concentrations (> or = 10 microM); 3) the specific binding of ANG II was inhibited by guanosine 5'-[gamma-thio]triphosphate; and 4) ANG II induced a losartan-sensitive increase in Ins(1,4,5)P3. In postconfluent cultures, ANG II elicited a rapid biphasic elevation in Cai2+, which was abolished by losartan, whereas in growing cultures, this response was either absent or greatly attenuated. It is concluded that AT1-receptors coupled to phospholipase C via a G protein are expressed in the proliferative as well as in the contractile SMC phenotype and that their coupling to Cai2+ release is impaired in the proliferative phenotype. No evidence for AT2-receptor expression during phenotypic modulation of SMC was found.

Actins↗
PubMed1993

Vascular relaxation and cyclic guanosine monophosphate in a rat model of high output heart failure.

OBJECTIVE: Low output heart failure induces abnormalities of endothelium dependent vasodilation, but the mechanisms responsible for this remain unclear. As blood flow can alter endothelial cell function, in particular nitric oxide (NO) release, the activity of endothelium derived relaxing factor (EDRF) was investigated in a rat model of high output heart failure. METHODS: The thoracic aorta upstream of an aorto-caval fistula in rats was submitted to hormonal changes (similar to those in heart failure) and to high blood flow (opposite to that found in low output heart failure). Functional and biochemical arterial properties were studied in aorto-caval fistula rats and in sham operated rats three months after operation. The vascular responses were studied by exposing aortic segments from fistula and sham operated rats to increasing concentrations of agonists. Aortic cyclic guanosine monophosphate (cGMP) concentration was assessed as an index of NO synthase activity. The effect of NO synthase blockade on functional and biochemical arterial properties was also studied. RESULTS: Plasma atrial natriuretic factor (ANF) was increased in fistula rats compared to sham operated rats. The concentrations of acetylcholine or the calcium ionophore A23187 required to produce 10% and 50% maximum relaxation (EC10 and EC50) were similar in the two groups. Relaxation in response to low concentrations of Sin-1 (an NO donor) was shifted rightwards in fistula rats and EC10 was greater than in the controls. The aortic cGMP concentration was higher in aorto-caval fistula rats than in sham operated rats (p = 0.008). The differences between aorto-caval fistula rats and sham operated rats were probably the result of increased basal EDRF-NO release in the former, since NO synthase blockade abolished the differences in both aortic cGMP and the dose-response curve to Sin-1. CONCLUSIONS: The arterial wall upstream of a chronic aorto-caval fistula has increased cGMP content and hyposensitivity to Sin-1, which may be due to enhanced basal EDRF-NO release. These changes, strikingly different from those found in the low output heart failure, suggest that haemodynamic rather than neuroendocrine factors play a determinant role in the altered vasodilator response in heart failure.

Acetylcholine↗
PubMed1992

L-arginine induces relaxation of small mesenteric arteries from endotoxin-treated rats.

The effect of arginine (Arg) was studied on norepinephrine- (1 microM) precontracted small mesenteric arteries removed from rats treated with E. coli lipopolysaccharide (LPS). The addition of L- (but not D-) Arg (1 mM) relaxed, within 3 min, the small mesenteric arteries from LPS-treated but not from control rats, the maximal relaxation (65.3 +/- 11%) being reached with less than 100 microM L-Arg. NG-Nitro-L-arginine methyl ester (1 mM) and methylene blue (10 microM) restored contractions to the level reached before addition of L-Arg. These results show that LPS induces the production of an L-Arg-derived, nitric oxide-like, relaxing factor in small mesenteric arteries.

Animals↗