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K Schauenstein

Publications and source records attributed to K Schauenstein.

At least 37 records · Page 2Linked to original sources
PubMed1999

N-acetylserotonin is a better extra- and intracellular antioxidant than melatonin.

Both melatonin and its precursor N-acetylserotonin have been reported to exert antioxidant properties both in vitro and in vivo. Since little is known about their antioxidant activity in lymphocytes, we investigated their effects on spontaneous and on oxidant-induced reactive oxygen species formation in human peripheral blood lymphocytes in comparison to the antioxidant trolox, a water-soluble analogue of alpha-tocopherol. Both melatonin and N-acetylserotonin exhibited antioxidant properties against t-butylated hydroperoxide- and diamide-induced reactive oxygen species formation in peripheral blood lymphocytes. N-acetylserotonin turned out to be about three times more effective than melatonin. In resting cells, the intracellular reactive oxygen species concentration was only decreased by N-acetylserotonin and trolox, melatonin had no effect. In t-butylated hydroperoxide-mediated cell death, N-acetylserotonin was as effective as trolox in protecting peripheral blood lymphocytes from cell death and required 10-fold lower concentrations than melatonin. Furthermore, in an aqueous cell-free solution, the capacity of N-acetylserotonin to scavenge peroxyl radicals was much higher than that of melatonin. These results clearly indicate N-acetylserotonin to be a much better antioxidant than melatonin.

Adult↗
PubMed1999

Norepinephrine stimulates in vitro growth but does not increase pathogenicity of Salmonella choleraesuis in an in vivo model.

Norepinephrine stimulates growth of Escherichia coli, Yersinia enterocolitica, and Pseudomonas aeruginosa in serum-supplemented media, and in vivo increases in norepinephrine may be important in the pathogenesis of sepsis by gram-negative bacteria. Because salmonellosis often is associated with stress, the effects of norepinephrine on in vitro growth, and in vivo pathogenicity of the swine pathogen Salmonella choleraesuis were investigated. When RPMI 1640 with and without pig serum was inoculated with fewer than 100 S. choleraesuis/ml and incubated overnight, bacterial numbers were 10(4) to 10(6) lower in RPMI containing serum. Norepinephrine restored bacterial growth in RPMI with serum to normal levels, but it did not increase growth in serum-free RPMI. Similar results were obtained with SAPI, a nutrient-poor medium previously used to study the effect of norepinephrine on growth of gram-negative bacteria. Conditioned media were produced by growing S. choleraesuis in RPMI containing serum with and without norepinephrine and filter sterilizing. Conditioned medium produced with norepinephrine stimulated growth of S. choleraesuis but not E. coli, whereas conditioned medium produced without norepinephrine stimulated growth of both bacteria. To determine the in vivo effects of norepinephrine, rats were implanted with tablets that secrete norepinephrine for 20 to 24 hours or with identical tablets without norepinephrine and infected intraperitoneally with graded doses of S. choleraesuis. The LD-50 of S. choleraesuis was the same in both groups, and norepinephrine did not affect the carrier rate at 30 days after infection. We concluded that although norepinephrine stimulates in vitro growth of S. choleraesuis in serum-based media, the increase in norepinephrine levels in the present in vivo system was probably not sufficient to influence the pathogenesis of S. choleraesuis infection.

Animals↗
PubMed1999

Early rheumatoid arthritis is associated with diminished numbers of TH1 cells in stimulated peripheral blood.

Rheumatoid arthritis (RA) has been associated with an altered TH1/TH2 balance. Here we present first results with a technique to quantitate stimulated TH1 and TH2 subsets in whole blood by means of cytofluorimetric detection of intracytoplasmic TH1 and TH2 cytokines. A group of 10 patients suffering from initial stages of RA exhibited a significantly reduced percentage of TH1 cells (11.0 +/- 2.0%) in the peripheral blood as compared to 13 healthy, age matched controls (28.8 +/- 2.0%). The TH2 response, as determined by intracellular expression of IL-4, remained unchanged. The data may indicate a defect in the TH0-TH1 differentiation or/and a selective trapping of TH1 cells into the affected joints.

Adult↗
PubMed1999

The IgG1/G2 subclass shift--a sensitive, tissue non-specific marker for malignancy. Diagnostic performance with squamous cell carcinoma of the head and neck.

A significant decrease in %IgG1 accompanied by an increase in %IgG2 in total serum IgG has been previously reported as a highly sensitive marker for detecting early stages of carcinomas of various localizations. Here we investigated the question as to whether this phenomenon is also observed in sera of patients with squamous cell carcinoma of the head-neck region (SCC-HN), and to evaluate its diagnostic performance in the post-operative monitoring. Using quantitative affinity chromatography, serum concentrations of IgG1, IgG2 and total IgG were determined in 81 patients with different stages of primary and untreated SCC-HN, in 51 SCC-HN patients in post-therapeutical follow up, and in 33 patients with organ matched benign diseases. The data were compared with a total of 174 healthy controls. It was found that (i) 105 SCC-HN patients exhibited a mean value of 56.0 +/- 0.7% IgG1, which likewise differed from healthy controls (63.2 +/- 0.5) and benign diseases (61.5 +/- 1.0) with P < 0.0005, (ii) sensitivities and specificities for discriminating primary malignancies from healthy controls were 70 and 74% respectively, and from benign diseases 65 and 76%, (iii) highest sensitivities and specificities were observed with post-therapeutic cases suffering from tumour recurrence (88% and 75%) or patients with distant metastases (87% and 86%), (iv) apparently tumour-free post-therapeutic patients showed a mean %IgG1 not different from the normal value. The decrease in %IgG1 accompanied by increased %IgG2 is an efficient, sensitive and early marker of SCC-HN, which appears particularly useful for the post-therapeutic monitoring.

Aged↗
PubMed1999

Decreased melatonin synthesis in patients with coronary artery disease.

AIMS: Decreased night-time plasma levels of melatonin were recently reported in patients with coronary artery disease, and it was postulated that melatonin production may be impaired, due to a lack of synthesizing enzymes. However, since artefacts possibly influencing the release pattern were not taken into account, this interpretation was strongly criticized. We therefore carefully investigated night-time melatonin production in patients with coronary artery disease using an appropriate experimental approach. Furthermore, we examined the effect of beta-blockers, a frequently used drug in coronary artery disease therapy. METHODS AND RESULTS: Forty-eight male patients with angiographically documented severe coronary artery disease, 24 of them taking beta-blockers daily in therapeutic dosages, were included. Eighteen age-matched men, with no evidence of coronary sclerosis, served as controls. To determine melatonin production, 6-sulfatoxymelatonin (aMT6s) was measured radioimmunologically from overnight urine. Urinary aMT6s concentration was significantly decreased in patients, and beta-blocker treatment did not further suppress melatonin production. CONCLUSIONS: The data obtained using this investigative approach provide clearcut evidence that melatonin production in patients with coronary artery disease is decreased. Whether a decreased melatonin level may be a predisposing factor for coronary artery disease, or whether the occurrence of coronary artery disease decreases melatonin synthesis remains to be determined.

Adrenergic beta-Antagonists↗
PubMed1999

Long-term follow-up of cytokines and soluble cytokine receptors in peripheral blood of patients with juvenile rheumatoid arthritis.

Plasma levels of interleukin-1beta (IL-1beta), IL-2, soluble IL-2 receptor (sIL-2R), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and the p60 soluble TNF receptor (sTNFR) were repeatedly determined by enzyme-linked immunosorbent assays (ELISA) in 35 patients with different subtypes of juvenile rheumatoid arthritis (JRA) during an observation period of up to 36 months. The data were related to conventional inflammatory parameters and disease activity. Patients with systemic disease showed the most pronounced elevations of plasma cytokines, followed by polyarticular and pauciarticular JRA. Soluble receptors sIL-2R and sTNFR were consistently elevated in patients of all JRA subtypes and indicated disease activity even in patients with normal C-reactive protein (CRP). In contrast, the determination of IL-1beta, IL-2, IL-8, and TNF-alpha revealed strikingly different individual profiles in patients of the same clinical subtype of JRA and irrespective of disease activity. It is concluded that the determination of sIL-2R and sTNFR may be relevant for monitoring JRA, as they indicate disease activity also in cases with unaltered conventional inflammatory parameters. The different individual cytokine profiles of patients within identical subtypes of disease suggest JRA to be even more heterogeneous than hitherto assumed. The data should be considered in attempts to develop anticytokine strategies in the therapy of JRA.

Adolescent↗
PubMed1998

Nervousness and pain sensitivity: I. A positive correlation.

Neuroanatomical studies suggest a close interrelationship between brainstem centers regulating arousal and pain sensitivity. Nervousness, as assessed with a Visual Analog Scale, and pain sensitivity, as assessed with a cold pressor test, were used to clarify whether a physiological association of nervousness and pain sensitivity can be found in healthy subjects. Forty healthy volunteers were included in the study. We demonstrate a significant positive correlation between self-rated nervousness and pain threshold. These data suggest that there is a coupling between nervousness and endogenous pain control. Based on the results, a nervousness-pain-threshold quotient was calculated as a possible measure of the interrelationship of the endogenous pain control system to autonomic activity. A different nervousness-pain-threshold quotient, indicating a different coupling, may provide information on changes in accessory neurophysiologic functions.

Adult↗
PubMed1998

Nervousness and pain sensitivity: II. Changed relation in ex-addicts as a predictor for early relapse.

We recently demonstrated a coupling between nervousness and pain sensitivity in healthy volunteers, and we defined a mean ratio of nervousness/log pain threshold of 1.95 +/- 1.47 for healthy humans. Because in another study former opiate addicts were found to exhibit a persistent opioid independent analgesia, we wondered whether nervousness is also changed in these patients, or if the balance between nervousness and pain sensitivity is altered. Forty unmedicated former opiate addicts during long-term rehabilitation and 40 age-matched control subjects were included in the study. The subjects rated their nervousness prior to a cold pressor test on a Visual Analog Scale. It turned out that the average nervousness rating was higher than in the control subjects and that a distinct subgroup of pain sensitive ex-addicts exhibited a higher ratio of nervousness vs. pain threshold. In this group the risk for relapse was three to four times higher than in the other ex-addicts.

Adult↗
PubMed1998

Cytokines in juvenile rheumatoid arthritis (JRA).

Juvenile rheumatoid arthritis (JRA), unlike rheumatoid arthritis of adulthood (RA), is a heterogenous disease comprising at least five subtypes that differ in clinical course and prognosis, and require different therapeutical approaches. As compared to RA, the production of local and systemic cytokines in JRA have not yet been as extensively investigated. In this article we review the available literature on cytokine expression in serum and synovial fluid in all five different subtypes of JRA. Even though the data are still fragmentary, the evidence so far suggests that the determination of serum cytokines yields relevant information as to clinical subtype and inflammatory activity of the disease. Furthermore, the cytokine data suggest that the pathogenesis of JRA may even by more heterogenous than defined by the clinical subtypes. Finally, future directions of research in this area are proposed, and-based on the latest results-arguments for (anti)cytokine therapies in JRA are critically discussed.

Arthritis, Juvenile↗
PubMed1998

Lack of calmodulin antagonism of melatonin in T-lymphocyte activation.

Despite various reported effects of the pineal hormone melatonin on the immune system, its mechanism of action on immune cells is still unknown. Since melatonin has been suggested as a physiological antagonist to calmodulin in certain cell types, we investigated effects of melatonin on calmodulin-dependent IL-2 production and proliferation of activated T-lymphocytes. It was found, however, that, in contrast to the calmodulin antagonists trifluoperazine and W7, melatonin neither inhibited the IL-2 production of activated lymphoblastoid Jurkat T-cells nor decreased the mitogen response of peripheral blood mononuclear leukocytes. Preincubation of Jurkat cells with melatonin did not influence trifluoperazine effects on IL-2 production indicating that melatonin does not bind to the same sites of calmodulin as trifluoperazine, as has been postulated. In conclusion, these results did not give any evidence for a calmodulin antagonism of melatonin in T-lymphocyte activation. Thus, melatonin as a calmodulin antagonist appears not to be a universal phenomenon.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Rat lymphocytes produce and secrete acetylcholine in dependence of differentiation and activation.

Previous data from this laboratory suggested for the first time that immune cells of the immune system of different species are capable to synthesize the neurotransmitter acetylcholine. In the present study we detected the RNA message for choline acetyltransferase in thymic, splenic and peripheral blood lymphocytes of rats using RT-PCR. Furthermore, using a sensitive radioimmunoassay, we measured acetylcholine in thymic, splenic and peripheral blood lymphocytes. T-cells were found to contain about three times the amount of acetylcholine as compared to B-cells, and CD4+ cells showed significantly higher levels as compared to CD8+ cells. Mitogenic stimulation with PHA increased the acetylcholine levels in lymphoid cells as well as the release into the supernatants.

Acetylcholine↗
PubMed1998

[Quantitative changes in the immunoglobulin G subclass system--a reliable tumor marker in squamous epithelial carcinoma in the area of the head-neck].

AIM: Until now no serological markers were available towards the diagnosis of squamous-cell carcinomas of the head and neck (HNSCC) particularly in the detection of posttherapeutic recurrent diseases and metastases. Previous reports described patients with malignant diseases of various tissues exhibiting a characteristic and highly significant alteration in the subclass composition of serum IgG, consisting of a reduction in %IgG1 and an increase of %IgG2. In this study we present for the first time results of this IgG-shift in patients suffering from HNSCC. PATIENTS AND METHODS: A total of 111 patients was investigated at our clinic, all suffering from primary, histopathologically verified squamous cell carcinomas of the head and neck. These patients were investigated as to %Ig G1/IgG2 prior to any treatment. A second group consisted of 35 patients with local recurrences, 15 patients with distant metastases and 27 patients without tumour at the time of investigation, who were in observation for 1 to 5 years after primary treatment (T0). Thirdly, a total of 33 patients was included who were afflicted with a variety of benign diseases of the head and neck, such as chronic rhinosinusitis, chronic tonsillitis and also lateral or median cysts of the neck. Data of the three groups were compared with those of 174 healthy volunteer controls. 5 ml blood were taken from a forearm vein and the quantitation of subclasses IgG1, IgG2 and total IgG was performed by affinity chromatography. The single values obtained with all experimental groups and healthy controls showed normal distribution for primary cancer patients versus healthy control. Accordingly, significant differences between mean values were calculated with the two-sided Students t-test, and cut-off values were calculated as the arithmetic means of mean values obtained from the groups to be compared. Diagnostic sensitivities and specificities were defined as percentages of patients with %IgG1 smaller, and of healthy controls with %IgG1 greater than the cut-off value. RESULTS: We found a highly significant alteration in the subclass composition of serum IgG, consisting of a reduction in %IgG1 and an increase in %IgG2 in our HNSCC groups. The present data suggest the changes in %IgG1 and %IgG2 as a useful serological tumour marker to detect primary or recurrent and/or metastatic squamous-cell carcinomas of the head and neck. CONCLUSION: The shift in %IgG1/%IgG2 exhibited diagnostic sensitivities and specificities comparable to, or--particularly at early tumour stages--by far higher than conventional serological tumour markers. Whereas conventional serological markers directly correspond to tumourogenically derived products, the shift in %IgG1/IgG2 represents an indirect marker, consisting of a change of the host's immune system due to the presence of malignant tumours.

Adult↗
PubMed1998

Circadian rhythm of the soluble p75 tumor necrosis factor (sTNF-R75) receptor in humans--a possible explanation for the circadian kinetics of TNR-alpha effects.

Circadian alterations of several immune functions in vivo are well established, and may have important physiological and clinical implications. In line with this, tumor necrosis factor (TNF)-alpha has been implicated in the circadian regulation of body temperature. As soluble TNF receptors (TNF-R) act as naturally occurring competitive inhibitors of this cytokine, we investigated plasma levels of the soluble sTNF-R55 and sTNF-R75 in comparison with plasma cortisol and body temperature in nine healthy male volunteers during a defined 16 h light/8 h dark cycle. It was found that sTNF-R75, but not sTNF-R55, exhibited a clear-cut circadian rhythm with a significant (P < 0.01) peak at 7:51 a.m. +/- 58 min. The phase of the sTNF-R75 rhythm preceded that of cortisol by approximately 1 h and inversely corresponded to the circadian rhythm of body temperature. Moreover, the individual amplitudes of sTNF-R75 and body temperature exhibited a significant (P < 0.01) positive correlation. These results suggest that (i) the two sTNF-R are regulated independently, (ii) the sTNF-R75 rhythm is not primarily due to the cortisol rhythm and (iii) the fluctuation of the sTNF-R may contribute to the regulation of body temperature by modulating the availability of free TNF.

Adult↗
PubMed1998

Adrenergic/cholinergic immunomodulation in the rat model--in vivo veritas?

For several years, our group has been studying the in vivo role of adrenergic and cholinergic mechanisms in the immune-neuroendocrine dialogue in the rat model. The main results of these studies can be summarized as follows: (1) exogenous or endogenous catecholamines suppress PBL functions through alpha-2-receptor-mediated mechanisms, lymphocytes of the spleen are resistant to adrenergic in vivo stimulation, (2) direct or indirect cholinergic treatment leads to enhanced ex vivo functions of splenic and thymic lymphocytes leaving PBL unaffected, (3) cholinergic pathways play a critical role in the "talking back" of the immune system to the brain, (4) acetylcholine inhibits apoptosis of thymocytes possibly via direct effects on thymic epithelial cells, and may thereby influence T-cell maturation, (5) lymphocytes of the various immunological compartments were found to be equipped with the key enzymes for the synthesis of both acetylcholine and norepinephrine, and to secrete these neurotransmitters in culture supernatants.

Acetylcholine↗
PubMed1997

[Interaction of the epiphysis and the immune system].

First indications that the pineal gland may be involved in endocrine immunomodulation came from early reports on anti-tumor effects of pineal extracts in animals and humans. In the meantime, evidence has accumulated suggesting that melatonin, the major endocrine product of the pineal gland-as a well preserved molecule during evolution-is indeed involved in the feedback between neuroendocrine and immune functions. At present we are beginning to understand the mechanisms of action by which melatonin affects cellular functions, and from the variety of possible direct and indirect interactions it appears that melatonin may play a complex physiological role in neuroimmunomodulation. In this article we present a critical review of the numerous reports on the influence of melatonin on immune functions and discuss the possible underlying molecular pathways. In addition, a short comment is given on the current public discussion as to the clinical value of melatonin.

Animals↗