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Biomedical subjects

C J Wiedermann

Publications and source records attributed to C J Wiedermann.

At least 109 records · Page 6Linked to original sources
PubMed1993

Increased levels of serum neopterin and decreased production of neutrophil superoxide anions in chronic heart failure with elevated levels of tumor necrosis factor-alpha.

OBJECTIVES: The purpose of this study was to examine the role of tumor necrosis factor-alpha and tetrahydrobiopterin and superoxide anion release from neutrophils in severe chronic heart failure. BACKGROUND: Previous studies have demonstrated elevated production of tumor necrosis factor-alpha and free radical-induced endothelial cell damage in severe heart failure. METHODS: Plasma and serum levels of immunoreactive interleukin-1, interleukin-6, interferon-gamma, neopterin and tumor necrosis factor-alpha and the release of superoxide anions from circulating neutrophils both at basal conditions and after triggering with f-Met-Leu-Phe or phorbol 12-myristate 13-acetate were measured in 16 patients with severe heart failure and in 11 healthy control subjects. RESULTS: Circulating levels of tumor necrosis factor-alpha and neopterin were elevated in patients with heart failure compared with values in control subjects. A significant correlation between the two was found. Basal and phorbolester-triggered release of oxygen radicals from neutrophils was not affected in patients with heart failure. However, formylpeptide-stimulated release of oxygen radicals by neutrophils was significantly reduced. CONCLUSIONS: Suppressed neutrophil function in patients with heart failure exhibiting elevated levels of tumor necrosis-alpha factor may indicate self-protection against the deleterious effects of neutrophil-derived oxygen radicals. Through induction of tetrahydrobiopterin synthesis (as reflected by increased neopterin), tumor necrosis factor-alpha may affect nitric oxide synthesis.

Atrial Natriuretic Factor↗
PubMed1993

Induction of normal human eosinophil migration in vitro by substance P.

To investigate the role of tachykinins in allergic inflammation, the effect of substance P (SP) on normal human eosinophil migration was examined in Boyden chamber type assays. SP stimulated eosinophil migration in vitro with an EC50 of about 1-10 pM and maximal effects were seen at 100 pM. A carboxy-terminal fragment of SP possessed appreciable activity whereas an amino-terminal fragment was inactive. Data represented in this paper and previous studies suggest that eosinophils are attracted by SP and activated to enhanced mediator release and cytotoxic activity.

Chemotaxis, Leukocyte↗
PubMed1993

High-affinity substance P binding sites of neurokinin-1 receptor type autoradiographically associated with vascular sinuses and high endothelial venules of human lymphoid tissues.

BACKGROUND: Factors that affect leukocyte-endothelial cell interaction in high endothelial postcapillary venules and vascular sinuses of lymphatic tissues indirectly regulate immune function. Studies in sheep demonstrated that acute infusion of substance P (SP) into cannulated popliteal lymph node afferent lymphathics produced a marked and prolonged increase in the output of lymphocytes into nodal efferent lymph. The proposed mechanism is an influence of SP on lymph vascular systems. Such functional importance of the immunoregulatory properties of SP in man is unknown. EXPERIMENTAL DESIGN: The expression and distribution of SP receptors in human lymphoid tissue was investigated using slide-mounted fresh-frozen sections of lymph node, hyperplastic tonsillitis, and spleen for ligand binding and autoradiographic studies. RESULTS: Specific binding of radiolabeled SP to lymph node and tonsils reached a plateau within approximately 40 minutes, being half-maximal at 20 minutes. The specific binding was between 65 and 75% of total binding. In contrast, iodinated neurokinin A under identical incubation conditions, did not significantly associate with the tissues. Neither the SP nor the neurokinin A tracer specifically associated with spleen. Binding specificity of radiolabeled SP was analyzed in binding competition experiments. Synthetic SP, SP (3-11), a selective neurokinin-1 agonist and a neurokinin-1 antagonist competed with the specific binding of SP to lymph node and tonsil sections. The half-maximal inhibition of binding was obtained at a concentration of about 0.5 nmol/liter of SP. The fragment SP (1-4) and selective neurokinin-2 ligands did not compete with the specific binding of SP. Scatchard and nonlinear algorithm analyses revealed two binding sites for SP. For lymph node and tonsil, one site showed a high affinity of about 0.4 nmol/liter and 0.7 nmol/liter and a low capacity for SP, respectively. The second site exhibited a lower affinity of 100 nmol/liter and 50 nmol/liter and a higher capacity for SP in lymph node and tonsil, respectively. Autoradiographic localization of the binding sites shows a very high concentration of silver grains when compared with controls. The reaction occurred mainly over vascular sinuses and high endothelial venules with heterogenous density. Silver grain accumulation was also noticed over the marginal sinuses of the B cell follicles. CONCLUSIONS: The biochemical results indicate the presence of neurokinin-1 receptors in human lymph node and tonsil. We suggest that the neurokinin-1 receptors localized to vascular tissues of lymph node and tonsil mediate the affects of SP on lymphocyte traffic, and we propose that SP plays a regulatory role in lymphocyte homing in man.

Autoradiography↗
PubMed1993

Circulating interleukin-1 and tumor necrosis factor antagonists in liver disease.

The proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha are thought to play important roles in the pathophysiology of liver disease. Specific antagonists of these cytokines have been found in recent years. Interleukin-1 receptor antagonist is a specific interleukin-1 antagonist. The soluble receptor derived from the cell-surface p55 tumor necrosis factor receptor p55 is a naturally occurring substance that inhibits the biological effects of tumor necrosis factor. We used specific radioimmunoassays to detect circulating interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor p55 levels in 14 patients with acute viral hepatitis and in 160 patients with various chronic liver diseases. Levels of interleukin-1 receptor antagonist and, especially, tumor necrosis factor soluble receptor were markedly increased in most patients with chronic liver disease regardless of pathogenesis and in viral hepatitis. Patients with chronic liver disease and cirrhosis showed significantly higher levels of both cytokine antagonists than did noncirrhotic patients. Correlations between interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor were more significant than those of either antagonist with C-reactive protein or blood sedimentation rate. Interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor levels were also positively correlated with bilirubin and AST levels. We conclude that circulating levels of interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor may reflect ongoing disease activity and probably modulate some effects of endogenous interleukin-1 and tumor necrosis factor.

Adult↗
PubMed1992

Suppression of superoxide release from human monocytes by somatostatin-related peptides.

Somatostatin and octreotide share with vasoactive intestinal peptide the property of having an inhibitory effect on leukocyte functions. While there are studies reporting the inhibitory effect of the latter on respiratory burst in human monocytes, no such reports are available about similar inhibitory effects of the former. The aim of the present study was to investigate such effects of somatostatin and octreotide on human monocytes. Release of superoxide anion from monocytes was measured by superoxide dismutase-inhibitable reduction of cytochrome c in vitro. Somatostatin 1-14, somatostatin 1-28 and octreotide inhibited release of superoxide anion from stimulated monocytes. Formylpeptide-stimulated reduction of cytochrome c was inhibited by 1 mumol/l of octreotide and somatostatin 1-14 by about 50% and 35%, respectively. The effect was dose-dependent with half-maximal effective peptide concentrations at about 10 nmol/l. Somatostatin 1-28, which is the major form found in circulating plasma, also antagonized formylpeptide-stimulated respiratory burst activity; when directly compared to the effect of 1 mumol/l of somatostatin 1-14, somatostatin 1-28 was significantly more active (P less than 0.05). Our observations suggest that somatostatin-related peptides have a regulatory role in oxygen radical metabolism and a mediator role in the neuro-immune axis.

Cytochrome c Group↗
PubMed1992

Calcitonin gene-related peptide in patients with and without early reperfusion after acute myocardial infarction.

Plasma concentrations of calcitonin gene-related peptide (CGRP), a potent regulator of vascular tone, creatine kinase, myoglobin, and cardiac troponin T were assessed in 31 patients with acute myocardial infarction. In patients who had sustained acute myocardial infarctions, maximum CGRP concentrations (median, 3.2 pmol/L; interquartile range, 1.5 to 4.8 pmol/L) were markedly elevated as compared with healthy control subjects (n = 23; median, 1.02 pmol/L; p = 0.02). However, no marked differences in CGRP levels were observed between patients with early reperfusion (n = 19; median, 3.5 pmol/L) and patients without early reperfusion (n = 12; median, 2.6 pmol/L; p = 0.96), as well as between those with congestive heart failure (n = 8; median, 3.9 pmol/L) and those without congestive heart failure (n = 23; median, 3.2 pmol/L; p = 0.62). CGRP did not correlate closely with myocardial protein release or hemodynamic parameters (heart rate and blood pressure) or the occurrence of arrhythmias. Therefore we conclude that elevated peripheral venous CGRP concentrations in patients who have sustained an acute myocardial infarction are independent of successful reperfusion and hemodynamic state. Although the cause of CGRP increase is not yet identified, CGRP may play a role in the regulation of coronary vascular tone in patients after acute myocardial infarction.

Adolescent↗
PubMed1992

Regulation of human T lymphoblast growth by sensory neuropeptides: augmentation of cholecystokinin-induced inhibition of Molt-4 proliferation by somatostatin and vasoactive intestinal peptide in vitro.

The effects on proliferation of Molt-4 lymphoblasts of cholecystokinin (CCK-8), somatostatin-14 (SS), vasoactive intestinal peptide (VIP) and substance P (SP) were investigated using different combinations of the peptides, peptide analogs and their antagonists. In vitro proliferation of the cells was measured by a colorimetric assay for cell growth and survival. Results indicate that SP and SP (3-11) stimulated, whereas CCK-8, VIP and SS inhibited, proliferation in a dose-dependent manner (P < 0.05). Unsulfated CCK-8 had no effect on growth of Molt-4 lymphoblasts, and a specific antagonist of CCK, at a concentration 10(-6) M, diminished the inhibitory effect of CCK-8 on Molt lymphoblasts (P < 0.05). This suggests that the inhibitory action of CCK-8 was mediated by peripheral-type CCK receptors. SS and VIP, at equimolar concentrations of 10(-6) M, significantly augmented the CCK-8-induced inhibition of Molt-4 lymphoblast proliferation. However, none of the inhibiting neuropeptides suppressed stimulation of Molt-4 lymphoblast proliferation in response to SP. These data suggest a role of sensory neuropeptides including CCK in modulating human T lymphoblast proliferation during neuroendocrine interactions with the immune system.

Humans↗
PubMed1992

In vivo activation of circulating monocytes by exogenous growth hormone in man.

Animal studies have shown that administration of growth hormone improves wound healing. Monocyte activation is a prerequisite for optimal repair of damage. In vitro, human recombinant growth hormone was shown to be a potent human monocyte chemoattractant. It induced random migration and chemotaxis at picomolar concentrations of recombinant human growth hormone; combinations of growth hormone with other chemoattractants deactivated the chemotactic response. Other functions of monocytes that are activated by growth hormone include release of superoxide anion and production of cytokines. In order to test activation of human monocytes by growth hormone in vivo, we investigated the effects of recombinant human growth hormone administration on monocyte migration in nine healthy young adults. After a single dose of recombinant human growth hormone (4 IU subcutaneously injected), random migration of circulating monocytes significantly increased, whereas chemotaxis of monocytes that was maximally stimulated with f-Meth-Leu-Phe decreased (p < .05). The alterations paralleled the concomitantly measured plasma levels of growth hormone. After recombinant human growth hormone administration, no changes were seen in plasma levels of proinflammatory cytokines. These in vivo data on monocyte migration are comparable to effects of growth hormone on monocyte migration in vitro and strongly suggest that recombinant human growth hormone can activate circulating monocytes in man.

Adult↗
PubMed1992

Decreased immunoreactive beta-endorphin in mononuclear leucocytes from patients with rheumatic diseases.

The neuroendocrine polypeptide hormone beta-endorphin (beta-END), which is released from various tissues including the anterior pituitary gland and cells of the immune system, has recently been implicated as having an immunoregulatory role. We used a radioimmunoassay to measure beta-END levels in circulating mononuclear leucocytes from normal subjects and patients with various rheumatic diseases. Levels of beta-END in leucocytes from patients were lower than in leucocytes from healthy subjects (P less than 0.001). Whereas levels of beta-END in leucocytes from patients with the various rheumatic disorders were not significantly different, an inverse correlation was found between beta-END levels in leucocytes and expression of rheumatoid factor (P less than 0.025) and erythrocyte sedimentation rate (P less than 0.025). This study demonstrates decreased content of beta-END in cells of the immune system related to parameters of inflammatory activity in rheumatic diseases.

Blood Sedimentation↗
PubMed1992

Proinflammatory cytokines in cardiac myxomas.

Serum levels of various cytokines were measured in three patients with cardiac myxomas presenting with and without constitutional symptoms, immunological features and elevated plasma levels of interleukin-6. Interleukin-6 but not other cytokines (interleukin-1, tumour necrosis factor-alpha, interferon-gamma) relate to immunological features of the patients. Circulating levels of atrial natriuretic peptide correspond to haemodynamic changes but not to the tumour-bearing state itself.

Atrial Natriuretic Factor↗
PubMed1992

Priming of polymorphonuclear neutrophils by atrial natriuretic peptide in vitro.

In ischemia-reflow states of coronary artery disease, the activation of PMN precedes the initiation of tissue damage. Release of atrial natriuretic peptide (ANP) from myocytes occurs within minutes after the onset of myocardial ischemia, which suggests a possible role of ANP in PMN activation. To investigate this possibility, we tested the effects of ANP on functions of PMN in vitro. ANP is a potent signal for priming the PMN respiration burst to secrete superoxide anion. Phorbol 12-myristate 13-acetate, opsonized zymosan, or FMLP could all be used as triggering stimuli to demonstrate the priming of PMN activation by ANP. Only ANP fragments 1-28 and 7-28 enhanced respiration burst activity but identical preparations of ANP fragments 13-18 or 1-11 failed to do so. This structure-activity relationship is typical of receptors for ANP found in other tissues. In addition, ANP stimulated the release of beta-glucuronidase From PMN triggered by FMLP. The observed inhibition by ANP of FMLP-stimulated chemotaxis of PMN may be due to their enhanced adhesiveness. These data show that a classic cardiac hormone is involved in regulating important functional activities of PMN. These data support the possibility that ANP could act as a preinflammatory substance in ischemia-reperfusion states and myocardial necrosis.

Atrial Natriuretic Factor↗
PubMed1991

Priming of normal human neutrophils by tachykinins: tuftsin-like inhibition of in vitro chemotaxis stimulated by formylpeptide or interleukin-8.

Tachykinins have priming effects on polymorphonuclear neutrophils, since they may activate the neutrophils to exhibit an exaggerated inflammatory response to phlogistic mediators. In order to investigate mechanisms involved in this action, we determined the influence of substance P and neurokinin A on chemotaxis of human neutrophils towards gradients of formymethionyl-leucyl-phenylalanine or recombinant human interleukin-8. As seen with other neutrophil-priming agents such as tumor necrosis factor-alpha, exposure of neutrophils to substance P or neurokinin A had an inhibitory effect upon a stimulated migration, with effective concentrations being in the nanomolar range. Tuftsin, a known neutrophil activating peptide, similarly inhibited stimulated migration. Analysis of structure-activity relationships revealed that activity of tachykinins is located in amino-terminal, tuftsin-like sequences. The inhibition of stimulated migration was partly reversed by (Pro1)-tuftsin, a partial tuftsin receptor antagonist, which suggests that the effects of amino-terminal tachykinins involves activation of tuftsin receptors of neutrophils.

Amino Acid Sequence↗
PubMed1991

Suppression of thyroid function by interferon-alpha 2 in man.

Profound biological changes occur in patients treated with interferon. Observations of endocrine changes prompted us to examine the effects of subcutaneous alpha-interferon administration in single doses on circulating levels of thyroid stimulating hormone, total thyroxine, and total triiodothyronine in 10 volunteers (5 healthy subjects and 5 patients with hepatitis C). Blood samples were taken on an out-patient basis immediately before and 2, 12, 24, 48, and 72 h after administration of 1, 3, or 5 x 10(6) units of recombinant alpha-interferon. Application of the different dose levels was randomly assigned. Plasma samples were stored at -80 degrees C; after collection of samples had been completed hormone levels were measured using commercially available test kits. At all time points before and after injection of alpha-interferon, standard deviations of measured hormone levels of healthy control subjects and patients overlapped to a considerable extent. At a dose level of 5 x 10(6) units, alpha-interferon significantly increased cortisol levels as described, and decreased the level of thyroid stimulating hormone in the group receiving alpha-interferon as compared to placebo-treated healthy volunteers. The effects occurred 12 h after injection. Maximum suppression of thyroid stimulating hormone levels was observed 24 h after injection, when serum levels of thyroxine and triiodothyronine also were significantly reduced. We conclude that subcutaneous alpha-interferon treatment with doses as low as 5 x 10(6) units affects the control of thyroid function.

Adult↗
PubMed1991

In vitro activation of neutrophils of the aged by recombinant human growth hormone.

Several functions of polymorphonuclear neutrophils (PMNL) have been found to be altered in the aged. As the neuroendocrine network, in particular growth hormone (GH), may interfere with the regulation of nonspecific host defense mechanisms, a recently described PMNL-priming activity of recombinant human (rH) GH in vitro was investigated. Oxidative metabolism of PMNL from young and old subjects was studied by measuring reduction of nitroblue tetrazolium (NBT) or cytochrome c. In the absence of stimulating agents, PMNL from old subjects reduced NBT to a significantly lesser extent than did PMNL from young subjects. Addition of rHGH to PMNL from old subjects reversed the suppressed spontaneous oxidative metabolism. No differences between young and old were observed for the increase of stimulated oxidative metabolism. The results suggest that altered PMNL function in the aged may be reversed by rHGH and that the ability of PMNL to respond to rHGH does not decline with age.

Adult↗
PubMed1991

Priming of normal human neutrophils by recombinant human growth hormone.

Growth hormone (GH) plays an important role in the development, maintenance and function of the immune system. Previous data has demonstrated that GH is also a newly defined macrophage-activating factor. Activation of polymorphonuclear neutrophils (PMN) by GH has not yet been examined. This paper presents studies demonstrating the effects of GH on the migratory behaviour and respiratory burst of PMN. In a modified Boyden chamber chemotaxis assay, GH did not stimulate PMN locomotion when added directly to the cells but potently inhibited formylpeptide-stimulated chemotaxis with effective concentrations in the picomolar range. The migration inhibition observed is known from studies on PMN priming-factors to be due to enhanced adhesiveness of PMN to artificial surfaces such as nitrocellulose, suggesting that GH stimulates PMN adhesiveness. Priming of PMN by GH was confirmed by direct demonstration of a stimulatory effect on reduction of nitroblue tetrazolium. These findings suggest that GH may be involved in the regulation of PMN functions.

Cell Adhesion↗