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Biomedical subjects

M Herold

Publications and source records attributed to M Herold.

At least 127 records · Page 7Linked to original sources
PubMed1993

Spontaneous bacterial peritonitis is associated with high levels of interleukin-6 and its secondary mediators in ascitic fluid.

We investigated 37 patients with ascites and liver cirrhosis in order to examine whether on the basis of correlation of cytokines and acute phase proteins of the ascitic fluid, prognosis of spontaneous bacterial peritonitis can be made. Significantly enhanced levels of interleukin-6, as well as acute phase reactants alpha-1-antitrypsin and C-reactive protein were found in the ascitic fluid of patients with spontaneous bacterial peritonitis. The levels of tumour necrosis factor alpha (TNF-alpha), neopterin, interleukin 2-receptor and granulocyte-macrophage colony stimulating factor were higher in patients with spontaneous bacterial peritonitis, but without statistical significance, whereas no differences were found between the interferon gamma, interleukin-2 and interleukin-1 levels. In addition, interleukin-6, TNF-alpha and neopterin levels were found to correlate significantly with the outcome of the disease. These findings show that acute phase reaction occurs in the ascitic compartment in correlation with the development of spontaneous bacterial peritonitis.

Acute-Phase Proteins↗
PubMed1993

Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease.

Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice.

Animals↗
PubMed1993

Elevated concentrations of circulating intercellular adhesion molecule 1 (ICAM-1) in HIV-1 infection.

The membrane-bound glycoprotein intercellular adhesion molecule 1 (ICAM-1) plays an important role for many cell-contact-dependent immune functions. A soluble, circulating form of ICAM-1 (cICAM-1) has been detected in the serum of healthy persons and increased concentrations in tumor patients have been reported. We measured serum levels of cICAM-1 in HIV-1-infected individuals with a recently developed ELISA. In contrast to HIV-seronegative controls (median value of 294 ng/ml, range of 185-408 ng/ml; n = 22), significantly elevated concentrations were detected in 76 HIV-1-infected persons (median of 487 ng/ml, range of 231-1,524 ng/ml; p < 0.0001). In HIV-1-infected individuals, cICAM-1 values did not correlate with the absolute number of CD4+ T cells or with disease progression according to the Walter Reed staging classification. Concentrations of cICAM-1 correlated with the serum concentrations of IL-6 (p = 0.0015; Spearman's rank correlation analysis) and with urinary neopterin (p = 0.005), but not with the C-reactive protein. Since there is evidence that cICAM-1 can interfere with immunological functions, the high amounts circulating in HIV-1-positive individuals could contribute to the disturbance of the immune system in HIV-1 infection.

Adult↗
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↗
PubMed1993

[The optimal diagnostic approach in myocardial infarct].

In the submitted review the authors discuss rational criteria for the diagnosis of myocardial infarction, indications for thrombolysis, coronarography and possibly PTCA, the method of indirect (non-invasive) assessment of an occluded coronary artery and the most frequent mistakes in the diagnosis of infarction. Essential examinations in the acute stage of myocardial infarction are: case-history, ECG, CK-MB (possibly echocardiography). For indication of thrombolysis of acute PTCA case-history and ECG (or echocardiography) are sufficient. Indications of early coronarography before discharge from hospital: postinfarction angina pectoris, malignant arrhythmia (except on the first day), haemodynamic instability, evidence of myocardial ischaemia (restricted symptoms) during a maximal load before discharge.

Humans↗
PubMed1992

Gastrointestinal transit and digestibility of maltitol, sucrose and sorbitol in rats: a multicompartmental model and recovery study.

Using data obtained with a dye marker and the gavage technique, the kinetics of gastrointestinal transit of different loads of sugar substitutes (maltitol, sorbitol) and sugar (sucrose) in the rat were analysed using a linear multicompartmental model over a range from the realistic to the non-physiologic high, of carbohydrate intake levels and using only a few experimental time points. The model gave detailed insight into intestinal propulsion and gastrocecal transit time. Rate constants of transport between the compartments investigated were determined; they showed characteristics which could be related to the substance and the dosage administered. Analyses of the gastrointestinal content and calculations of the intestinal net water movement showed that the digestibility and absorption of the disaccharide sugar alcohol, maltitol, in the small gut depended inversely on the dose ingested. For all substances tested, caloric availability in the small intestine was calculated. At a physiological low level of maltitol intake, the results also indicated an insignificant calorie-saving effect in comparison to sucrose, an effect based mainly on the slow absorption rate of the maltitol cleavage product sorbitol.

Animals↗
PubMed1992

Coenzyme binding of a folding intermediate of aspartate aminotransferase detected by HPLC fluorescence measurements.

Equilibrium dissociation and unfolding of dimeric aspartate aminotransferase from Escherichia coli proceeds via two compact monomeric intermediates which have similar hydrodynamic volumes but different fluorescence properties. We probed binding of the coenzyme pyridoxal 5'-phosphate to these intermediates by coupling fluorescence detection to size-exclusion HPLC. This procedure gave additionally an internal conformational probe of the unfolding transitions of the enzyme. It was shown that the first intermediate, M, is able to bind the coenzyme, whereas the second intermediate, M*, is not. It is likely that M is the correctly folded monomer of the protein.

Aspartate Aminotransferases↗
PubMed1992

Collapsed intermediates in the reconstitution of dimeric aspartate aminotransferase from Escherichia coli.

Aspartate aminotransferase from Escherichia coli, which had been denatured by guanidinium chloride, refolded and reassembled to active dimers in two distinct phases. The unfolded monomer U collapsed within 20 s to an intermediate I* that was inactive, fluoresced more strongly than, but had the same peptide CD signal as the native dimer. The formation of crosslinkable dimers, as well as the recovery of enzyme activity, occurred with a biphasic progress curve which was independent of protein concentration. The half-lives of the two phases were 100 s and 2000 s. The data are consistent with a three-step mechanism, in which the overall rate of reassembly is determined by an isomerization of I* to the assembly-competent monomer M. The latter does not accumulate because it dimerizes rapidly to the active enzyme (D). Reassembly of the enzyme from the compact intermediate M*, which is stable at 1.0 M guanidinium chloride, also proceeded in a rapid and a slow phase. Moreover, the formation of M* from the unfolded state was rapid, whereas its refolding to the native dimer was slow. Both the transient intermediate I* and the equilibrium intermediate M* qualify as 'collapsed intermediate' or 'molten globule' states.

Aspartate Aminotransferases↗
PubMed1992

A short multilingual quality of life questionnaire--practicability, reliability and interlingual homogeneity.

International cooperative clinical trials require a multilingual quality of life questionnaire. The 'International Society for Chemo- and Immunotherapy' therefore designed a study to develop and test a 'health accentuated' quality of life questionnaire in the eight languages spoken in this society. The objective was to examine practicability, reliability and interlingual homogeneity. Versions of the questionnaire in Czech, German, Hungarian, Italian, Kroatian, Polish, Romanian and Slovakian have been prepared. The results are based on data of 1,104 adult patients. They demonstrate that the developed questionnaire is practicable. Patients need 10-15 min to answer it, usually without assistance. The proportion of missing values is for all but two questions less than 3%. The questionnaire also found high acceptance reflected by only 2.7% refusals. It is reasonably reliable in each language. Interlingual homogeneity could be shown by demonstration of strong structural similarities between the different versions using multidimensional scaling, factor analysis and comparison of mean profiles.

Adolescent↗
PubMed1992

Serum levels of cytokines in chronic liver diseases.

Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and C-reactive protein (CRP) were investigated in patients with chronic liver diseases (CLD) and correlated with the type of underlying disease and various clinical and laboratory parameters. Two hundred sixty-four patients suffering from various CLD were studied; 136 cases presented with liver cirrhosis, and 128 patients were in the noncirrhotic stage of their underlying liver diseases. Serum levels of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and CRP were elevated in patients with CLD. Endogenous cytokine patterns in CLD were stage dependent and only marginally affected by the type of underlying disease. The cirrhotic group of CLD patients showed higher serum levels in IL-1 beta, IL-6, TNF-alpha, and CRP than did noncirrhotic cases, and these differences reached the level of statistical significance. IL-1 beta and TNF-alpha values were closely correlated but did not correlate with IL-6 levels. Elevated concentrations of cytokines represent a characteristic feature of CLD regardless of underlying disease. This and the apparent stage-dependency suggest that enhanced endogenous cytokine levels represent a consequence of liver dysfunction rather than of inflammatory disease.

Adolescent↗
PubMed1992

Investigation of ACTH responses of chickens with autoimmune disease.

An altered immunoendocrine feedback regulation within the hypothalamo-pituitary-adrenal axis may modulate the pathogenesis of an avian autoimmune disease. To date studies have been hampered by a lack of reliable, specific, and sensitive methods for determining adrenocorticotropic hormone (ACTH) in chickens. The present study describes the determination of ACTH in plasma of chickens with a commercial radioimmunoassay, the antibody of which binds to the midregion of human ACTH 1-39. The chickens, kept on a 12-hr day and 12-hr night shift with artificial light, showed changes in plasma ACTH concentrations during the light phase with maximum values 8 hr after the light was turned on. ACTH was not measurable after treatment with dexamethasone. Intravenous administration of supernatants from concanavalin A-stimulated spleen cells increased basal plasma ACTH concentrations more than 20-fold within 1 hr. This increase in plasma ACTH was higher and longer lasting in UCD 200 chickens, an animal model for scleroderma, compared with outbred and inbred normal White Leghorn chickens.

Adrenocorticotropic Hormone↗
PubMed1992

Endogenous serum levels and surface receptor expression of GM-CSF and IL-3 in patients with myelodysplastic syndromes.

The majority of patients suffering from myelodysplastic syndromes (MDS) die of complications due to cytopenia. Clinical trials have demonstrated that in an essential number of MDS patients cytopenia can be ameliorated by exogenously supplied growth factors. We investigated endogenous serum levels of GM-CSF and IL-3 in 15 healthy individuals and 34 patients suffering from MDS. No circulating growth factors were detected in the serum of healthy controls, nor was IL-3 measurable in MDS patients. GM-CSF serum levels, however, were elevated in a significant number of patients (26.5%). Levels did not correlate with FAB classification, leukocyte count or chromosomal abnormalities. No significant differences in GM-CSF or IL-3 receptor expression were detected between healthy individuals and MDS patients. One patient with increased endogenous GM-CSF serum level and normal surface receptor expression responded to exogenously applied GM-CSF. In the light of these results, a functional alteration of growth factor receptors or disturbances of signal transduction pathways must be discussed for MDS.

Adult↗
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

[Cellular immunity in pregnancy-induced hypertensive diseases].

Cytokines (IL-1, sIL-2R, IL-3, IL-6, TNF-alpha, IFN-gamma, GM-CSF and neopterin) were measured in sera of 37 patients with hypertensive disorders of pregnancy, 10 healthy pregnant and 10 healthy non-pregnant controls. With the exception of neopterin (p = 0.004) there were no statistically significant differences in cytokine concentrations between healthy pregnant and non-pregnant controls. No statistically relevant differences between healthy pregnant women and hypertensive patients could be found in cytokines of T-lymphocytic origin except GM-CSF in patients with HELLP syndrome (p = 0.02). Elevated levels of IL-6, TNF-alpha and neopterin were observed in hypertensive women. Differences to healthy pregnant controls were statistically significant for IL-6 (p = 0.008), TNF-alpha (p = 0.009) and neopterin (p = 0.04) and were more pronounced in severe forms of the disease. These 3 parameters of monocytic origin showed significant positive correlations amongst each other. A participation of cell-mediated immunity (especially monocytes/macrophages) in the pathomechanism of hypertensive disorders of pregnancy can thus be assumed.

Biopterins↗