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Biomedical subjects

A Stelzner

Publications and source records attributed to A Stelzner.

At least 19 recordsLinked to original sources

Coxsackievirus B3-induced production of tumor necrosis factor-alpha, IL-1 beta, and IL-6 in human monocytes.

Infections by coxsackievirus B3 (CVB3) have previously been shown to cause acute and chronic myocarditis characterized by a heavy mononuclear leukocyte infiltration and myocyte necrosis. Because clinical and experimental evidence suggested that cardiac damage may result from immunologic rather than viral mechanisms, we examined in this study the in vitro interaction of CVB3 with human monocytes. CVB3 was capable of infecting freshly harvested monocytes as revealed by immunofluorescence and release of infectious virus particles. Virus infection did not reduce monocyte viability but, on the contrary, enhanced spreading and adherence. In a dose-dependent manner, CVB3 stimulated the release of cytokines from monocytes. Whereas a potent production of TNF-alpha, IL-1 beta, and IL-6 was dependent on exposure to infectious CVB3, IFN release was also induced by UV-inactivated virus. On a molecular level, CVB3 stimulated cytokine gene expression as shown by a marked TNF-alpha, IL-1 beta, and IL-6 mRNA accumulation. Supernatants of CVB3-infected monocytes displayed cytotoxic activity against Girardi heart cells which could be abrogated by an anti-TNF-alpha antiserum. These data suggest that CVB3-induced cytokine release from monocytes may participate in virus-induced organ damage such as myocarditis, which may either occur by a direct cytotoxicity of cytokines or by activation of cytotoxic lymphocytes.

Cell Adhesion

Lipopolysaccharide suppresses cytokine release from coxsackie virus-infected human monocytes.

Infections by coxsackie virus B3 (CVB3) have been reported to be associated with an enhanced influx of mononuclear leukocytes into afflicted tissue. Current evidence indicates that monocytes/macrophages are specifically involved in CVB3-induced myocarditis by maintaining a chronic inflammatory response. To examine susceptibility and reactivity to CVB3, freshly isolated human monocytes were exposed to various virus doses (0.1-10 MOI) in the presence or absence of macrophage-activating lipopolysaccharide (LPS). CVB3 infection alone induced an activation of monocytes as evidenced by enhanced adherence, release of cytokines and secretion of prostaglandin E2 (PGE2). Simultaneous addition of LPS almost entirely suppressed LPS-specific production of tumour necrosis factor alpha (TNF alpha) and PGE2, partially inhibited release of interleukin 1 beta (IL 1 beta) and did not affect interleukin 6 (IL6) synthesis of CVB3-infected monocytes. These data show that CVB3 activates monocytes to cytokine production but renders them unreactive to further activating stimuli. Further studies should determine the extent to which continuous cytokine release from persistently CVB3-infected monocytes, and their apparent unresponsiveness to other stimuli, contribute to chronic myocarditis.

Coxsackievirus Infections

A phagocytosis capacity assay: parallel measurement of the phagocytosis and the intracellular killing in granulocytes and the influence of some substances on these processes.

A radiometric technique is described for the assessment of phagocytosis and killing of viable yeast cells by granulocytes. This technique does not require separation of extra- and intracellular microorganisms. In this method the phagocytes which contain viable yeast cells (Saccharomyces cerevisiae and Candida albicans) were disrupted by Triton X-100, and only the remaining yeast cells were isotope-labelled. The uptake of [75 Se]L-selenomethionine was used to measure the killing ability of phagocytes. This method is recommended to measure the influence of biological and pharmacological agents to ingest and kill leucocytes in vitro. The following substances affected phagocytosis and killing: Granatomycin C (decreased phagocytosis), cis-DDP (no influence), bestatin (stimulation of phagocytosis) and Z 190/69-HCl (oxazole) (stimulation of phagocytosis and killing).

Candida albicans

Induction of cytokine release from human monocytes by coxsackievirus infection.

Coxsackievirus B3 (CVB3) infections produce an inflammatory and immune response that suggests the involvement of cytokines. In this in vitro study, we exposed purified human monocytes to CVB3 and determined the release of interferon (IFN), interleukin 1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha). Exposure to CVB3 did not alter the viability of monocytes, however, it induced an increased adherence. After 12 and 24 h of CVB3 exposure, monocytes released large amounts of IFN, IL-1 beta and TNF-alpha. These data show that CVB3 strongly affects human monocytes and activates them to production of biologically active cytokines, particularly IL-1 beta and TNF-alpha. It is suggested that both cytokines, when released in large amounts and for a prolonged period, may contribute to a strong inflammatory response and eventual tissue damage in afflicted organs such as the myocardium.

Coxsackievirus Infections

[The effect of potential antineoplastic antibiotics and the metal complex compound cisplatin on in vitro phagocytosis].

Under standardized conditions the influence of the drugs lambdamycin, violamycin, granatomycin C, daunorubicin and cisplatin on the phagocytosis has been tested. Therapeutical doses of lambdamycin, daunorubicin and cisplatin did not have any obvious impairment on the phagocytosis. Contrarily to this granatomycin C (an isochromanchinon antibiotic) and violamycin (an anthracyclin in high concentrations) significantly depressed the phagocytosis of PMN.

Aminoglycosides

[Interferon induction under in vitro conditions].

The procedures generally used for the in vitro induction of interferon exploit fibroblast or leucocyte culture suspensions. Several factors and conditions influencing the capacity for IFN induction were studied, with the following results. In contrast to previous findings, optimum IFN induction was obtained at 37 degrees C, rather than 30 degrees C, when human fibroblasts were induced with 100 micrograms/ml of Poly (IC). There was a direct correlation between the dose of the inducing agent applied and the amount of IFN produced. Also, the cells were excellently super-inducible with metabolic inhibitors like actinomycin D and cycloheximine. In addition, priming procedures enhanced IFN induction in human fibroblasts. Comparing different cell types with respect to their ability to be induced for IFN production, we found that different cell types show great differences in their inducer sensitivity. Finally, the response of different cell culture systems was highly variable when induced with different compounds.

Cells, Cultured

Abnormal macrophages and NK cell cytotoxicity in human systemic lupus erythematosus and the role of interferon and serum factors.

Macrophage (MO) and natural killer (NK) cell mediated cytotoxicity to K562 target cells were strikingly decreased in patients with systemic lupus erythematosus (SLE). SLE NK cells failed to release soluble factor(s) for lysing the targets. IFN-induced enhancement of both types of cytotoxicity was impaired. NK cells from healthy subjects kept their activity in culture with or without IFN for more than six days whereas SLE NK cell activity declined to zero at day 3. So, the increased IFN level of many SLE patients and a possible prior IFN priming effect seemed unrelated to the insensitivity to exogenous IFN in vitro. Inhibition factor(s) of SLE serum suppressed NK cytotoxicity in the presence of IFN whereas IFN sensitivity of MO remained unaffected indicating the complex regulation by serum components of immune reactions.

Chromium Radioisotopes

[Investigations on the standardization of the lysoplate technique for assay of lysozyme].

In this paper studies for the standardization of the estimation of lysozyme in low concentrations concerning the lysoplate technique are reported. The influence of the conditions of diffusion, the concentration and the age of the bacteria as well as the judgement of different pictures of lysis and contrast resp. have been measured and compared. Sufficient results have been obtained with "Purified agar" (Difco) in a concentration of 0.9% and with living, 48 h old strains from Micrococcus luteus. After this a mixture of the bacteria in a concentration of 2.75 x 10(8)/ml with 5 ml "Purified agar" at 60 degrees C can be recommended. Using conditions of incubation with 50 degrees C and a final time of 4 h lysozyme can be estimated certainly with a sensitivity of 1 microgram/ml.

Agar

[The anticomplementary effect of animal sera--a contribution to the precise definition of the complement-binding reaction].

Photometric procedures (standardised complement fixation reaction) were used to determine the anticomplementary action of animal sera. Multiplication factors, K, of 3.0 to 5.0, related to human sera, were recorded and were found to be capable of reducing or offsetting anticomplementary serum action in CFR in terms of a definitive complement excess. Anticomplementary action of animal sera, for all practical purposes, does no longer apply to dilution ratios of 1:16. The complement excess necessary for titres of 1:4 and 1:8 should be precisely defined and can then be calculated in constant measures. Hence, titres of 1:8 may be rendered accessible to safe assessment. Titres of 1:4 will continue to be problematic. The following order of animal sera was defined in comparison to human sera: cattle, pigeon, duck, sheep, cat, turkey, swine, coypu, hen, dog.

Animals

[Experimental studies of in vitro IFN induction by different polynucleotides in human cell culture systems].

Several polynucleotides were tested for interferon induction in comparison with the standard Poly (IC) in human diploid fibroblasts and in human leukocyte suspensions. We received high IFN-titre following superinduction of the polynucleotides in human fibroblasts. These results show that under superinduction conditions partly 3 times more interferon is induced in comparison with the standard inductor Poly (IC). The tested concentration of 10 micrograms/ml polynucleotides did not result in any IFN yields or only in very low ones in human leukocytes, which were only within the range of detectability.

Cells, Cultured

[Comparative studies of bronchial secretions in children with chronic, nontuberculous lung diseases. 3. The detection of lysozyme, transferrin, alpha 1-antitrypsin, alpha 2-macroglobulin, haptoglobin and alpha 1-acid glycoprotein].

In 166 bronchial secretions from 63 children with chronic nontuberculous lung diseases lysozyme, transferrin, alpha 1-antitrypsin, alpha 2-macroglobulin, haptoglobin and alpha 1-acid glycoprotein were estimated. In patients with hard bronchoscopic or bronchographic alterations a reduction of lysozyme, alpha 1-antitrypsin and alpha 2-macroglobulin could be found. These proteins were measured more frequently in cases with dark altered mucosa. Moreover no relation could be found between transferrin, alpha 1-antitrypsin and alpha 2-macroglobulin and the outbreak of the diseases. -In bacterial contaminated secretions transferrin could be demonstrated more frequently in comparison with sterile bronchial secretions.

Adolescent

[Comparative studies of bronchial secretions in children with chronic, nontuberculous lung diseases. 2. The detection of IgA, sIgA, IgG, IgM and albumin].

The aim of the present study was to estimate some proteins in bronchial secretions from children with chronic nontuberculous lung diseases. In 166 samples from 63 children the immunoglobulins IgA, sIgA, IgG, IgM and albumin were measured. With rising deterioration of the state of the disease IgG, IgA and albumin were found to be increased, maximal values were observed in patients with dark altered mucosa. With increasing duration of the disease and in comparison with relapsing and deforming bronchitis IgA and sIgA are elevated in patients with chronic bronchitis. The other proteins had a decreasing tendency. In comparison with the later states of illness in sucklings with beginning of the lung disease IgA and sIgA could be estimated less frequently.

Adolescent

[Comparative studies of bronchial secretion in children with chronic, nontuberculous lung diseases. 1. Methodico-technical studies of secretion collection and interpretation of the results].

The aim of the present study was to estimate different proteins in 166 bronchial secretions from 63 children with chronic nontuberculous lung diseases. In a first publication some methodological problems as the age of patients, the position of the bronchoscope, the bronchoscopic and bronchographic situation resp. and the mode of extraction are analysed. With increasing age the concentration of sIgA is elevated - in contrast to the IgG concentration. Only in severe diseases albumin declines with increasing age. Some variations in the concentration of proteins have been observed in relation to the position of the bronchoscope and in regard to a repeated extraction of bronchial secretions. No important differences in the concentration of proteins have been found in secretions obtained during diverse days. The different protein patterns in the bronchial secretions could be explained only partly by variations in the course of diseases.

Adolescent

[Bacteriological findings in bronchial secretions of children with chronic, nontuberculous lung diseases and their relationship to local transferrin values].

In 142 bronchial secretions from 63 children with chronic nontuberculous lung diseases the content of transferrin was studied. In 68 samples (= 48%) transferrin has been found in concentrations between 0.1 and 13.9 mg/100 mg total protein. Fifty six of the secretions were analysed bacteriologically, microbes have been isolated in 37 of them (66%). Of the detected bacteria 5 species were considered as potentially pathogenic. The bacterial growth has been shown more frequently in secretions of patients with heavily inflamed bronchial mucosa. In bacterially contaminated secretions the occurrence of transferrin was reduced.

Bacteria

[Microbiologic aspects of inflammatory joint diseases].

Regarding of microbiological aspects of arthritis three forms of joint diseases are under investigation: the septic arthritis, the reactive arthritis and the Rheumatoid Arthritis. In 95% of patients with septic arthritis microorganisms as causative agents responsible for the disease are described: Staphylococci, Streptococci, some gram-negative bacteria. By an haematogenic route of infection predominantly patients with immunosuppressive therapy are altered. In newborns and children septic arthritis is to observe more rarely. A reactive arthritis is a postinfectious sterile process in dependence on an infection occurred at an earlier time. As etiologic agents Yersinia, Enterobacteriaceae and Campylobacter have been discovered. 80% of the patients suffering such a reactive arthritis are carrier of the HLA-B27 system. The etiology of the Rheumatoid Arthritis is an open, unanswered problem. Of importance are: immunogenetic conditions, autoimmune phenomena, endocrinologic, dietetic and psychologic factors as well as bacteria and viruses as causative agents: cocci, bacilli, Diphteroids, endoparasitic bacteria (Listeria, L-forms, Mycoplasma, Chlamydiae), viruses (Adeno-, Mumps-, Measles-, ECHO-, Coxsackie-A- and B-, Hepatitis-, Cytomegalo-, Para-influenza-, Retro-, Parvo- and Rubella viruses). In the last years the EBV is of interest covering the question of a distinct virus persistence in tissues and the adequate limiting factors. Perhaps a defect of the hu-IFN-gamma-system might be of immunopathological and clinical significance.

Arthritis, Infectious

[Immunoglobulin A and its significance for mucosa immunity--a contribution to the understanding of microbial interactions].

The secretory immunoglobulin A is still dominating with regard to knowledges and further investigations of the causes of mucosal immunity. Origin, formation, structure and mode of action of s-IgA are extensively explored. In the clinical range results of researches on symptoms and consequences of selective IgA deficiency are gaining importance, increasingly. Patients with IgA defect suffer up to 40 times more frequently from allergies and autoimmunopathies. In the induction of the immune response cellular components of mucosa immunity attaining the Lamina propria and the epithelium with the effector cells of Peyer's patches play a particular role.

Animals

Development of mathematical models for an in vitro-phagocytosis test system.

Phagocytosis tests have been carried out by many authors using different methods under different conditions. The results have been interpreted in different ways, as well sometimes with conflicting notations. In order to get to a more systematic data analysis and to separate intrinsic from methodic influences, the possibility to apply mathematical models to a phagocytosis test has been studied. In agreement with previous experiences that phagocytosis can well be represented by a mathematical treatment as Michaelis-Menten-type enzyme kinetics concerning its initial rate and by an exponential function under in vivo conditions, in vitro-phagocytosis was phenomenologically described as an analogon of an irreversible bimolecular chemical reaction. In this way, rate and capacity of phagocytosis may be quantified separately. On the basis of systematic deviations of the data from this model, modifications have been developed which could be connected with pertinent observations. The design of further experiments from preliminary results on the basis of our models is discussed.

Granulocytes