PubMed Health⌕ Search

Biomedical subjects

H Rieder

Publications and source records attributed to H Rieder.

At least 91 records · Page 5Linked to original sources

Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha.

Interleukin 6 (IL6) is the new definition of a group of cytokines previously named according to their biological activity, e.g. B cell stimulatory factor 2 (BSF-2), hybridoma plasmocytoma-growth factor (HGF), interferon-beta 2 (IFN-beta 2), hepatocyte stimulating factor (HSF). It has recently been suggested that IL6 may represent the major mediator of acute-phase protein response whereas IL1 beta and TNF-alpha could play a minor role. We compared the effect of the three cytokines on hepatic protein synthesis by performing in vitro as well as in vivo experiments. Human hepatoma cells (PLC/PRF5) were exposed to each cytokine separately for 20 h, and the effect was then studied at the protein and RNA level. All three cytokines reduced albumin and increased C3 and ceruloplasmin biosynthesis. The cytokines induced the same effect at the RNA level indicating that the modulation was pretranslational. The effect of the cytokines was specific since actin gene expression was not changed; furthermore the effect was blocked by specific antibodies against the cytokines. The effect of the single cytokines was dose and time dependent, and quantitatively comparable. None of the cytokines was able to alter alpha 1-anti-trypsin synthesis. In vivo experiments with mice showed that IL1 beta and TNF-alpha both induce serum amyloid A (SAA) mRNA in the mouse liver and increase factor B (Bf) gene expression. Human recombinant IL6 induced SAA gene expression and it also had a weak positive effect on Bf gene expression after i.p. injection. These data demonstrate that the three cytokines studied are quantitatively and qualitatively comparable, and that all three are probably involved in acute-phase protein response.

Acute-Phase Reaction↗

Guinea pig Kupffer cells can be activated in vitro to an enhanced superoxide response. I. Comparison with peritoneal macrophages.

Guinea pig Kupffer cells were obtained by partial digestion of the liver with pronase and collagenase and purified by centrifugal elutriation. Cells were kept in monolayer culture and their capacity to secrete superoxide anion in response to phagocytosis of zymosan was determined by the cytochrome c method. Compared to resident peritoneal macrophages, Kupffer cells produced somewhat less superoxide (60% +/- 30%). Both cell types were activated by 24 h preincubation with lipopolysaccharide from Salmonella minnesota or muramyl dipeptide to give twice as high a superoxide response to zymosan. The same effect was achieved when Kupffer cells in vitro were incubated for 3 days with supernatants from phytohaemagglutinin-activated peripheral T lymphocytes or recombinant gamma-interferon. These data demonstrate that the resident macrophages of the liver, the Kupffer cells, are able to increase their capacity to secrete reactive oxygen intermediates after proper activation; this fact is possibly important in the pathogenesis of hepatocyte damage upon inflammatory reactions in the liver.

Acetylmuramyl-Alanyl-Isoglutamine↗

Guinea pig Kupffer cells can be activated in vitro to an enhanced superoxide response. II. Involvement of eicosanoids.

In the preceding paper it was shown that Kupffer cells isolated by digestion of the liver and purified by centrifugal elutriation can be activated in vitro by lipopolysaccharide and muramyl dipeptide to an enhanced superoxide response upon zymosan phagocytosis. Lipopolysaccharide and muramyl dipeptide also led to a strongly increased prostaglandin E2 release during the phagocytosis of zymosan. This activation was accompanied by an increased production of prostaglandin E2 during the incubation with the stimuli. Prostaglandin E2 synthesis was inhibited by the cyclooxygenase inhibitor indomethacin, reduced by dexamethasone, but only slightly decreased by the lipoxygenase inhibitor nordihydroguaiaretic acid. Indomethacin and dexamethasone also reduced the superoxide response, which only in the case of indomethacin is reversed by exogenous prostaglandin E2. Dexamethasone reduced the superoxide response in unstimulated cells as well. From these results it is deduced that cyclo-oxygenase products, especially prostaglandin E2, but not lipoxygenase products, i.e. leukotrienes, play some regulatory role in the activation process of Kupffer cells; in addition, a prostaglandin-independent inhibition exerted by dexamethasone seems to exist.

Acetylmuramyl-Alanyl-Isoglutamine↗

Alpha- and gamma-interferon (IFN alpha, IFN gamma) but not interleukin-1 (IL-1) modulate synthesis and secretion of beta 2-microglobulin by hepatocytes.

Soluble serum beta 2-microglobulin has been thought to result from membrane shedding by activated T-lymphocytes. This hypothesis could explain the increase of beta 2-microglobulin serum levels during virally induced mononucleosis, but not elevated levels as observed in other virally induced and in malignant diseases. In this paper we demonstrate that beta 2-microglobulin is a true secretory protein, and that its synthesis in hepatocytes is modulated by IFNs but not by IL-1. While the 45,000 MW HLA antigen can be found only in cell lysates, beta 2-microglobulin is shown to be secreted also into the culture medium like other secretory proteins (e.g. albumin-factor B-complement C3). Furthermore, interferon alpha (IFN alpha) as well as interferon gamma (IFN gamma) directly stimulate, in a dose- and time-dependent manner, beta 2-microglobulin synthesis by human hepatoma cells (Mz-Hep-1 and PLC/PRF5) and murine hepatocyte primary cultures. The increase of beta 2-microglobulin production induced by interferons is demonstrated at both the protein and the RNA level, indicating that interferon acts at a pretranslational level. The interferon effect on beta 2-microglobulin synthesis is specific since synthesis of secretory proteins like complement C3 or albumin, and of a structural protein like actin, remains unchanged. In contrast to IFN, IL-1, the main mediator of acute phase response, does not change beta 2-M biosynthesis rate. These data indicate that (i) beta 2-microglobulin is a secretory protein, (ii) IFNs but not IL-1 can mediate increased beta 2-M serum levels, and (iii) the liver may be its primary source.

Albumins↗

Demonstration of antibodies to the surface (anti-p41) and core proteins (anti-p24) of the human immunodeficiency virus (HIV) in individuals positive for anti-HIV.

Diagnosis of infection with the human immunodeficiency virus (HIV) relies on the demonstration of antibody to this virus. Occasionally, the combined analysis of sera using ELISA and western blot reveals false-positive results. We have compared a newly developed test to detect antibodies to the core (anti-p24) and surface (anti-p41) proteins of HIV with the established tests described above. Anti-p24 and anti-p41 were negative in three individuals positive for anti-HIV by ELISA and immunoblot; they had a low risk to acquire HIV infection and were clinically and immunologically normal and suspected false positive previously. In 62 individuals at risk, anti-p41 was always positive while anti-p24 was negative in 24/62 individuals including all but one patient with AIDS. The data indicate that this new test may replace the western blot as a reliable, widely available, and standardized confirmatory assay. In addition, preliminary evidence needs to be confirmed that quantitative analysis of anti-p24 might be of prognostic value in the course of HIV infection.

Acquired Immunodeficiency Syndrome↗

Fat storing cells (FSC) of rat liver synthesize and secrete fibronectin. Comparison with hepatocytes.

Fat storing cells (FSC) of rat liver were isolated and kept in culture for up to 2 weeks. Freshly isolated cells and cells in culture were characterized functionally (vitamin A content) and morphologically. Their synthetic capacity for fibronectin was studied quantitatively by ELISA-measurement and qualitatively by biosynthetic labeling, immunoprecipitation and SDS-PAGE analysis. The synthesis product and the kinetics of the synthesis and secretion were compared with those obtained from culture of hepatocytes. FSC were shown to synthesize and secrete fibronectin under the culture conditions used. No fibronectin synthesis was detected during the first 3 days of culture. Thereafter the synthesis increased continuously up to 2600 ng/24 h/100 micrograms cell protein. The molecular weight of fibronectin synthesized by fat storing cells seems to be the same as the one synthesized by hepatocytes, but the secretion proceeds faster in hepatocytes than in FSC. No differences between the two molecules were observed when both cell populations were treated with tunicamycin (TM), an antibiotic which inhibits the N-glycosylation of the primary translation product.

Animals↗

Expression of Ia-antigens on guinea pig Kupffer cells. Studies with monoclonal antibodies.

The expression of the Ia-antigen on guinea pig Kupffer cells was studied employing two monoclonal antibodies against two different determinants of the Ia-molecule. The study was performed in situ on liver sections and on isolated highly purified Kupffer cells kept in culture up to 6 days. The influence of guinea pig hepatocyte culture supernatant and of supernatants of phytohemoagglutinin (PHA)-stimulated human peripheral blood lymphocytes (PBL) on the Ia expression was measured. Immunofluorescence staining of cryostat sections revealed that the monoclonal antibodies used are able to detect Ia-antigens on liver macrophages in situ. The in vitro studies strongly suggest that all Kupffer cells are able to express Ia-antigens. The expression of Ia-antigens on Kupffer cells decreased during the culture time and was no longer detectable on day 5. At this time, incubation of the cell cultures with PBL conditioned medium induced the reexpression of Ia-antigens. Supernatants from guinea-pig hepatocyte cultures did not have any negative influence on the expression of the Ia-antigen on Kupffer cells in vitro. These data support the hypothesis that liver macrophages have the potential to behave immunologically as accessory cells and might contribute to local immune responses in acute as well as chronic states of liver diseases.

Animals↗

Phagocytosis of hepatocyte mitochondria by rat Kupffer cells in vitro.

Kupffer cells in primary culture bind and endocytose rapidly added rat liver mitochondria. Using phase contrast microscopy various stages of the uptake and digestion of these organelles were documented. Activities of mitochondrial enzymes within the Kupffer cells increased during the early phase of phagocytosis; they later declined, reaching the endogenous level of the Kupffer cell mitochondria after 3 to 4 h. The uptake was enhanced in the presence of heparin or rat serum, while iodoacetate, cytochalasin B or anti-fibronectin antisera were inhibitory. The transient presence of enzymatically active hepatocyte mitochondria renders Kupffer cells capable of producing urea. This mechanism partially explains earlier observations of urea formation in non-parenchymal rat liver cells.

Animals↗

[Field experiences with the 6-month Singapore therapy in the treatment of open lung tuberculosis in Cambodian refugees].

The particular situation of a refugee camp with transit character, as represented by "holding Centre Khao-I-Dang" (KID) for Cambodian refugees in Thailand, had to be taken into consideration when determining the therapy plan for the disease that is epidemiologically most important, smear-positive pulmonary tuberculosis. Under Singapore conditions daily administration of isoniazid (H) and rifampicin (R) for 6 months combined with a 2-month intensive phase of streptomycin (S) and pyrazinamide (Z) daily proved highly effective. The large-scale transfers in KID in February and March 1981 led to consistent administration of this therapy plan, which is recommended by the WHO. By the end of September 1981 61 patients aged 15 years and over had entered the "Thai/Swiss Red Cross TB Programme". Criterion for entrance was the presence in sputum of acid-fast bacilli in the Ziehl-Neelsen stain. The routine examinations consisted of three microscopic sputum examinations per month, a sputum culture and a chest x-ray before commencement of therapy, followed by a chest x-ray at the end of the intensive phase and at the end of therapy. Efficacy and side effects of the 6-month therapy in our collective were similar to those of the Singapore study.

Adolescent↗

[Assessment of aminoglycoside serum concentrations. Comparative study using gentamicin (author's transl)].

Four methods were used to assess gentamicin concentrations in 37 sera of patients treated with gentamicin. It was shown that the bioassay (agar diffusion) and the enzyme immunoassay correlated well, and the latex agglutination inhibition test badly, with the radioenzyme assay which was used as the reference method. Among presently available methods only the bioassay can be performed with relatively little equipment.

Gentamicins↗

NADP-dependent dehydrogenases in rat liver parenchyma. III. The description of a liponeogenic area on the basis of histochemically demonstrated enzyme activities and the neutral fat content during fasting and refeeding.

The activities of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase(6PGDH), malic enzyme (ME) and isocitrate dehydrogenase (ICDh) were investigated with optimized histochemical methods (Rieder it al 1978), and the activity of 3-hydroxybutyrate dehydrogenase (3HBDH) and neutral fat content with conventional techniques in the liver of male rats under the following experimental dietary conditions: (A) Fasting for 0, 12 and 84h; (B) 84-h fasting followed by refeeding with a low-fat, high-carbohydrate diet for 6 h and for 2, 3, 5, 7, 11 and 14 nights; (C) refeeding with standard diet for 5 nights; (D) low-fat high-carbohydrate diet for 7 an 14 nights. The activities of G6PDH, 6PGDH and ME decreased slightly during fasting primarily in zone 1 and increased dramatically on refeeding with a low-fat, high-carbohydrate diet. This activity increase was confined mainly to zone 3 during the first 3 days and was accompanied by a deposition of neutral fats that began in zone 3 and progressed to zone 1. Neutral for accumulation was maximal after 3 nights, with a uniform accumulation of large droplets in all the hepatocytes; this was followed by a release that started in zone 3 and proceeded in a periportal direction. On the other hand, G6PDH, 6PGDH and ME attained their maximum activities after 5 amd 7 nights of low-fat diet, the activities being nearly homogeneously distributed over the liver acinus in a few cases. Subsequently the activities fill mainly in zone 1, causing the activity patterns and levels to approach those of the animals in group (D). In contrast to this, the activity of ICDH increased during fasting principally in zone 1, so that the otherwise steep activity gradient in favor of zone 3 lessened. Refeeding led at first to a fall of activity below the initial value, but later the normal distribution pattern was restored. The activity of 3HBDH showed a behavior similar to that of ICDH. The findings are discussed with reference to the functional heterogeneity of the liver parenchyma, and the existence of a liponeogenic area in zone 3 is proposed.

Animals↗

Extracellular polysaccharide synthesized by the oral bacterium Streptococcus mutans of serotype a to e in vitro.

Extracellular polysaccharide (EPS) synthesized in vitro by Streptococcus mutans belonging to serotypes a, b, c, d and e was shown to consist mainly of glucan. Only strains of type b and e regularly produced substantial amounts of fructan, too. Strains of type d synthesized significantly higher quantities of glucan than strains of the other types per gram of bacterial mass. The percentage of insoluble glucan was lowest in samples from strains of type a and c, and highest in samples from strains of type d. In contrast to the insoluble glucan, the linkage pattern of the soluble glucan of the five types showed only small differences. The percentage of alpha-1,3-linked glucose units was highest in the insoluble glucan from strains of type d and e, and lowest in glucan from type c. The differences were significant. Incubation of Strep. mutans under various culture conditions showed that the quantities and composition of EPS formed depend on the culture condition used. The effect of culture conditions, however, was similar for all strains. Therefore the differences found with respect to the quantities and composition of EPS synthesized in vitro by Strep. mutans of different types are apparently type-dependent.

Culture Media↗