[Radiologic diagnosis of congenital choledochal cyst].
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Adolescent↗
Biomedical subjects
S Krause
Publications and source records attributed to S Krause.
Increased generation of reactive oxygen species in mononuclear blood cells from hypercholesterolemic patients.
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Adult↗
Functional behaviour of mononuclear blood cells from patients with hypercholesterolemia.
Mononuclear cells were prepared from venous blood obtained from 20 patients with a newly diagnosed hypercholesterolemia and without clinical signs of vascular disease, and from 19 age and sex matched controls. Adhesiveness to plastic surface, phagocytic activity measured as ingestion of zymosan particles, and spontaneous motility of mononuclear cells from patients were significantly higher by 57%, 19% and 50%, respectively, when compared to controls. In controls chemotaxis induced by the chemotactic peptide FMLP was slightly higher than spontaneous motility measured in absence of FMLP, whereas in patients FMLP significantly inhibited cell motility by about 47%. With the exception of FMLP-induced chemotaxis the results indicate that mononuclear cells are hyperreactive in hypercholesterolemia.
Adult↗
Ex vivo investigation of blood monocyte and platelet behaviour in pigs maintained on an atherogenic diet.
Domestic pigs aged 4 months were fed for 16 weeks an atherogenic diet rich in cholesterol and saturated fatty acid. The increase of plasma cholesterol and triacylglycerol levels was found to be accompanied by a significant increase in the number of blood monocytes and platelets when compared to control animals. Furthermore, the atherogenic diet produced a small but significant reduction in the blood monocyte phagocytic capacity and adhesion to plastic surface. No significant differences between both groups were found when spontaneous platelet aggregation in whole blood was studied. However, platelets from pigs fed the atherogenic diet had a smaller mean cell volume compared to controls. The results indicate than an atherogenic diet may affect blood monocytes and platelets in pigs.
Animals↗
Interferon-gamma-induced expression of tissue factor activity during human monocyte to macrophage maturation.
The expression of tissue factor (TF) during differentiation of human monocytes (MO) to macrophages (MAC) in vitro is investigated in this study. In MO, TF activity can be induced by the addition of lipopolysaccharides (LPS) as detected by Northern blot analysis and measured functionally as procoagulant activity (PCA), while IFN gamma alone has only marginal stimulatory activity. During in vitro differentiation of MO into MAC, however, there is a steady increase in IFN gamma-induced PCA with a maximum on day 7. While MO during the first 2 days in culture are more responsive to LPS, IFN gamma becomes the prominent stimulus for mature MAC. The response to IFN gamma is rapid with a peak within 6-8 h and a subsequent downregulation to baseline activity within 24 h. Our results demonstrate that IFN gamma can effectively induce TF in human MAC and that its expression is developmentally regulated during MO to MAC maturation in vitro.
Blood Coagulation Factors↗
Defective function of blood granulocytes in patients with diabetes mellitus-associated marginal periodontitis.
In ten periodontitis patients suffering from type I diabetes mellitus, phagocytic activity, aggregation and chemiluminescence generation of blood granulocytes were determined. Compared to controls with clinically healthy periodontal conditions, the phagocytosis of zymosan particles and the aggregation response induced by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine were significantly decreased, whereas aggregation induced by the platelet-activating factor, a potent mediator of inflammation, was significantly enhanced.
Adult↗
On the flexibility of myosin in solution.
Rabbit skeletal muscle myosin from the same rabbit was prepared by two different methods, and then purified by either Sephadex or hydroxylapatite chromatography. The resulting myosin samples were analyzed in 2-10 mM sodium pyrophosphate solutions at pH 9 using transient electric birefringence. The birefringence decay signals were fitted using a Fortran program called DISCRETE and two relaxation times, 49.7 +/- 5.6 and 11.2 +/- 2.5 microseconds, were determined. These relaxation times were independent of the method of myosin preparation, the method of myosin purification, the concentration of sodium pyrophosphate between 2 and 10 mM, the concentration of myosin between 0.08 and 1.59 mg/mL, and the temperature between 4.0 and 20.0 degrees C, after correction to 20.0 degrees C. The longer relaxation time is consistent with a rigid, linear myosin molecule. The shorter relaxation time is consistent with myosin that has a completely flexible hinge region in the myosin tail. Both relaxation times are inconsistent with the previously reported single relaxation time of myosin obtained by fitting the birefringence decay data to only 90% of the decay signal. By forcing some of the birefringence decay data in the presence work to fit 90% of the decay signal with a single relaxation time, approximately the same relaxation time as previously reported was obtained.
Animals↗
Large-scale production of human tumorcytotoxic macrophages grown from blood monocytes of cancer patients.
For adoptive immunotherapy protocols using cells of the macrophage (M phi) system, well differentiated and functionally competent effector cells are required. In this presentation the generation of a large number of M phi grown in vitro from blood monocytes (mo) is reported. Mononuclear cells (MNC) were collected by cytapheresis and subsequent Ficoll centrifugation. Mean yield was 6.9 x 10(9) MNC (range from 3 x 10(9) to 1.2 x 10(10), n = 18) with a mean mo count of 22 +/- 14%. MNC were cultured at 5 x 10(6)/ml in suspension on hydrophobic Teflon foils with 2% autologous serum for 7 days with recombinant human interferon-gamma (rhIFN-gamma) being present for the last 18 h of culture. Cells were harvested and activated mo-derived M phi separated from lymphocytes by counter-current centrifugal elutriation. On average, 42% of mo cultured could be recovered as M phi, the maximal number of M phi generated being 1.7 x 10(9) with a purity of up to 96%. Mo-derived M phi appeared to be mature by their expression of maturation-associated antigens and proved to be cytotoxic to allogeneic tumor targets in vitro. They secreted large quantities of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and granulocyte-macrophage colony stimulating factor (GM-CSF) upon stimulation with endotoxin. Using the technology described, this study revealed that large amounts of tumorcytotoxic M phi can be generated from the peripheral blood of cancer patients to be used in adoptive immunotherapy trials.
Adult↗
A new approach to adoptive immunotherapy of cancer using tumorcytotoxic macrophages grown from peripheral blood monocytes.
Clinical trials to evaluate the potential of adoptive immunotherapy in cancer patients have been restricted to the use of lymphoid effector cells. Of the other probably even more important host defense system against tumor growth, the mono-nuclear phagocyte system, only monocytes (mo) have been reinfused which, however, represent immature precursor cells and acquire full functional competence only upon further maturation. This is a report on 7 patients who received autologous macrophages (MO) grown in vitro from blood mo and activated by interferon-gamma (IFN gamma). Mononuclear cells were isolated from whole blood by cytapheresis and cultured for 7 days with 2% autologous serum on hydrophobic Teflon foils. Eighteen house before cell harvest, recombinant human IFN gamma was added at 200 IU/ml. Mo-derived MO were purified by counter-current elutriation. Starting with 10(8) MO cells, therapy was escalated up to the maximal number of MO obtainable from one single preparation cycle. Currently, 26 therapies have been performed with the maximal dose being 1.7 x 10(9) MO per infusion. Except for low grade fever (less than 38 degrees C), MO autografts were well tolerated, with no side effects observed. Biological response was followed by analyzing the serum levels of beta 2-microglobulin, neopterin, interleukin-6, tumor necrosis factor, and lysozyme. While in 3 out of 7 patients serum neopterin increased in response to MO therapy, other biological response parameters remained at pretreatment levels. Radiolabeled MO were shown to first accumulate in the lungs, then to pool into liver and spleen.(ABSTRACT TRUNCATED AT 250 WORDS)
Biopterins↗
Adoptive transfer of tumor cytotoxic macrophages generated in vitro from circulating blood monocytes: a new approach to cancer immunotherapy.
Cells of the macrophage lineage are considered to be of special importance in the defense of the host against tumor development and spread. Immunotherapeutic strategies to stimulate macrophage (MAC) tumor cytotoxicity make use of activating compounds such as gamma-interferon which are given systemically. However, there are several lines of evidence that in malignant disease the generation of cytotoxic effector MACs is impaired. Both defective cell maturation and loss of responsiveness to activation are described. Here, a first clinical phase I trial of adoptive immunotherapy in cancer patients using autologous MACs generated in vitro from blood monocytes (MOs) is reported. Mononuclear cells were isolated by cytapheresis and density centrifugation and cultured in hydrophobic Teflon bags for 7 days with 2% autologous serum and recombinant human gamma-interferon being present for the last 18 h. Cytotoxic MO-derived MACs were then purified by countercurrent elutriation and reinfused into the patient. A total of 72 therapies have been performed with patients being treated i.v. (n = 8) and i.p. (n = 7). In vitro generated MACs proved to be mature as judged by the expression of maturation-associated surface molecules (MAX antigens, CD16, CD51, CD71), were cytotoxic to U937 tumor cells, and were efficient secretory cells. Cell dose escalation was performed in the first patients beginning with 10(8) MACs to finally infuse the total number of cells recovered from one single cycle of isolation and culture. MAC yield varied from 1 to 17 x 10(8) representing 13-79% of MOs initially seeded. Adoptive MAc transfer was well tolerated. Side effects observed were low-grade fever (less than 38.5 degrees C), induction of the coagulation cascade, and abdominal discomfort after i.p. application. The procoagulant activity of MAC autografts was cell dose dependent and demonstrated by detection of circulating fibrin monomers and thrombin-antithrombin complexes. Biological responses observed included elevated serum neopterin levels and the appearance of interleukin-6 in sera and ascitic fluids. Indication of a possible therapeutic effect was only observed in i.p.-treated patients and consisted of disappearance of malignant ascites in 2 of 7 patients.
Adult↗
Cloning and characterization of major antigenic determinants of human cytomegalovirus Ad169 seen by the human immune system.
Starting from a cosmid library of HCMV Ad169-DNA random fragments of DNA were generated. Fragments about 200 to 600 bp in length were selected and cloned into open reading frame (ORF) expression vectors to create ORF-libraries that represent either the entire viral genome or defined subregions. About 120,000 clones were isolated and screened immunologically for the synthesis of fusion proteins consisting of an antigenic peptide encoded by the CMV sequence coupled to a truncated E. coli beta-galactosidase molecule. Anti-CMV sera raised in animals as well as human hyperimmune globulin were used for colony screening. Distinct sets of antigenic fusion proteins were recognized by different antisera. Ten of the clones giving strong reactions with human immune sera were mapped on the CMV genome and the sequences of the CMV inserts determined. Antibodies against fusion proteins were raised in mice or rabbits to identify the corresponding CMV proteins. Antigenic fusion proteins described here were recognized by most individual human CMV immune sera tested. They allow determination of the humoral immune response to defined determinants and may therefore be particularly useful in diagnosis and vaccine development.
Amino Acid Sequence↗
Aggregation behaviour of blood granulocytes in patients with periodontal disease.
This behaviour was studied in 17 patients with severe marginal periodontitis and in 16 healthy controls. Aggregation induced by platelet-activating factor (PAF-acether), a potent mediator of inflammation, was significantly enhanced in the patients, whereas no significant difference was observed between patients and controls when aggregation was induced by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP). When the patients were subdivided into categories of progressive adult periodontitis, juvenile or post-juvenile periodontitis, aggregation induced by PAF-acether was enhanced in all three subgroups. However, FMLP-induced aggregation was slightly increased only in progressive adult and post-juvenile periodontitis, but decreased in juvenile periodontitis.
Adolescent↗
[The phagocytic activity of the blood neutrophilic granulocytes in patients with marginal periodontitis].
The ingestion of opsonized zymosan particles by neutrophil blood granulocytes and the chemiluminescence in samples of whole blood, induced by zymosan, Streptococcus mutans as well as phorbol myristate acetate, as a measure of the generation of reactive oxygene species were studied in patients with various forms of marginal periodontitis. Compared to a control group the phagocytic activity was found to be enhanced in progressive adult periodontitis and diminished in juvenile periodontitis whereas no differences to controls were found in chronic nonprogressive or postjuvenile periodontitis. With respect to the height of the chemiluminescence signals increased values were only measured in chronic nonprogressive periodontitis after stimulation by phorbol myristate acetate. The results indicate that impairment of blood granulocyte functions may be a pathogenetic factor for the development and the progression of marginal periodontitis.
Adolescent↗
Influence of substances affecting cell sulfhydryl/disulfide status on adherence of human monocytes.
An in-vitro model is described for investigating the adherence of human monocytes. Mononuclear cells (MNC) isolated from peripheral blood were incubated in plastic multiwell cell culture plates. The adherence of monocytes was quantified on the basis of their DNA content. The cell adherence proceeds rapidly; after 30 min of incubation about 85% of maximum adherent cells were attached to the plastic surface. On testing the effects of various sulfhydryl-affecting substances on monocyte adherence we found that the thiol-oxidizing compound diamide (0.1-1 mmol/l) inhibited the adherence by about 60%. Incubation with an extract of the plant feverfew, which contains materials that neutralize cellular sulfhydryl groups, also diminished monocyte adherence. The soluble thiol 2-mercaptopropionylglycine, in a concentration range of 0.5 to 10 mmol/l, had no effect on adherence in this system. The results suggest that cellular sulfhydryl groups play an important role in the adherence of monocytes.
Cell Adhesion↗
Polyhydramnios with maternal lithium treatment.
Severe polyhydramnios, probably due to fetal lithium toxicity, is described. The mother had been treated with lithium because of manic-depressive psychosis. The plasma lithium level during the pregnancy was in or below the therapeutic range. From the 26th week of gestation, polyhydramnios developed. In the 35th week, 11.5 L of amniotic fluid was removed over a period of 12 hours by transabdominal amniocentesis. A cesarean delivery was performed in the 39th week of gestation because of fetal distress. The infant presented with the following symptoms, which in previous reports have been associated with lithium toxicity: asphyxia, apnea, cardiac decompensation, respiratory distress, hypoglycemia, thrombocytopenia, diabetes insipidus, hypotonia, and convulsions. The polyhydramnios was probably caused by fetal diabetes insipidus, possibly combined with cardiac decompensation. Lithium can be toxic to the infant and the fetus even though the mother is not affected and has a normal or low plasma lithium level. Polyhydramnios may be a sign of fetal lithium toxicity.
Adult↗
[The energy preservation requirement of growing pigs of different sexes fed normal and high protein diets. 4. Determination of parameters in the blood for estimating metabolic status].
In connection with experiments for the ascertainment of energy and nutrient metabolization in castrated pigs, sows and boars over the complete fattening period and with alternating maintenance and growth feeding as well as the inclusion of an extreme protein supply level, blood parameters were studied of 3 animals per variant in order to recognize possible deviations in the metabolism and to be able to better assess the results of the measurements of energy metabolism. The results of the determination of the content of glucose, insulin, ketoses, ammonia, urea and amino acids in the blood are announced, the results of glucose elimination contained in the intravenous glucose tolerance test are depicted as tolerance curves. As a result, there was to be seen, arranged according to animal categories, a ranking of the glucose elimination rate of castrated pigs greater than sows greater than boars. The same sequence was observed with regard to insulin secretion, which corresponds to the blood sugar level. On the whole, the results of the blood tests do not show critical states of the metabolism hat can lead to an influentiation of energy metabolism.
Amino Acids↗
Monoclonal antibody to a supertypic determinant associated with HLA-DRw52.
A cytotoxic mouse monoclonal antibody UL-52 (IgG2b) was obtained after immunization of a BALB/c mouse with the lymphoblastoid cell line STA homozygous for HLA-A3, B8, Cw7, DR3, DRw52, DQw2, DPw2. Fluorescence analysis on a panel of B lymphoblastoid cell lines from the 10th International Histocompatibility Workshop 1987 showed almost exact concordance of UL-52 reactivity with the presence of the HLA-DRw52 antigen. Cytotoxicity testing of UL-52 on mononuclear cells of HLA-typed individuals revealed a pattern of reactivity closely associated with the HLA-DRw52 specificity as defined by conventional alloantisera (R = 0.77). UL-52 precipitated appropriate 29,000- and 33,000-dalton bands on SDS- polyacrylamide gels under reducing conditions from an HLA-DRw52 positive B lymphoblastoid cell line. Thus, by serological and biochemical criteria UL-52 defines a supertypic determinant associated with HLA-DRw52. In contrast to most DRw52- like monoclonal antibodies, UL-52 binds to DRw8 positive cells.
Animals↗
[Cellular chemiluminescence of activated phagocytes of whole blood].
Both, the phagocytic process and the activation of phagocytes with soluble stimuli are accompanied by increased production of reactive oxygen species (ROS). Chemiluminescence (CL) measurement is a simple and sensitive method for the detection of ROS generation. Phagocytes (mainly polymorphonuclear leukocytes, PMNL) were stimulated with soluble stimulus or via phagocytosis in diluted whole blood, and the generation of Luminol-enhanced CL was registered. The time dependence of CL, determined in whole blood, corresponds to the CL from isolated leukocytes. A relationship between peak CL and the number of leukocytes as well as of PMNL was observed. The specific CL, i.e. the CL response related to a defined PMNL number, increases with the age of investigated healthy individuals. No correlations were found between CL and the capacity of PMNL to ingest zymosan particles. Relations between CL and spontaneous platelet aggregation suggest, that reactivity of blood platelets may be a contributing factor to the kinetics of the CL signal in our test system. The inhibition of CL by the sulphydryl reagents diamide and fever few extract indicate the role of cellular sulphydryl groups for phagocyte function. Measurement of CL in whole blood is proved to be a simple assay for assessment of PMNL function and allows measurements in very small blood samples (greater than or equal to 10 ul).
Cell Separation↗