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Biomedical subjects

H Schroten

Publications and source records attributed to H Schroten.

At least 55 records · Page 3Linked to original sources
PubMed1993

Glycogen storage disease type Ib: infectious complications and measures for prevention.

A patient with glycogen storage disease (GSD) type Ib, neutrophenia, chronic inflammatory bowel disease and recurrent abscesses was treated with recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF (and also granulocyte colony stimulating factor) therapy markedly increased the neutrophil counts and reduced the frequency of infections and inflammation. We conclude that myeloid growth factors are effective for the treatment and prevention of acute infections and chronic inflammatory complications in patients with GSD Ib.

Abscess↗
PubMed1993

Inhibition of adhesion of S-fimbriated E. coli to buccal epithelial cells by human skim milk is predominantly mediated by mucins and depends on the period of lactation.

Expression of S-fimbriae is frequent in Escherichia coli strains causing sepsis and meningitis in the newborn period. We analysed the ability of human skim milk to inhibit adhesion of S-fimbriated E. coli to human buccal epithelia. Adhesion was inhibited by up to 90% using colostrum (5%) and up to 50% with mature milk (5%), indicating that this anti-infective mechanism depends on the period of lactation. Elimination of up to 99% of immunoglobulins and 91% of lactoferrin by affinity chromatography had no effect on the inhibition of adhesion. After separation of high- (> 10 kD) and low-molecular-weight fractions of skim milk, only the fraction > 10 kD was found to be able to inhibit bacterial adhesion. In order to further characterize receptor molecules for bacteria, we investigated binding of isolated S-fimbriae to glycoprotein bands on Western blot strips. Fimbriae mainly bound to a high-molecular-weight band (> 200 kD). According to molecular weight and staining behaviour, this band most likely represents mucins. We conclude that carbohydrate residues on secreted mucins of human skim milk are able to inhibit bacterial adhesion to mucosal surfaces. This could provide protection against neonatal sepsis and meningitis caused by E. coli.

Age Factors↗
PubMed1993

Specificity of S fimbriae on recombinant Escherichia coli: preferential binding to gangliosides expressing NeuGc alpha (2-3)Gal and NeuAc alpha (2-8)NeuAc.

The adhesins of Escherichia coli strains HB101(pANN801-13) and HB101(pAZZ50), which express S fimbriae encoded by a recombinant plasmid containing the sfaI and sfaII gene clusters, respectively, were characterized with regard to the detailed structural requirements of their binding to sialyloligosaccharides on (neo)glycoproteins and (neo)glycolipids. From binding and binding inhibition studies in solid-phase enzyme immunoassays with isolated S fimbriae, several major conclusions can be drawn. S fimbriae bind specifically to sialic acid on gangliosides. The most active structural variant of sialic acid on GM3 ganglioside is N-glycolylneuraminic acid (NeuGc). In contrast to previous reports, high binding activities were measured also for b-series gangliosides expressing NeuAc alpha (2-8)NeuAc. In agreement with earlier studies, the site of sialic acid substitution to subterminal sugars strongly influences the binding to sialyloligosaccharides, i.e., alpha-6-linked sialic acid is only poorly recognized by the adhesin compared with alpha-3-linked sialic acid. C-8 and C-9 hydroxyl groups form essential structural elements of sialic acid in the binding event.

Animals↗
PubMed1992

Inhibition of adhesion of S-fimbriated Escherichia coli to epithelial cells by meconium and feces of breast-fed and formula-fed newborns: mucins are the major inhibitory component.

We investigated the ability of meconium, feces from human milk-fed (HMF) newborns, and feces from formula-fed (FF) newborns to inhibit adhesion of S-fimbriated E. coli to human buccal epithelial cells. S-fimbriae are a common property of E. coli strains causing sepsis and meningitis in neonates. Meconium had the highest content of neuraminic acid and the strongest inhibitory effect on bacterial adhesion. HMF also exerted high inhibitory activity while FF was markedly less active: To achieve inhibitory effects comparable to HMF a sixfold amount of FF was required. Glycoproteins from excretions were separated by gel chromatography. Fractions obtained were analyzed for adhesion-inhibiting activity. In all excretions analyzed, the mucin-containing fraction could be identified as the major inhibitory component. Inhibition was probably mediated by specific interaction of this fraction with S-fimbriae, as shown by binding of isolated fimbriae on Western blots after electrophoretic separation of glycoproteins. In conclusion, our data support the view that the mucin-containing fraction from meconium and human milk exerts antibacterial functions by preventing adhesin-mediated binding of pathogenic bacteria to mucosal epithelia.

Adult↗
PubMed1992

Treatment of patients with chronic granulomatous disease with recombinant human interferon-gamma does not improve neutrophil oxidative metabolism, cytochrome b558 content or levels of four anti-microbial proteins.

Recombinant interferon-gamma (rIFN-gamma) has been described to enhance phagocyte functions in vitro and in vivo in several patients with chronic granulomatous disease (CGD). To demonstrate the clinical usefulness of this treatment, 128 patients were treated in a randomized, double-blind multi-centre study with a placebo preparation or with rIFN-gamma. We analysed parameters of neutrophil oxidative and non-oxidative metabolism in 16 patients enrolled in this study. No enhanced superoxide-release was observed in patients treated with rIFN-gamma compared to placebo-treated patients. Phagocyte cytochrome b558 content also remained unchanged. Levels of four non-oxidative antimicrobial proteins (cathepsin G, azurocidine, p29b, lactoferrin) rose, fell, or remained unchanged, irrespective of treatment with rIFN-gamma or placebo.

Blood Proteins↗
PubMed1992

Inhibition of adhesion of S-fimbriated Escherichia coli to buccal epithelial cells by human milk fat globule membrane components: a novel aspect of the protective function of mucins in the nonimmunoglobulin fraction.

We investigated the presence of factors in human milk that inhibit invasion of pathogenic bacteria. The effect of human milk fat globule membrane (HMFGM) components on adhesion of cloned S-fimbriated Escherichia coli to human buccal epithelial cells was analyzed. S fimbriae are a common feature of E. coli strains causing sepsis and meningitis in newborns and are bound to epithelia via sialyl-(alpha-2-3)galactoside structures. Human milk fat globules (HMFG) could be agglutinated by the above-mentioned bacteria. Agglutination could be inhibited by fetuin, human glycophorin, and alpha 1-acid glycoprotein. In addition, pretreatment of HMFG with Vibrio cholerae neuraminidase markedly reduced bacterium-induced agglutinations, indicating the involvement of neuraminic acid-containing glycoproteins. In contrast, lipid droplets of infant formula or artificial lipid emulsions (Intralipid) could not be agglutinated. HMFG were present in stools of breast-fed neonates as shown by indirect immunofluorescence staining with a monoclonal antibody directed against carbohydrate residues present on HMFGM. These HMFG could be agglutinated by bacteria. HMFG inhibited E. coli adhesion to buccal epithelial cells. To further characterize relevant E. coli binding structures, HMFGM components were separated by gel chromatography. The mucin fraction showed the most pronounced inhibitory effect on adhesion of S-fimbriated E. coli to human buccal epithelial cells. Our data suggest that HMFG inhibit bacterial adhesion in the entire intestine and thereby may provide protection against bacterial infection.

Bacterial Adhesion↗
PubMed1992

[Farquhar disease. Reduced phagocyte function in a 9-year-old girl with erythrophagocytic lymphohistiocytosis].

We report phagocyte function tests in a female infant with familial hemophagozytotic lymphohistiocytosis. Chemiluminescence and killing of Saccharomyces cerevisiae by monocytes and granulocytes before chemotherapy and in remission were examined. Patients' monocytes and granulocytes showed a markedly reduced chemiluminescence and killing capacity irrespective of the stage of disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Control of proven pulmonary and suspected CNS aspergillus infection with itraconazole in a patient with chronic granulomatous disease.

An 11-year-old boy with chronic granulomatous disease caused by cytochrome b deficiency developed right upper lung lobe aspergillosis. Intracerebral lesions developed on maximum doses of flucytosine and amphotericin B. Treatment with 16 mg/kg oral itraconazole was followed by a dramatic clinical improvement and almost complete disappearance of the intracerebral lesions. Plasma itraconazole levels were between 40 and 3440 ng/ml depending on concomitant medication. Toxicity was restricted to transient elevation of alkaline phosphatase and gamma glutamyl transferase. We conclude that further trials with itraconazole are justified in high risk patients in whom conventional therapy has failed.

Antifungal Agents↗
PubMed1991

Granulocyte and granulocyte-macrophage colony-stimulating factors for treatment of neutropenia in glycogen storage disease type Ib.

Two children with glycogen storage disease type Ib associated with numerous recurrent bacterial infections as a result of neutropenia and neutrophil dysfunction were treated with recombinant human granulocyte colony-stimulating factor (G-CSF). One of the two patients was previously treated with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF); therapy had to be discontinued because of severe local side effects. Both colony-stimulating factors at dosages of 3 and 8 micrograms/kg/per day, respectively, increased the average neutrophil counts from less than 300 cells/microliters to more than 1200 cells/microliters. Two subpopulations of neutrophils could be identified by their capacity to produce H2O2: one subpopulation generated H2O2 normally and a second was defective in H2O2 production. The doses of G-CSF effectively enhanced and maintained that subpopulation of neutrophils which produced normal amounts of H2O2. Moreover, these colony-stimulating factor-induced neutrophils demonstrated effective phagocytosis of zymosan particles and killing of staphylococci. Chemotaxis was decreased and could not be normalized by treatment with G-CSF. We conclude that maintenance treatment with G-CSF improved the quality of life in both patients: The number and severity of bacterial infections decreased markedly during treatment. Long-term treatment with G-CSF (12 and 10 months, respectively) was well tolerated, and no adverse clinical events were observed.

Adolescent↗
PubMed1991

Binding of cloned S-fimbriated E. coli to human buccal epithelial cells--different inhibition of binding by neonatal saliva and adult saliva.

Investigations were carried out on the adhesion of cloned S-fimbriated E. coli, labelled with fluoresceinisothiocyanate (FITC) to human buccal epithelial cells. Fluorescence microscopic analysis revealed binding of bacteria to 75-95% of epithelial cells. Inhibition experiments with fetuin, alpha 1-acid glycoprotein and N-acetyl neuraminic acid confirmed the specificity of bacterial binding to sialoglycoproteins. Further studies using saliva as an inhibitor resulted in a 4-5 times stronger binding inhibition by newborn saliva in comparison to adult saliva coinciding with a 4-5 times higher content of total N-acetyl neuraminic acid in samples of newborn saliva. In Western blot analysis sialoglycoprotein bands with a molecular weight greater than 200 kD reacting with wheat germ agglutinin (WGA), were only identified in samples of newborn saliva. These bands are classified as mucins on account of molecular weight and staining. These data suggest that saliva mucins could represent a major defense mechanism against bacterial infections at a stage of ontogeny where the secretory IgA-system is not yet developed.

Adult↗
PubMed1991

[Speech cannula for children with tracheotomy and oxygen inhalation therapy].

Because of various possible problems tracheotomy in children should be performed only in urgent cases and should be sewed up as soon as possible. Early language therapy and the use of cannulas with speaking device promote language development. We propose a special silver cannula with speaking device for children with oxygen dependence due to bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗
PubMed1989

Deficiency of the eighth component of complement. Evidence for linkage of C8 alpha-gamma pattern with C8 beta deficiency in sera of twelve patients.

The C8 alpha-gamma subunit of the eighth component of complement was analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and immunoblotting in sera from 68 normal individuals, 12 C8 beta-deficient patients (from seven unrelated families), and 10 of the parents of the latter. Three different forms of the C8 alpha-gamma subunit were observed: 34/68 normal individuals were found to have a C8 alpha-gamma triple band (termed C8 alpha-gamma 1, C8 alpha-gamma 2, C8 alpha-gamma 3 variants), 23/68 the C8 alpha-gamma 2 and C8 alpha-gamma 3 variants, and 11/68 the C8 alpha-gamma 1 and C8 alpha-gamma 3 variants. In contrast, all C8 beta-deficient patients had detectable C8 alpha-gamma 2 and C8 alpha-gamma 3 variants but lacked the C8 alpha-gamma 1 variant in addition to the C8 beta subunit. Three out of ten parents of the C8 beta-deficient patients were found to have the C8 alpha-gamma triple band, whereas 7/10, like their children, had the C8 alpha-gamma 2 and C8 alpha-gamma 3 variants only. We conclude that there is a linkage between the C8 alpha-gamma pattern and C8 beta deficiency. These data may support earlier findings that in humans the genes encoding for C8 alpha-gamma and C8 beta are closely linked on chromosome 1.

Adult↗
PubMed1988

Biosynthesis of cancer-associated sialyl-X antigen by a (1----3)-alpha-L-fucosyltransferase of human amniotic fluid.

Activity of a hitherto unknown (1----3)-alpha-L-fucosyltransferase that acts on IV3-alpha-NeuAc-nLcOseCer as acceptor substrate was demonstrated in human amniotic fluid. The 14C-labelled product IV3-alpha-NeuAc-III3-alpha-Fuc-nLcOseCer was detected autoradiographically after t.l.c. and identified after desialylation by immunostaining with monoclonal antibody Leu Ml. The enzyme is assumed also to catalyze the last step in the biosynthesis of sialyl-X antigen carried by mucins in human amniotic fluid.

Amniotic Fluid↗
PubMed1988

[Preventive long-term intravenous immunoglobulin infusion in children with acute lymphatic leukemia. II. Zymosan opsonization is decreased and is not increased by IgG infusions].

Zymosan opsonisation was determined in sera of 38 normal individuals and 20 children with acute lymphocytic leukemia (ALL). All patients underwent chemotherapy according to the CoALL 82 protocol. Intravenous gammaglobulin (ivGG) was given prophylactically to replace deficient specific antibodies. Zymosan opsonisation in normal sera ranged from 65% to 133% of a serum pool, whereas sera of children with ALL exhibited markedly decreased opsonisation ranging from 7% to 141% (of the pooled serum standard) at different times during an observation period of 20 months. No significant changes could be observed over time, neither induced by the ivGG infusion itself (short term effect) nor during the 20 months observation period (long term effect). Before ivGG therapy was initiated, a positive correlation was found between zymosan opsonisation and complement parameters (CH 50: p less than 0.01; AP 50; p less than 0.001; C3: p less than 0.05). No correlation could be noted between zymosan opsonisation and IgG concentration. Experiments with complement deficient sera clearly demonstrated the dependence of zymosan opsonisation from complement function. In contrast, sera with little or no IgG but intact complement, showed normal zymosan opsonisation. Deficient zymosan opsonisation might contribute to the immune deficiency of ALL patients. The present study suggests, that the zymosan opsonisation cannot be corrected by ivGG infusions.

Agammaglobulinemia↗
PubMed1987

Lectin mediated adhesion of Streptococcus pneumoniae and its specific inhibition in vitro and in vivo.

According to our hypothesis, bacterial lectins play an important role in the organotropy of infectious diseases which is analogous to the metastasis of tumor cells. As a model for proving this, we investigated the specific lectin of Streptococcus pneumoniae, which has N-acetyl-D-glucosamine/D-galactose (GlcNAc-Gal) specificity. In vitro, after incubation with Streptococcus pneumoniae, cryotome sections of various organs from Balb/c-mice showed remarkable quantitative differences of bacterial adhesion to the organ cells. Whereas lungs and meninges were closely settled with bacteria, attachment to other organs (e.g. liver, spleen, brain) was lacking. In vitro lectin-blocking by GlcNAc completely prevented the adherence of Streptococcus pneumoniae to lungs and meninges. Other non-related carbohydrates (e.g. D-mannose, D-xylose) showed no effect. During in vivo experiments with Balb/c-mice, intratracheal application of Streptococcus pneumoniae led to a diffuse settlement of the lung. However, bacterial lectin-blocking with intratracheal GlcNAc administration completely inhibited adhesion to the organ cells of the lung. Therefore blocking of bacterial adhesins with competitive specific monosaccharides can completely prevent bacterial adhesion processes, a fact, which opens therapeutical aspects.

Animals↗
PubMed1987

[Varying rates of phagocytosis of human blood monocytes and breast milk macrophages: effect of intralipid and milk fat globules].

Phagocytosis of antibody/complement or anti-D coated and neuraminidase treated erythrocytes by human blood monocytes and milk macrophages has been investigated. About 90% of the blood monocytes phagocytized erythrocytes whereas only 40% of the milk macrophages engulfed pretreated red blood cells. After preincubation of blood monocytes with Intralipid, no erythrocytes were phagocytized, while after preincubation with milk-fat-globules half the monocytes ingested erythrocytes.

Erythrocytes↗