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Biomedical subjects

H L Ko

Publications and source records attributed to H L Ko.

At least 73 records · Page 4Linked to original sources

The role of lectins and lipoteichoic acid in adherence of Staphylococcus saprophyticus.

Staphylococcus saprophyticus strains S 1 and S 35 demonstrated lectin like surface receptors specific for N-acetylgalactosamine (S 1) or N-acetylneuraminic acid (S 35). Adhesion assays with human uroepithelial cells together with blocking experiments with competitive carbohydrates suggested that specific attachment of S. saprophyticus to host cells is apparently mediated by lectins. Staphylococcal lipoteichoic acid (LTA) was also shown to interfere with S. saprophyticus adherence to human uroepithelial cells.

Bacterial Adhesion↗

Immunomodulatory effects of staphylococcal lipoteichoic acid in early Listeria monocytogenes infection in Balb/c-mice.

Balb/c-mice were intravenously infected with 5 X 10(4) viable cells of Listeria monocytogenes SLCC 4013. Liver, lung and spleen of the animals showed heavy organ colonization 48 h after infection. Pretreatment of experimental animals with staphylococcal lipoteichoic acid (LTA; 2 mg i.p. 7 and 3 days before challenge) significantly reduced the bacterial count in these organs. In vitro, peritoneal macrophages from LTA-treated mice significantly reduced listerial viability as compared to control cells (p less than 0.0025). In vitro, exposure of macrophages from non-treated animals to LTA did not influence their bacterial killing ability.

Animals↗

Lectin-mediated cell-attachment and phagocytosis of Staphylococcus saprophyticus strain S1.

Adhesion studies with cryotome sections of human kidney and lung respectively uroepithelial cells together with blocking experiments with competitive carbohydrates suggested that specific attachment of S. saprophyticus strain S 1 to host cells apparently is mediated by lectins. Accordingly, microbial lectin blocking with specific glycoconjugates or lectin dysfunction (after treatment of bacteria with subinhibitory concentrations of tunicamycin) significantly decreased staphylococcal adherence to epithelial cells. Chemiluminescence measurements of human polymorphonuclear leukocyte (PMN) function yielded results suggesting importance of lectin-receptor interaction in phagocytosis, too, since PMN activity was significantly decreased after staphylococcal lectin blocking or dysfunction.

Bacterial Adhesion↗

Immunostimulating staphylococcal lipoteichoic acid prevents pulmonary tumor colonization in BALB/c-mice.

Immunostimulating and antineoplastic activities of staphylococcal lipoteichoic acid (LTA) were studied in Balb/c-mice. Systemic administration of LTA (1 mg or 2 mg i. p., 7 and 4 days prior to challenge) significantly enhanced chemiluminescence response of peritoneal macrophages (p less than 0.0125) and induced enlargement of the spleen (p less than 0.025) as compared to non-treated controls. In vivo the number of lung colonies was significantly lower (p less than 0.0125) in LTA-treated mice 14 days after challenge with L-1 sarcoma cells.

Adjuvants, Immunologic↗

Studies on a biological response modifying LYSAT from Propionibacterium avidum KP 40.

Propionibacterium avidum KP 40 cells were mechanically disintegrated in order to obtain the soluble immunostimulatory (antineoplastic) LYSAT. Chemiluminescence measurements of human leukocyte function yielded enhanced activation of the cells after incubation with 2.5 and 5 mg of LYSAT. As compared to non-treated controls, administration of LYSAT to BALB/c-mice (1, 2.5 and 5 mg; intraperitoneally, subcutaneously, intranasal; 7, 4 and 2 days prior to challenge) induced a significant enlargement of the spleen as well as significantly reduced sarcoma L-1 lung colonization 14 days after challenge and evidently enhanced chemiluminescence response of peritoneal macrophages.

Adjuvants, Immunologic↗

Granulocyte activating factor released from Propionibacterium acnes. A possible mediator of inflammation in acne vulgaris.

Incubation of Propionibacterium acnes but not of Propionibacterium granulosum or Propionibacterium avidum (for 30 min at 37 degrees C in physiological saline) released a soluble factor that produced enhanced chemiluminescence response of human granulocytes as well as increased chemotactic motility of these cells. Sephadex G-25 filtration of the granulocyte activating factor (GAF) revealed its low molecular weight and apparent peptide character. Thus, GAF may be a stimulus for inflammation in acne vulgaris since low molecular weight chemotactic factors can be expected to penetrate follicular walls.

Acne Vulgaris↗

Investigations on the opsonin-dependent interaction of Klebsiella bacteria and human polymorphonuclear leukocytes.

Encapsulated and nonencapsulated Klebsiella strains with different types of fimbriation were tested for their opsonin-dependent stimulation of human polymorphonuclear leukocytes (PMNs). Chemiluminescence (CL) of the PMNs was determined since CL-response can be used indirectly to quantitate phagocytosis. Apparently, the interaction between Klebsiella bacteria and human PMNs is dependent on the type of fimbration and on the presence of capsules. Evaluation of the bactericidal capacity of human PMNs against Klebsiella bacteria positively correlated with the chemiluminescence response demonstrating the importance of fimbriation and capsulation for this process, too.

Bacterial Adhesion↗

Intestinal microflora of BALB/c-mice and function of local immune cells.

BALB/c-mice were treated for 7 days with oral nonabsorbable dosages of mezlocillin to achieve digestive tract decontamination. Such a procedure resulted in rapid eradication of most species of aerobic and anaerobic intestinal microflora. Various functions of peritoneal macrophages (e.g. chemiluminescence response, chemotactic motility, bactericidal and cytostatic ability) and lymphocyte proliferation were decreased in decontaminated animals as compared to non-treated controls.

Animals↗

Prevention of experimental liver metastases by D-galactose.

The metastasis of malignant tumors from a primary site to near and distant secondary sites is probably the most important event in the pathogenesis of cancer and it accounts for most cancer deaths. Whereas advances in the treatment of primary cancer have led to increased patient survival, metastatic cancers are still the most difficult group of diseases to treat successfully. As organ-characteristic lectins play an important role in the organ manifestation of metastatic islets, it might be possible (e.g. during surgical operations on malignant tumors) to block those organ-characteristic lectins with the appropriate receptor-bearing glycoconjugates in order to inhibit the metastatic spread. Recent experiments have demonstrated that neuraminidase treatment of tumor cells (mouse sarcoma-1) alters in vivo (Balb/c-mice) the organotropic distribution of metastases; instead of being found exclusively in the lung, they are found both in lung and liver. However, pre-injection and regular application of D-galactose--the same holds for arabinogalactan--prevents the setting of metastases in the liver but does not influence the metastatic process to the lung, whereas mannan--as a galactose-free control substance--does not alter the initial pattern of metastasis to lung and liver.

Animals↗

Immunostimulating cell surface substance from Staphylococcus epidermidis strain ATCC-31432 prevents metastatic lung colonization in Balb/c-mice.

The antineoplastic activity of cell surface substance from Staphylococcus epidermidis ATCC-31432 (CSS-subfraction 2) in mice and its influence on the activation of human leucocytes was studied. After in vitro incubation with CSS-subfraction 2, human polymorphonuclear leucocytes were evidently stimulated. In vivo (Balb/c-mice) intraperitoneal application of subfraction 2 of CSS induced a considerable splenomegaly and greatly increased IgM levels indicating a strong immuno-stimulating activity. In order to evaluate antineoplastic effects of CSS-subfraction 2, we used sarcoma L-1 cells (Balb/c-mouse origin) which cause heavy tumor colonization of the lung. After single systemic injection of subfraction 2 of CSS, the number of lung tumor-cell colonies drastically decreased. The combination of this immunomodulating therapy with a temporary anticoagulation resulted in a further reduction of tumor colonies in the lungs of Balb/c-mice.

Adjuvants, Immunologic↗

Inhibition of liver metastasis in mice by blocking hepatocyte lectins with arabinogalactan infusions and D-galactose.

According to our hypothesis, organ-specific lectins (e.g., the D-galactose-specific hepatic binding protein) play an important role in the organ location of metastatic malignant cells. The rapid clearance and uptake by the liver of tritiated alpha 1-acid-(asialo)glycoprotein from the circulation of Balb/c mice was markedly delayed after preinjection of D-galactose or arabinogalactan. The preinjection (1 h) and regular application (for 3 days after tumor cell inoculation in Balb/c mice) of the receptor blocking agents D-galactose and arabinogalactan prevented the settling of sarcoma L-1 tumor in the liver completely, but did not influence the settling in the lung. Other galactans, dextrans, and phosphate-buffered saline showed no effect. Therefore, when lectins were blocked with competitive-specific glycoconjugates, colonization was prevented.

Animals↗

Combined immunostimulation (Propionibacterium avidum KP 40) and anticoagulation (heparin) prevents metastatic lung and liver colonization in mice.

The antineoplastic activity of Propionibacterium avidum KP-40 and its enhancement by anticoagulation with heparin was studied. In Balb/c mice syngeneic sarcoma L-1 exclusively caused tumor colonization of the lungs. After neuraminidase treatment the organotropism of this tumor was changed, with tumor nodules developing in lung and liver. After single systemic application of Propionibacterium avidum KP-40 the number of lung and liver colonies decreased evidently. Combination of this immunomodulating therapy with temporary anticoagulation resulted in further reduction of tumor colonies in lung and liver.

Adjuvants, Immunologic↗

Lectin-mediated bacterial adhesion to human tissue.

In vitro experiments with frozen sections of human lung and kidney demonstrated that adhesion of Streptococcus pneumoniae Pn 629 Type 14 and Pseudomonas aeruginosa ATCC 27853 to human cells was mediated by bacterial lectins (adhesins) with N-acetyl-D-glucosamine/D-galactose or N-acetyl-neuraminic acid specificity. Blocking of the lectin binding sites on bacterial surfaces with competitive carbohydrates completely prevented the bacterial adherence, whereas non-specific carbohydrates (D-mannose, D-xylose) did not inhibit adherence.

Acetylglucosamine↗

Modification of glycosylation by tunicamycin treatment inhibits lectin-mediated adhesion of Streptococcus pneumoniae to various tissues.

Oligosaccharide moieties of cell surface glycoconjugates are thought to be involved in recognition events associated with infectious diseases. Treatment of Streptococcus pneumoniae (which exhibits well defined surface lectins) with subinhibitory concentrations of the antibiotic tunicamycin was found to block the protein glycosylation of the bacterial surfaces. Since bacterial lectins (adhesins) are in most cases glycoproteins and play an important role in the organ specificity of infectious diseases, adhesion of Streptococcus pneumoniae to frozen sections of lung, meninges and kidney (from Balb/c-mice) was almost totally lacking after inhibition of the biosynthesis of N-linked carbohydrate chains which are important for an adequate lectin function. Chemiluminescence measurements of human granulocyte stimulation yielded results suggesting a great importance of lectin-carbohydrate interactions in this process, too. These experimental data indicate that the presence of specific cell surface carbohydrates is required for a successful completion of the adhesion phase of pathogenic bacteria in infectious diseases and for the induction of granulocyte stimulation.

Animals↗

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↗

Antibiotic treatment, intestinal aerobic microflora and experimental sarcoma L-1 growth in Balb/c-mice.

The present paper deals with the influence of a 10 days treatment with mezlocillin, piperacillin, cefotaxime, clindamycin or gentamicin on the endogenous intestinal microflora of Balb/c-mice and on the local growth of sarcoma L-1 tumor. Clindamycin and gentamicin demonstrated no influence, whereas cefotaxime and piperacillin caused the eradication of gram-negative resp. gram-positive bacteria but these antibiotics didn't produce a growth inhibition of local L-1 sarcoma tumor. The oral or parenteral application of mezlocillin (a 3 days treatment was sufficient) eradicated the complete aerobic and anaerobic intestinal microflora. This effect was significantly correlated with an increase of the cecum weight and the inhibition of local tumor growth. Possible mechanisms of these effects are discussed.

Animals↗

Cell surface antigen of encapsulated Staphylococcus epidermidis ATCC 31432.

The cell surface antigen (CSA) from encapsulated Staphylococcus epidermidis ATCC 31432 was isolated and fractionated by DEAE-Sephadex ion-exchange chromatography. It yielded a single precipitin line against rabbit antiserum and was composed of galactose, glucosamine, and two (so far) unidentified carbohydrates linked to a protein backbone. Glycerol could not be detected. In an experimental mouse infection, CSA showed some protective activities, enhancing the stimulation of granulocytes as well as the immunoglobulin M response. Apparently, CSA is different from teichoic acid.

Animals↗