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Biomedical subjects

H L Ko

Publications and source records attributed to H L Ko.

At least 19 recordsLinked to original sources

Application of standardized mistletoe extracts augment immune response and down regulates metastatic organ colonization in murine models.

The immunomodulatory and antimetastatic activity of standardized aqueous mistletoe extracts from plants grown on fir trees (ME-A) and pine trees (ME-P) were evaluated in BALB/c-mice. Regular subcutaneous (s.c.) and intraperitoneal (i.p.) applications (three times per week for 14 consecutive days; 5 and 50 microg per injection and mouse) upregulated thymus weight and peripheral blood leukocyte counts in tumor bearing mice. To check the influence of ME-A and ME-P treatment on growth of experimental metastases, RAW 117 H 10 lymphosarcoma cells and L-1 sarcoma cells were intravenously inoculated into BALB/c-mice to establish liver and lung colonization. ME-A and ME-P were regularly administered starting 24 h after tumor cell challenge. Organ colonization was investigated on day 14 after tumor cell inoculation and demonstrated statistically significant (P<0.05) reductions of experimental liver and lung metastases for ME-A and ME-P treated mice.

Adjuvants, Immunologic↗

Evaluation of absorbed radiation dose to working staff during cardiac catheterization procedures.

BACKGROUND: Cardiac catheterization has been used frequently for the evaluation and treatment of patients with heart diseases. The working staff, particularly cardiologists who perform these procedures, have the highest potential risk of receiving high radiation doses due to close contact with patients. The purpose of this study was to measure and evaluate the accumulated radiation dosage of the cardiologists while they were performing clinical procedures in the cardiac catheterization laboratory. The working environment of the catheterization laboratory was also monitored for radiation. METHODS: Thermoluminescent dosimeters (TLDs) with very high sensitivity were employed for dose evaluations. They were taped to various parts of the body of the cardiologists during catheterization procedures. For environmental monitoring, TLDs were also distributed at several sites of the catheterization rooms for a period of 2 to 4 weeks. RESULTS: The study showed that the left wrist of the cardiologists received the highest radiation dose (338 microsieverts [microSv]/procedure) and the left lens received the second highest dose (149 microSv/procedure) during the procedures. The dose to the knees was unexpectedly high (92 microSv/procedure), partly due to radiation leakage from the lead curtain shielding under the patient couch. On average, the effective radiation dose per year was 37 mSv/y for a cardiologist who performs 10 catheterization procedures per week. Compare this to the occupational exposure limit of 50 mSv/y. The estimated accumulated equivalent dose to the lens was 152 mSv/y, which exceeded the regulatory limit for occupational exposure. CONCLUSIONS: Using proper lead shielding and increasing the distance from the radiation source are good strategies for reducing the radiation dose in medical staff. The work area outside the catheterization room was considered safe because the radiation level was essentially equivalent to the background radiation level.

Cardiac Catheterization↗

Adhesive properties of P-like fimbriae in Klebsiella-species.

Clinical isolates of three encapsulated Klebsiella strains with type 1 (mannose-sensitive, MS+MR-), type 3 (mannose-resistant, MS-MR+), type 1.3 (MS+MR+) fimbriae and facultatively coexpressing P-like fimbria were investigated for their ability to adhere to uroepithelial cells (UECs) and tracheal epithelial cells (TECs). Irrespective of the type of epithelial cells, adhesion of the MS+MR+ (type 1.3) fimbriated Klebsiella strain was significantly stronger than adhesion of strains carrying only type 1 (MS+MR-) or type 3 (MS-MR+) fimbriae. The coexpression of P-like fimbriae increased the adhesive properties of Klebsiella strains to UECs but not to TECs. Adhesion of P-like fimbriated Klebsiella strains to UECs was significantly inhibited in the presence of the P+ fimbriae-specific Gal alpha-4-Gal beta (galabiose). Such adhesion was unrelated to the coexpression of type 1, type 3 or type 1.3 fimbriae. However, adhesion to TECs was only moderately inhibited.

Bacterial Adhesion↗

Importance of lectins for the prevention of bacterial infections and cancer metastases.

Adhesion of bacteria and of metastasizing tumour cells have much in common, especially the participation of lectins in this process. In the future it might be possible to inhibit the metastatic process and bacterial adhesion by blocking with lectins specific for appropriate (oligo) saccharides or glycoconjugates. Initial clinical trials are very promising.

Animals↗

Blood group phenotype determines lectin-mediated adhesion of Pseudomonas aeruginosa to human outer ear canal epithelium.

Pseudomonas aeruginosa is the most frequent bacterial pathogen causing acute diffuse otitis externa. In a recent prospective phase II study we demonstrated that lectin-mediated bacterial adhesion can be blocked by receptor-analogue carbohydrates in patients suffering from Pseudomonas aeruginosa-induced acute otitis externa. In this investigation, human ABO blood group antigens were analysed on outer ear canal epithelial cells with standard routine histological procedures by monoclonal antibodies for the blood groups A and B, and with Ulex europaeus I lectin for the blood group O, respectively. In all cases (n = 20) the blood groups could be shown immunohistologically. P. aeruginosa-specific adhesion and inhibition assays were performed in the presence of N-acetylgalactosamine (GalNAc), N-acetylglucosamine (GlcNAc), D-mannose and A-like substance. Outer ear canal tissue sections were incubated with P. aeruginosa (strain PA 60), presenting lectin-specificity for GalNAc. Sections from patients presenting with blood group A were closely settled with bacteria in the presence of non-specific GlcNAc, D-mannose and PBS however, GalNAc and A-like substance inhibited the microbial adhesion. Amongst others, P. aeruginosa present adhesion molecules (lectins) with specificity for GalNAc. Thus, the correlation between blood group A phenotype and P. aeruginosa-induced acute diffuse otitis externa was investigated. Statistical evaluation proved a highly significant association. These data support the hypothesis that P. aeruginosa lectins with GalNAc specificity apparently adhere to GalNAc moieties, representing the terminal blood group A-determinant and further indicate that patients presenting with blood group A may have a genetic disposition for this form of otitis externa.

ABO Blood-Group System↗

The role of ABO blood groups in infections induced by Staphylococcus saprophyticus and Pseudomonas aeruginosa.

Recently, considerable evidence has been accumulated showing that carbohydrate-containing blood group substances represent prime candidates for the specific interaction with microbial surface lectins in infectious diseases. Accordingly, clinical studies have proved that urinary tract infections by Staphylococcus saprophyticus and outer ear canal infections by Pseudomonas aeruginosa can be positively correlated with the patients blood group. Apparently, the blood group antigens (terminal carbohydrates) represent receptors recognized by S. saprophyticus and P. aeruginosa surface lectins.

ABO Blood-Group System↗

Influence of propionibacterium avidum KP-40 on the proliferation, maturation, emigration and activity of thymocytes and monocytes.

Inactivated cells of Propionibacterium avidum KP-40 could be shown to induce thymocyte proliferation and maturation in BALB/c-mice after intraperitoneal administration of the optimal immunomodulating dosage (1 mg per mouse). The increase in thymus weight and thymocyte numbers per mg organ weight was most pronounced and statistically significant 10 days after P. avidum KP-40 administration. Determinations of lymphatic subsets revealed a considerable up-regulation of mature cells expressing helper/inducer (L3T4+) or cytotoxic/suppressor (Lyt-2+) phenotypes and immature cells presenting both L3T4+/Lyt-2+ antigens. Obviously, P. avidum KP-40 administration accelerated murine thymocyte proliferation and maturation. Counts of BALB/c-mouse peripheral blood lymphocytes (PBL) and monocytes (PBM) revealed statistically significant increases after P. avidum KP-40 administration with peak values after 6-10 days. The determination of activated PBL (expressing interleukin-2 receptors) or PBM (expressing MAC-3 antigens) proved that P. avidum KP-40 induced a potent immunostimulation since counts of these cells were significantly enhanced after P. avidum KP-40 treatment.

Animals↗

Respiratory burst of human polymorphonuclear leukocytes in response to the galactoside-specific mistletoe lectin.

The phagocytic activity of human polymorphonuclear leukocytes (PMNLs) towards Staphylococcus aureus Cowan 1 was evaluated in chemiluminescence assays. As to check its activating ability, galactoside-specific mistletoe lectin (ML-1) was coincubated with PMNLs which were then challenged with S. aureus. Statistically significant (p < 0.001) chemiluminescent response (correlating with phagocytic activity) could be demonstrated at optimal experimental condition, viz: 1 x 10(6) PMNLs incubated with 0.005 ng ML-1 for 30 and 60 minutes before S. aureus challenge. Other experimental schedules (different timing and PMNL/ML-1 concentrations) did not present with statistically relevant changes in chemiluminescent response. These studies suggest that optimal ML-1 concentrations enhance the phagocytic activity of PMNLs which might be of benefit in thus treated patients as to prevent (or lower the rate of) infections under antineoplastic therapy.

Adult↗

[In vitro activity of Mercurius cyanatus complex against relevant pathogenic bacterial isolates].

The antimicrobial activity of mercurius cyanatus complex (Oligoplex) and its components Mercurius cyanatus D5, Echinacea angustifolia D1, Ailanthus glandulosa D3, Ammonium bromatum D3, Baptisia tinctoria D3, Euspongia officinalis D2, alcohol 5% (dilution: D1 = 1: 10, D2 = 1 : 100 etc.) was tested in vitro by serial dilution tests against 105 clinical isolates (grampositive/negative, aerobes and anaerobes with relevance for pharyngitis). The bactericidal activity was compared with that of vancomycin when appropriate. One component of the composition (Mercurius cyanatus) exerted a considerable bactericidal activity against S. pyogenes, S. agalactiae, S. pneumoniae, S. aureus, E. faecalis in serial dilutions of the clinical relevant concentration D5. However, growth of H. influenzae, Bacteriodes sp. and Actinobacillus actinomycetemcomitans was not inhibited by Mercurius cyanatus and any other component of the composition. The composition, however, exerted a bactericidal range similar to that of Mercurius cyanatus, but less efficient. Analysis of the bactericidal effect of Mercurius cyanatus and vancomycin revealed comparability for S. pyogenes, S. agalactiae, S. pneumoniae, S. aureus and E. faecalis for vancomycin concentrations of 0.063-2 mg/l, which are clinically relevant.

Anti-Bacterial Agents↗

[Immunoactive effects of various mistletoe lectin-1 dosages in mammary carcinoma patients].

Cellular aspects of the immunomodulating activity of a proprietary mistletoe extract (Eurixor) standardized for mistletoe lectin-1 (ML-1) were investigated in patients suffering from mammary carcinoma (n = 20). Regular subcutaneous injections of the different dosages (0.5 and 1.0 ng ML-1/kg body weight, twice a week, for 5 weeks) yielded statistically significant increases of defined peripheral blood lymphocyte subsets (helper T-cells, natural killer (NK)-cells) which are generally believed to be involved in antitumor activity. Moreover, administration of either ML-1 concentration resulted in enhanced expression of activation markers such as interleukin-2 receptors and HLA/DR-antigens on peripheral blood T-lymphocytes. This study suggests that regular subcutaneous administration of both ML-1 concentrations (0.5 and 1.0 ng/kg body weight) can efficiently stimulate the cellular immune system of cancer patients.

Adjuvants, Immunologic↗

Immunomodulating ability of galactoside-specific lectin standardized and depleted mistletoe extract.

Commercially available mistletoe extract standardized for the galactoside-specific lectin (ML-1; Eurixor) and a chromatographically ML-1-depleted preparation (same charge no. and composition of remaining components) were tested for their immunomodulating potency. In BALB/c-mice, regular subcutaneous administration of the optimal immunomodulating dosage (1 ng ML-1/kg body weight) could be shown to induce no influence on spleen weight, a non-significant increase of thymus weight, a significant increase of thymocyte, peritoneal macrophage, peripheral blood leukocyte, lymphocyte and monocyte and monocyte counts, and a significant decrease of peripheral blood granulocyte counts. Administration of analogue volumes (concentrations) of ML-1-depleted extract, however, did not induce any immunopotentiation. Accordingly, it may be assumed, that the galactoside-specific lectin (ML-1) represents the main immunomodulating component in commercially available mistletoe extracts.

Adjuvants, Immunologic↗

Combined immunomodulation (Propionibacterium avidum KP-40) and lectin blocking (D-galactose) prevents liver tumor colonization in BALB/c-mice.

The protective effect of combined treatment (immunomodulation with Propionibacterium avidum KP-40; liver lectin blocking by D-galactose administration) on the liver colonization of RAW 117-H10 lymphosarcoma was investigated in BALB/c-mice. Both, immunomodulation with P. avidum KP-40 as well as liver lectin blocking by D-galactose treatment significantly decreased the number of liver tumor colonies in this experimental model. However, the combination of P. avidum KP-40 and D-galactose obviously proved to be superior to each monotherapy since the liver colonization by RAW 117-H 10 lymphosarcoma could be completely inhibited.

Animals↗

[Immunoactive action of mistletoe lectin-1 in relation to dose].

Galactoside-specific mistletoe lectin-1 (ML-1) was isolated by affinity chromatography from proprietary mistletoe extract and checked in BALB/c-mice for its immunoactive potency. To investigate the optimal immunomodulating dosage, ML-1 (0.5, 1.0, 2.5, 5.0 ng/kg body weight, b.w.) was subcutaneously administered for three subsequent days followed by another injection 48 h later. These studies proved that injections of 1 ng ML-1/kg b.w. induced optimal immunomodulation, since thymocyte proliferation, maturation and emigration were significantly enhanced in this murine model as compared to non-treated control mice. Further on, counts of peripheral blood lymphocytes and monocytes as well as expression of relevant activation markers on these cells revealed significant increases after ML-1 (1 ng/kg b.w.) administration. However, increase of cell counts and activity of peritoneal macrophages were less pronounced but still statistically significant for this ML-1 concentration. Determination of immune responses after low dose ML-1 treatment (0.5 ng/kg b.w.) presented relevant (partly statistically significant) increases, too. However, high dose ML-1 treatment (2.5, 5.0 ng/kg b.w.) did not enhance (but suppress) relevant immune functions. For future clinical/therapeutical treatment strategies, ML-1 dosages ranging from 0.5-1.0 ng/kg b.w. may be supposed to be optimal.

Adjuvants, Immunologic↗

Hepatocellular injury inhibits lectin-mediated tumor colonization into BALB/c-mice livers.

Acute (hepatitis) and chronic (cirrhosis) liver injuries were experimentally induced in BALB/c-mice by administration of D-galactosamine and carbon tetrachloride, respectively. In both experimental liver diseases the incidence of hepatic tumor colonization of sarcoma L-1 was significantly reduced as compared to non-treated control animals. Thus, it seems that either dysfunction or loss of organ-characteristic lectins (galactosyl-specific hepatic lectins) prevented liver colonization. Histochemical staining of liver sections from D-galactosamine or carbon tetrachloride-treated mice with appropriate galactose-containing (neo)glycoproteins supported this hypothesis, since the lectin-dependent binding was greatly reduced as compared to sections from non-treated animals.

Animals↗

[Effect of mistletoe lectin therapy on serum level of defined serum proteins (acute phase proteins) in tumor patients].

The influence of galactoside-specific mistletoe lectin (ML-1) administration on defined acute phase reactants in the serum of cancer patients (mammary carcinoma, n = 4; larynx carcinoma, n = 11; TNM-stages II to IV; after appropriate surgery, chemotherapy, radiation) was studied. Regular subcutaneous injections of the optimal doses of ML-1 (1 mg/kg body weight, twice a week) yielded statistically significant increases of certain acute phase reactants (C-reactive protein, haptoglobin, coeruloplasmin, C3-complement, albumin, immunoglobulin IgM) after four weeks of treatment. However, serum concentrations of transferrin, C4-complement and the immunoglobulins IgG and IgA were found within the biological range (means +/- 2 s). The increase of acute phase reactants after administration of ML-1 correlates positively with the activity of lymphatic cells (e.g. expression of IL-2 and HLA-DR receptors) in FACS (fluorescence-activated cell sorter) staining experiments and indicates the immunoreactive potency of this substance which may be speculated to be cytokine-induced.

Acute-Phase Proteins↗

[Comparative studies on the immunoactive action of galactoside-specific mistletoe lectin. Pure substance compared to the standardized extract].

Comparative Studies on the Immunoactive Potency of Galactoside-specific Lectin from Mistletoe/Pure substance against standardized extract. Cellular and humoral aspects of the immunomodulating activity of the galactoside-specific lectin from mistletoe (ML-1) were investigated in cancer patients suffering from mammary carcinoma and compared to the immunoactive potency of a proprietary mistletoe extract standardized for ML-1 (ML-1 stand., Eurixor). Regular subcutaneous injections of the optimal dose of ML-1 and ML-1 stand. (1 ng/kg body weight; twice a week; for 4 weeks) yielded statistically significant increases of certain lymphocyte subsets (helper T-lymphocytes, natural killer (NK)-cells) which are generally believed to be involved in antitumor activity. Moreover, administration of either ML-1 preparation resulted in enhanced expression of interleukin (Il)-2 receptors on lymphatic cells and significantly increased serum levels of defined acute phase reactants (c-reactive protein, haptoglobin, C3 complement) as indicator of cellular and humoral activity. In vitro, exposition of human lymphocytes to ML-1 and ML-1 stand. resulted in enhanced expression of Il-2 receptors, which substantiated the capacity of both ML-1 preparations to affect immunological parameters within the host defense system. The effects of ML-1 and ML-1 stand. were comparable.

Acute-Phase Proteins↗

[Immunomodulating effects of antibiotics influencing digestive flora].

Mucosal surfaces are habitats of the physiological microflora and are closely related to the mucosal immune compartment (mucosa-associated lymphoid tissue, MALT). Recently, considerable evidence has been accumulated showing that various members of the physiological microflora liberate low molecular weight peptides which, apparently, are essential for adequate immune responses of the host. Antibiotic decontamination (e.g. of the BALB/c-mouse intestinal tract) results in a lack of generation of immunopriming microbial peptides leading to immunosuppression. Biochemical analysis of the peptides revealed reproducible chromatographic fractions which selectively influence maturation, proliferation, and activation of lymphatic cells.

Adjuvants, Immunologic↗