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Biomedical subjects

H L Ko

Publications and source records attributed to H L Ko.

125 records · Page 7Linked to original sources

In vitro and in vivo inhibition of lectin mediated adhesion of Pseudomonas aeruginosa by receptor blocking carbohydrates.

In vitro and in vivo experiments with Balb/c mice and Pseudomonas aeruginosa ATCC 27853 supported our hypothesis that bacterial lectins play an important role in the organotropy of infectious diseases. In vitro and in vivo adhesion of P. aeruginosa was mediated by N-acetylneuraminic acid (NANA) receptors. Blocking of the binding sites (lectins) on the bacterial surfaces with competitive specific carbohydrates (NANA) completely prevented the bacterial adhesion process in vitro. In vivo the number of adherent organisms in various organs decreased dramatically in the presence of NANA, whereas non-related carbohydrates (e.g. D-galactose) just showed negligible effects. Additionally, the application of NANA-treated organisms protected the animals from septicemia and death. Therefore, blocking of bacterial lectin receptors with specific carbohydrates might be of clinical relevance to prevent bacterial attachment to organ cells.

Animals↗

Chemiluminescence response of human polymorphonuclear and mononuclear phagocytic cells induced by Staphylococcus saprophyticus, lectinophagocytosis versus opsonophagocytosis.

Two strains of Staphylococcus saprophyticus with well characterized cell surface structures were studied to determine the contribution of lectinophagocytosis versus opsonophagocytosis exerted by human phagocytic cells from five healthy donors. The luminol specific chemiluminescence assay was used to evaluate the response of phagocytes. Human polymorphonuclear leukocytes (PMNL) were demonstrated to have surface lectin receptors, since the chemiluminescence response towards both S. saprophyticus strains was inhibited by lectin-specific glycoconjugates for those organisms. Phagocytosis of S. saprophyticus by mononuclear cells was not inhibited by microbial lectin-specific glycoconjugates but was inhibited by D-mannose, suggesting that human monocytes express D-mannose specific lectins on their surface.

Hemagglutination Tests↗

Inhibition of liver tumor cell colonization in two animal tumor models by lectin blocking with D-galactose or arabinogalactan.

Repeated administration of the hepatic lectin blocking agents D-galactose or arabinogalactan completely prevented the settling of metastatic cells of sarcoma L-1 tumor in the liver of Balb/c mice and greatly reduced the colonization process of highly metastatic ESb lymphoma cells of the liver of DBA/2 mice. Therefore, when hepatic lectins were blocked with competitive glycoconjugates, tumor cell colonization of the liver could be prevented in two different model systems.

Animals↗

Local immunotherapy of stomach and intestinal carcinoma by Propionibacterium granulosum.

The effect of cell suspension of Propionibacterium granulosum strain KP-45 injected intratumorally was estimated in patients with advanced malignant neoplastic disease of the upper and lower part of the digestive tract. These patients received no other anticancer treatment, and results of therapy with P. granulosum were compared with a control group of nontreated patients. In the course of immunotherapy, general clinical state, dynamics of tumor growth as judged by endoscopy and morphologic, biochemical and immunologic parameters of the peripheral blood, were evaluated. Treatment with KP-45 preparation usually resulted in partial regression of tumor growth, accompanied by improvement of the clinical state of these patients, as well as reappearance of normal values of blood picture and biochemical parameters. Enhancement of cellular immune response, evaluated by increased number of peripheral blood T lymphocytes and increased skin reactivity to PHA and PPD, was observed. No serious side effects or complications of local immunotherapy were noted. No patients who had immunotherapy suffered from bacterial infection; this was not the case in the control group.

Adenocarcinoma↗

Application-dependent immunomodulating and antimetastatic efficacy of thymic peptides in BALB/c-mice.

The immunomodulating and antimetastatic activity of clinically approved, low molecular weight, standardized thymic peptide (TP) preparations was evaluated in BALB/c-mice. Daily applications (subcutaneously, s.c.; intraperitoneally, i.p.; intramusculary, i.m.) of two commercially available TP preparations (7 consecutive days, 10, 50 and 100 micrograms per mouse and injection) up-regulated the thymus weight and thymocyte counts as well as peripheral blood leukocyte and lymphocyte counts in liver metastases-bearing mice. The immunomodulating activity of TP application was most pronounced and statistically significant for thymus weight and counts of thymocytes, leukocytes and lymphocytes after s.c. administration of both TP preparations and concentrations. I.p. and i.m. TP-injections were less effective at reaching statistical significance, however, for defined dosages and parameters, only. To evaluate the influence of TP on experimental liver metastases, RAW 117 lymphosarcoma cells were intravenously inoculated into BALB/c-mice. TP (10, 50, 100 micrograms/mouse) were s.c., i.p. and i.m. administered daily for 7 consecutive days starting 24 hours after tumor cell challenge. Liver colonization was investigated on day 14 after tumor cell inoculation and demonstrated a statistically significant (p < 0.05) reduction of experimental liver metastases for s.c. (both preparations and concentrations) as well as i.p. and i.m. (dose-dependent) TP-treated mice.

Adjuvants, Immunologic↗

Enhancement of circulating dendritic cell activity by immunomodulators (OK432 and KP-40).

The effects of biological response modifiers (BRMs) on the functions of two types of dendritic cells (DCs) were examined in relation to anti-tumor therapy. The two BRMs studied in our assay system were OK432 (a streptococcal preparation) and KP-40 (Propionibacterium avidum: a heat-inactivated bacterial vaccine). Recently, techniques for isolating human DCs from peripheral blood have been established, and DCs can be divided into two subsets: CD11c+ DCs (myeloid DC population) and CD11c- DCs (lymphoid DC population). Both OK432 and KP-40 were found to up-regulate the activity of myeloid-lineage DCs: the expression of major histocompatibility complex (MHC) class II molecules and adhesion/costimulatory molecules increased, and the production of IL-12 also increased. Therefore, DCs pulsed with OK432 and KP-40 could be applied to vaccination as a new adjuvant for specific immunotherapies.

Adjuvants, Immunologic↗

Standardized mistletoe extract augments immune response and down-regulates local and metastatic tumor growth in murine models.

The immunomodulatory and antimetastatic activity of standardized aqueous mistletoe extract (sME) was evaluated in BALB/c-mice. Regular subcutaneous (s.c.) applications (three times per week for 14 consecutive days; 2, 20, 100 and 500 micrograms per injection and mouse) up-regulated thymocyte and peripheral blood leukocyte counts in tumor-bearing mice. Tumor weight and tumor volume were significantly down-regulated after application of sME doses greater than 20 micrograms per injection. To check the influence of sME 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, respectively. sME was regularly administered starting 24 hours 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 sME-treated mice.

Adjuvants, Immunologic↗

Enhancement of immune responses to neem leaf extract (Azadirachta indica) correlates with antineoplastic activity in BALB/c-mice.

An aqueous plant extract from Azadirachta indica and its chromatographic fraction F1 (neem extract) exerted immunomodulating and antimetastatic activities in BALB/ c-mice. Regular subcutaneous administration of neem extract yielded significantly increased spleen weight and significant enhancement of peritoneal macrophage activity in the chemiluminescence assay, and activation marker CD-44 expression. The thymus weight and thymocyte counts did not show significant differences in the control and neem extract-treated groups, however, determination of peripheral blood cells revealed significant up-regulations of leukocyte subsets, the lymphocytes and monocytes. Flow cytometric analaysis of lymphocyte supopulations documented increased counts of CD-4 and CD-8 cells and an inreased activation marker expression on lymphocytes (CD-25) and monocytes (MAC-3) in neem-treated mice compared to the control animals. To evaluate the antimetastatic activity of neem extract, sarcoma L-1 cells and lymphosarcoma RAW cells were intravenously inoculated into BALB/c-mice. In these model systems the number of experimental lung and liver metastases decreased relevantly, however, biometrically non-significantly in neem extract-treated animals, as compared to the control mice which received injections of saline solutions. Neem extract can be regarded as an immunomodulating and antimetastatic substance which holds promise for further experimental and clinical investigation.

Animals↗

Intratumoral application of standardized mistletoe extracts down regulates tumor weight via decreased cell proliferation, increased apoptosis and necrosis in a murine model.

The cytotoxic in vitro activity of standardized mistletoe extracts (ME) was examined by established assays towards the human ductal breast carcinoma cell line BT474. A dose-dependent (optimum 25 mg/mL medium) and significantly (p < 0.05) enhanced cytotoxic activity towards the BT474 cells was demonstrated. In vivo experiments on the antitumor activity of ME-A and ME-M were performed in a BALB/c-mouse / BT474 ductal breast carcinoma model. ME-A and ME-M were intratumorally administered according to an application schedule which was found to be optimal concerning dosage and time of administration. Standardized intratumoral application of ME-A and ME-M induced a significantly (p < 0.05) decreased tumor weight in experimental mice. Histological investigations were performed comprising analysis of mitosis and proliferation rates (Ki67 expression), as well as necrosis and apoptosis induction (ssDNA detection). As compared to tumors of control mice with intratumoral phosphate-buffered saline (PBS) injections, tumors of the ME-A and ME-M treated groups showed a decreased cell proliferation rate, as well as an increased cell necrosis and apoptosis rate. Standardized mistletoe extracts, interfering with defined tumor cell functions, e.g., proliferation, necrosis and apoptosis, may have an impact on local cancer treatment.

Animals↗

Influence of treatment with the immunomodulatory effective dose of the beta-galactoside-specific lectin from mistletoe on tumor colonization in BALB/c-mice for two experimental model systems.

Mistletoe extracts have approval for clinical application. This warrants the quest for the definition of the active substances to optimize their application. Thus, the extent of immunomodulating and antimetastatic activity of the beta-galactoside-specific lectin from mistletoe extract (ML I) was investigated. In BALB/c-mice regular subcutaneous (s.c.) injections of small nontoxic doses of ML I yielded significant enhancement of peritoneal macrophage activity, as measured in chemiluminescence assays, as well as significant weight gain of thymus. Spleen weight, however, increased without statistical significance. To evaluate the anti-metastatic activity of ML I we intravenously (i.v.) inoculated sarcoma L-1 and fibrosarcoma RAW 117-H 10 cells which cause tumor colonization of lungs and livers in BALB/c-mice, respectively. After regular s.c. administration of ML I, the number of lung and liver tumor colonies significantly decreased in both experimental tumor models as compared to control mice which received injections of saline solution. Accordingly, ML I can be regarded as a potent immunomodulating and antimetastatic substance, which seems to be promising for clinical trials in human oncology.

Adjuvants, Immunologic↗

Immunoprotective activity of the galactoside-specific mistletoe lectin in cortisone-treated BALB/c-mice.

Hydrocortisone-acetate (HA)-treatment of BALB/c-mice induced a profound suppression of the lymphatic immune system with statistically significant decreases of thymocyte proliferation and maturation rates as well as peripheral blood lymphocyte (PBL) counts. To check its putative immunoprotective/immunorestoring activity, the optimal immunomodulating dosage of commercially available mistletoe extract standardized for the galactoside-specific mistletoe lectin (ML-1) was regularly administered (1 ng ML-1 per kg body weight; subcutaneously). As compared to counts of thymic lymphatic subsets of HA-treated mice, a considerable up regulation of mature cells expressing helper/inducer (L3T4+) as well as cytotoxic/suppressor (Lyt-2+) phenotypes and immature cells expressing both antigens (L3T4+/Lyt-2+) could be found after ML-1 co-administration. Counts of BALB/c-mouse peripheral blood mononuclear cells also revealed statistically significant increases after ML-1 co-administration, as compared to HA-treated animals. Accordingly, ML-1 treatment may be supposed to restore the lymphatic system after immunosuppressive corticoid treatment and thus this treatment may be of great benefit to patients.

Adjuvants, Immunologic↗

Enhancement of immune responses to suramin correlates with antineoplastic activity in BALB/c-mice.

The antiparasitic naphthylurea suramin (SUR) could be shown to exert immunomodulating and antimetastatic activity in BALB/c-mice. Regular intraperitoneal administration of SUR yielded significant weight gain of spleen and significant enhancement of peritoneal macrophage activity in chemiluminescence assays. The number of thymocytes per mg organ weight did not show evident differences in control and SUR treated groups; however, determinations of lymphocyte subsets revealed up-regulation of mature cells expressing helper/inducer (L3T4) or cytotoxic/suppressor (Lyt-2) phenotypes but down-regulation of immature cells presenting both L3T4/Lyt-2 antigens. Accordingly, administration of SUR obviously accelerated murine thymocyte maturation. Counts of BALB/c-mice peripheral blood lymphocytes (PBL) revealed evident (but statistically non-significant) increases after SUR administration. The determination of activated T-cells expressing interleukin (Il-2) receptors further proved that SUR induced a potent immunostimulation since these cells were significantly enhanced after treatment. To evaluate the antimetastatic activity of SUR, sarcoma L-1 cells were intravenously inoculated into BALB/c-mice. In this model system the number of experimental lung metastases significantly decreased, as compared to control mice which received injections of saline solution. Accordingly, SUR can be regarded as an immunomodulating and antimetastatic substance which seems to be promising for clinical trials in oncology.

Animals↗

Thymocyte proliferation and maturation in response to galactoside-specific mistletoe lectin-1.

Commercially available mistletoe extract standardized for the galactoside-specific mistletoe lectin-1 (ML-1) could be shown to induce thymocyte proliferation and maturation in BALB/c-mice after regular subcutaneous administration of the optimal immunomodulating dosage (1ng lectin/kg body weight). The increase in thymocyte numbers per mg organ weight was statistically significant. Determinations of thymic lymphatic subsets revealed considerable up-regulation of mature cells expressing helper/inducer (L3T4) or cytotoxic/suppressor (Lyt-2) phenotype and immature cells presenting both (L3T4/Lyt-2) antigens. Thus, administration of ML-1 accelerated murine thymocyte proliferation and maturation. Counts of BALB/c-mouse peripheral blood lymphocytes (PBL) revealed evident (but statistically non-significant) increases after ML-1 administration. The determination of activated PBL expressing interleukin (Il)-2 receptors proved, however, that ML-1 induced a potent immunostimulation since these cells were significantly enhanced after ML-1 administration.

Adjuvants, Immunologic↗

Immunostimulation by propionibacteria--effects on immune status and antineoplastic treatment.

Experimental studies were performed to investigate further the effects of immunotherapy with Propionibacterium avidum KP-40 on thymocyte proliferation, maturation and emigration in BALB/c-mice. Thymus weight and thymocyte counts, especially cells presenting the immature or cytotoxic/suppressor phenotype were significantly increased. Due to enhanced emigration, peripheral blood lymphocyte and monocyte counts as well as expression of activation markers were significantly upregulated. The antimetastatic effect of Propionibacterium avidum KP-40 was demonstrated in BALB/c-mice, where RAW 117-H10 lymphosarcoma liver colonization was significantly reduced after immunostimulation. Clinical investigations proved that surgical treatment of colorectal carcinoma induced an evident decrease of peripheral blood lymphocytes as compared with preoperative counts. However, single preoperative Propionibacterium avidum KP-40 administration induced a considerable increase of peripheral white blood cell counts, especially lymphocytes. Clinical effects of preoperative immunostimulation by Propionibacterium granulosum KP-45 were investigated in a prospective randomized trial in colorectal carcinoma patients. Positive effects on survival time, local tumor recurrence and distant metastasis could be demonstrated in stages I and II, whereas no advantage of immunotherapy was found in advanced stages III and IV. A recent prospective randomized clinical trial was initiated on the quality of life of colorectal carcinoma patients. Three months after surgical treatment negative effects could not be determined after immunotherapy. Quality of life even proved to be better in patients with abdominoperineal resection as compared to non Propionibacterium avidum KP-40 treated control patients.

Adjuvants, Immunologic↗