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Biomedical subjects

H L Ko

Publications and source records attributed to H L Ko.

At least 91 records · Page 5Linked to original sources

[Animal experiment studies on the modification of the immune system by ofloxacin].

Ofloxacin, one of the new group of quinolone antibiotics, was investigated with respect to its possible interactions with different parameters of the immune system. The study was performed in vivo on Balb/c-mice treated for seven days with different doses of the antibiotic and in vitro on human phagocytes from peripheral blood. It was found that ofloxacin does not affect cellular or humoral immune responses in mice. Moreover, human phagocytic cells exposed in vitro even to high concentrations of the drug did not show any significant changes in their function. On the other hand, it was observed that subinhibitory concentrations of ofloxacin induced an increased susceptibility of Staphylococcus aureus 511-Jena to the bactericidal activity of phagocytes.

Animals↗

Effects of ciprofloxacin on the humoral and cellular immune responses in Balb/c-mice.

The effects of a 7 days chemotherapy with ciprofloxacin on the humoral and cellular immune responses in Balb/c-mice were examined. Ciprofloxacin-doses used were calculated on a body weight basis from therapeutic dosages in humans. In a dose-dependent way IgM as well as IgG responses were significantly increased. The delayed-type hypersensitivity reaction to oxazolone was not significantly changed. In in vivo as well in vitro experiments ciprofloxacin showed no modulatory activity on the concanavalin A and LPS-induced proliferative activities of mouse spleen cells.

Animals↗

Opsonin independent interaction of Klebsiella strains with human polymorphonuclear leukocytes.

Nine encapsulated Klebsiella strains with different types of fimbriation and their nonencapsulated mutants were tested for their stimulatory potency for human polymorphonuclear leukocytes in the absence of opsonins. The luminol chemiluminescence assay was used for these experiments. It could be shown that the interaction between Klebsiella bacteria and human leukocytes is rather complex depending not only on the presence of capsules but also on the hydrophobicity of Klebsiella surface and on the type of fimbriation existing.

Fimbriae, Bacterial↗

Investigations on opsonin-independent antistaphylococcal activity of human neutrophilic granulocytes, monocytes and lymphocytes.

Using cells from 20 healthy human donors the opsonin-independent staphylococcal killing abilities of peripheral blood neutrophilic granulocytes, monocytes and lymphocytes were studied. S. aureus strains T 1 and T 14, S. sciuri strain S I, S. saprophyticus strain S III and S. simulans strain S V were selected for these experiments because of their differing cell wall composition, surface hydrophobicity, protein A content and extracellular enzyme activity spectrum. We could demonstrate a very individual activity range of these cells against staphylococci. On the other hand each staphylococcal strain examined behaved in a very typical way in its susceptibility against the killing by human phagocytes and lymphocytes. Repeated tests in monthly intervals showed that the staphylococcal killing activity range of phagocytes and lymphocytes of a certain healthy donor remains constant and stable.

Humans↗

Small-cell lung cancer and immunochemotherapy with Propionibacterium granulosum KP 45.

Seventy-nine patients with small-cell lung cancer were treated with vincristin, methotrexate, and cyclophosphamide in inductive therapy and with methotrexate, cyclophosphamide, and procarbazine in maintenance therapy. Patients were divided at random into two groups: one group received chemotherapy alone and the second group was additionally subjected to systemic immunotherapy with Propionibacterium granulosum strain KP-45. In general, differences in the frequency of therapy response and in duration of remission could not be stated between the two groups of patients, but patients responding to chemotherapy showed a significantly longer remission time and lower complication rates. This benificial effect of chemoimmunotherapy is not related to a direct antitumor activity of the immunomodifier used, but to the lowered risk of myelosuppression and infections. Immunomodulation in combination with chemo- and/or radiotherapy can be recommended for the treatment of small-cell lung cancer.

Adult↗

Antibiotics and immunomodulation: effects of cefotaxime, amikacin, mezlocillin, piperacillin and clindamycin.

The effects of 7 days' chemotherapy on the humoral and cellular parameters of the host immune system are described. In Balb/c mice the effects of cefotaxime, amikacin, mezlocillin, piperacillin and clindamycin were examined. The delayed-type hypersensitivity reaction, as well as the IgM and IgG responses, were suppressed by four of the five drugs tested: cefotaxime, amikacin, mezlocillin and piperacillin. One to two weeks after completion of chemotherapy with cefotaxime and amikacin, these parameters returned to normal values, whereas the mezlocillin- or piperacillin-modified reactions were still suppressed after 20 days. The concanavalin A and lipopolysaccharide-induced proliferative activities of mouse spleen cells were suppressed, especially by mezlocillin. The possible consequences of the immunomodulating effects of antibiotics for antimicrobial chemotherapy are discussed.

Amikacin↗

Effects of cefotaxime, clindamycin, mezlocillin, and piperacillin on mouse sarcoma L-1 tumor.

For the study described in the paper, the effects of 10 days' chemotherapy with cefotaxime, clindamycin, mezlocillin, and piperacillin on local tumor growth and on spontaneous or artificial metastatic spread into the lungs were studied. For the animal tumor model Balb/c mice and the mouse sarcoma L-1 tumor were used. Chemotherapy was administered before, immediately after, or some time after the injection of tumor cells. The antibiotic dosage given to mice was calculated on a body weight basis from the doses recommended for humans. Cefotaxime and clindamycin did not influence the animal tumor model, whereas mezlocillin and piperacillin showed positive or negative effects depending on the chemotherapy schedule. In vitro none of the four antibiotics caused cytotoxic activity in cell cultures of mouse sarcoma L-1, human lung cancer E-14, or human malignant melanoma MEW.

Animals↗

Immunotherapy of chronic active viral hepatitis B with propionibacterium granulosum.

12 HBsAg-positive patients with chronic active hepatitis B were treated monthly with cell walls (5 or 10 mg) of Propionibacterium granulosum KP-45 (PG) intravenously administered for a period of 6-10 months. The clinical state was evaluated according to an arbitrary 6-grade scale based on serum biochemical tests, HBV markers and the morphology of liver biopsy samples. Intravenous administration of PG was well tolerated, and no serious side effects were observed. All patients exhibited complete or partial normalization of biochemical parameters and HB5AG and DNA-polymerase levels were decreasing after 6 months of therapy. Prior to treatment, HBeAG was detected in 9 patients, in 4 of whom seroconversion occurred with appearance of anti-HBeAg. Excellent results were seen in 3 patients and beneficial results in a further 3 patients; signs of improvement were seen in 5 patients, and only one patient did not react in a clearly positive way. In 11 of these patients, before and during treatment, isolated peripheral blood lymphocytes were investigated for their ability to show rosette E formation, their reactivity to phytomitogens (PHA, ConA), and their suppressor T lymphocyte activity. In five patients interferon levels were investigated.

Adjuvants, Immunologic↗

Immunochemotherapy of breast cancer with Propionibacterium granulosum.

Eighty-two patients with metastatic breast cancer were treated with adriamycin, cyclophosphamide, and 5-fluorouracil (FAC). These patients were divided by randomization into two groups. One was receiving cytostatic drugs only, while another received the identical cytostatic medication plus additional therapy consisting of IV infusions of gamma-radiation-sterilized cells of Propionibacterium granulosum strain KP-45. Metastases were localized in six different sites and/or organs. Multiple parameters for monitoring changes in metastatic lesions and laboratory tests were performed serially in all patients. The addition of P. granulosum to standard (FAC) chemotherapy of metastatic breast cancer influenced metastases in the liver. It also resulted in increased survival time within the observation period. Possible mechanisms of immunomodulating activity of P. granulosum in this disease are discussed.

Adult↗

A 2.5-year follow-up of local immunotherapy of advanced stomach and intestinal adenocarcinoma with Propionibacterium granulosum.

Intratumoral injections of 10 mg cells walls from Propionibacterium granulosum strain KP-45 (PG) were applied in 14 patients with advanced, metastatic stomach (five cases) and colorectal (nine cases) adenocarcinoma. Each patient had his own "twin" control. All patients received no other anticancer treatment, except analgetics and/or palliative surgery. Treatment with PG resulted in partial regression of tumors accompanied by improvement of the clinical state of these patients as well as the reappearance of normal values in blood count biochemical parameters. In each pair of twin cases, survival of the PG-treated patient was longer than the untreated control. The mean survival of PG-treated patients was 23.5 months (4 of 14 patients being still alive after 2.5 years follow-up), while all control patients died with a mean survival period of 6.4 months. The difference between these two patient groups of about 17 months is significant (p greater than 0.01).

Adenocarcinoma↗

Hemolysin of Propionibacterium avidum.

Thiol-activated extracellular hemolysin produced by a strain of Propionibacterium avidum was partially purified and several properties were examined. The hemolysin was heat labile and inactivated by proteases and deoxyribonuclease. Hemolysin adsorbed to erythrocytes at 0 degrees C. Cu++ at 1 mM inhibited hemolysis partially. Lecithin prevented the activity completely. The hemolytic spectrum was relatively wide and the activity was high with rabbit, dog, horse, and pig erythrocytes.

Animals↗

Comparative study on the immunostimulatory potency of different Propionibacterium strains.

198 strains of Propionibacterium acnes, P. avidum, and P. granulosum were tested for their immunostimulatory potency using splenomegaly as index of stimulation, the activity differed widely from strain to strain. The antitumor and antimetastatic properties of six strains with differing stimulation activities were carefully examined. A close correlation between spleen enlargement and antitumor effects could be observed. The simple spleen enlargement test is recommended for determination of the immunopotency of propionibacteria and for the standardisation of vaccine preparations.

Adjuvants, Immunologic↗

Postirradiation recovery of hemopoiesis in mice treated with Propionibacterium granulosum.

The effect of Propionibacterium granulosum on spontaneous regeneration of hemopoiesis in nonlethally (250 or 400 rads) irradiated mice was investigated and measured by peripheral blood leukocyte counts each 2 days after irradiation and incorporation of 3H-thymidine into spleen and thymus in vivo. P. granulosum injected intraperitoneally in a dose of 1.5 mg per mouse, 7 days before or 4 days after irradiation, resulted in accelerated recovery of hemopoiesis after nonlethal irradiation with significantly higher leukocytosis, as compared with a control non-treated with bacteria. This was accompanied by elevated spleen and thymus weight and higher incorporation of 3 H-thymidine into spleen cells.

Animals↗

Macrophage and T lymphocyte content of tumors in mice treated with Propionibacterium.

Macrophage and T lymphocyte content of sarcoma tumors in mice treated with Propionibacterium granulosum (PG) by different routes was investigated and compared with the effectiveness of the therapy. Two different methods for tumor macrophage detection, the Fc receptor analysis and phagocytic properties, were employed. Indirect fluorescent staining of theta-antigen on lymphocytes was used to evaluate the proportion of tumor T cells. Systemic treatment with PG appeared to be effective if given soon after tumor implantation; however, this route of administration failed to affect the tumor growth if given when the tumor was already advanced. The therapeutic efficiency of intralesional PG injection was almost as effective as early systemic treatment. We obtained evidence indicating that effectiveness of PG therapy was associated with an increase of the macrophage and T cell content of tumors.

Animals↗

Immunostimulation by systemic administration of Propionibacterium granulosum in patients with primary or secondary lung tumours.

The effect of a cell suspension of Propionibacterium granulosum strain KP-45 given intravenously to patients with advanced primary or secondary lung carcinoma, and simultaneously treated with cytostatic drugs, was estimated. The control group consisted of patients treated with cytostatics only. The clinical state of patients treated with the KP-45 preparation and with this immunostimulant plus cytostatics, was compared by evaluation of tumour size by X-ray examination, peripheral blood picture, and biochemical and immunological parameters. Treatment with P. granulosum KP-45 did not cause any serious adverse reaction or complication. No evident inhibitory effect on primary or secondary lung tumour development was observed. However, injections of the KP-45 preparation in cytostatics-treated patients resulted in decreased adverse effect of these drugs on the haemopoietic system and absence of bacterial infections, in contrast to patients treated with cytostatics only.

Adult↗

Qualitative and quantitative investigations on the resident bacterial skin flora in healthy persons and in the non-affected skin of patients with seborrheic Eczema.

The composition of the aerobic and anaerobic bacterial skin flora was investigated quantitatively and qualitatively in 25 patients with seborrheic eczema (SE) and in 35 healthy persons. In SE patients, the geometric mean count for propionibacteria in the pilosebaceous ducts of the forehead was reduced to a statistically significant extent in comparison with the control group. There was the same tendency with regard to the geometric mean count of the superficial anaerobic bacterial flora of the back, whereas the geometric mean counts of the coagulase-negative staphylococci were the same in the two groups. These results may explain earlier findings of a reduction of free fatty acids in the surface lipids in SE patients. According to the results of differentiation in 295 propionibacteria and 157 micrococcaceae, 7 biotypes and 10 phage types of propionibacteria which were so far unknown could be demonstrated. Significant differences between the groups with regard to the frequency of different biotypes, serotypes, and phage types could be demonstrated neither in propionibacteria nor in coagulase-negative staphylococci. The results of typing, however, showed that patients with SE displayed much more frequently several different propionibacterial species and types as well as different micrococcal species and types than persons with healthy skin.

Adult↗

The in vivo cytostatic effect induced by Propionibacterium granulosum on murine tumor cells.

The cytostatic action of Propionibacterium granulosum was studied in a mouse sarcoma in vivo. Kinetic analysis of tumor cells 28 days after tumor implantation and systemic immunotherapy showed that the cell cycle time was identical in both treated and untreated tumors. P. granulosum treatment resulted in a marked prolongation of the S phase and shortening of the G1 phase of the cell cycle. A pronounced drop in the number of labeled interphases and the reduction of the growth fraction were observed in tumors obtained from mice given injection of P. granulosum. Cloning efficiency of tumor cells from P. granulosum treated animals was quantitatively similar to that of control animals and only differences in the size of lung colonies were observed.

Animals↗