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Biomedical subjects

J Beuth

Publications and source records attributed to J Beuth.

At least 37 records · Page 2Linked to original sources

Killing effects of antibiotics and two-fold antimicrobial combinations on proliferating and non growing staphylococci.

Antimicrobial agents are generally tested against bacteria in the log phase of multiplication to produce the maximal bactericidal effect. In case of foreign body infections, bacteria may multiply less optimally. We examined the effects of several classes of lipophilic antistaphylococcal agents to determine their antimicrobial activity towards coagulase-positive and coagulase-negative staphylococci during the non-growing and slowly growing phases. Only two-fold combinations containing rifampicin were bactericidal (3-log kill) against Staphylococcus aureus. This was in contrast to growing bacteria in the log phase, in which a variety of antibiotics produced relevant killing. Concerning the staphylococci examined, antibiotic killing was greatly dependent on the growth rate. Most of the two-fold combinations containing rifampicin showed additive and synergistic antibacterial activity both in growth and stationary states as measured by the killing kinetics. The theoretical and clinical implications of delayed killing by chemotherapeutic agents for established bacterial infections and infections involving foreign bodies are discussed. Antimicrobial combinations including rifampicin and a second lipophilic antistaphylococcal drug may be most promising and appropriate as coating substances for intravascular devices or for clinical application in cases of implant infections.

Anti-Bacterial Agents↗

Microflora-associated defense stimulating factors.

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

Animals↗

Clinical relevance of immunoactive mistletoe lectin-I.

Recent investigations have shown that defined, non-toxic doses of the galactoside-specific mistletoe lectin (mistletoe lectin-I, a constituent of clinically approved plant extracts) have immunomodulatory potencies. The obvious ability of certain lectins (e.g. mistletoe lectin-I) to activate (non)-specific defence mechanisms supports the assumption that lectin-carbohydrate interactions may induce clinically beneficial immunomodulation. Initial clinical trials were promising and currently prospectively randomized multicentre trials are being performed to evaluate the ability of complementary mistletoe lectin-I treatment to reduce the rate of tumor recurrences and metastases, to improve the overall survival as well as the quality of life and to exert immunoprotection in cancer patients under tumor destructive therapy.

Adjuvants, Immunologic↗

Influence of Propionibacterium avidum KP-40 on the cellular immune system after intensive sport activity.

Intensive sport activities resulted in temporary downregulation of defined immune functions. To check its influence on the cellular immune system, 15 male professional ice hockey players of a German first league club were observed and a decrease of lymphocyte subset counts and activities was found after anaerobic exercise. To stabilize cellular immune functions, the players were orally treated with Propionibacterium avidum KP-40 (10 mg per administration; twice a day; 7 days), a well documented bacterial immunmodifier. After administration of Propionibacterium avidum KP-40, lymphocyte counts and activities after anaerobic exercise resembled normal values. For some subjects, defined lymphocyte subset counts and activities even exceeded normal values.

Exercise Test↗

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↗

Effect of immunomodulation with galactoside-specific mistletoe lectin on experimental listeriosis.

BALB/c-mice (n = 10 per experimental group) were intravenously infected with 5 x 10(4) and 5 x 10(5) viable cells of Listeria monocytogenes SLCC 4013. About 50-80 h after this challenge, all mice of the untreated control groups succumbed to their infection. Pretreatment of experimental animals on the optimal immunoactive schedule with the galactoside-specific mistletoe lectin (ML-1; 1 ng/kg body weight; days 1, 4, 5, 6 before challenge), however, evidently reduced the lethality of listerial infection (survival rate 60%).

Animals↗

Problems and priorities for controlling opportunistic pathogens with new antimicrobial strategies; an overview of current literature.

An International Study Group on New Antimicrobial Strategies (ISGNAS) has been formed in response to the recognition that development of microbial resistance to antibiotics is becoming a serious, world-wide problem. The group met in 1993 for the first time to discuss the feasibility of developing rational alternatives to the use of antibiotics and prepared, as a result, a comprehensive overview of normal (physiological) mechanisms involved in the control of potentially pathogenic (oppotunistic) microorganisms. One objective of ISGNAS is to understand the conditions which allow opportunistic microbes present among the symbionts to cause an infection. There is a need for more coherent information concerning the habitat, growth requirements and host and pathogen properties which allow opportunistic pathogens to cause life-threatening infections. In particular, information is urgently being sought to understand the complexity of the interactions between the vast number of microbial species, and the interactions between the microbes and their host. Another goal is to inspire and enable basic and clinical research that will lead to the development of new therapies for regulating colonization, translocation and infection by opportunistic micro-organisms in patients during periods of decreased resistance. With a sufficient amount of knowledge of how healthy individuals keep opportunistic micro-organisms under control, it may become feasible for physicians to maintain host resistance and inter-microbial factors involved in the containment of opportunistic microbes. Therapies aimed at boostering natural resistance mechanisms will be of critical importance to individuals whose resistance has been compromised as a result of another clinical condition.

Adjuvants, Immunologic↗

Murine thymocyte proliferation, maturation and emigration in response to selenium.

Systemic (intraperitoneal) administration of sodium selenite (CAS 26970-82-1, Se) for 7 subsequent days (0.1 or 0.2 micrograms Se daily per 20 g of body weight; these concentrations were calculated from recommendations in human medicine) into BALB/c-mice could be shown to induce thymocyte proliferation and maturation. The increase in thymocyte numbers per mg organ weight was most pronounced after administration of the higher Se concentration. Determination of thymic lymphatic subsets revealed considerable up-regulations of mature T-cells expressing helper/inducer (L3T4) phenotype and immature cells expressing both (L3T4/Lyt-2) antigens. Thus, administration of Se (0.2 micrograms per mouse for a defined period) accelerated murine thymocyte proliferation and maturation. Counts of BALB/c-mice peripheral blood lymphocytes (PBL) revealed statistically significant increases after Se administration. The determination of activated PBL expressing interleukin (IL)-2 receptors proved that administration of Se induced a potent immunostimulation since these cells were significantly enhanced.

Adjuvants, Immunologic↗

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↗

Efficacy of local Bacillus Calmette-Guérin treatment in superficial bladder cancer relapsing under Keyhole-Limpet Hemocyanin immunotherapy.

The efficacy of local immunotherapy with Keyhole-Limpet Hemocyanin (KLH) and Bacillus Calmette-Guérin (BCG) in preventing recurrence of superficial bladder cancer (stages pTa to pT1; grades 1 to 3) was checked in 96 patients. All tumours were resected and all patients were presumed to be free of malignant disease at initiation of prophylactic KLH instillations. Before starting KLH instillations (20 mg/administration week for 6 weeks, followed by regular (bi)monthly instillations for 3 years altogether) all patients were intracutaneously immunized with 1 mg KLH. Tumour relapse under this therapeutic schedule was the indication for BCG instillations (120 mg BCG-Connaught; administration in analogy to KLH treatment). This study has proved that (1) prophylactic KLH treatment reduced superficial bladder cancer relapse rate after surgical intervention without considerable local/systemic side effects and (2) local BCG-administration was therapeutically effective in relapsing/progressive disease under KLH treatment. There were, however, pronounced side effects.

Adjuvants, Immunologic↗

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↗

Immunohistological findings in patients with superficial bladder carcinoma after intravesical instillation of keyhole limpet haemocyanin.

OBJECTIVE: To determine whether keyhole limpet haemocyanin (KLH) instilled intravesically improves the local cellular response within the bladder wall of patients suffering from superficial bladder carcinoma. PATIENTS AND METHODS: Twelve patients (10 men and two women, mean age 67 years, range 42-85) with superficial carcinomas of the bladder were treated for 6 consecutive weeks and then monthly for 1 year with 20 mg KLH in 20 mL saline instilled intravesically after complete resection of the tumours. Biopsies were taken for immunohistochemical examination before treatment and again 6 weeks, 3, 6 and 9 months after treatment. Six patients with no evidence of cystitis or malignant bladder disease acted as a control group. Immunofluorescent staining of the biopsies was performed using monoclonal antibodies to the T-cell markers CD4 and CD8, and to CD14 (monocytes), CDw15 (granulocytes), CD19 B-cells (Pan-B), CD68 (macrophages) and HLA-DR. Anti-KLH antibody-producing plasma cells were detected using a standard technique. A semiquantitative analysis of locally infiltrating cell types was performed. RESULTS: After treatment with KLH the increase of CD8+ suppressor cells was less pronounced than that of CD4+ helper cells. The T-helper/inducer to T-suppressor/cytotoxic cell ratio thus altered from 0.8:2.0 before treatment to 1.6:2.3 afterwards. Hence, the number of T-helper cells had increased considerably, whereas there was only a moderate increase in the number of T-suppressor cells. This cellular ratio could be detected for 9 months after KLH therapy. The numbers of activated HLA-DR+ immune cells in the submucosa and among urothelial cells also increased after KLH instillation. The degree of mononuclear cell infiltration of the submucosa increased considerably, but granulocyte infiltration was only moderate. Lymph follicles with enhanced B-lymphocyte counts were also detected. CONCLUSION: Immune-cell infiltration into the urothelium and enhanced activation (expression of class II antigens) suggests distinct processes of cellular antigen recognition, which could be detected for up to 9 months after the beginning of KLH therapy. This may represent a basic functional mechanism of KLH therapy.

Administration, Intravesical↗

[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↗