Biomedical subjects

J Beuth

Publications and source records attributed to J Beuth.

At least 127 records · Page 7Linked to original sources

PubMedDate not supplied

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↗

PubMedDate not supplied

Are ABH antigenic determinants on human outer ear canal epithelium responsible for Pseudomonas aeruginosa infections?

The outer ear canal expression of ABH human blood group antigens has been analyzed with a standardized routine histological procedure by monoclonal antibodies in the case of blood groups A and B, and a corresponding lectin in the case of blood group 0, respectively. In all 20 cases the blood groups were histochemically confirmed. Furthermore, Pseudomonas aeruginosa-specific inhibition experiments were performed with different sugar solutions as well as A-like substance incubating outer ear canal tissue sections with P. aeruginosa strain (No. 60) presenting lectin specificity for N-acetyl-galactosamine (GalNAc). P. aeruginosa lectins with GalNAc specificity apparently adhere to GalNAc as terminal blood group A determinant and indicate that patients presenting with blood group A may have a genetic predisposition to this form of otitis externa.

ABO Blood-Group System↗

PubMedDate not supplied

Beneficial treatment of patients with advanced cancer using a Newcastle disease virus vaccine (MTH-68/H).

Newcastle Disease Virus Vaccine (MTH-68/H) was administered to patients suffering from advanced neoplastic diseases after non-efficient tumor-destructive treatment. Case reports of selected patients suggest promising effects of this treatment. A prospectively-randomized clinical study (phase III; in accordance with Good Clinical Practice, GCP) was proposed to confirm these results and is currently under consideration.

Adult↗

PubMedDate not supplied

Immunomodulating and antimetastatic activity of thymic peptides in BALB/c mice.

The immunomodulating and antimetastatic activity of a clinically approved low molecular weight, standardized thymic peptide (TP) preparation was evaluated in BALB/c-mice. Daily subcutaneous application of TP (7 consecutive days, 1 and 10 micrograms per mouse) upregulated counts and activity of peripheral blood cells, as measured on day 14. To check the influence of TP on experimental liver metastases (liver colonization), RAW H10 lymphosarcoma cells were intravenously inoculated into BALB/c-mice. TP (1,10,100 micrograms/mouse) was subcutaneously administered daily for 7 consecutive days starting 24 hrs 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 TP treated mice.

Adjuvants, Immunologic↗

PubMedDate not supplied

Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe.

Malignant glioma patients were prospectively enrolled into a clinical trial. All the patients were provided with the internationally recommended oncologic standard treatment (neurosurgery, radiation, basic clinical care according to protocol and indication) and randomly divided into a treatment group (receiving complementary immunotherapy with a galactoside-specific lectin from mistletoe, ML-1) and a control group (without additional complementary treatment). Whereas the beneficial effects of ML-1 treatment on immunological rescue and quality of life have been recently shown, evaluation of relapse free/overall survival was performed after a 50 months follow up time. Non-stratified analysis of all the patients revealed non-relevant prolongation of relapse-free intervals/overall survival time for the treatment group. However, analysis of stratified stage III/IV glioma patients demonstrated: 1. a tendency for a prolongation of relapse-free survival for patients of the treatment group (17.43 +/- 8.2 months) vs. the control group (10.45 +/- 3.9 months) 2. a statistically significant (BRESLOW p = 0.035) prolongation of the overall survival for the treatment group (20.05 +/- 3.5 months) as compared to the control group (9.90 +/- 2.1 months). These promising data warrant confirmation in a GCP-based prospectively randomized (multicenter) study, which is currently under consideration.

Adjuvants, Immunologic↗

PubMedDate not supplied

The recombinant human histones H1 zero and H1.2 cause different toxicity profiles on the human leukemia cell line K562.

The human histones H1 zero and H1.2 were expressed in E. coli and purified to homogenity. Their cytotoxicity on the human leukemia cell line K562 and on PBMC from healthy volunteers was compared with the cytotoxic effect of a bovine histone H1 preparation. In this preparation, histone H1.2 was identified as the main compound. All three histone preparations induced a significant dose-dependent toxicity on the leukemia cell line. Compared with the recombinant histone H1 zero, the bovine preparation and recombinant H1.2 showed stronger cytotoxicities. Cytotoxic effects on K562 cells were observed immediately after addition of the histones, whereas the histone preparations failed to induce significant cytotoxicity on PBMC during the first hour of incubation. However, after 24 hours all three histone preparations induced toxic effects on PBMC which were comparable to those observed on the leukemia cell line.

Animals↗

PubMedDate not supplied

Low molecular thymic peptides stimulate human blood dendritic cells.

Dendritic cells are considered to be the most potent antigen-presenting cells and are thus promising new tools for the immunotherapy of cancer. They respond to various stimuli by differentiation (expression of CD83) and up-regulation of costimulatory surface molecules. Thymic peptides have immunostimulatory and immunomodulating properties. Their therapeutic potential in immunotherapy of cancer has been discussed. To test whether thymic peptides act on dendritic cells, we examined the effects of a standardized thymic peptide preparation on cultured human monocyte-derived dendritic cells. Addition of thymic peptides resulted in enhanced expression of the specific differentiation marker CD83 in a dose dependent manner. Moreover, thymic peptides induced the up-regulation of costimulatory molecules including CD86, CD80, HLA-DR and HLA-ABC. After priming with thymic peptides dendritic cells showed an enhanced expression of IL-8 and TNF-alpha mRNA and protein release. Dendritic cells stimulated with thymic peptides were able to induce proliferation of autologous T cells as measured by 3H-thymidine incorporation in mixed Lymphocyte reaction. In combination with a low dosage of keyhole limpet hemocyanin, thymic peptides showed additive effects in the up-regulation of CD83 and costimulatory surface markers. Our findings indicate that thymic peptides per se act on professional antigen-presenting cells in a stimulatory manner and were presented by these cells. Furthermore, thymic peptides enhance the response of dendritic cells to low dosages of a standard nominal antigen. Therefore, thymic peptides could improve the immunological activity especially against low amounts of endogenous antigens.

Amino Acid Sequence↗

PubMedDate not supplied

Thymic humoral factor-gamma 2 augments immune cell response and exerts antitumor activity in murine model systems.

The immunomodulatory and antimetastatic/antitumor activity of thymic humoral factor-gamma 2 (THF-gamma 2) was evaluated in BALB/c-mice. Daily subcutaneous applications (7 consecutive days, 20, 200 ng of THF-gamma 2 per injection/mouse) upregulated counts of thymocytes and peripheral blood cells in tumor bearing mice. To check the influence of THF-gamma 2 treatment on the growth of experimental metastases, RAW 117 H10 lymphosarcoma cells or L-1 sarcoma cells were intravenously inoculated into BALB/c-mice to establish liver or lung metastases, respectively. Local tumor growth was induced by subcutaneous injection of L-1 sarcoma cells. THF-gamma 2 was subcutaneously administered daily for 7 consecutive days starting 24 hrs after tumor cell challenge. Organ colonization as well as local tumor growth were investigated on day 14 after tumor cell inoculation and demonstrated a statistically significant (p < 0.05) reduction of experimental liver and lung metastases and local tumor growth for THF-gamma 2 treated mice.

Adjuvants, Immunologic↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Changes in immunological characteristics of white blood cells after administration of standardized mistletoe extract.

After administering standardized mistletoe extract, Viscum album L, (Iscador injections of 0.1 mg twice and 1.0 mg in defined intervals) the functional characteristics of microcirculation and immunological behavior of the white blood cells in different target tissues (derma, intestine) were investigated in healthy volunteers by vital microscopic investigation over 13 days of observation. The investigations showed a temporarily improved function of the microcirculation and an increased adhesion and transmigration of white blood cells in the target tissue areas. This observation was evaluated as a biologically relevant immunomodulation. Further investigations under pathophysiological conditions with regard to complementary administration of the test substance (e.g. to cancer patients) appear promising.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Anticancer activity of rViscumin (recombinant mistletoe lectin) in tumor colonization models with immunocompetent mice.

The antitumoral and immunostimulating properties of rViscumin (recombinant mistletoe lectin) were investigated in two mouse tumor models. After intravenous inoculation with RAW-117-P or L-1 sarcoma cells in Balb/c mice, rViscumin was given s.c. at non-toxic doses ranging from 0.3 to 150 ng rViscumin/kg. One set of experiments was performed to investigate the survival of rViscumin-treated animals. Another set was carried out to analyze the effect of rViscumin treatment on the number of tumor colonies in infiltrated lungs (RAW-117P) or liver (L-1) and the activation of immune cell subsets, respectively. An overall prolonged survival time after treatment with rViscumin and a reduction in the number of tumor colonies after administration of certain rViscumin doses was observed. Immunophenotyping of the peripheral leukocytes of treated mice revealed increased numbers of T-lymphocytes, pan-NK cells and activated monocytes. The results indicate that rViscumin has antineoplastic properties and might therefore be a promising candidate in cancer therapy.

Adjuvants, Immunologic↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Cytokine release of whole blood from adult female donors challenged with mistletoe lectin-1 standardised mistletoe extract and E. coli endotoxin or phytohaemagglutinin (PHA).

Cytokine (TNF, alpha, interleukin-6) release of whole blood from healthy donors was challenged with mistletoe extract standardised for mistletoe lectin-1 (sML) and control substances (E. coli endotoxin; phytohaemagglutinin). The rationale of this investigation was non-proven warnings that pro-inflammatory cytokines induce by the application of standardised mistletoe lectins may induce tumor cell proliferation. These investigations provided evidence that non-cytotoxic concentrations of sML did not induced enhanced TNFa or interleukin-6 secretion compared to non-challenged control cells. Cytotoxic concentrations of sML, however, induced significantly higher cytokine levels than the control, obviously due to non-physiological stimuli. Immunomodulation with clinically relevant, low-dose sML incubation did not induce proinflammatory cytokine secretion in vitro.

Adult↗

PubMedDate not supplied

Influence of postoperative complementary treatment with lectin-standardized mistletoe extract on breast cancer patients. A controlled epidemiological multicentric retrolective cohort study.

This epidemiological study was performed to evaluate the influence of postoperative complementary treatment with lectin-standardized mistletoe extract (sME) on breast cancer patients. The design (retrolective cohort analysis with parallel groups) and conduct of the study were in agreement with current standards for prospectively randomized clinical trials. A cohort of 1,248 breast cancer patients on postoperative chemo-, radio-, hormone-therapy were studied in 27 randomized centers. Patients with complementary medications other than sME were excluded from the evaluation and the final analysis was performed on data of 689 patients. From this cohort 219 patients received a complementary treatment exclusively with sME (therapy group), while 470 patients were without complementary treatment (control group). The median follow-up time was 284 days (therapy group) and 285 days (control group). The primary end-point of the study was to determine the impact of complementary sME treatment on disease- or therapy-induced adverse reactions in breast cancer patients. Imbalances for causal effects (covariates) were adjusted by propensity scores. Final evaluation was performed by estimating the linear regression between change in symptom score and propensity score with all data and using the regression line to calculate the change in symptom score expected for each patient. Tumor-associated events were evaluated by number and time until event. The safety of sME treatment was analysed in terms of number, severity, duration and outcome of adverse reactions. As compared to breast cancer patients without complementary treatment (control group), the administration of sME (therapy group) resulted in a significant reduction of adverse reactions induced by the tumor-destructive therapies (e.g. nausea, gastro-intestinal tract symptoms, depression, fatigue, mental symptoms) and prolonged relapse-free intervals, most pronounced for UICC stages IIa and IIb. The rate of sME-associated adverse reactions was 12.8%. All side-effects were mild to moderate, predominantly local skin reactions and self-limiting without therapeutic intervention. Complementary treatment of breast cancer patients with lectin-standardized mistletoe extract (sME) proved to be a well tolerated optimization of standard tumor-destructive therapies, mainly improving quality of life and relapse-free intervals in defined UICC stages.

Adult↗

PubMedDate not supplied

Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial.

Standardized aqueous mistletoe extracts have been applied to cancer patients for several decades as complementary medicine. A multicentric, randomized, open, prospective clinical trial was conducted in three oncological centers in the People's Republic of China in Bejing, Shenyang and Tianjin. Following the guidelines of "Good Clinical Practice" (GCP) this study was performed to get information on efficacy safety and side-effects of the standardized mistletoe extract (sME). Two hundred and thirty-three patients with breast (n=68), ovarian (n=71) and non-small cell lung cancer (NSCLC; n=94) were enrolled into this study. Two hundred and twenty-four patients fulfilled the requirements for final analysis (n=115 treated with sME HELIXOR A; n=109 comprising the control group being treated with the approved immunomodulating phytopharmacon Lentinan). All patients were provided with standard tumor-destructive treatment schedules and complementarily treated with sME or Lentinan during chemotherapy according to treatment protocol. Biometrically, the patients of the control and sME treatment group were comparable regarding distribution, clinical classification (WHO) and treatment protocols. Analysis was performed according to the "Intention to treat principle". Quality of life (QoL) was significantly (p<0.05) improved for patients who were complementarily treated with sME, as determined by the questionnaires FLIC (Functional Living Index-Cancer), TCM (Traditional Chinese Medicine Index) and the KPI (Karnofsky Performance Index) in comparison to the control group. Additionally, the occurrence of adverse events (AEs) was less frequent in the sME than in the control group (total number of AEs 52 versus 90 and number of serious AEs 5 versus 10 in study and control group, most of them due to chemotherapy). Only one serious AE was allocated to complementary treatment in each group (1 angioedema in sME group). All other side-effects of the sME (7 harmless local inflammatory reactions at subcutaneous injection site, 4 cases with fever) were self-limiting and did not demand therapeutic intervention. This study showed that complementary treatment with sME can beneficially reduce the side-effects of chemotherapy in cancer patients and thus improve quality of life.

Antineoplastic Agents↗

PubMedDate not supplied

Influence of complementary Viscum album (Iscador) administration on microcirculation and immune system of ear, nose and throat carcinoma patients treated with radiation and chemotherapy.

With the techniques of vital microscopic and reflection spectrometric imaging, representative characteristics of microcirculation and immunology of white blood cells were evaluated before, during and after radiotherapy and chemotherapy of patients suffering from ear, nose and throat carcinomas. Adverse effects of radiotherapy and chemotherapy on the microcirculation and the immune system were decreased and reconstitution processes were accelerated by complementary administration of a standardized mistletoe extract (Iscador).

Aged↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Safety and efficacy of local administration of contractubex to hypertrophic scars in comparison to corticosteroid treatment. Results of a multicenter, comparative epidemiological cohort study in Germany.

OBJECTIVES: To investigate the safety and efficacy of Contractubex administration to hypertrophic scars in routine out-patient practice and to compare it to corticosteroid treatment. PATIENTS AND METHODS: This was a multicenter, retrospective cohort study, based on 38 randomly selected practices representatively distributed in Germany, including dermatologists and general practitioners. Data from 859 patients fulfilling the inclusion criteria were assessed and analyzed. Of these, 771 patients were eligible for the per protocol treatment with Contractubex (n=555) and corticosteroid (n=216). The safety and efficacy of local administration of Contractubex to hypertrophic scars was compared to corticosteroid treatment. RESULTS: At the end of defined treatment periods (minimum 28 days for local therapy with 1 intralesional corticosteroid application), normalization of the pre-treatment pathological parameters (erythema, pruritus, consistency) of hypertrophic scars was more frequent (42.5%) after Contractubex per protocol treatment as compared to corticosteroid per protocol treatment (22.2%). After adjusting imbalances of baseline characterisics between the treatment groups by the propensity score, the odds ratio was 2.274, demonstrating a significant superiority (p<0.001) of Contractubex treatment as compared to corticosteroid treatment. The time to normalization of erythema, pruritus and consistency was significantly (p=0.034) shorter with Contractubex treatment (median 344 days) than with corticosteroids (median 507 days). No unexpected or severe adverse events occurred in the Contractubex-treated patients. Apart from moderate pruritus (10% Contractubex vs. 1% corticosteroids), adverse events were significantly (p<0.001) more frequent in corticosteroid-treated patients (teleangiectasias 15% vs. 7% Contractubex; cutaneous atrophy of scars 10% vs. 2% Contractubex; cutaneous atrophy of scar surrounding skin tissue 11% vs. 1% Contractubex). CONCLUSION: For the primary aim of this study (assessment of normalization of erythema, pruritus, and consistency of hypertrophic scars) and for time to normalization, local administration of Contractubex was significantly more effective than corticosteroid treatment. Concerning safety, Contractubex treatment was associated with significantly less adverse events (e.g. teleangiectasias, cutaneous atrophy of scars and surrounding skin tissue) than topical corticosteroid application.

Administration, Cutaneous↗