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Biomedical subjects

U Wagner

Publications and source records attributed to U Wagner.

At least 163 records · Page 9Linked to original sources
PubMed1993

GLP-1 stimulates secretion of macromolecules from airways and relaxes pulmonary artery.

Recent data revealed the existence of specific receptors for glucagon-like peptide-1(7-36)amide (GLP-1) on rat lung membranes. Utilizing slide-mount autoradiography of fresh frozen lung tissue sections, we have localized binding sites for GLP-1 on mucous glands in the trachea and on vascular smooth muscle of the pulmonary artery. When tracheas were incubated in a modified Ussing chamber, the addition of GLP-1 to the submucosal side increased 35S-sulfate-labeled macromolecule secretion (191 +/- 12% above basal, P < 0.005). The optimal secretory response elicited by GLP-1 was approximately 23% of the maximal secretory response after a maximal acetylcholine stimulation. Other proglucagon-derived peptides such as glucagon, oxyntomodulin, and GLP-2 had no effect. In isolated rings of arteries, GLP-1 (10(-8) to 10(-5) M) induced a dose-dependent and time-reversible relaxation of preconstricted arteries. In a preparation with denuded epithelium, GLP-1 lost its effect. In conclusion, GLP-1 might represent another neuropeptide that acts as neurotransmitter of the peptidergic, nonadrenergic-noncholinergic nervous system that innervates the airways.

Animals↗
PubMed1993

Idiotypic cascades after injection of the monoclonal antibody OC125: a study in a mouse model. Induction of antibodies against OC125 and CA125 after immunization with an anti-CA 125 (MAb OC125) monoclonal antibody by activation of the idiotypic network.

By immunization of mice with the anti-CA 125 monoclonal antibody OC125, we tried to induce antibodies directed against the tumour-associated antigen CA125, via activation of the idiotypic network. Mice immunized by repeated administrations of F(ab')2-fragments of the OC125 antibody produced anti-idiotypic antibodies, imitating the original target antigen of the OC125. After induction of these anti-idiotypic antibodies (Ab2 beta) a murine IgG-anti-CA125 (Ab3) response was detected. The induction of idiotypic cascades offers the possibility of immunization against tumour-associated antigens, without using the original antigen and breaking antitumour tolerance.

Animals↗
PubMed1993

Monitoring cancer antigen 125 in serum of ovarian cancer patients after administration of 131I-labeled F(ab')2 fragments of OC125 antibody.

We evaluated the effect of repeated administration of OC125 F(ab')2 fragments on cancer antigen (CA) 125 determination in 210 serum samples from 30 patients. We found falsely high CA 125 concentrations in 142 (68%) samples, using a homologous CA 125 enzyme immunoassay (EIA) with OC125 antibodies. The Truquant OV2 method, which involves two other murine antibodies, and the IMx CA 125 method, which uses sheep antibodies as capture antibodies, resulted in only slightly increased (false-positive) values in some samples with exceptionally high CA 125 EIA values. We measured falsely low CA 125 values in 37 (18%) samples with the Truquant OV2 method. Interferences could be eliminated by removal of serum IgG. Our results suggest that interferences are to some extent caused by anti-idiotypic IgG induced by OC125 administration. Assays involving nonmurine anti-CA 125 antibodies as capture antibodies seem to be most suited for CA 125 determination after OC125 treatment, but in every case an apparent increase of CA 125 after OC125 infusion should be validated.

Antibodies, Anti-Idiotypic↗
PubMed1992

Unilateral lesion in the tuberomammillary nucleus region: behavioral asymmetries and effects of histamine precursor.

The subnuclei of tuberomammillary nucleus are located in the posterior part of the hypothalamus adjacent to the basolateral surface of the mammillary bodies. The neurons of this nucleus innervate extensive parts of the brain with several transmitters, particularly with histamine. In fact, they represent the only source of histaminergic projections in the brain. The present study deals with the effects of a lesion in this region on behavior. Unilateral electrolytic direct current (DC) lesions in the tuberomammillary nucleus led to an asymmetry in thigmotactic scanning; i.e., at 11 days, but not 1 day postlesion, the rats scanned the walls of an open field more with the vibrissae contralateral to the lesion than with those of the ipsilateral side. Furthermore, they emitted more ipsiversive than contraversive wide angle turns. The behavioral asymmetries are, in general, opposite in direction to those induced by lesion of the neighboring lateral hypothalamus and substantia nigra, indicating that they are specific to the tuberomammillary region destroyed. Application of the histamine precursor histidine led to a compensation of these asymmetries, suggesting that the tuberomammillary's histaminergic efferents are functionally related to the lesion-induced behavioral effects.

Animals↗
PubMed1992

[Photodynamic laser therapy with antibody-bound dyes. A new procedure in therapy of gynecologic malignancies].

In the present paper, a new therapeutic concept of photodynamic laser therapy using antibody-linked dyes for the treatment of gynecological malignancies is described. So far, HPD (hematoporphyrin derivative) has been employed in this area, but is associated with toxic systemic reactions. We see a solution to this problem in the linking of a systemically non-toxic dye--known to induce photodynamic reactions while not itself being selectively accumulated within tumor cells--to an antibody directed against a selective tumor-associated antigen. The results of our study demonstrate the efficacy of this therapeutic concept as exemplified by the selective destruction of dye-labeled ovarian carcinoma cells by laser light of a defined wavelength (675 nm). The potential of this form of photodynamic therapy extends far beyond its use in ovarian carcinoma.

Antibodies, Monoclonal↗
PubMed1992

Effects of tumour necrosis factor alpha on bone marrow aspirates of patients with acute myelogenous leukemia determined by flow-cytometric cell-cycle analysis.

Tumour necrosis factor alpha (TNF alpha) exerts cytotoxic and antiproliferative effects on neoplastic cells. It has been used as a therapeutic agent for solid tumours and haematological malignancies. We report on the ex vivo determination of the effect of recombinant human rhuTNF alpha on bone marrow aspirates by a bromodeoxyuridine/propidium iodide method. Cell samples were drawn after 0.5, 2, 4, 6, 8, 10, 22, and 25 h from short-term suspension bone marrow cultures from patients with acute myelogenous leukemia (AML). Flow-cytometric cell-cycle analysis was performed after double DNA staining with propidium iodide and anti-BrdU antibodies. By this method the effect of rhuTNF alpha on cell proliferation can be evaluated after only 35 h. In about two-thirds of the bone marrow aspirates of AML an inhibiting effect on rhuTNF alpha can be demonstrated, developing to its full extent after 10 h.

Biopsy, Needle↗
PubMed1992

[Clinical use of photodynamic therapy in gynecologic tumor patients--antibody-targeted photodynamic laser therapy as a new oncologic treatment procedure].

The clinical report addresses the first application of a antibody-targeted photodynamic laser therapy with Phthalocyanines. Photodynamic therapy (PDT) has been proposed as a further treatment modality in oncology. The concept of PDT is based on the interaction between a dye which is accumulated in the target and laserlight. The phototoxic effect is achieved by the augmentation of oxygen radicals. The improvement of the selectivity and the reduction of side-effects is achieved by our concept of using an antibody-targeted phthalocyane induced PDT. The clinical application of the antibody-targeted Phthalocyanine was performed in 3 patients suffering from an advanced ovarian carcinoma (FIGO III). By means of an ultramicroscopical analysis a selective devitalisation of tumor cells was demonstrated. The perspective of PDT reaches far beyond the application for the ovarian carcinomas and relates to all tumor types, where the presence of tumor-associated antigens implicates a treatment in a similar way.

Combined Modality Therapy↗
PubMed1991

Structure/activity investigations in eight arylalkyltriazenes comparison of chemical stability, mode of decomposition, and SCE induction in Chinese hamster V79-E cells.

A series of seven 1-aryl-3.3-dialkyltriazenes, including 1-phenyl-3.3-dimethyltriazene (DMPT), 1-phenyl-3.3-di-(trideuteromethyl)-triazene (DMPT-ds), 1-p-methylphenyl-3.3-dimethyltriazene (DMpMPT), 1-p-nitrophenyl-3.3-dimethyltriazene (DMpNPT), 1-phenyl-3.3-diethyltriazene (DEPT), 1-phenyl-3.3-di-n-propyltriazene (DnPrPT) and 1-phenyl-3.3-diisopropyltriazene (DiPrPT) and 1.3-diphenyl-3-methyltriazene (DPMT), was synthesized and characterized by UV/VIS, IR and 1H-NMR spectroscopy. Chemical half-life was determined in phosphate buffer at 37 degrees using UV/VIS spectroscopy. With the exception of DMpNPT, which was stable, the triazenes underwent pH-dependent hydrolytic decomposition (acid catalysis). By means of UV/VIS spectra, TLC and HPLC, phenol, aniline and secondary azocoupling products were identified after complete hydrolytic cleavage of the parent compounds. Pathways of spontaneous hydrolysis are proposed and discussed. Genotoxic activity of the triazenes was assayed by measurement of sister chromatid exchanges (SCE) in V79-E cells without and with rat liver S9 mix as an exogenous metabolizing system. In the direct SCE assay (without S9 mix), all triazenes except DMpNPT exerted a toxic action (cell cycle delay) in a narrow concentration range between no effect and overt cytotoxicity. This non-specific toxicity depended on the pH of the incubation system and was inversely proportional to chemical half-life. The toxicity of these agents is most likely due to the arenediazonium cation which is a relatively stable intermediate. In a sublethal concentration range most triazeness induced significant increases of SCE rates. These are interpreted as an indirect consequence of cytotoxicity. Upon metabolic activation, the compounds were genotoxic in a dose-dependent fashion. Their SCE-inducing capacity depended on the nature of the alkylating species generated, i.e., the alkyldiazonium cation, and on chemical stability. Surprisingly, no deuterium isotope effect was observed in DMPT-d6. The order of genotoxic activity among the aryldialkyltriazenes was DMpNPT much greater than DMPT = DMPT-ds greater than DMpMPT much greater than DEPT greater than DnPrPT greater than or equal to DiPrPT. DPMT was a marginal SCE inducer but very toxic upon metabolic activation. As monooxygenation of DPMT, like spontaneous hydrolysis, should generate a phenyldiazonium cation, the results suggest that arylation of DNA causes a very low SCE induction, if any.

Animals↗
PubMed1991

Photodynamic laser therapy of carcinomas--effects of five different photosensitizers in the colony-forming assay.

Photodynamic therapy (PDT) with laser radiation opens a new field in the treatment of malignancies. We evaluated the phototoxic effects of five different substances for photodynamic therapy in concentrations showing no systemic toxicity. We used gynecologic tumor cells and evaluated the photodynamic effects for cell growth in a colony-forming assay. For Indigocarmin we found a reduction in the colony-forming assay compared to the control group from 87% to 66% after irradiation at 50 mumol/l and 608 nm wavelength. "IR 132" showed a reduction in the colony-forming assay from 73% to 72% 50 mumol/l (590 nm). For the incubation of the HeLa cells with 50 mumol/l of "Sulfo-Phthalocyanin" we found a reduction of the colony-forming potential from 81% to 67% (595 nm). The most strikingly differences were found for the incubation and irradiation of Methylene Blue, showing a reduction from 77% to 16% caused by a toxic effect of the substance itself (5 mumol/l, 660 nm) and "Sulfo-Aluminium-Phthalocyanin" stained cells, which shows a reduction from 86% to 17% (50 mumol/l, 675 nm). We see the possibility of a photoactivation and cell devitalisation by "Sulfo-Aluminium-Phthalocyanin" and laser radiation. A future clinical trial would seem justified.

Cell Survival↗
PubMed1991

The development of a community-based HIV/AIDS counselling service in a rural area in Uganda.

This paper describes the evolution of a counselling service in the context of an HIV/AIDS research programme in rural Uganda. The background to AIDS counselling both in Europe/America and in Africa is outlined first, and the cultural context of the programme explained. The evolution of the counselling procedure is then described and village case studies are used to illustrate the development and the difficulties that have been faced in finding an appropriate counselling model. It is noted that the Euro-American model of person-to-person counselling needs to be adapted to the rural African setting, by placing the emphasis on support for the family. It is emphasized that the approach to counselling needs to remain flexible and sensitive to the sociocultural context in which it is developed.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Locoregional ascites therapy with cytostatic drugs and immune modulators in gynecologic neoplasms].

35 ovarian cancer patients with ascites have been treated intraperitoneally with mitomycin C or mitoxantrone or interferon beta or tumor necrosis factor (TNF). We observed nor or a little bit ascites in 87.5 per cent after TNF and in 66.5 per cent after mitoxantrone. In addition we applied a systemic monochemotherapy. After mitomycin C or interferon beta only in 40 per cent each an effect could be observed. TNF to day is the most effective substance for treating ascites with moderate toxicity.

Ascites↗
PubMed1991

Probing the distance between the two binding sites of hirudin for its interaction with the active site and the fibrin(ogen)-binding site of alpha-thrombin.

The interaction of delta (Ser50)-hirudin with alpha-thrombin has been investigated. Deletion of Ser50 of r-hirudin caused a 2.7 fold increase of the Ki for its complex with alpha-thrombin. Determination of the rate constants kon and koff for complex formation showed that this effect was mainly due to a change in koff.

Amino Acid Sequence↗