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Biomedical subjects

W A Müller

Publications and source records attributed to W A Müller.

At least 55 records · Page 3Linked to original sources

[The effect of a subretinal injection of Toxoplasma gondii on the serum antibody titer in a rabbit model of ocular toxoplasmosis].

A single subretinal injection of RH toxoplasma initiated an experimental toxoplasmosis of the eyes in big chinchilla rabbits. This animal model was used to study the development of the serum IgG level against toxoplasma. As a rule, the specific antibody level rose between the 9th and the 20th day following injection. At that time, the peak of inflammation had already been exceeded. An influence of cyclophosphamide0 or complete Freund's adjuvant on the humoral immune response of the animals to toxoplasma could not be detected. An attempt is made to interpret the findings deviating from the toxoplasmosis of the human eye.

Animals↗

[The production of hybrid cells producing monoclonal antibodies against Toxoplasma gondii].

Hybridomas that secrete monoclonal antibody to Toxoplasma gondii have been developed. Two groups of 10 female BALB/c mice each were immunized either over a shorter (71 d) or longer (117 d) period at first with Toxoplasma lysate antigen and afterwards with intact tachyzoites of the RH strain. Higher titres of antibody were obtained with the long-period immunization. The fusion experiments have shown that both schemes of immunization approximately result in the same number (16 and 14% respectively) of hybridoma cell lines producing antigen-specific monoclonal antibodies. Hybridoma cultures secreting antitoxoplasma monoclonal antibodies were screened parallel by indirect immunofluorescence antibody test (IFAT) and enzyme immunoassay (EIA). 16 of the hybridoma cell cultures produced positive results only in the IFAT, 112 reacted only in the EIA and 21 were positive in both tests. The monoclonal antibodies 5B10, 5G6 and 1B2, which are positive in the IFAT form a chemical compound with the major antigens on the surface of RH tachyzoites. The patterns of fluorescence produced by these monoclonal antibodies are in conformity with those produced by using polyclonal sera of Toxoplasma gondii infected hosts (mouse, rabbit, man).

Animals↗

Production and characterization of antibodies to rat pancreatic acinar cells.

The contribution of immunologic noxae to the damage of the cells and the induction of autodigestion in the course of acute pancreatitis in rats should be regarded. The isolation of intact acinar cells from rat pancreas offers a new approach to a more specific antiserum being directed against antigens at the outside of the cell membrane. Proof of circulating antibodies was performed using the indirect immunofluorescence reaction method (IFAR). A defined membrane fluorescence was observed at the surface of the acinar cells in vitro and a fluorescence at the septa of lobules marking the borders of acini in vivo.

Acute Disease↗

Activation of endogenous C-type retroviral genomes by internal alpha-irradiation of mice with 224Radium.

Sensitive cocultivation techniques were applied to study the radiation-induced activation of endogenous retroviral genomes in different mouse strains by the alpha-emitting radionuclide 224Radium. Activated infectious C-type retroviruses were detected in spleen, bone marrow and bone tissues of C57BL/6-, BALB/c- and NMRI mice. The titres of high-dose-irradiated animals were higher than those found in low-dose-irradiated animals. Infectious retrovirus could be detected with a dose of 13.2 rad (maximum dose rate 0.9 rad/day) in the skeleton, and a dose of 4.2 rad (maximum dose rate 0.3 rad/day) in the spleen. The virus activation pattern was different in the three mouse strains. These data indicate that activation of endogenous retroviral genomes by alpha-irradiation shows a dose-effect relationship and a dependence on the genetic background of the mouse.

Alpha Particles↗

[Demonstration of antigen-specific suppressor cells in Toxoplasma infection of man].

Detection of antigenspecific suppressor cells in Toxoplasma infection of man. Investigations adapted to demonstrate the action of antigen-specific suppressor cells were carried out in subjects with acute toxoplasmosis (n = 5) and latent infections (n = 16) and compared to non-infected controls (n = 11). The investigations were carried out in vitro in the form of autologous one-way lymphocyte mixed culture. Suppressor cells were activated by toxoplasma lysate antigen (325 micrograms/ml) and, for comparison, by concanavalin A (10 micrograms/ml). Responder cells were stimulated by toxoplasma lysate antigen (200 micrograms/ml). In the acute cases, antigen-specific suppressor cells were identified which caused the lymphocyte transformation to be suppressed (tritium thymidine incorporation) to the same extent as did the mitogen-activated cells. The subjects with latent infections revealed a statistically significant difference (p less than 0.01) between the means of the percentage suppression of suppressor cells activated by toxoplasma lysate antigen or concanavalin A, suggesting a diminishing suppressive action of antigen-specific cells at this stage of infection. In addition to the effect on phagosome formation in macrophages, the activation of suppressor cells too should be considered as a factor of virulence for Toxoplasma gondii.

Acute Disease↗

Retinoids and pattern formation in a hydroid.

The retinoids (retinol, retinal, retinoic acid) cause alterations in the pattern of limb elements in vertebrates (Summerbell & Harvey, 1983). As shown here, retinoids also influence pattern specification in hydroid polyps (Hydractinia echinata) in a way suggesting interference with the generation and transmission of signals responsible for the dimension and spacing of structures. A pulse-type application of low doses (e.g. retinoic acid 10(-6) to 10(-10) M, 4 h) causes metamorphosing primary polyps to develop more tentacles but fewer stolons per unit circumference, to shorten the length of the hydranth while the stolon elongates, and to bud secondary hydranths at high frequency 2-3 days after treatment (Fig. 3). Dose-response curves display optimum peaks. It is argued that the increase in budding rate is due to a reduction of the range of spacing signals emitted by the primary hydranth. In regenerating hydranths, low doses (10(-10) to 10(-9) M) improve the rate of head formation, whilst medium doses (10(-8) to 10(-6) M) result in more tentacles being regenerated. However, prolonged treatment with high doses (10(-6) to 10(-5) M) causes the animals to reduce all head structures and to transform eventually into stolons, in contravention of the rule of distal transformation that they normally obey (Fig. 8). The effects of the retinoids are counteracted by a putative morphogen, the endogenous inhibitor isolated from Hydra by Berking (1977). The Hydra-derived 'head-activator' displayed no stimulating effect on the number of tentacles and buds formed.

Animals↗

The role of time-factor and RBE for the induction of osteosarcomas by incorporated short-lived bone-seekers.

In a large series of experiments, fractionated injections of short-lived bone-seekers have been shown in many cases to cause a remarkable increase of the osteosarcoma incidence compared with a single administration of the same total skeletal dose. This effect has been observed with both alpha- and beta-emitters. In addition the latency period was shortened by protracting the dose. The total skeletal doses investigated ranged between 0.9 and 20 Gy for alpha-emitters (224Ra and 227Th) and between 28 and 112 Gy for the beta-emitter (177Lu). In all cases the protracted dose had higher or at least equal effects when compared with a single application. Reference experiments with long-lived alpha- and beta-emitting bone-seeking nuclides (226Ra and 90Sr) showed that the incidence of osteosarcomas per Gy was sometimes lower than that observed when the same skeletal dose was applied by protraction of short-lived radionuclides. The dependence of osteosarcoma incidence on dose-time distribution, duration of internal irradiation, and radiation quality is discussed. In this context the possibility that the critical initial dose rate may be related to the initiating event within the multi-stage hypothesis of carcinogenesis is considered.

Animals↗