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Biomedical subjects

E M Fabricius

Publications and source records attributed to E M Fabricius.

At least 37 records · Page 2Linked to original sources

The serological clostridium tumour test--application of discriminance analysis.

The microbiological tumour test is based on the detection of humoral antibodies to clostridial rods following intravenous injection of apathogenic clostridial spores. As serological methods we used the complement fixation test with a simultaneous short-time warm and long-time cold incubation as well as the passive haemagglutination test after absorption of clostridial group-specific antibodies. The evaluation of titre dynamics was rendered difficult by normal clostridial antibodies, by serological cross-reactions and, above all, by border-line reactions. The serological test results from 189 dogs investigated were evaluated in a multivariate analytical procedure. We determined the adequate combination of methods and antigens, thus improving the reliability of the test results and objectifying the predictive value of low sero-positive titres. On the basis of the computer-calculated individual weighting factors and the corresponding reference value it has become possible to evaluate and classify actual serological data emerging from the previous overall investigation.

Animals↗

The role of cell population kinetics in the efficacy of penicillin--an experimental analysis and stochastic modeling of the tumour tetanus and wound tetanus of the mouse.

When investigating tetanus lethality summation curves of mice under comparable quantitative conditions following a temporarily limited administration of penicillin, the curves obtained can be calculated by the kinetics of tumour cells or wound fibroblasts. In particular, it has been shown that the optimal efficacy of penicillin, after short-time usage as compared with a long-time administration schedule, is determined by the generation time of the tetanus rods as a function of the mitotic cycle of the "pace-making" tumour cells or wound fibroblasts. Further variables of the mathematical model imply the pharmacokinetics of penicillin and the recovery process of the "hit" tetanus rods. From these results some basic experimental and clinical tetanus issues can be elucidated; thus, the mitosis theory of tetanus is being verified for the stage of incubation and of clinical manifestation, while the classical necrosis theory of the pathogenesis of tetanus infection should be valid only for the final stage.

Animals↗

[Eye involvement in AIDS].

Between 1984 and 1987 (over two-and-a-half years) 30 hospitalized patients with HIV infections of different degrees of severity were ophthalmologically examined. Ocular involvement was found in 17 patients (approx. 57%). In 16 of these 17 patients with pathologic ophthalmologic findings (approx. 94%), AIDS was already fully developed. Ocular involvement is therefore a sign of poor prognosis. Fourteen patients had a microvascular retinal syndrome and four patients had infectious (chorio-)retinitis (causative organisms: cytomegalovirus in three cases, Cryptococcus neoformans in one). Further findings included sicca syndrome with superficial punctate keratitis in two cases, keratitis in one patient with generalized mucocutaneous candidiasis, Kaposi's sarcoma of the eyelids in two cases, Kaposi's sarcoma of the conjunctiva in one case, papilledema with cryptococcal meningitis in one case, and atypical hordeolum in one case. Morphologic and pathogenetic aspects of the ophthalmologic findings, their importance and course in AIDS patients, and therapeutic problems are discussed.

Acquired Immunodeficiency Syndrome↗

Conception and stages of development of the microbiological cancer test.

Pathology and experimental bacteriology have, in scientific medicine, created fundamental methodical presuppositions for the description and recognition of etiologic entities. With the tumour-tetanus phenomen, two pathogenic principles--cancer growth and tetanus infection--coincide in a so far unknown manner. Analytical experiments have led to the novel idea of the mitosis-stimulated anaerobic tetanus infection. This specific pathomechanism and its mathematical model formed the basis for the development of the serological Clostridium-tumour test with nontoxic, apathogenic Butyricus Clostridia as test microbes. As viable diagnostic agents the test spores are subject to the 12th Regulation of the Drug Act of the GDR. Only the histopathological judgement allows for the detection of micro-tissue alterations following i.v. overdoses of spores. The test spores were confirmed as safe and effective, and the microbiological cancer test approved to be appropriate for a clinical trial.

Animals↗

[Evaluation of thrombocyte-induced immunomodulation in the tetanus-infected mouse].

The infection model of the mouse-tetanus assay was utilized in experiments to test for immunomodulating effects of thrombocyte preparations. It has been established that the substances of platelets cause alteration of tetanus reactivity in mice which occurs in two phases: a non-specific early effect starting only a few hours after application displaying a drastic increase of resistance of the animals to sporangium activity (possibly through enhancement of phagocytosis or bypass operation). A late phase of effectiveness develops after weeks, visible by an increase of morbidity and mortality following a repeated challenge which may be due to a decrease of a specific immune response. The immune modulating action is that of an inducer acting in xenogeneic systems and altering also the immune response to transplantation antigens.

Animals↗

[The tumour-tetanus phenomenon as a basis for computation of cell kinetic parameters of tumour growth (author's transl)].

A verbal description of a mathematical model is given which theoretically explains the basis of the biological specificity of the tumour-tetanus phenomenon. The main postulate of the model concerns a mitosis-controlled clostridial growth. It is based on the experimental and mathematical demonstration that clostridia are stimulated by the dividing tumour cells. In particular, we have shown that the parameters which describe the kinetics of the pacemaker cells of the host can be deduced from the experimental tetanus lethality curves of the animals. Using these mathematical parameters one obtains stimulated curves which excellently fit the experimental test results. The pacemaker mechanism is the prerequisite of a specific clostridium-tumour assay utilizing serological methods with atoxic non-oncolytic clostridial strains as test microbes.

Animals↗

[Application of the serological clostridium assay in tumour diagnostics (author's transl)].

The suitability for serologic tumour diagnostics of the non-oncolysing strain Clostridium butyricum CNRZ 528 has been investigated. By introducing the transplantable Brown Pearce tumour of the rabbit and spontaneous tumours of the dog as test models the antibody production against clostridial rods--indicating malignant growth as had been proved with the Möse strain Cl. oncolyticum M55--has been evaluated. It could be established--utilizing the complement fixation test--that one serological method alone is not sufficient for obtaining clear-cut test results in anyone case. It is to be recommended that the indirect hemagglutination and the complement fixation tests ought to be combined. Our studies on specific clostridial antigens and on optimization of techniques will be continued.

Animals↗

[Investigations on the characterization of a clostridial strain for tumour diagnosis (author's transl)].

Careful delineation of a clostrial strain for human tumour diagnosis as against oncolytic tissue-active clostridial strains should be obligatory. We investigated the possibility to differentiate Clostridium butyricum CNRZ 528 (Bergère) against three different strains kept in our institute by means of biological, biochemical and by phage typing procedures. In addition, consistency in the control of half-technological spore production is required. It could be confirmed by this study that oncolytic properties of clostridial strains are biologically testable with adequate sensitivity in the hamster A Mel 3 tumour model. By means of typing procedures, we were able to clearly differentiate between Clostridium butyricum CNRZ 528 on one hand and Clostridium oncolyticum M 55 as well as Clostridium butyricum Jena H 8 on the other. The results of the tests are unsuitable for identifying Clostridium butyricum CNRZ 528 or Clostridium butyricum McClung 1672 A, respectively, nor can we distinguish Clostridium oncolyticum M 55 from Clostridium butyricum Jena H 8.

Animals↗

[Experimental studies on the pathogenicity of tetanus spores regarding eucaryotic cell systems (author's transl)].

After injection of known numbers of viable tumour cells admixed with tetanus spores into the subcutaneous tissue between the shoulder blades the sigmoidal tetanus lethality curves of mice can be quantitatively analysed following the underlying growth of tetanus clostridia and tumour cells. We suggest that the "driving force" for exponential clostridial growth and toxin synthesis are oxygen-consuming clones of tumour cells. Our experimental data are in good accordance with a stochastic mathematical model which allows for computing the cloning probability of one single spore on the basis of a 1-mitosis-1-clostridium division-principle.

Animals↗

[The microbiological cancer test--further studies with experimental mouse tumor tetanus and wound tetanus].

A re-evaluation of the specificity of the tumour-tetanus assay of the mouse was performed by analysing the wound-tetanus assay under comparable test conditions. This was achieved by injecting 1 X 10(6) viable Ehrlich carcinoma cells admixed with 1 X 10(2) tetanus spores subcutaneously, in a 0.1 ml dose volume or, 1 X 10(2) tetanus spores suspended in 5% CaCl2 solution, respectively. By comparison, these two groups of mice developed about the same tetanus mortality rates, however, following tetanus antitoxin therapy with 3 doses of 100 IU each day on days 0, 4 and 7 after infection, clinical signs of late tetanus exclusively belonged to tumour bearing animals. This typical tetanus behaviour may be explained by a spatial-temporal association between growing tetanus rods and proliferating cells of warm-blooded animals. In this manner tumour tissue can be differed from wound granulomatous tissue by way of permanently cloning stem cells.

Animals↗

[In-vitro effect of X-irradation on respiration and glycolysis of Ehrlich-ascitic carcinoma cells of the mouse--an experimental comparison with the mouse tumour-tetanus assay (author's transl)].

Depending on the dose of X-rays, in-vitro irradiation of Ehrlich-ascitic carcinoma cells of the mouse affected both respiration and glycolysis. 15,000 R irradiation suppressed the aerobic and anaerobic energy metabolism rather strongly followed by a reduction of the "take" and growth of the subcutaneously injected tumour cells, as opposed to the growth behaviour of non-irradiated cells. In analogy, tetanus mortality rates were reduced in the mouse tumour-tetanus assay with 15,000 R irradiated cells. On the other hand, irradiation with 2,000 R of Ehrlich carcinoma cells resulted in unchanged rates of respiration and glycolysis, in spite of the strongly limited growth capacity of the tumour cells. The tumour-tetanus assay of the mouse showed good correlation with subcutaneous tumour growth; no such correlation was found in the tetanus assay and the manometric values of respiration and glycolysis with 2,000 R irradiated tumour cells.--After subcutaneous injection of mixed cell suspensions consisting of 1 x 10(5) viable and 1 x 10(6) 15,000 R irradiated Ehrlich-ascitic carcinoma cells as well as of 3 x 10(2) tetanus spores per single dose, we observed similar rates of tumour growth, or tetanus mortality, respectively, if 1 x 10(5) viable tumour cells alone were administered together with 3 x 10(2) tetanus spores, without addition of irradiated tumour cells.

Animals↗

[The determination of the oncolytic effect of clostridia with the hamster amelanotic Melanoma no.3--a quantitative study utilizing defined criteria of evaluation (author's transl)].

With a view of satisfying the practical demands on a diagnostic tumour clostridium assay the development of a biological tumour test model is of prime importance. We are interested in a safe method for differentiating between oncolytic clostridia and clostridial strains exerting no oncolytic capacity. It was therefore attempted to develop a reproducible assay system using hamster A-Mel-3 as a reference tumour. This was finally attained by quantifying oncolysis taking into account the criterium of spontaneous onconecrosis of this tumour. The proposed oncolytic assay system was submitted to a mathematical regression analysis using different strains of clostridia as well as different batches of cultivated spores of one and the same strain. The results are critically compared with the current literature.

Animals↗

Inhibition of subcutaneous Ehrlich carcinoma by antihuman-somatotropic hormone serum of the horse as determined by the tumour-tetanus assay of the mouse.

Utilizing a quantitative tumour tetanus assay of the mouse it could be shown that antisomatotropic hormone serum of the horse exerts protective effects against solid Ehrlich carcinoma of the subcutaneous tissue and concomitantly, against tetanus mortality rates as an indicator of tumour growth. The positive correlation of the inhibitory action of antisomatotropic hormone serum against both transplantable tumour cells and subcutaneous regenerative tissue as a control lends further support to the assumption that a selective mechanism interrelates proliferative mammalian cell populations and multiplying toxinogenic clostridia, thus stimulating a new field of application of antisomatotropic hormone serum.

Animals↗

[Experiments concerning the enhancement of clostridial growth (Clostridium butyricum 1672 A McClung) by means of the anaerobic metabolism of Ehrlich ascites carcinoma cells of the mouse (author's transl)].

Ehrlich ascites carcinoma cells stimulate the vegetative growth of Clostridium butyricum in a modified Parker medium under N2 atmosphere. The enhancement of clostridial growth depends on the number of tumour cells added. The Ehrlich ascites carcinoma cells keep the ordinary transplantability after anaerobic incubation with the vegetative forms of Clostridia. Further means for the manometric investigations of the tumour clostridium phenomenon are discussed.

Anaerobiosis↗