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Biomedical subjects

H Werner

Publications and source records attributed to H Werner.

At least 253 records · Page 14Linked to original sources

Aspects of cellular immunity in multiple sclerosis. Antigen-reactivity of lymphocytes and lymphokine activity.

Some new results of cell-mediated immunity in multiple slcerosis (MS) are presented, based on the determination of charge-changing lymphokines as products of antigen sensitive lymphocytes (C PAL), obtained by several forms of the electrophoretic mobility (EM) method. Lymphocytes from MS react to myelin basic protein (BP), the reactivity in other neurological diseases depending on the degree of destruction of nervous parenchyma. Applying a membrane-associated antigen from normal brain (NTA), positive reactivity of MS lymphocytes was obtained. Besides the usual determination of lymphokines in vitro the sensitive EM test allows the demonstration of lymphokine activities in vivo; i.e. in body fluids such as cerebrospinal fluid (CSF) and serum. In CSF of MS a high lymphokine activity was found. The differentiation of lymphokines and comparison between in vitro and in vivo activity were carried out. Moreover, a characteristic lymphokine pattern for MS with high activities in all regions of molecular weight, especially in the CSF, could be detected. On the basis of these findings, important also from the pathogenetic point of view, a diagnostic scheme for MS is suggested, consisting of a program of determination of the immuno-reactive CSF syndrome and some special procedures, including examination of lymphocyte reactivity.

Brain↗

Structural changes of Toxoplasma gondii bradyzoites and cysts following therapy with sulfamethoxypyrazine-pyrimethamine: studies by light and electron microscopy. Consequences for chemotherapy.

Mastomys natalensis chronically infected with Toxoplasma gondii strain ALT over two months were treated with sulfamethoxypyrazine-pyrimethamine for 10 and 25 days. 72 hours after discontinuation of therapy the animals were sacrificed. The brains were removed and, following corresponding preparation, studied for the presence of the parasite and structural changes of cysts by light and transmission electron microscopy. More or less pronounced structural changes could be found in cyst walls, bradyzoites, and in particular in the endodyogeny stages. The degree of damage proved to be proportional to the intensity of the bradyzoite metabolism. The combination of drugs used was capable of passing the cyst membrane as long as the bradyzoites maintained their metabolism irrespective of its intensity. In cysts with a largely dormant metabolism that had been subject to therapy, no micromorphological differences of the ultrastructure could be recognized when compared with untreated controls of identical age; these cysts could not be influenced by treatment.

Animals↗

The effect of Toxoplasma cell fractions and mycobacterial immunostimulants against virulent Toxoplasma gondii in mice.

Toxoplasma gondii tachyzoites were disrupted in a Ribi cell fractionator and separated into cell walls and protoplasm by differential centrifugation. These products were used alone or combined with a mycobacterial glycolipid (P3) and injected either as oil-in-water emulsions or incorporated in Freund's incomplete adjuvant. Mice were vaccinated by intravenous or intradermal routes and challenged intraperitoneally with a highly virulent strain of Toxoplasma gondii. A local granuloma formation was induced after i.d. inoculation of Toxoplasma vaccines containing P3 as this glycolipid enabled an adherence of the antigens on the mineral oil droplets. The adjuvant effect of P3 on antibody formation was also observed. Most of the fractions showed a low, but statistically significant prolongation of survival time. Vaccination by the i.v. route with homologous or heterologous antigens, including Trypanosoma cruzi, were not significantly effective, with the exception of a high dose of Toxoplasma protoplasm associated with P3.

Adjuvants, Immunologic↗

[Value of the electrophoresis mobility test in the differential diagnosis of obscure kidney findings].

The differential diagnosis of unclear carcinoma-suspicious renal findings often finishes with the test-exposition and nephrectomy. Also when all modern diagnostic possibilities are used not always a clear establishment of the diagnosis may be achieved. The cell electrophoresis mobility test after Field and Caspary may contribute to the differential-diagnostic clarification of the findings, when adequate antigens are used. For this purpose 10 own cases are discussed and these results are compared with suitable comparative groups. Summarizingly by the present study can be shown that the immunologic diagnostics of tumours in the field of unclear renal tumours may be a very good help in the diagnostics. When adequate antigens are used in the cell electrophoresis mobility test a coordination concerning the histospecificity can be achieved.

Adult↗

Comparison of three methods of susceptibility testing of bacteroidaceae, peptococcaceae and other anaerobes to doxycycline.

The in vitro activity of doxycycline against 147 strains of gram-positive and gram-negative anaerobes was determined by broth dilution, agar dilution and agar diffusion tests. The strains were isolated from clinical specimens in 1977. Saccharolytic Bacteroides strains (39 B. fragilis, 6 B. thetaiotaomicron, 4 B. vulgatus) showed broth dilution MICs of less than or equal to 0.0625-4.0 microgram/ml after 5 h incubation and MICs of less than or equal to 16 microgram/ml after 15 h incubation at 37 degrees C. With strains of B. oralis, B. melaninogenicus ss. intermedius, B. corrodens, Veillonella sp. and Megasphaera elsdenii the broth dilution MICs were less than or equal to 0.0625-32 microgram/ml after 15 h incubation. Peptostreptococcus spp., Propionibacterium acnes, Eubacterium sp., Bifidobacterium sp. and Clostridium sp. had broth dilution MICs of less than or equal to 2 microgram/ml, whereas Peptococcus spp. were inhibited by less than or equal to 0.0625 to greater than 32 microgram/ml. With the great majority of strains tested, MICs were 2 to 256 times higher in agar than in broth dilution tests. Clinical and experimental studies seem to be needed to determine which of the in vitro data are correlated to the outcome of doxycycline therapy. Several groups and species were separately considered for statistical analysis of the relationship between zone size and MIC. With gram-positive anaerobes, correlation was poor between broth dilution MIC and zone size (correlation coefficients r = - 0.168 for Peptococcaceae, and r = - 0.108 for P. acnes). When calculating the regression lines for agar dilution MICs and zone diameters, a higher correlation was found (r = - 0.9 for Peptococcaceae; r = - 0.397 for P. acnes). With B. fragilis and other Bacteroides species correlation coefficients were r = - 0.807 to r = - 0.891 for broth and agar dilution MICs and zone size but stochastic linearity was lacking.

Anaerobiosis↗

[Aspects of immunologic diagnosis of brain tumors. Results with tumor-associated membrane antigens and the electrophoretic mobility test (author's transl)].

In cell-mediated immune processes the products of antigen-sensitive lymphocytes are detectable as charge-changing lymphokines by means of the cell electrophoretic mobility method (EM test). the improvement of the method concerns the measuring procedures (indicator particle and automation) and the application of specific antigens. The employment of special membrane antigens (3 M KCl extracts) from tissue of normal brain and brain tumors is decisive for further differentiating results. The application of tumor-associated membrane antigens (TAA) from various kinds of brain tumors shows some diagnostically important reaction patterns. Using a common tumor antigen, the TAA-X3 mixture, a (1) characteristic result of general significance for neoplasms can be obtained; in applying the different TAA of brain tumors the findings in EM test point out an (2) organospecific reactivity and/or a (3) histogenetic reaction pattern. The distinct neuroepithelial and mesodermal brain tumors produce predominantly an organospecific reaction and only partly a histogenetical profile. For this type of reactivity to the TAA in brain tumors, a series of factors depending on neuroimmunological specialities are important.

Adult↗

Application of teem-test for investigations of cellular immune phenomena in multiple sclerosis.

Some evidence is presented for usableness of tanned erythrocytes in electrophoretic mobility (TEEM)-test. Two possibilities of application of TEEM-test for immunological investigation in multiple sclerosis are discussed: detection of lymphocyte sensitization against a soluble antigen (3 M KCl extracted) derived from a normal brain and measurement of mixed lymphocyte reactin (MLR) after a short-time lymphocyte culture. Results show some connection between autosensitization (TEEM-test using normal tissue antigen) and predisposition (TEEM-MLR-test).

Antigens↗

Immunodiagnostic of multiple sclerosis by estimation of lymphokines in vitro and in vivo.

The basis of our investigations is a hypothesis about immunomechanisms responsible for aetiopathogenesis of multiple sclerosis including immungenetic connection (predisposition) and autoimmunity (pathogenesis). Some new results about cellular immunity using cell electrophoresis mobility technique, especially sensitization against normal brain tissue antigen (NTA) and investigations of lymphokines in cerebrospinal fluid are represented. The intention of this paper is to demonstrate a combined diagnostic regime for early detection of multiple sclerosis as well as for follow-up studies in course of treatment.

Antigens↗

A contribution to immunological tumour diagnostics in urology.

Fifty-four patients with malignant and other diseases of the urinary bladder and the prostate were examined for lymphocyte sensitization by means of electrophoretic mobility test (EM test). In this antigens from brain tissue (EF) and from malignomas of kidney, urinary bladder and prostate were used. Positive HEP values were obtained in 40 patients out of 42 with malignant tumours and in 5 patients out of 12 with other kidney diseases. With the corresponding tumour-associated antigens (TAA) in the EM-test, the histological tumour diagnosis could be confirmed in every case. Positive findings after using EF as well as the corresponding TAA are with great probability an indication of a malignant disease.

Adenocarcinoma↗

In vitro activity of tiamulin (81.723 HFU), a new pleuromulin derivative, against clinically significant anaerobes.

The susceptibility of more than 40 strains of Gram-negative and Gram-positive anaerobes to tiamulin (Sandoz 81.723 hfu), a new pleuromulin (pleuromutilin) derivative, was determined by broth dilution and agar dilution tests. The influences of density of the inoculum upon MICs was studied by a specially designed pour plate-technique. Bacteroides fragilis, B. vulgatus, B. splanchnicus, B. oralis, B. asaccharolyticus, B. melaninogenicus, Fusobacterium fusiforme (F. nucleatum), Sphaerophorus necrophorus, Clostridium perfringens, C. fallax, Propionibacterium acnes and several species of Peptococcaceae showed broth dilution MICs of 0.03 similar to 1 microgram/ml. Members of B. thetaiotaomicron, B. distasonis and S. freundii (F. mortiferum) were inhibited by 8 similar to 32 microgram/ml and 2 strains of S. varius had a broth dilution MIC of 256 microgram/ml. With most strains, the agar dilution MICs were 2 similar to 4 similar to 8 times the broth dilution MICs. In pour plate-tests, the MICs were not considerably influenced influenced by varying initial concentrations of viable cells. With most anaerobes, the MBCs of tiamulin were more than 100-fold higher than the MICs. The results obtained indicated that, apart from S. varius, B. thetaiotaomicron, B. distasonis and S. freundii (F. mortiferum), members of 16 other anaerobic species including B. fragilis were without exception sensitive to tiamulin.

Anti-Bacterial Agents↗

Types of cells involved in antigen-stimulated and spontaneous rosette formation with Toxoplasma gondii.

Antigen-binding cells were identified by using rosette formation of Toxoplasma gondii and defined lymphoid populations under different experimental conditions. Treatment of immunized spleen cell suspensions with anti-Thy 1 serum plus complement inhibited 5 to 29% of the rosette-forming cells (RFC). Higher numbers of thymus-derived lymphocyte-RFC were obtained after incubation at 4 degrees C and by the centrifugation method than by simple incubation at 20 degrees C. RFC were also observed with thymocytes. Combined treatment with anti-Thy 1 serum plus complement and depletion of adherent cells indicated that the major proportion, 46 to 70%, of RFC were B cells. Spleenocytes of nu/nu mice formed similarly high numbers of rosettes. Spontaneous RFC were observed in nonimmunized mice with both spleen and thymus populations. Numbers of rosettes varied considerably depending on the method and the source of cell population used. Removal of adherent cells from spleen suspensions resulted in RFC reduction of 14 to 25% in immunized and 14 to 33% in nonimmunized animals. Pretreatment with anti-mouse immunoglobulin inhibited completely the spleen and spontaneous thymus RFC and partially the thymus RFC in immunized animals.

Animals↗

[Susceptibility testing of anaerobes (author's transl)].

The methodology of susceptibility testing of anaerobes has not yet been standardized and many individual test methods are in use. Among the factors which may influence the outcome of susceptibility tests are test organisms, antimicrobials and methods of susceptibility testing. Comparative studies have shown that the density of the inoculum largely influences the MICs of sulphonamides and certain other antimicrobials. In testing susceptibility of anaerobes to doxycycline, the MICs determined by agar dilution tests were 2--4--8 times the MICs obtained by broth dilution technique. However, with certain cephalosporins and beta-lactamase-producing strains of Bacteroides fragilis and other Bacteroides species the MICs obtained by the two methods differed by four to five dilution steps. Judging by the broth dilution test, the majority of the beta-lactamase-producing Bacteroides strains would be classified as resistant, whereas with beta-lactamase-negative strains of Sphaerophorus varius the broth dilution test gave much lower MICs than the agar dilution technique. These findings pose the rather embarrassing problem as to whether strains are to be regarded as resistant or sensitive. As is demonstrated by lack of stochastic linearity and/or low correlation coefficients, the results of standardized anaerobic agar diffusion tests are for the most part not correlated to MICs determined by either method of quantitative susceptibility testing.

Anaerobiosis↗

The effect of passively transferred heterologous serum on Toxoplasma gondii in NMRI mice. Influence of the treatment on course of infection and cyst formation.

Anti-Toxoplasma serum from rabbits or normal Toxoplasma negative serum from humans was administered to NMRI mice by intraperitoneal, intravenous or oral routes. Transfer of immune serum intrapertioneally 48 hours before lethal challenge with cyst forming Alt strain conferred significant resistance to normal recipients as assessed by a 55% reduction in the number of brain cysts and 89% survival rate. Survivors of the groups receiving oral administration of immune or normal serum 48 hours prior to challenge also showed a reduction in the number of brain cysts of 50% and 21% respectively. Animals given immune serum by intrapertioneal or oral routes 48 hours after, or a small intravenous dose one day before challenge showed higher survival rates in comparison to controls but had an "enchancement" of infection as revealed by increased number of brain cysts.

Animals↗