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Biomedical subjects

W Zschiesche

Publications and source records attributed to W Zschiesche.

At least 55 records · Page 3Linked to original sources

Effect of a microbial growth inhibitory factor on the cyclic nucleotide metabolism of peritoneal macrophages.

Precultured mouse peritoneal macrophages were incubated with a microbial growth inhibitory lymphokine prepared from cell-free ascites of rat Zajdela hepatoma. Cyclic nucleotide metabolism was followed in parallel to experiments demonstrating inhibition of intracellular growth of Corynebacterium murium kutscheri. Maximum increase of cAMP, adenylate cyclase and cAMP-phosphodiesterase activities was found after 60 to 90 min, while inhibition of microbial growth was evident only after 2-3 h. Both effects showed concordant dose dependence. It is concluded that cAMP induces cellular metabolic changes which lead to inhibition of bacterial growth by macrophages.

3',5'-Cyclic-AMP Phosphodiesterases↗

Pathogenicity of Mengo virus to mice. III. Potentiation of infection by immunosuppressants.

Mengo virus has been described to cause, in dependence on the virus dose, lethal panencephalomyelitis and exocrine pancreatitis in mice after i.p. inoculation. Two immunosuppressive agents, cyclophosphamide and 1,3-bis(piperidinomethyl)-5-ethyl-5-phenyl-barbituric acid (ZIMET 176/68), were shown to potentiate Mengo virus infection as demonstrated by histopathology and enhanced mortality. Organotropism of Mengo virus did not change under the drug treatment. However, the histological lesions in brain, spinal cord and pancreas failed to exhibit any inflammatory reaction in case of cyclophosphamide, due to its antiphlogistic properties. Considering the mode of action of the drugs employed and the pathogenesis of Mengo virus infection in mice, it is concluded that in the system used both cyclophosphamide and ZIMET 176/68 exert their potentiating effects by interfering with primary virus-macrophage interaction.

Animals↗

Induction of cytokines by tilorone hydrochloride.

Tilorone hydrochloride, an interferon inducer in small laboratory animals, was demonstrated to elicit formation of macrophage migration affecting and microbial growth inhibitory cytokines after peroral drug administration to mice. Serum kinetics of the migration inhibitory cytokine resembled those of interferon, exhibiting a peak after about 24 h, whereas the bactericidal cytokine showed a steady increase up to 48 h after drug treatment. Both the factors were found to have molecular weights of 10,000--30,000 daltons as determined by Sephadex G-200 chromatography, to be stable at pH 2 and at 56 degrees C for 30 min, sensitive to chymotrypsin and resistant to RNase digestion. The migration enhancing serum activity could not finally be characterized so far. The physicochemical data are discussed in comparison to those of lymphocyte-derived cytokines. It is suggested that cytokine production may be, at least partially, responsible for the immunological effects of tilorone and possibly contribute to its antiviral action.

Animals↗

Antiviral activity of dipyridamole derivatives.

Among 46 novel pyrimido [5.4-d] pyrimidine derivatives, 26 compounds were found to exhibit antiviral activity as revealed in a test programme against Mengo, Coxsackie B1, fowl plague, vaccinia and pseudorabies viruses, as concerns inhibition of plaque formation and of infectious virus yield. Attempts to disclose structure-activity relationships by discriminant analysis pointed to a possible importance of hydrophobic substitution for the antiviral effectiveness against Mengo virus of the derivatives investigated.

Antiviral Agents↗

[Quantitative determination of hippuric acid in urine using high pressure liquid chromatography (author's transl)].

A simple method to determine hippuric acid in urine by high pressure liquid chromatography is described. An ion exchange column is used for the separation. The detection is carried out with a photometer. The analytical criteria of the reliability of the method are tested. The results for the precision and the accuracy of the method meet the guidelines of the statistical quality control. 34 urinary constituents were tested for their interference in order to examine the specificity. Measuring urine samples from 46 normal persons yielded hippuric acid concentrations between 160 and 2010 mg/1. The median was 400 mg/1, equivalent to 357 mg/g creatinine. These results are compared to those given in the literature. Comparative investigations of those urine samples by a gas chromatographic method matched well, with a coefficient of regression of 0.86.

Chromatography, Gas↗

Effects of tilorone hydrochloride on experimental flavivirus infections in mice.

The effect of tilorone hydrochloride on experimental infections of mice with West Nile, Langat and Dengue type 2 viruses were studied. The drug significantly reduced the mortality after intraperitoneal inoculation of West Nile virus, but failed to affect intracerebral infection with Langat or Dengue viruses. Tilorone partially reversed cyclophosphan-enhanced mortality after extraneural inoculation of West Nile and Langat viruses. The possible modes of action of tilorone, interferon-inducing ability and stimulation of humoral immunity, are discussed.

Animals↗

Effect of tilorone hydrochloride on graft-versus-host (GvH) reaction in mice.

The effects of tilorone hydrochloride (TH), a powerful interferonogenic agent exhibiting also immune modulatory properties, on GvH reaction was studied, using the popliteal lymph node assay in mice. Administration of TH at ten days 0 or +2 relative to cell transfer to recipient mice led to a significant dose-dependent reduction of GvH reaction, whereas treatment of prospective donor mice at day -4 or -2 induced an enhanced GvH re activity of donor spleen cells. This effect was found not to be due to an altered proportion in the spleen cell inoculum of B and T lymphocytes, which latter are responsible for induction for GvH reaction. However, since normal parental lymphocytes are prepared for an enhanced GvH reactivity by addition of TH-treated macrophages, a stimulatory effect of the latter cells via macrophage-derived mediators, induced by TH, is suggested.

Animals↗

The interferonogenic agent tilorone as a modulator of GvH reaction in mice.

The effects of tilorone hydrochloride (TH), a powerful interferongenic agent exhibiting also immune modulatory properties on GvH reaction was studied, using the popliteal lymph node assay in mice. Administration of TH at days 0 or +2 relative to cell transfer to recipient mice led to a significant dose-dependent reduction of GvH reaction, whereas treatment of prospective donor mice at days-4 or-2 induced an enhanced GvH reactivity of donor spleen cells. This effect was found not to be due to an altered proportion in the spleen cell inoculum of B and T lymphocytes, the latter of which are responsible for induction of GvH reaction. However, since normal parental lymphocytes are prepared for an enhanced GvH reactivity by addition of TH-treated macrophages, a stimulatory effect of the latter cells via macrophage-derived mediators, induced by TH, is suggested.

Animals↗

Induction of lymphokines by tilorone.

Serum obtained 16 hr after p.o. application of tilorone [2, 7-bis/2-diethylaminoethoxy/-fluoren-9-one dihydrochloride] to ABD2F1 mice demonstrated both interferon and migration inhibitory (MIF) activity. Kinetic studies showed a close correspondence between interferon and MIF serum levels. The physiochemical characteristics of tilorone-induced MIF (heat and pH lability, molecular size) are compared with those of MIF generated in in vitro lymphocyte cultures. The findings are discussed in relation to production of lymphocytogenic lymphokines.

Animals↗

Presence and characterization of lymphokines in mouse ascites tumor fluids.

Considerable skin-reactive and macrophage-disappearance-inducing activities were detected in cell-free fluids of 2 mouse ascites tumors (Ehrlich ascites tumor, leukemia L 1210). Fractionation of the supernatants by ammonium sulfate precipitation, gel filtration on Sephadex G-200, and DEAE-Sephadex A-50 column chromatography resulted in characterization of the proteinaceous substance which accounts for skin-reactive activity. The factor responsible bears a close physicochemical and biological resemblance to the skin-reactive factor of lymphocytic origin which is known to be generated by specific or nonspecific stimulation of lymphocytes in vitro, or to be produced spontaneously by lymphoblastoid cell lines. The biological significance of the findings is discussed.

Animals↗

[Macrophage depletion test in guinea pigs].

In the present investigations heterologous lymphokine-containing fluids were examined in albino guinea pigs for their macrophage depletion activity. Cell-free ascites from Ehrlich ascites tumor and leukemia L 1210 of mice as well as supernatants of PHA-stimulated peripheral blood lymphocyte cultures were used. Ascites of Ehrlich's ascitic tumor and Leukemia L 1210 led to a significant depletion of macrophages. The application of supernatants of PHA-stimulated human lymphocyte cultures resulted in a dose-dependent reduction of peritoneal macrophages. On the other hand, a stimulation of the number of peritoneal macrophages by control supernatants of non-stimulated lymphocyte cultures was observed. The findings indicate the existence of two lymphokines having opposite effects.

Animals↗

[Effect of 17beta-estradiol-3-monobenzoate on humoral antibody formation in mice].

17beta-Estradiol-3-monobenzoate injected s.c. in mice led to a dose-dependent stimulation of the global reticuloendothelial clearance function. Furthermore, a significant depression of serum hemagglutinin levels, being independent of the anitgen dose, was noticed. Although a slight decrease of antigen-sensitive (memory) cells was revealed, estradiol treatment before priming failed to impair immunological memory as assayed by hemagglutinin titers in the secondary reaction. Estradiol administration was followed by charakteristic organ weight changes (liver, thymus, adrenals). According to the literature it is suggested that estradiol, like diethylstilbestrol, is capable of depressing humoral antibody formation by differential effects on the reticuloendothelial system.

Adrenal Glands↗

[Purification of skin reactive factor (SRF) in mice].

For the purification and further characterisation of the skin-reactive factor (SRF) of the mouse, the SRF-containing ascitic fluid of Ehrlich ascites tumor was exposed to different separation or elution procedures. After preliminary purification by (NH4)2SO4 precipitation when the total activity was not in the dialysable supernatant, gel-chromatographic separation (Sephadex G-200), immune electrophoretic investigations as well as ion exchange chromatography were performed. The skin-reactive activity in fraction I of gel chromatiography is presumably caused by a toxic substance with skin-irritating properties. The SRF demonstrable in fraction II/2 has a molecular weight similar to that of albumin, can be found in the ion exchange chromatography (DEAE-Sephadex A-50-column) in fraction III, and is of proteinic nature.

Animals↗

Influence of certain immunodepressants on experimental flavivirus and enterovirus infections in mice.

The effects of cyclophosphamide and 1,3-(piperidinomethyl)-5-phenyl-5-ethylbarbituric acid on certain flavi- and enterovirus infections in mice were studied. Differential enhancement of mortality rates after extraneural and, less markedly, intracerebral virus inoculation was noted. While depression of humoral and/or cell-mediated immunity is considered to be responsible for the effects observed in flavivirus infections, impaired function of the reticuloendothelial system seems to contribute mainly to the potentiation of Mengo virus infection by the immunodepressants used.

Animals↗

[Antiviral thiosemicarbazone and related compounds. III. Quantitative relationships between structure and antiviral activity of isantin-beta-isothio-semicarbazone against mengo virus].

The virostatic activity of isatin-beta-isothiosemicarbazones can be described quantitatively by hydrophobic, electronic, and steric substituent constants using multivariate regression analysis. A preceding Free-Wilson analysis allows data smoothening, and thus improved adaptation. Predictions made on the basis of the quantitative structure-action relationships obtained could be confirmed experimentally by synthesizing and testing the corresponding compounds.

Antiviral Agents↗