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W Schulze

Publications and source records attributed to W Schulze.

At least 19 recordsLinked to original sources
PubMed1992

Fluorenone-azomethines, a novel class of microtubule inhibitors that specifically affect cell proliferation.

The effects of various azomethine derivatives on microtubule (MT) assembly in vitro as well as on cell proliferation, cell shape, and the cytoskeleton of some cultured murine cell lines were studied. 3 of them, the alpha-diphenylene-N-(p-[bis-(beta-hydroxyethyl)-amino]-phenyl)-nit rone (DHPN), alpha-diphenylene-N-(p-[N-(hydroxyethyl)-N-(gamma-hydroxypropyl)- amino]-phenyl)-nitrone, and alpha-diphenylene-N-(p-diethylaminophenyl)-nitrone, strongly inhibit the assembly of microtubules (MTs) in vitro (50% inhibition at 4 to 7 mumol/l). The same compounds are also able to disrupt preformed microtubules. Moreover, they were found to inhibit proliferation of leukaemia L 1210, melanoma B16 K, fibroblast L 929, and embryo fibroblast cells down to 1 to 10 mumol/l, completely. Immunofluorescence microscopy revealed that DHPN, used as a representative of the active azomethines, causes a reversible destruction of the microtubule part of the cytoskeleton. Apparently resulting from microtubule disruption, the intermediate filament system collapsed whereas the microfilament system remained unaffected. The results indicate that the antiproliferative action of the azomethines is based, at least partially, on their ability to attack microtubules.

Animals↗
PubMed1992

Limited selectivity of a synthetic erbstatin derivative for tyrosine kinase and cell growth inhibition.

The natural tyrosine kinase inhibitor erbstatin and a synthetic analog (1302) were co0pared for their inhibitory activity on EGF receptor kinase, PDGF receptor kinase and a src-type kinase from bovine brain. Erbstatin inhibited both growth factor receptor kinases equally well and had little effect on the src kinase. The analog exhibited similar potency for inhibition of purified EGF receptor tyrosine kinase as erbstatin, however, was clearly less effective for inhibition of purified PDGF receptor kinase as well as the src-type kinase. The selectivity was, however, not seen when the derivative was assayed with respect to inhibition of autophosphorylation of both growth factor receptors in Swiss 3T3 cell membranes. The latter finding might explain a lack of selectivity of the compound for inhibition of DNA synthesis in 3T3 cells when the cells were stimulated comparatively with EGF, insulin, EGF plus insulin or PDGF. The results suggest that the environment of growth factor receptors in the cell membrane can remarkably modify their susceptibility to tyrosine kinase inhibitors.

3T3 Cells↗
PubMed1992

[Vasovasostomy after vasectomy. The surgical results 1986-1989].

The frequency of vasovasostomy has increased dramatically in recent years. A significant percentage of men who have previously undergone vasectomy are now seeking restoration of their fertility. The most common reason for requesting a reversal is remarriage. There were 90 bilateral vasovasostomies performed in 90 patients between 1986 and 1989. The procedure was done according to the technique described by Howards, in a single layer with 7 x 0 prolene and under fourfold magnification. The success rate was 87% for presence of spermatozoa in the ejaculate, 48% for pregnancy. The fertility rate decreases slowly with increasing interval between vasectomy and reanastomosis. These results are statistically significant. In cases of good anatomical and andrological conditions, the chance of restoration of fertility is good. The experience of the urologist is often more important than the details of the technique.

Adult↗
PubMed1991

Synergistic cytotoxicity of human recombinant tumour necrosis factor alpha combined with microtubule effectors.

Combinations of human recombinant tumour necrosis factor alpha (rhTNF alpha) with each of four different agents disturbing the microtubule system of the cellular cytoskeleton were tested for synergistic cytotoxic action against murine melanoma B16K and L-M(S) cells. In addition to the known microtubule effectors colchicine, vincristine, and taxol, the influence of the fluorenone-azo-methine derivative alpha-diphenylene-N-(p-[bis-(beta-hydroxyethyl-amino]-phenyl)- nitrone (DHPN) on the rhTNF alpha cytotoxicity was studied. Applying a novel computer-based isobole method [Suehnel J (1990) Antiviral Res 13:23-40] concentration ranges of synergistic, zero, and antagonistic interaction were found after in vitro combination of rhTNF alpha with each of the drugs tested in a 72-h cytotoxicity assay. In contrast, a 24-h exposure of B16K cells to these combinations still did not inhibit in vitro colony formation to a greater extent than either drug alone. A preliminary in vivo experiment revealed an increased antitumour effect after treatment of established subcutaneous melanoma B16 tumours with a combination of rhTNF alpha and DHPN.

Animals↗
PubMed1991

Immunocytochemical localization of G-proteins (alpha subunits) in rat heart tissue.

The subcellular localization of peptide antibodies against G-protein alpha subunits was studied by the indirect immunogold technique with Lowicryl K4M embedded rat cardiac tissue. Two antibodies were used. The alpha common peptide antibody recognizes the alpha subunits of Gs, Gi and Go. The alpha i common peptide antibodies recognize the alpha subunits of all Gi alpha subtypes (G1-3). Immunoreactivity against alpha common and alpha i common antibodies was found along the cell surface of cardiomyocytes and endothelial cells. No immunoreactivity was seen on sarcoplasmic reticulum membranes. T-tubule membranes showed a little reactivity. Distribution patterns obtained with alpha common and alpha i common antibodies were identical. Immunogold was seen in cardiocytes from both atria and ventricles. In light-microscopical studies with peroxidase-conjugated secondary antibodies, heavy immunostaining was seen in SA and AV nodes.

Adenylyl Cyclases↗
PubMed1991

G protein function in the ischaemic myocardium.

The activity of adenylyl cyclase (AC) is controlled by its interaction with receptor-regulated G proteins. The efficiency to form cyclic AMP is strongly influenced by the amount, the subspecies and function of these regulatory proteins. An impairment of AC function has been shown to occur in sarcolemmal preparations (SL) of hearts exposed to either local or global ischaemia. To examine the contribution of G protein function to this phenomenon, cholera toxin (CT)-catalysed ADP-ribosylation of Gs and pertussis toxin (PT)-catalysed ADP-ribosylation of G proteins have been investigated in SL of porcine hearts exposed to global ischaemia for 15-45 min. ADP-ribosylation by CT of an approximately 45 kDa polypeptide was 0.46 +/- 0.06 and ADP-ribosylation by PT of three 39-41 kDa polypeptides was 4.77 +/- 0.77 pmol mg-1 protein in SL of non-ischaemic myocardium. Whereas no change was observed in CT-catalyzed ribosylation after 30 min of ischaemia, there was a reduction in PT-catalyzed ADP-ribosylation to 3.7 +/- 0.35 pmol mg-1 protein after 30 min of ischaemia. Prolongation of ischaemia to 45 min did not reduce further ADP-ribosylation capacity. Quantitative immunoblotting of PT-sensitive G proteins suggests that the diminution of ADP-ribosylation occurred because of a loss of alpha-subunits of G0, Gi-1, and Gi-2 from sarcolemmal membranes.

Adenosine Diphosphate Ribose↗
PubMed1991

Tachykinin (substance-P) gene expression in Leydig cells of the human and mouse testis.

Specific substance-P immunoreactivity can be detected in the Leydig cells, particularly of human testes, and to a lesser degree in mouse Leydig cells, but not in the rat. Using a modified polymerase chain reaction (PCR) assay, preprotachykinin-A (substance-P) mRNA could be detected in extracts of human, mouse, and bovine testes, but not in rat or boar testes or in bovine thyroid or corpus luteum used as negative controls. This assay is able to discriminate among the alpha, beta, and gamma transcripts of the gene and shows that only the beta and gamma transcripts are present in the testes. Sequencing analysis of the PCR products from bovine hypothalamus, mouse brain, and human testis confirmed the structure of these transcripts, which encode both substance-P and neurokinin-A (substance-K) neuropeptide hormones. Using a variant of this assay it was possible to identify tachykinin transcripts in as few as 500 freshly prepared purified mouse Leydig cells. In parallel studies PCR analysis was also able to confirm the presence of mRNA for both substance-P and neurokinin-A receptors in human testes. Thus, the tachykinins substance-P and neurokinin-A must now be added to the list of potentially paracrine substances regulating intratesticular function.

Aged↗
PubMed1991

[Histochemical investigations of the intracellular localization of adenylate cyclase activity after mitogenic or beta-adrenergic stimulation of T-lymphocytes of the mouse].

The role of AC at the beginning of an immune response is not fully understood until now. Using the specific substrate AMP-PNP we could show AC-activity in ConA-stimulated murine spleen lymphocytes histochemically. In contrast to beta-adrenergic stimulation (by Isoproterenol) ConA-induced AC-activity was found not only at the cell membrane and the nuclear membrane but also at some structures of the Golgi apparatus of the cells. The difference in AC-activity after beta-adrenergic or mitogenic stimulation is discussed.

Adenylyl Cyclases↗
PubMed1990

Synergistic cytotoxic effect of human recombinant tumor necrosis factor alpha combined with dihydroambazone.

Dihydroambazone (DHA) is a water-soluble derivative of the experimental anticancer drug ambazone. In vitro, a combination of DHA and human recombinant tumor necrosis factor alpha (TNF) exerted a strong synergism of cytotoxicity against both mouse melanoma B16K cells and the TNF-sensitive mouse fibroblast line L-M (S). Furthermore, in a colony-forming assay with B16K cells a combination of TNF and DHA inhibited colony-formation much more severely than either drug alone. An increased antiproliferative efficiency was also confirmed in vivo against established subcutaneous melanoma B16 tumors of C57BL/6 mice.

Animals↗
PubMed1990

A comparative study in twelve mammalian species of volume densities, volumes, and numerical densities of selected testis components, emphasizing those related to the Sertoli cell.

Morphometric studies were performed on 12 mammalian species (degu, dog, guinea pig, hamster, human, monkey, mouse, opossum, rabbit, rat, stallion, and woodchuck) to determine volume density percentage (Vv%), volume (V), and numerical density (Nv) of seminiferous tubule components, especially those related to the Sertoli cell, and to make species comparisons. For most species, measurements were taken both from stages where elongate spermatids were deeply embedded within the Sertoli cell and from stages near sperm release where elongate spermatids were in shallow crypts within the Sertoli cell. Montages, prepared from electron micrographs, were used to determine Vv% of Sertoli cell components in seminiferous tubules. Excluding the tubular lumen, the Sertoli cell occupied from a high of 43.1% (woodchuck) to a low of 14.0% (mouse) of the tubular epithelium. There was a strong negative correlation (r = -0.83; P less than 0.005) of volume occupancy of Sertoli cells with sperm production. Nuclear volume, as determined by serial reconstruction using serial thick sections, ranged from a high of 848.4 microns 3 (opossum) to a low of 273.8 microns 3 (degu). There was no correlation (r = 0.02) of nuclear volume with volume occupancy (Vv%) in the tubule. Sertoli cell volume was determined by point-counting morphometry at the electron-microscope level as the product of the nuclear size and points determined over the entire cell divided by points over the nucleus. Sertoli cell V ranged from 2,035.3 microns 3 (degu) to 7,011.6 microns 3 (opossum) and was highly correlated (r = 0.85; P less than 0.001) with nuclear size. However, there was no significant correlation between the Sertoli cell size (V) and volume occupancy (Vv%; r = 0.13) or sperm production (r = -0.21). Stereological estimates of the numerical density (Nv) of Sertoli cells ranged from a high of 101.9 x 10(6) (monkey) to a low of 24.9 x 10(6) (rabbit) cells per cm3 of testicular tissue. There was no correlation of numerical density of Sertoli cells with sperm production (r = 0.002). A negative correlation was, however, observed between the numerical density of the Sertoli cells and the Sertoli cell size (r = -0.79; P less than 0.002). Data from the present study are compared with those previously published. This is the first study to compare Sertoli cell morphological measurements using unbiased sampling techniques. Morphometric data are provided which will serve as a basis for other morphometric studies.

Animals↗
PubMed1990

Combination of the peroxidase anti-peroxidase (PAP)- and avidin-biotin-peroxidase complex (ABC)-techniques: an amplification alternative in immunocytochemical staining.

A combination of the PAP- and ABC-techniques was developed to enhance the intensity of the immunocytochemical staining with monoclonal antibodies at light and electron microscopical levels. This amplification technique could be performed in 4 (single PAP + ABC) or 6 (double PAP + ABC) sequential steps depending on the quality of the primary antibodies used and the processing of the tissue before the immunocytochemical reaction: First step--Incubation of the tissue sections with the monoclonal primary antibodies; Second step--biotinylated anti-rat or anti-mouse IgG; Third step--monoclonal PAP complex; Fourth step--ABC complex which binds to the biotinylated secondary antibody. If stronger enhancement of the immunostaining has required the steps 2 and 3 could be repeated followed by the 6th step--the ABC complex. Choline acetyltransferase-like immunoreactivity of the rat hypoglossal nucleus and desmin- and vimentin-like immunoreactivity of human testis were studied. After the 4- and more pronounced the 6-step reaction a significant increase of the staining intensity was observed for all the reactions under study. ChAT-like immunoreactivity was observed to longer distances of the nerve cell dendrites after their emerging from the perikarya and within a greater number of structures in the neuropil as compared to the standard techniques. At electron microscopical level the technique permits longer fixation of the tissue which is important for the better preservation of the ultrastructure as well as for the easier recognition of the reaction product even in the smallest dendrite branches and the axons of the nerve cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Collagen as a carrier for heart cell cultures].

Extracellular collagen from rat tail (types 1 and 3) is a suitable matrix for isolated neonatal heart cell cultivation. The fine structure and the physiological response to isoproterenol for instance is similar for neonatal cardiomyocytes cultured in the medium Sm 20-1 with or without collagen matrix. For electron microscopical routine preparation it is easier to use matrix-grown cardiomyocytes because additional preparation steps (centrifugation) are unnecessary.

Animals↗
PubMed1990

Influence of age on antileukemic action, subacute toxicity and tissue distribution of ambazone in B6D2F1 mice.

The influence of age of experimental animals on the antileukemic activity, toxicity and distribution of ambazone, a new potential antineoplastic agent, was studied in 2- and 12-month-old B6D2F1 mice. The predominant effect observed was a significant reduction of the antileukemic action of this compound in old-aged mice. Together with a slight increase in several toxicity parameters this caused a marked reduction of the therapeutic index in 12-month-old mice compared to younger individuals. Furthermore, a general tendency to increased ambazone levels in liver, kidneys and thymus of old-aged mice was observed. Our data therefore provide further evidence that age has to be taken into consideration as one factor that may account for the variety of drug response frequently observed during clinical therapy with anticancer agents.

Aging↗
PubMed1990

[Antineoplastic activity and toxicity of dihydroambazone in comparison with ambazone (1,4-benzoquinone-guanylhydrazone-thiosemicarbazone)].

Dihydroambazone 1, a soluble derivative of ambazone, was tested with an admixture of ascorbic acid (0.1, 0.25, or 0.5% in distilled water) for antineoplastic activity by different routes (i.p., p.o., s.c., i.v.) against leukemia P388, and by s.c. application against Lewis lung carcinoma on B6D2F1-mice. The results were compared with that of ambazone. 1 was as active as ambazone upon the per os d 1-4 schedule only. Ascorbic acid, added for stabilization of 1, had no significant influence on the results. Intravenously given 1 was of low activity. It proved to be toxic at 100 mg/kg body mass. The i.v. toxicity was estimated approximately on B6D2F1-mice (LD50: 150 mg/kg; LD100: 175 mg/kg; maximum tolerated dose (MTD): 100 mg/kg. A comparison between the MTD's of 1 and ambazone in mice and rats (Wistar) showed partly a somewhat better p.o. compatibility of 1. The expectation of a favourable i.v. applicable derivative from the otherwise in water nearly insoluble ambazone could not be realized.

Animals↗
PubMed1990

[BCG osteitis].

After first describing the course of BCG osteitis in young children, the problems associated with the routine prophylactic BCG inoculation in countries with a low incidence of tuberculosis are discussed. There is good reason to draw attention to the recommendation of the Inoculation Commission attached to the Federal Health Office calling to the fact that newborn infants should be inoculated only if they belong to the high-risk groups.

BCG Vaccine↗