Animal experimental studies on the thrombolytic effect of streptokinase

The purpose of this investigation was to explore the feasibility of enhancing the electrochemical stability of dental amalgam restorations by a process of "selective interfacial amalgamation." If dental amalgam restorations can be selectively alloyed at the tooth-amalgam interface, to a minor thickness as compared with the dimensions of the bulk amalgam, so as to present a more electrochemically stable phase than psi2 to the oral environment, corrosion will be reduced and desirable qualities of existing amalgams can be utilized. It was found that selective interfacial amalgamation was indeed possible and that it could be readily accomplished using a silver suspension as a cavity liner. By then placing a conventional silver-tin amalgam according to ordinary dental techniques, mercury expressed during hand condensing reacted with the silver in the liner resulting in the formation of an integral amalgam restoration with the more noble psi1 phase adjacent to tooth structure. In vitro corrosion tests of samples so prepared exhibited corrosion resistance far superior to unlined control samples.     

Lipid-protein interactions with native and modified myelin basic protein

The basic protein of central nervous system myelin has been shown to form complexes with acidic lipids in vitro. We measured the interaction of myelin basic protein with several charged and neutral lipids in a biphasic chloroform/methanol/water system and investigated the effect of decreasing the electrical charge of the basic amino groups of the myelin basic protein by acetylation. The modified myelin basic protein, which has an average of eight acetyl residues incorporated, was characterised by gel electrophoresis and circular dichroism. Complexes formed between the acetylated myelin basic protein and acidic lipids exhibited a reduction in the amount of lipids bound, a value that could be correlated with the number of modified amino groups. The significance of these experiments with reference to protein-lipid interaction in the myelin membrane is discussed.     

Prostaglandin-F-levels in human plasma during late pregnancy and labour (author's transl)

The concentrations of prostaglandin F-equivalents were measured in peripheral plasma during labour at a cervical dilatation of 5 cm and at complete dilatation. After purification, extraction and chromatography the PGF-equivalents were measured radioimmunologically. The intraassay variation was 1.5%, the interassay variation 3.5%. The specificity for PGF was 96-98%. Logit/log transformation of the standardcurve yielded a sensitivity of the assay of 120 pg. At cervical dilatation of 5 cm PGF-equivalents varied between 1300 and 3200 pg/ml plasma. At complete dilatation values changed between 1200 and 5400 pg/ml. These fluctuations correlate timedepending to the uterine contractions recorded and may be interpreted as a result of uterine PGF-release.     

The influence of mepiprazol on monoamine metabolism in the rat CNS: demonstration of reduced norepinephrine activity and simultaneously enhanced serotonin and dopamine activities (author's transl)

Biochemical studies of monamine turnover and neuronal reuptake indicate that mepiprazole, a novel psychotropic pyrazole derivative, decreases norepinephrine receptor activity and enhances serotonin and to a lower extent also dopamine activity in the rat CNS. It can be concluded that mepiprazole might be of value in the treatment of certain types of depression and might be helpful to alleviate side effects of L-dopa in the treatment of parkinsonism.     

Beta-COP is essential for biosynthetic membrane transport from the endoplasmic reticulum to the Golgi complex in vivo

Experimental glomerulonephritis was induced in rats to investigate the consequence of the antigen-antibody interaction on the surface of glomerular endothelial cells (GENs). A lectin, Lens culinaris hemoagglutinin (LCH), was first planted in the left kidney by isolated perfusion of a left kidney, and then the circulation was reestablished. Rabbit anti-LCH antibodies were injected from the tail vein 3 minutes after the recirculation of the left kidney, and acute glomerulonephritis ensued. Fifteen minutes after the injection, rabbit immunoglobulin G (IgG), rat C3, and LCH were observed exclusively on the surface of GENs. Accumulation of platelets was prominent. Three hours later, the immune deposits were seen in the subendothelial space, and the polymorphonuclear cells were the dominant infiltrate in the glomeruli. Up to the seventh day, immune deposits were seen in the subendothelial space, and the widening of this area was increasingly observed. Fourteen days later, immune deposits containing rat IgG were observed in the subepithelial area, but they were only occasionally seen in the subendothelial space and in the mesangial area. No crescent formation was seen at day 14, but the mesangial area was expanded, with an increased number of cells. The number of nuclei in the cross-section of a glomerulus increased after the induction of glomerulonephritis, but the number of leukocyte common antigen-positive cells (infiltrating cells) decreased gradually from day 4 to day 14. The staining of Thy-1.1, a marker of mesangial cell, was markedly enlarged in the glomerulus at day 14. These data suggest that mesangial proliferative glomerulonephritis can be induced by the antigen-antibody interaction on the surface of GENs.     

Experimental demonstration of an identic antigenicity of the inner ear and kidney (author's transl)

An allergic glomerunephritis was produced in rats by injection of an anti-basement-membrane-serum (IgG-fraction), taken from rabbits which were sensitized against a basement membrane fraction of rat-glomerula. Tissues from heart, liver, brain, lung and inner ear were compared with the well known alterations of the glomerula. Exclusively in stria vascularis and renal glomerula heavy changements of the basement membranes and endothelial cells could be shown by electronmicroscopic examination and by immunohistological methods.     

A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides

During the last decade, episodes of sepsis have increased and Escherichia coli has remained the most frequent clinical isolate. Lipopolysaccharides (LPS; endotoxin) are the major toxic and antigenic components of gram-negative bacteria and qualify as targets for therapeutic interventions. Molecules that neutralize the toxic effects of LPS are actively investigated. In this paper, we describe a murine monoclonal antibody (MAb; WN1 222-5), broadly cross-reactive and cross-protective for smooth (S)-form and rough (R)-form LPS. As shown in enzyme-linked immunosorbent assay and the passive hemolysis assay, WN1 222-5 binds to the five known E. coli core chemotypes, to Salmonella core, and to S-form LPS having these core structures. In immunoblots, it is shown to react with both the nonsubstituted core LPS and with LPS carrying O-side chains, indicating the exposure of the epitope in both S-form and R-form LPS. This MAb of the immunoglobulin G2a class is not lipid A reactive but binds to E. coli J5, an RcP+ mutant which carries an inner core structure common to many members of the family Enterobacteriaceae. Phosphate groups present in the inner core contribute to the epitope but are not essential for the binding of WN1 222-5 to complete core LPS. Cross-reactivity for clinical bacterial isolates is broad. WN1 222-5 binds to all E. coli clinical isolates tested so far (79 blood isolates, 80 urinary isolates, and 21 fecal isolates) and to some Citrobacter, Enterobacter, and Klebsiella isolates. This pattern of reactivity indicates that its binding epitope is widespread among members of the Enterobacteriaceae. WN1 222-5 exhibits biologically relevant activities. In vitro, it inhibits the Limulus amoebocyte lysate assay activity of S-form and R-form LPS in a dose-dependent manner and it neutralizes the LPS-induced release of clinically relevant monokines (interleukin 6 and tumor necrosis factor). In vivo, WN1 222-5 blocks endotoxin-induced pyrogenicity in rabbits and lethality in galactosamine-sensitized mice. The discovery of WN1 222-5 settles the long-lasting controversy over the existence of anti-core LPS MAbs with both cross-reactive and cross-protective activity, opening new possibilities for the immunotherapy of sepsis caused by gram-negative bacteria.     

Localization of interferon-gamma and Ia-antigen in T cell line-mediated experimental autoimmune encephalomyelitis

This study reports the cellular localization of interferon-gamma (IFN-gamma) and MHC class II antigen (Ia) in the spinal cord of rats with experimental autoimmune encephalomyelitis induced by adoptive transfer of myelin basic protein-specific T cells. Numerous IFN-gamma-positive cells, stained with two different monoclonal antibodies against IFN-gamma, were present from days 3 to 7 after cell transfer. Their number was greatly reduced on day 10. A subpopulation of T cells was IFN-gamma positive. Moreover, a large number of ED1-positive macrophages contained IFN-gamma immunoreactivity. The transient presence of immune cells containing IFN-gamma immunoreactivity in experimental autoimmune encephalomyelitis suggests a pathogenic role of this cytokine in immune-mediated demyelination of the central nervous system.