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At least 721 records · Page 40Linked to original sources
PubMed1990

Sperm chromosome studies in an infertile man with partial, complete asynapsis of meiotic bivalents.

Meiotic and sperm chromosome studies were carried out in two semen samples from an infertile man with a 46,XY karyotype, oligoasthenoteratozoospermia and abundant exfoliation of spermatogenic cells. Meiotic preparations showed partial, complete asynapsis in a large proportion of metaphase I figures observed, and absence of metaphase II figures, while 24 of the 30 sperm chromosome karyotypes analysed were normal. The remaining sperm karyotypes were as follows: one with structural abnormalities, one with both structural abnormalities and hypohaploidy and four with hypohaploidy. The total frequency of chromosomal abnormalities (6.7%) is similar to that obtained by us in normal men (10.9%). The frequency of spermatozoa with structural abnormalities (6.7%) was not significantly different from that obtained by us in normal men (6.9%). These results suggest that, in some cases, asynaptic spermatogenic cells do not proceed further than metaphase I and only normal germ cells continue spermatogenesis.

Adult↗
PubMed2001

Improved binding of a bivalent single-chain immunotoxin results in increased efficacy for in vivo T-cell depletion.

Anti-CD3 immunotoxins exhibit considerable promise for the induction of transplantation tolerance in pre-clinical large animal models. Recently an anti-human anti-CD3epsilon single-chain immunotoxin based on truncated diphtheria toxin has been described that can be expressed in CHO cells that have been mutated to diphtheria toxin resistance. After the two toxin glycosylation sites were removed, the bioactivity of the expressed immunotoxin was nearly equal to that of the chemically conjugated immunotoxin. This immunotoxin, A-dmDT390-sFv, contains diphtheria toxin to residue 390 at the N-terminus followed by VL and VH domains of antibody UCHT1 linked by a (G(4)S)(3) spacer (sFv). Surprisingly, we now report that this immunotoxin is severely compromised in its binding affinity toward CD3(+) cells as compared with the intact parental UCHT1 antibody, the UCHT1 Fab fragment or the engineered UCHT1 sFv domain alone. Binding was increased 7-fold by adding an additional identical sFv domain to the immunotoxin generating a divalent construct, A-dmDT390-bisFv (G(4)S). In vitro potency increased 10-fold over the chemically conjugated immunotoxin, UCHT1-CRM9 and the monovalent A-dmDT390-sFv. The in vivo potency of the genetically engineered immunotoxins was assayed in the transgenic heterozygote mouse, tgepsilon 600, in which the T-cells express human CD3epsilon as well as murine CD3epsilon. T-cell depletion in the spleen and lymph node observed with the divalent construct was increased 9- and 34-fold, respectively, compared with the monovalent construct. The additional sFv domain appears partially to compensate for steric hindrance of immunotoxin binding due to the large N-terminal toxin domain.

Animals↗
PubMed2005

The bivalent metal hypophosphites Sr(H2PO2)2, Pb(H2PO2)2 and Ba(H2PO2)2.

The structures of isomorphous monoclinic strontium and lead bis(dihydrogenphosphate), Sr(H2PO2)2 and Pb(H2PO2)2, and orthorhombic barium bis(dihydrogenphosphate), Ba(H2PO2)2, consist of layers of hypophosphite anions and metal cations exhibiting square antiprismatic coordination by O atoms. The Sr and Pb atoms are located on sites with point symmetry 2, and the Ba atoms are on sites with point symmetry 222. Within the layers, each anion bridges four metal cations.

Journal Article↗
PubMed1998

Crystallization of succinylated concanavalin A bound to a synthetic bivalent ligand and preliminary structural analysis.

Crystals have been obtained of succinylated concanavalin A complexed to a novel bidentate synthetic ligand. The crystals are the first example of a lectin with a synthetic multivalent ligand and the first report of crystallization of succinylated concanavalin A. The crystals were obtained by sitting-drop vapour diffusion equilibrating with a solution of 20% polyethylene glycol, pH 5, 293. 5 K. Crystals are orthorhombic, belonging to space group C2221 with unit-cell dimensions of a = 99.1, b = 127.4, c = 118.9 A. The asymmetric unit contains a dimer, with over 65% of the volume occupied by water. The ligand cross links concanavalin A monomers. Succinylated concanavalin A is known to be a dimer in solution, yet it is found as the typical concanavalin A tetramer in the crystal. The contacts holding together the tetramer appear extensive and suggest that a fine balance between dimer and tetramers exists. Data to 2.65 A have been collected and the structure determined by the molecular replacement method.

Azides↗
PubMed2005

Bivalent effect of UV light on human skin mast cells-low-level mediator release at baseline but potent suppression upon mast cell triggering.

Ultraviolet (UV) irradiation is an established treatment for inflammatory skin diseases, although the precise mode of action is still unclear. Activating and suppressive effects on mast cell (MC) mediator release have been described. The aim of this study was to investigate systematically the effects of UVB, UVA-1, and psoralen plus UVA-1 at therapeutic doses on skin-derived human MC. Baseline and stimulated release of histamine, tryptase, and of interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) were examined. In resting MC, UV light induced a slight, yet significant histamine release corresponding to enhanced surface levels of lysosome-associated membrane proteins (LAMP). In contrast, UV pre-treatment caused a marked suppression of the anti-IgE-induced histamine release, accompanied by a diminished, anti-IgE-mediated increase in LAMP expression. The secretion of IL-6, IL-8, and TNF-alpha was inhibited in resting and activated MC, suggesting a different mode of action. Regarding the importance of MC in a variety of allergic and inflammatory processes, our data show a high susceptibility of this cell type towards UV light, which seems to partially depend on the state of cellular activation. Immunosuppressive effects predominate in activated MC, thus corresponding with the beneficial effects in inflammatory diseases, whereas in resting MC, both stimulatory and inhibitory effects are observed.

Cytokines↗
PubMed2006

Bivalent role of the phosphatidylinositol-3-kinase (PI3K) during influenza virus infection and host cell defence.

Infections with influenza A viruses result in the activation of a variety of intracellular signalling pathways. Recent findings suggest that in response to double-stranded RNA (dsRNA), which is commonly used as a mimic for accumulating viral RNA, the phosphatidylinositol-3-kinase (PI3K) is activated and mediates activation of the transcription factor interferon regulatory factor 3 (IRF-3). Thus, we investigated the function of PI3K during influenza virus infection. The pathway was activated upon infection and consistent with earlier findings using dsRNA, inhibition of PI3K itself or block of signalling by the PI3K product, the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), results in misphosphorylation and impaired dimerization of IRF-3 as well as reduced IRF-3-dependent promoter activity. This would imply an antiviral function of the kinase in influenza virus-infected cells. However, upon inhibition of PI3K, titers of progeny virus were reduced rather than enhanced. This was coincident with a strong decrease of viral protein accumulation that was not due to a block of protein synthesis or inhibition of the viral polymerase complex. Immunofluorescence studies revealed that PI3K rather appears to regulate a very early step during viral entry. Thus PI3K is a perfect example of a seemingly antiviral signalling component that is misused by the virus to support effective replication.

Animals↗
PubMed1997

The X bivalent in fetal bovine oocytes.

Wholemount preparations of oocytes from fetal bovine ovaries were examined in an attempt to study the incidence and type of chromosomes involved in pairing irregularities during different stages of early ovarian differentiation. Synaptonemal complexes exhibiting pairing irregularities were noted in meiocytes of all age groups. However, asynapsis and partial synapsis were more frequently noted in X chromosomes at the onset of meiosis in fetal bovine ovaries while the frequencies of similar errors in autosomes were relatively low and remained unchanged in the age groups included in this study. The significance and mechanisms of X chromosome asynapsis in excess of that expected on the basis of numerical ratio of the X to the bovine meiotic complement, are not known at present. We hypothesize that changes in the transcriptional status involving activation, inactivation, and reactivation of the X chromosomes during embryonic and ovarian differentiation on the conceptus, in addition to the inactivation undergone by the paternal X chromosome prior to fertilization, could be a factor rendering them susceptible to structural changes which, in turn may increase the incidence of sex chromosome asynapsis at the onset of meiosis in female fetuses.

Animals↗