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[Bivalent-vegetative long-term therapy with glauko biciron (author's transl)].

Long-term therapy using a combination of Pilocarpine and Phenylephrine in three different concentrations is described. The trial was carried out in the form of a multi-center study by general practitioners and showed the constant effect over lengthy periods of time, with no signs of tachyphylaxis or an increase in effect, which would have pointed to an increase in the effective level. The number of side-effects is minimal, due to the submaximal doses used.

Adult↗

A kinase-regulated mechanism controls CFTR channel gating by disrupting bivalent PDZ domain interactions.

Dynamic regulation of ion channels is critical for maintaining fluid balance in epithelial tissues. Cystic fibrosis, a genetic disease characterized by impaired fluid transport in epithelial tissues, is caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel activity. Recent studies have shown that binding of PSD-95/Dlg/ZO-1 (PDZ) domain proteins to CFTR is important for retaining it at the apical membrane and for regulating its channel activity. Here, we describe a phosphorylation mechanism that regulates CFTR channel activity, which is mediated by PDZ domains. The Na+/H+ exchanger regulatory factor (NHERF) binds to CFTR and increases its open probability (Po). Protein kinase C disrupts the stimulatory effect of NHERF on CFTR channel Po. Phosphorylation by PKC of Ser-162 in the PDZ2 domain of NHERF is critical for this functional effect. Furthermore, a mutation in PDZ2 that mimics phosphorylation decreases CFTR binding and disrupts the ability of NHERF PDZ1-2 to stimulate CFTR channel Po. Our results identify a role for PKC and suggest that phosphorylation of NHERF PDZ2 domain may be an important mechanism for regulating CFTR channel activity.

Amino Acid Sequence↗

The C-group pachytene bivalent with a locus characteristic for parachromosomally situated particulate bodies (parameres): a provisional map in human males.

During prophase stages of the first meiotic division in human males, an autosomal divalent in the C group (autosomes 6-12) characteristically has associated with it, at a specific locus, small, DNA-containing bodies (parameres). A pachytene chromomere map is presented, as is evidence suggesting that the parameres are disposed in two lateral loops, each of which is coaxial with one of the homologs. Stereophotographs of stacks of plates from electron micrographs of serial ultrathin sections show the parameres in their in situ configuration to be composed of tightly compacted fibrils, 85-90 A in diameter.

Chromosome Mapping↗

Loss of cholesterol 7 alpha-hydroxylase activity in vitro in the presence of bivalent metal ions and by dialysis of rat liver microsomes.

A loss in cholesterol 7 alpha-hydroxylase activity [cholesterol 7 alpha-monooxygenase; cholesterol,NADPH:oxygen oxidoreductase (7 alpha-hydroxylating), EC 1.14.13.17] was seen when rat liver microsomes were incubated in the presence of Ca2+, Mg2+, or Mn2+. The loss in enzyme activity was complete within only 5 min of incubation with Ca2+ and Mn2+, whereas Mg2+ required 10 to 15 min of incubation with microsomes to produce a similar inhibition. This effect of metal ions could be blocked if the incubations were carried out in phosphate buffer. Similarly, preincubation of microsomes in the presence of NaF completely prevented the loss in enzyme activity due to Ca2+ and Mg2+ ions, but only partially the loss due to Mn2+. These results suggest metal ion activation of an endogenous microsomal phosphatase, which in turn may inactivate cholesterol 7 alpha-hydroxylase through its dephosphorylation. Further, a dialyzable microsomal factor appears to be essential for stabilizing the enzyme, because dialysis of a microsomal suspension results in a considerable loss of enzyme activity.

Adenosine Triphosphate↗

Bivalent sequential binding model of a Bacillus thuringiensis toxin to gypsy moth aminopeptidase N receptor.

Specificity for target insects of Bacillus thuringiensis insecticidal Cry toxins is largely determined by toxin affinity for insect midgut receptors. The mode of binding for one such toxin-receptor complex was investigated by extensive toxin mutagenesis, followed by real-time receptor binding analysis using an optical biosensor (BIAcore). Wild-type Cry1Ac, a three-domain, lepidopteran-specific toxin, bound purified gypsy moth (Lymantria dispar) aminopeptidase N (APN) biphasically. Site 1 displayed fast association and dissociation kinetics, while site 2 possessed slower kinetics, yet tighter affinity. We empirically determined that two Cry1Ac surface regions are involved in in vivo toxicity and APN binding. Mutations within domain III affected binding rates to APN site 1, whereas mutations in domain II affected binding rates to APN site 2. Furthermore, domain III contact is completely inhibited in the presence of N-acetylgalactosamine, indicating loss of domain III binding eliminates all APN binding. Based upon these observations, the following model is proposed. A cavity in lectin-like domain III initiates docking through recognition of an N-acetylgalactosamine moiety on L. dispar APN. Following primary docking, a higher affinity domain II binding mechanism occurs, which is critical for insecticidal activity.

Animals↗

Mechanistic insights and functional determinants of the transport cycle of the ascorbic acid transporter SVCT2. Activation by sodium and absolute dependence on bivalent cations.

We characterized the human Na(+)-ascorbic acid transporter SVCT2 and developed a basic model for the transport cycle that challenges the current view that it functions as a Na(+)-dependent transporter. The properties of SVCT2 are modulated by Ca(2+)/Mg(2+) and a reciprocal functional interaction between Na(+) and ascorbic acid that defines the substrate binding order and the transport stoichiometry. Na(+) increased the ascorbic acid transport rate in a cooperative manner, decreasing the transport K(m) without affecting the V(max), thus converting a low affinity form of the transporter into a high affinity transporter. Inversely, ascorbic acid affected in a bimodal and concentration-dependent manner the Na(+) cooperativity, with absence of cooperativity at low and high ascorbic acid concentrations. Our data are consistent with a transport cycle characterized by a Na(+):ascorbic acid stoichiometry of 2:1 and a substrate binding order of the type Na(+):ascorbic acid:Na(+). However, SVCT2 is not electrogenic. SVCT2 showed an absolute requirement for Ca(2+)/Mg(2+) for function, with both cations switching the transporter from an inactive into an active conformation by increasing the transport V(max) without affecting the transport K(m) or the Na(+) cooperativity. Our data indicate that SVCT2 may switch between a number of states with characteristic properties, including an inactive conformation in the absence of Ca(2+)/Mg(2+). At least three active states can be envisioned, including a low affinity conformation at Na(+) concentrations below 20 mM and two high affinity conformations at elevated Na(+) concentrations whose Na(+) cooperativity is modulated by ascorbic acid. Thus, SVCT2 is a Ca(2+)/Mg(2+)-dependent transporter.

Amino Acid Sequence↗

Release of albumin from oligoester plastic matrices: effect of magnesium oxide and bivalent stearates.

Biodegradable implantable matrices containing bovine serum albumin were prepared from oligoesters by melting, and subsequently tested on in vitro albumin release. The linear poly (DL-lactic acid) and the branched terpolymer of DL-lactic acid, glycolic acid, and mannitol were synthesized. Products were of similar molecular weight and possessed different thermal and swelling characteristics. Oligoesters were loaded with 4% albumin and plasticized by 30% triacetin. Other additives added into the matrices as albumin stabilizers were divalent stearates and magnesium oxide. The influences of oligomer molecules constitution, divalent ion stearates or magnesium oxide addition, and triacetin concentration on the albumin release were quantified. SDS-PAGE revealed protein hydrolysis during the dissolution tests.

Albumins↗

Immunogenicity and immunological priming of the serogroup a portion of a bivalent meningococcal A/C conjugate vaccine in 2-year-old children.

Two-year-old children were vaccinated with 1 dose of meningococcal A/C conjugate (MACC) or meningococcal A/C polysaccharide (MACP) vaccine. Meningococcal serogroup A (MenA)-specific IgG geometric mean avidity indices (GMAIs) increased 1 month after vaccination with MACC (GMAI, 210; 95% confidence interval [CI], 140-300) and MACP (GMAI, 190; 95% CI, 120-310). One year after vaccination, the GMAI of the MACP-vaccinated cohort decreased to 130 (95%, CI 100-170), but a constant GMAI was maintained in the MACC-vaccinated cohort (210; 95% CI, 140-300), despite declining MenA-specific IgG antibody levels.

Antibodies, Bacterial↗

The distribution of early recombination nodules on zygotene bivalents from plants.

Early recombination nodules (ENs) are protein complexes approximately 100 nm in diameter that are associated with forming synaptonemal complexes (SCs) during leptotene and zygotene of meiosis. Although their functions are not yet clear, ENs may have roles in synapsis and recombination. Here we report on the frequency and distribution of ENs in zygotene SC spreads from six plant species that include one lower vascular plant, two dicots, and three monocots. For each species, the number of ENs per unit length is higher for SC segments than for (asynapsed) axial elements (AEs). In addition, EN number is strongly correlated with SC segment length. There are statistically significant differences in EN frequencies on SCs between species, but these differences are not related to genome size, number of chromosomes, or phylogenetic class. There is no difference in the frequency of ENs per unit length of SC from early to late zygotene. The distribution of distances between adjacent ENs on SC segments is random for all six species, but ENs are found at synaptic forks more often than expected for a random distribution of ENs on SCs. From these observations, we conclude that in plants: (1) some ENs bind to AEs prior to synapsis, (2) most ENs bind to forming SCs at synaptic forks, and (3) ENs do not bind to already formed SCs.

Chromosomes↗

Clinical trials of bivalent influenza A/New Jersey/76-A/Victoria/75 vaccines in the elderly.

This placebo-controlled evaluation in elderly persons of inactivated influenza virus vaccines containing 200 or 400 chicke cell-agglutinating units of both A/New Jersey/76 and A/Victoria/75 antigens revealed mild systemic reactions in 7.8% and moderate reactions in 4.9% of vaccinees. These reactions were more common after administration of whole-virus than subvirion vaccines, more frequent in females than males, and more frequent in persons with low initial titers of antibody to A/New Jersey antigen. Local inflammation occurred in 18.7% of vaccinees (predominantly females) and frequently was seen with systemic reactions, but did not correlate with antibody response. Titers of antibody to A/New Jersey antigen were initially high and 99% of vaccinees had titers of greater than 1:20 after vaccination. Titers of antibody to A/Victoria antigen were initially low, and 56% of vaccinees had titers of greater than 1:20 after vaccination. Fourfold or greater increases in titer occurred in about 50% of vaccinees for each virus, most often concomitantly. Antibody responses to subvirion and whole-virus vaccines were similar, and increased responses with higher doses coincided with increased reactogenicity. Later revaccinations because of low titers of A/Victoria antibody produced negligible antibody responses.

Adult↗