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[Optical properties of DNA complexes with antitumor compounds of bivalent platinum].

The optical properties of the DNA complexes with the compounds of bivalent platinum were studied. The compounds differed by the nature of the anionic and neutral ligands and their spatial arrangement about the platinum atom. It was shown that the same as cis-[Pt (NH3)2Cl2] the platinum compounds with the biological activity, i.e. [Pt (en) Cl2], cis-[PtNH3 (Bz) Cl2] and cis-[Pt (NH3)2NO2Cl] induced at low values of r (a ratio of the number of the platinum moles added to the number of the DNA nucleotide moles in the solution) an increase in the amplitude of the positive band in the spectrum of the circular dichroism (CD) of the linear DNA and a marked decrease in the amplitude of the negative band in the spectrum of the CD of the liquid crystalline microphase of DNA formed in the presence of polyethyleneglycol. By the character of the action on the CD spectrum of the linear and condensed DNA [Pt (tetrameen)Cl2] which had no selective antimitotic effect might be referred to the above platinum compounds. Trans-[Pt (NH3)2NO2Cl], [PtNH3PyCl2], cis-[Pt (NH3)2(NO2)2] and [Pt (NH3)3Cl]Cl having no biological activity either induced only a decrease in the amplitude of the positive band in the CD spectrum of the linear DNA or had no effect on the CD spectrum. The effect of these compounds on the CD spectrum of the liquid crystalline microphase of DNA was slightly pronounced or not observed.

Animals↗

[Effect of bivalent metal ions on enzymatic activity of Ca2+, Mg2+-dependent DNAse from sea urchin Stronglyocentrotus intermedius embryos].

Ca2+, Mg2+-dependent DNAse has been isolated in a homogeneous state from the embryos of the sea urchin Strongylocentrotus intermedius. The enzyme hydrolyzes DNA only in the presence of bivalent metal ions and is inhibited by EDTA and EGTA. The most effective activators are Mn2+ and Co2+. In the presence of Mg2+ + EGTA, Ca2+, Ba+2 and Sr2+ the DNA is hydrolyzed in a lesser degree. Mg2+ + Ca2+ as well as Mg2+ + Sr2+ produce a synergic activating effect. The concentration of Ca2+ making up to one half of the maximal activity in the presence of 5 mM MgCl2 decreases with an increase in DNA concentration from 1.10(-4) M Ca2+ for 1,7 . 10(-5) M DNA-P up to 3,0 . 10(-5) M Ca2+ for 16,0. 10(-5) M DNA-P. The value of V for enzymatic hydrolysis of DNA does not depend on the concentration of Ca2+, while Km(app) for the enzyme increases from 2,0 . 10(-5) M DNA-P for 5 . 10(-4) M Ca2+ up to 25 . 10(-5) M DNA-P for 1 . 10(-5) M Ca2+. The Km(app) of the enzyme for Mg2+ + EGTA is 3.2 . 10(-5) M DNA-P, for Ca2+--0,77 . 10(-5) DNA-P.

Animals↗

[Effect of bivalent copper ions on the catalytic properties of bovine liver glutamate dehydrogenase].

The effects of bivalent copper ions on the activity of bovine liver glutamate dehydrogenase (L-glutamate NAD (P) oxidoreductase, EC 1.4.1.3) were studied. Cu2+ effectively interacts with the enzyme; this interaction is accompanied by a loss of the enzyme activity in the reaction of reductive amination of alpha-ketoglutarate. The data obtained are indicative of a similar type of the enzyme inhibition by GTP and copper ions.

Animals↗

Bivalent tin metabolism and toxicity after intravenous injection in rats.

With progressing advances in radioisotope diagnostic methods in nuclear medicine new radiopharmaceutic agents have been introduced containing inorganic soluble compounds of bivalent tin (Sn+2). An important problem is to study the metabolism and toxicological effects of Sn+2. In the presently reported work the distribution of Sn+2 was determined in the organism of rats at different time intervals after intravenous administration of 113SnCl2 (from 10 minutes to 4 months) and the rate of its elimination from the whole body was studied. Sn+2 toxicity was determined calculating the LD50/30 dose of Sn+2 and by means of the OCT test (ornithine-carbamyltransferase level in the serum). The investigation demonstrated selective accumulation of Sn+2 in the liver and spleen where it remained for a long time, phasic elimination of tin from the whole body, and its moderate toxicity after intravenous administration.

Animals↗

Association between the elements of a bivalent compound stimulus.

Evidence that an association forms between the elements of a bivalent compound stimulus during inhibitory training was provided in four experiments with rats in a conditioned suppression task. This association occurred both in a conditioned inhibition paradigm, which intermixed A+ and AX- trials (Experiments 1 and 2), and in an extinction-inhibition paradigm, which presented A+ and AX- training sequentially (Experiments 3 and 4). The within-compound association appeared to be bidirectional inasmuch as excitatory changes in the value of either component affected responding to the associated component. After inhibitory training in Experiments 1-3, pairings of the inhibitory stimulus (X) with shock increased suppression to the associated excitatory stimulus (A). In Experiment 4, additional pairings of the excitatory stimulus (A) with shock after inhibitory training increased suppression to the associated inhibitory stimulus (X). These studies add to a growing body of evidence on within-compound associations and encourage the development of a conceptual framework that provides an integrated description of within-compound and stimulus-reinforcer learning.

Animals↗

[Muscular myosin structural and functional changes during interaction with ATP and bivalent ions].

The interaction of myosin with ATP and bivalent ions is shown to cause changes in myosin ultraviolet fluorescence. Such a change is more significant for myosin of skeletal muscles than for that of smooth muscles. Kinetics of the fluorescence change has a phase of a sharp rise immediately after ATP addition and a phase of a slow decrease of fluorescence. The changes in fluorescence are connected with formation of an intermediate complex of myosin with ATP (intermediate). It is established that calcium ions are specific in the myosin ATPase reaction and they accelerate considerably the decay of this complex, while magnesium ions inhibits this process.

Adenosine Triphosphate↗

Field safety and efficacy of in ovo administration of HVT + SB-1 bivalent Marek's disease vaccine in commercial broilers.

The field safety and efficacy of a bivalent Marek's disease (MD) vaccine (herpesvirus of turkeys + strain SB-1) administered in ovo were evaluated. The vaccine was administered to commercial broiler chicken eggs using Embrex's INOVOJECT automated egg-injection system. Comparisons were made with a conventional method of vaccination, in which the vaccine was administered subcutaneously to chicks at hatching. In ovo administration of the vaccine at day 17.5-18.5 of incubation significantly reduced the number of culled chicks, early mortality, and overall mortality during the grow-out period compared with conventional vaccination. However, hatchability was significantly lower in in ovo-treated chicks. Overall livability and feed efficiency were higher in the in ovo-treated chicks than in conventionally vaccinated chicks. Total field-caused condemnations and condemnations due to airsacculitis and septicemia/toxemia were also lower in the in ovo-vaccinated chicks. No difference in the leukosis (MD) condemnation rate was observed between the two treatment groups. In ovo vaccination provided 93.25% protection against challenge with a very virulent strain of MD virus (strain RB1/B); by comparison, the conventional vaccination method provided 89.58% protection.

Animals↗

Lysis of malignant B cells from patients with B-chronic lymphocytic leukemia by autologous T cells activated with CD3 x CD19 bispecific antibodies in combination with bivalent CD28 antibodies.

Bispecific antibodies (bi-MABs) can be used to target T cells to autologous tumor cells. It has been shown that the activation of resting human T cells requires two independent signals, namely the cross-linking of the T-cell receptor (TCR)-CD3 complex together with the CD28 homodimer. In the present study, we demonstrate the activation of T cells from patients with chronic lymphocytic leukemia (CLL) using bi-MABs against the CD3 and CD19 antigens (CD3 x CD19) in combination with monospecific, bivalent antibodies against the CD28 antigen. Mononuclear cells from patients with CLL were cultured with the bi-MAB CD3 x CD19 and monospecific CD28 antibodies. The CD3 x CD19 bi-MABs were isolated by the hybridoma-hybridoma fusion technique and purified by hydrophobic interaction chromatography. T-Cell activation as demonstrated by increased proliferation, upregulation of T-cell activation markers (CD25, CD38), and cytotoxicity against autologous CLL cells and allogeneic B cells was shown in seven of eight CLL specimens. The stimulation with CD3 x CD19 bi-MABs with CD28 antibodies preferentially induced proliferation of CD4+ T cells. The effective dose of purified antibodies required for optimal T-cell activation was 100 ng/mL in vitro, which suggests that this antibody combination may be useful for immunotherapy of patients with B-CLL.

Adult↗

Construction of an engineered bivalent vaccine strain consisting of Vibrio cholerae CT-B and LPS-O antigens.

In this study, the engineered E. coli strain 1046 containing V. cholerae LPS-O and CTB bivalent antigen genes has been successfully obtained by using DNA recombinant techniques. E. coli 1046 (pMG305) could not only express CT-B antigen but also secret CTB into medium as shown by GM1-ELISA. Meanwhile, whole cell O-antigen-ELISA, bacterial agglutination test and hemagglutination inhibition assay demonstrated that LPS-O antigen could be expressed on the cell surface by E. coli 1046 (pMG305) and shown LPS band specific for V. cholerae by SDS-PAGE assay. Mouse intraperitoneal immunization and challenge trial indicated that the E. coli 1046 (pMG305) provided good protection against virulent V. cholerae. The engineered vaccine strain reported here is expected to be a live oral candidate vaccine for V. cholerae.

Animals↗

"Anticardiolipin" autoantibodies recognize beta 2-glycoprotein I in the absence of phospholipid. Importance of Ag density and bivalent binding.

"Anticardiolipin" autoantibodies (aCL) bind to anionic phospholipids only in the presence of beta 2-glycoprotein I (beta 2GPI), a phospholipid-binding plasma protein. The exact role of beta 2GPI in the antigenic specificity of these autoantibodies is unclear, however. Experiments were performed to determine whether aCL recognize beta 2GPI in the absence of phospholipid or neo-Ags formed as a consequence of the beta 2GPI-phospholipid interaction. Although aCL+ IgG fractions did not bind to beta 2GPI alone in ELISAs that used standard polystyrene immunoassay plates, significant specific binding was detected when beta 2GPI was coated on gamma-irradiated ("high binding") polystyrene plates. This difference was associated with the greater density of beta 2GPI immobilized on the gamma-irradiated plates. Fab' fragments of patient IgG demonstrated little or no binding to immobilized beta 2GPI in ELISA, indicating a critical role for Ab bivalency. Inhibition studies of three aCL+ IgG fractions confirmed their specificity for beta 2GPI and demonstrated low affinity binding to fluid-phase beta 2GPI (Kd values of approximately 10(-5) M). aCL binding to beta 2GPI was not a result of phospholipid contamination of the assays, as determined by microphosphate assay and by lipid extraction of IgG and beta 2GPI preparations. In summary, these experiments indicate that IgG aCL are intrinsically low affinity Abs to beta 2GPI. Ab binding to beta 2GPI on a microtiter plate or anionic phospholipid membrane is dependent upon the marked increase in avidity provided by engagement of both Ag binding sites of a given IgG molecule. The data support the hypothesis that phospholipid-bound beta 2GPI is the physiologic target of aCL.

Antibodies, Anticardiolipin↗

Adverse reactions to 1975 bivalent influenza vaccine in children.

A questionnaire survey was undertaken to investigate incidence and types of reactions to a bivalent, zonally purified, killed influenza vaccine administered to 155 children aged 1 to 18 years in 1975. Local or systemic reactions or both occurred in 42 children (27%). However, these reactions were not considered serious and should not constitute a major drawback to future influenza programs in children under 3 years of age.

Adolescent↗

Synthesis and opioid receptor affinity of bivalent ligands derived from 3,8-diazabicyclo(3.2.1)octanes.

A new series of bivalent ligands (2a-d), derived from the previously reported analgesic 3-cinnamyl-8-propionyl-3,8-diazabicyclo(3.2.1)octane (1a), has been synthesized and tested in vitro for their affinity towards opioid receptors and in vivo for their analgesic potency. None of the new compounds showed either appreciable affinity for opioid receptors or analgesic activity comparable to that of the model 1a.

Analgesics↗

Protection against hemorrhagic enteritis and Newcastle disease in turkeys by embryo vaccination with monovalent and bivalent vaccines.

The feasibility of embryo vaccination against Hemorrhagic enteritis (HE) and Newcastle disease (ND) in specific-pathogen-free turkey embryos was studied. Turkey eggs were injected with marble spleen disease virus (MSDV) at embryonation day (ED) 24, and tissues of poults hatching from virus-injected eggs were examined for MSDV. The virus was detected in spleen, intestine, liver, and bursa between 4 to 10 days postinoculation (PI). The peak titer of MSDV was present in the spleen at 6 days PI. Poults hatching from eggs injected with MSDV produced antibodies to the virus and resisted a challenge with virulent hemorrhagic enteritis virus (HEV) at 4 weeks of age. The B1 strain of NDV (NDV-B1) injected in turkey eggs at ED 24 killed the embryos. NDV-B1 modified by treatment with ethylmethane sulfonate (NDV-B1-EMS) was not lethal for turkey embryos. Poults hatching from eggs injected at ED 24 with NDV-B1-EMS developed antibodies to NDV and were protected from challenge exposure with virulent NDV at 4 weeks of age. Poults from eggs inoculated at 24 ED with a bivalent vaccine containing MSDV and NDV-B1-EMS developed antibodies to both viruses and were resistant to challenge with both virulent viruses. The study showed that SPF turkeys may be immunized by in ovo injection of live viral vaccines.

Animals↗

Intradermal administration of bivalent and monovalent influenza vaccines.

Intradermal (ID) administration of 0.1 ml of a bivalent influenza vaccine containing 40 CCA units each of influenza A/New Jersey (Hswine 1N1) and A/Victoria (H3N2) virus antigens and of a monovalent vaccine containing 100 CCA units of influenza B/Hong Kong virus to 70 adult volunteers produced no serious reactions and only 7% bothersome side effects. Excluding persons with high (1:64 or greater) initial antibody titers, then 90% and 85% of persons had fourfold or greater rises in HAI antibodies to A/New Jersey and B/Hong Kong antigens, whereas 53% had rises to A/Victoria. The authors feel the ID route deserves further consideration for giving killed influenza vaccines to adults. However, an influenza virus type that was prevalent for many years may fail to give sufficient rise in HAI to consider the patient protected.

Adult↗

Construction of a stable and non-resistant bivalent vaccine candidate strain against Shigella flexneri 2a and Shigella sonnei.

The E. coli cs3 gene coding for CFA/II antigen was site-specifically integrated into the asd gene locus of S. flexneri 2a vaccine strain T32, resulting in the inactivation of the asd gene. Meanwhile, the gene cluster for S. sonnei O antigen was cloned into a non-resistant expression vector pXL378 to construct the plasmid pXL390. By transforming the asd-mutant of the T32 strain with pXL390, the bivalent vaccine candidate strain FS01 against S. flexneri 2a and S. sonnei was finally obtained. Experiments showed that the recombinant plasmid pXL390 was very stable in the asd-T32 strain without the use of any antibiotics; the FS01 strain was genetically stable and expressed two kinds of Shigella LPS-O antigens on the surface without any enhancement of its toxicity. Animal tests demonstrated that FS01 strain, when administered subcutaneously in mice, could provide 100% protection against the intraperitoneal challenges of virulent S. flexneri 2a and S. sonnei.

Animals↗

Homodimerization of erythropoietin receptor by a bivalent monoclonal antibody triggers cell proliferation and differentiation of erythroid precursors.

Erythropoietin (EPO) stimulates proliferation and differentiation of erythroid progenitor cells. Several lines of evidence indicate that the most likely mechanism of EPO receptor (EPO-R) activation by EPO is homodimerization of the receptor on the surface of erythrocyte precursors. Therefore, we argued that it should be possible to raise EPO-R monoclonal antibodies (MoAbs) that would activate the receptor by dimerization and thus mimic EPO action. We have identified such an agonist MoAb (MoAb34) directed against the extracellular EPO binding domain of the EPO-R. This bivalent IgG antibody triggers the proliferation of EPO-dependent cell lines and induces differentiation of erythroid precursors in vitro. In contrast, the monovalent Fab fragment, which cannot dimerize the receptor, is completely inactive. The mechanism of receptor activation by homodimerization implies that at high ligand concentrations the formation of 1:1 receptor/ligand complexes is favored over 2:1 complexes, thereby turning the ligand agonist into an antagonist. Thus, EPO and MoAb34 should self-antagonize at high concentrations in both cell proliferation and differentiation assays. Our data indeed demonstrate that EPO and MoAb34 antagonize ligand-dependent cell proliferation with IC50 values of approximately 20 and 2 mumol/L, respectively. Erythroid colony formation (BFUe) is inhibited at MoAb34 concentrations above 1 mumol/L. Furthermore, we analyzed the MoAb34:EPO-R interaction using a mathematic model describing antibody-mediated receptor dimerization. The data for proliferation and differentiation activity were consistent with the receptor dimer formation on the cell surface predicted by the model.

Animals↗

[Effectiveness and tolerability of oral liquid ferrous gluconate in iron-deficiency anemia in pregnancy and in the immediate post-partum period: comparison with other liquid or solid formulations containing bivalent or trivalent iron].

UNLABELLED: From the early months of pregnancy and even more so later, women suffer a deficiency of iron along with a decline in their red blood cell count. It is also now clear that women who take iron supplements during pregnancy do not suffer the same post-natal reduction in hemoglobin and ferritin as those who don't make it. A study was therefore conducted on 40 women aged 20-35, with iron-deficiency anaemia during or immediately after pregnancy all of whom presented Hb < 10 gr/dl, Ht < 33% and serum iron < 60 micrograms/dl. All women with pregnancy-related pathological conditions, pre-existing on concomitant disease (Type I diabetes, heart diseases etc.) were excluded from the study. The women whose blood chemical parameters were largely homogeneous at the start of the study were divided into four treatment groups of 10 patients each and were treated as follows: Group A with oral liquid ferrous gluconate (75 mg per diem in 2 vials a day); Group B with solid ferrous gluconate (80 mg per diem in a single effervescent tablet); Group C with solid ferrous sulphate (105 mg per diem in a single tablet); and Group D with ferric protein succinylate (80 mg per diem in 2 vials a day). All were given iron treatment for 30 days. Treatment efficacy was analysed by comparing basal and final parameters using the T-test for paired dependent samples. The tolerance of the 4 treatment protocols was assessed by the analysis of any side effects such as nausea, vomiting, epigastric pain, diarrhoea, constipation or other disorders reported by patients during treatment. RESULTS: Analysis of the therapeutic efficacy parameters (red blood cells, hemoglobin, hematocrit and serum iron) showed significant improvements but no statistically significant differences between the groups. However, the Group A patients treated with oral doses of liquid ferrous gluconate received a significantly lower cumulative dose of iron elements than the other groups: in detail 150 mg (p < 0.05) less than Groups B and D; 900 mg (< 0.001) less than Group C. By the end of treatment the Group A patients revealed significant increases versus basal values in red blood cells (p < 0.001) 1,051,000 per mm3 or 33%, in Hb (p < 0.001) 2.83 gr/dl or 32%, in Ht (p < 0.001) 8.32% or 32%, in serum iron (p < 0.05) 19.5 micrograms/dl or 61%. The same group also showed an increase in Ferritin amounting to 7.8 micrograms/dl or 24% of the basal value. As to safety, only Group A patients reported no side effects and produced no drop-outs. Gastrointestinal and other aspecific side effects caused 1 drop-out each in Groups B and C and 2 drop-outs in Group D. CONCLUSION: Numerous preparations containing bivalent or trivalent iron are available for the treatment of iron-deficiency anaemia during or immediately after pregnancy. It has been shown that preparations containing ferrous salts (+2) are more easily absorbed than those containing ferric salts (+3) since the former can be immediately absorbed by the duodenal mucosa. The study reported here reveals that oral ferrous gluconate in liquid form is more effective and above all better tolerated than other solid or liquid formulations containing elementary iron.

Administration, Oral↗

Bivalent influenza vaccination with inactivated vaccines administered by nasal or oral route.

Influenza vaccinations were performed either by administration of a bivalent A2 + B vaccine, or by successive application of monovalent B and A2 vaccines. During an influenza epidemic caused by an A2 strain, the following observations could be made: a) the best efficiency (no influenza cases) was recorded in adults and aged persons (over 65 years) irrespective of the vaccination scheme; b) in schoolchildren the best results (no influenza cases) were obtained in the lot having received monovalent A2 vaccine, and in the lot vaccinated nasally with monovalent B vaccine and 14 days later with monovalent A vaccine.

Administration, Intranasal↗