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PubMed2001

Rate of homologous chromosome bivalents in spermatocytes may predict completion of spermatogenesis in azoospermic men.

Abstract. The rate of bivalent formation during meiosis was correlated with the presence and amount of spermatozoa in the testes of azoospermic men. Four pairs of chromosomes, X-Y, 9, 15, and 18, were evaluated. In addition, left and right testes were compared. Three biopsies from each testis were undertaken to extract spermatozoa for intracytoplasmic sperm injection. In addition, one sample from each testis was used for histological definition, spermatozoa count and detection of chromosome bivalents in spermatocytes. A significantly higher rate of bivalents of all homologous chromosomes was found whenever spermatozoa were detected. The rate of bivalent X-Y was found to be the most sensitive predictor for detection of spermatozoa, with a cut-off value of 47%. The R(2) was 27% ( P=0.003) for the percent of spermatozoa in the minced sample as well as the number of mature spermatids per tubule in the histological section. All pairs of testes were in concord in regard to the likelihood of finding spermatozoa. In the testes where no spermatozoa were found on biopsy, the rate of X-Y bivalent indicated the presence of spermatozoa in the opposite side. Thus, it may be concluded that the rate of X-Y bivalent formation in spermatocytes may predict the presence and amount of spermatozoa in the testicular tissue of azoospermic men. It is suggested that when no spermatozoa are located by testicular fine-needle aspiration, X-Y bivalent evaluation may be conducted if spermatocytes are evinced. A high rate of X-Y bivalents may impel one to continue with testicular open biopsies.

Biopsy↗
PubMed1991

Bivalent ACTH antagonists: influence of peptide and spacer components on potency enhancement.

The antagonist potency of a series of bivalent adrenocorticotropic hormone (ACTH) peptides was examined using suspensions of inner zone rat adrenocortical cells. Bivalent antagonists were prepared by bis(maleimide) covalent cross-linking of carboxyl terminal cysteine sulfhydryl groups of synthetic ACTH peptides, Cys25 ACTH(7-25) and Cys39 ACTH(7-39). Antagonist potency enhancement was defined by shifts in ACTH(1-39) concentration-steroidogenic response curves relative to monovalent antagonist analogs. The EC50 values measured in the presence of 0.5 microM monovalent antagonist were 110 +/- 28 pM for Cys25 ACTH(7-25)-S-N-ethylsuccinimide and 44 +/- 9 pM for Cys39 ACTH(7-39)-S-N-ethylsuccinimide. Some bivalent ACTH antagonists displayed much greater antagonist potency than their monovalent analogs, which supports the findings of Stolz and Fauchere (Helv Chim Acta 71: 1421-1428, 1988). The level of potency enhancement, however, was found to be dependent upon the spacer used to link receptor binding domains and the length of the ACTH peptide used in bivalent antagonist synthesis. The most potent inhibitor, bis(Cys25 ACTH(7-25)-S-succinimidopropionyl)2-hydroxy-1,3-propanediamine, was 28 times more potent than its monovalent analog, Cys25 ACTH(7-25)-S-N-ethylsuccinimide. However, a bivalent Cys25 ACTH(7-25) peptide containing two bis(succinimidopropionyl)2-hydroxy-1,3-propanediamine spacers that had been linked end-to-end via dithioerythritol showed no potency enhancement. Cys25 ACTH(7-25) based peptides containing one receptor binding domain and having the structure peptide-spacer-cysteine displayed no enhancement in antagonist potency. Bivalent Cys39 ACTH(7-39) linked by bis(succinimidopropionyl)2-hydroxy-1,3-propanediamine spacer exhibited only 4-fold enhancement in antagonist potency relative to Cys39 ACTH(7-39)-S-N-ethylsuccinimide. We therefore conclude that the potency enhancement observed with bivalent ACTH peptides: (1) is optimal with spacers less than approximately 40 A in length, (2) is not due to direct interactions between the spacer and cell surface, and (3) is dependent on the length of the ACTH peptide component. In addition, these results indicate that electrostatic interaction between bivalent ACTH peptides and plasma membrane lipids does not adequately account for the potency enhancements observed.

Adrenal Cortex↗
PubMed2004

Bivalent antibody phage display mimics natural immunoglobulin.

We report the development of a system for displaying bivalent antibody fragments on M13 bacteriophage in a manner that effectively mimics the binding behavior of natural antibodies. In the "bivalent display" format, two copies of antigen binding sites are displayed on the coat of a single phage particle. Bivalent display was first achieved by the insertion of a dimerization domain, consisting of an IgG1 hinge region and a homodimerizing GCN4 leucine zipper, between a Fab and the C-terminal domain of the M13 gene-3 minor coat protein. In a phagemid-based display system, the resulting "Fab'-zip-phage" particles display bivalent Fabs that resemble natural IgGs. An important functional consequence of bivalent display is an avidity effect, which results in a greatly reduced off-rate for phage bound to immobilized antigen. The avidity effect improved the capture and retention of bivalent Fab'-zip-phage relative to monovalent Fab-phage both with antigen immobilized on plates and with cell surface antigen. To examine the requirements for bivalent display on phage, we systematically trimmed down the dimerization domain and found that a single cysteine was sufficient to confer the same avidity effect conferred by the complete dimerization domain. Bivalent antibody phage display should be useful for many applications. In particular, the technology should aid in the production of antibodies against difficult antigens, and also, in selections that require dimerization for activity.

Amino Acid Sequence↗
PubMed1986

Micromanipulated bivalents can trigger mini-spindle formation in Drosophila melanogaster spermatocyte cytoplasm.

Single (individual) bivalents in cultured Drosophila melanogaster primary spermatocytes were detached from the spindle with a micromanipulation needle and placed in the cytoplasm. Such bivalents are prevented from rejoining the spindle by a natural membrane barrier that surrounds the spindle, but they quickly orient as if on a spindle of their own and the half-bivalents separate in anaphase. Serial section electron microscopy shows that a mini-spindle forms around the cytoplasmic bivalent, i.e., the microtubule density in the vicinity of the bivalent is much greater than in other cytoplasmic regions. This microtubule population cannot be accounted for solely by kinetochore nucleation and/or capture of microtubules. Furthermore, the mini-spindles frequently form at odd angles to the main spindle, so that at least one pole has no relationship to the poles of the main spindle. We conclude that a bivalent, or factors that become associated with the bivalent as a result of the manipulation, can either stabilize microtubules or promote their assembly. The bivalent activates latent microtubule organizing centers, or alternatively, polar organizing material has been passively transported from the main spindle to the cytoplasm by the micromanipulation procedure.

Animals↗
PubMed1990

The origin of aneuploidy: bivalent instability and the maternal age effect in trisomy 21 Down syndrome.

The mechanism behind the high rate of maternal first meiotic non-disjunction and the maternal age effect in trisomy 21 is unknown. Much attention has been paid to the causal role of univalence 21 by lack of chiasma formation. Here I suggest that not only achiasmatic bivalents may be susceptible to nondisjunction, but the chiasmatic bivalent shape per se may play an important role. Considering the topology of the chiasmata and the orientation of the bivalent at first meta- and anaphase, some bivalent shapes may have a greater segregational potential than others. For any one chromosome there may at first meta- and anaphase be an optimal balance between chromosome coiling/condensation on the one hand and chiasma frequency distribution on the other. Chromosome coiling/condensation may play an interesting dual role in both determining bivalent flexibility and dictating chiasma formation. I propose that the higher rate of double- and triple-chiasma bivalents 21 in oocytes contributes to its higher rate of spontaneous first meiotic nondisjunction; and the maternal age effect is associated with chromosome laxity, secondary to an impairment of appropriate chromosome coiling/condensation in oocytes of older women. In spermatocytes of older men some compensatory increase in chiasma frequency with a shift towards double- and triple-chiasma bivalents 21 might take place, i.e., if a general age-related chromosome decondensation is counteracted by an auto-regulatory "length effect" remaining intact in pachytene spermatocytes.

Aneuploidy↗
PubMed2002

A bivalent polyploid model for linkage analysis in outcrossing tetraploids.

Polyploids can be classified as either allopolyploids or autopolyploids based on their presumed origins. From a perspective of linkage analysis, however, the nature of polyploids can be better described as bivalent polyploids, in which two chromosomes pair at meiosis, multivalent polyploids, in which more than two chromosomes pair, and general polyploids, in which bivalent and multivalent formations occur simultaneously. In this paper, we develop a statistical method for linkage analysis of polymorphic markers in bivalent polyploids. This method takes into account a unique cytological pairing mechanism for the formation of diploid gametes in tetraploids-preferential bivalent pairings at meiosis during which two homologous chromosomes pair with a higher probability than two homoeologous chromosomes. The higher frequency of homologous over homoeologous pairing, defined as the preferential pairing factor, affects the segregation patterns and linkage analysis of different genes on the same chromosome. A maximum likelihood method implemented with the EM algorithm is proposed to simultaneously estimate linkage and parental linkage phases over a pair of markers from any possible marker cross type between two outbred bivalent tetraploid parents demonstrating preferential bivalent pairings. Simulation studies display that the method can be well used to estimate the recombination fraction between different marker types and the preferential pairing factor typical of bivalent tetraploids. The implications of this method for current genome projects in polyploid species are discussed.

Algorithms↗
PubMed1994

Bivalent ligands as probes of estrogen receptor action.

The estrogen receptor (ER) is a hormone-regulated transcription factor which is thought to bind to specific DNA sequences as a homodimer. In order to better understand structural requirements for dimerization and its functional role in ER action, we synthesized a series of bivalent ligands based on the non-steroidal estrogen hexestrol. These molecular probes join two hexestrol molecules of the erythro (E, active) configuration with either 4 or 8 carbon linkers (designated E-4-E and E-8-E series, respectively), or with longer linkers comprised of ethylene glycol units (E-eg-E series). Several other bi- and monovalent control compounds were prepared. The bivalent ligands bind to ER with a relative affinity 1-7% that of estradiol. While most of the ligands demonstrated normal monophasic displacement curves in competitive binding assays with [3H]estradiol, uncharacteristic biphasic competitive binding curves were seen for some of the ligands, indicating possible structure-specific, negative site-site interaction. In ER-deficient Chinese hamster ovary (CHO) cells transfected with an expression vector encoding ER, one series of bivalent ligands (E-4-E) had little stimulatory activity and inhibited transcription stimulated by hexestrol, as determined by a transient transfection assay using an estrogen-responsive reporter gene construct [(ERE)2-TATA-CAT, containing two estrogen response elements linked to a TATA promoter and the chloramphenicol acetyl transferase reporter gene]. Monovalent or control bivalent ligands failed to antagonize hexestrol-stimulated activity and were as fully active as hexestrol itself. Studies performed in MCF-7 human breast cancer cells, which contain endogenous ER, yielded similar bioactivity profiles for the E-4-E bivalent inhibitory ligands, showing them to be effective estrogen antagonists, when using either induction of progesterone receptor or (ERE)2-TATA-CAT transcriptional activation as the endpoint. The E-8-E ligand, however, acted as a partial agonist/antagonist of ERE-reporter gene transactivation and a full agonist of progesterone receptor induction in MCF-7 cells, thus showing cell- and response-specific differences in the effects of this bivalent ligand. These bivalent ligands for ER do not show enhanced potency or receptor binding affinity; however, some of them display binding properties that suggest the possibility of structure-specific negative site-site interaction, and some of them function as quite effective estrogen antagonists.

Animals↗
PubMed2003

Synthesis and characterization of potent bivalent amyloidosis inhibitors that bind prior to transthyretin tetramerization.

The misfolding of transthyretin (TTR), including rate-limiting tetramer dissociation and partial monomer denaturation, is sufficient for TTR misassembly into amyloid and other abnormal quaternary structures associated with senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy. Monovalent small molecules that bind to one or both of the unoccupied thyroid hormone binding sites at the TTR quaternary structure interface stabilize the native state, raising the kinetic barrier for tetramer dissociation sufficiently that the rate of dissociation, and therefore amyloidosis, becomes slow. Bivalent amyloid inhibitors that bind to both binding sites simultaneously are reported herein. The candidate bivalent inhibitors are generally unable to bind to the native TTR tetramer and typically do not engage in monovalent binding owing to a strong inhibitor orientation preference. However, the TTR quaternary structure can assemble around several of the bivalent inhibitors if the inhibitor intercepts the protein before assembly occurs. Some of the wild-type TTR.bivalent inhibitor complexes prepared in this fashion retain a tetrameric structure when subjected to substantial denaturation stresses (8 M urea, 120 h). The best bivalent inhibitor reduced acid-mediated TTR (3.6 microM) amyloid fibril formation to 6% of that exhibited by TTR in the absence of inhibitor, a significant improvement over the approximately 30% observed for the best monovalent inhibitors (3.6 microM, 72 h). The apparent dissociation rate of the best bivalent inhibitor is effectively zero, consistent with the idea that TTR tetramer dissociation and inhibitor dissociation are linked-as a result of the inhibitor-templating tetramer assembly. X-ray cocrystal structures of two of the complexes demonstrate that the bivalent inhibitors simultaneously occupy both sites in TTR, consistent with the 1:1 binding stoichiometry derived from HPLC analysis. The purpose of this study was to demonstrate that bivalent inhibitors could be useful; what resulted are the best inhibitors produced to date. In this context, molecules capable of intercepting TTR during folding and assembly in the lumen of the endoplasmic reticulum would be of obvious interest.

Amyloid↗
PubMed2003

Solid-phase synthesis for the identification of high-affinity bivalent lectin ligands.

The development of carbohydrate-based therapeutics has been frustrated by the low affinities that characterize protein-carbohydrate complexation. Because of the oligomeric nature of most lectins, the use of multivalency may offer a successful strategy for the creation of high-affinity ligands. The solid-phase evaluation of libraries of peptide-linked multivalent ligands facilitates rapid examination of a large fraction of linker structure space. If such solid-phase assays are to replicate solution binding behavior, the potential for intermolecular bivalent binding on bead surfaces must be eliminated. Here we report the solid-phase synthesis and analysis of peptide-linked, spatially segregated mono- and bivalent ligands for the legume lectin concanavalin A. Bead shaving protocols were used for the creation of beads displaying spatially segregated binding sequences on the surface of Tentagel resins. The same ligands were also synthesized on PEGA resin to determine the effect of ligand presentation on solid-phase binding. While we set out to determine the lower limit of assay sensitivity, the unexpected observation that intermolecular bivalent ligand binding is enhanced for bivalent ligands relative to monovalent ligands allowed direct observation of the level of surface blocking required to prevent intermolecular bivalent ligand binding. For a protein with binding sites separated by 65 A, approximately 99.9% of Tentagel(1) surface sites and 99.99% of the total sites on a PEGA bead must be blocked to prevent intermolecular bivalent binding. We also report agglutination and calorimetric solution-phase binding studies of mono- and bivalent peptide-linked ligands.

Amino Acid Sequence↗
PubMed1985

Interlocked bivalents in reconstructed metaphase I cells of bread wheat.

Complete reconstructions of all the bivalents were made from electron micrographs of serial sections through six pollen mother cells at metaphase I of meiosis in Triticum aestivum (hexaploid bread wheat). At least two of these metaphases contained interlocked pairs of bivalents. In one, two ring bivalents were interlocked, while in another a rod bivalent ran through the centre of a ring bivalent. Two other groups of bivalents were too closely appressed to allow separation into individual bivalents and may have contained interlocks. Meiosis in other anthers of the same plants examined by light microscopy was considered normal. The frequency of interlocking found was much higher than reported from light-microscope spreads. Not all interlocks in metaphase I cells need adversely affect meiosis, but knowledge of their regularity and form may facilitate understanding the processes of chromosome pairing.

Centromere↗
PubMed1992

Effect of bivalent interaction upon apparent antibody affinity: experimental confirmation of theory using fluorescence photobleaching and implications for antibody binding assays.

The affinity of a monoclonal antibody for its tumor-associated antigen is one of several parameters governing in vivo monoclonal antibody distribution. However, there is a lack of apparent correlation between the affinity of a bivalent monoclonal antibody measured using equilibrium binding experiments and its in vivo delivery. Furthermore, differences in the reported affinity for identical antibody/antigen pairs are quite common in the literature. In this paper, both of these discrepancies are addressed in terms of variation in avidity due to bivalent interaction. The enhancement of avidity afforded by bivalent attachment is addressed theoretically by extending the model of Crothers and Metzger (Immunochemistry, 9: 341-357, 1972). Theoretical assessment of Lineweaver-Burk, Scatchard, Steward-Petty, Langmuir, fluorescence recovery after photobleaching, and Sips models demonstrates quantitatively that the measured affinity using equilibrium binding experiments may vary over four orders of magnitude with similar variation in experimental cellular antigen density. Further, the measured affinity is a function of the experimental protocol. Predictions of avidity enhancement were confirmed experimentally using fluorescence recovery after photobleaching. These experiments measured the equilibrium binding constant and concentration of binding sites for an immunoglobulin G monoclonal antibody and its F(ab) fragment directed against the rabbit VX2 carcinoma cell line. Bivalent binding data agree quantitatively with those predicted by the bivalent model with no adjustable parameters. It is concluded that bivalent equilibrium binding constants are useful only in antibody screening, where experimental conditions are identical for all series. They must be used with caution in predicting in vivo antibody distribution, and it is recommended that the intrinsic, monovalent affinity be measured in tandem with any bivalent antibody study as a standard reference.

Animals↗
PubMed1997

Targeting BCL1 lymphoma with anti-idiotype antibodies: biodistribution kinetics of directly labeled antibodies and bispecific antibody-targeted bivalent haptens.

The mouse BCL1 lymphoma model has been used for evaluating immunotherapy with anti-idiotype (anti-Id) antibodies, including Id immunisation, IgG therapy and bispecific (Bs) antibody-targeted cytotoxicity. Here, we provide quantitative data on the targeting of small (25 +/- 12 mg) intrasplenic BCL1 tumours, using anti-Id IgG, F(ab')2 and anti-Id x anti-hapten BsF(ab')2 covalently labelled with 125iodine, as well as noncovalent complexes of BsF(ab')2 and 125I-labelled bivalent hapten. The results are the following: 1) up to 115% of the injected dose per gram (% ID/g) of spleen can be localised in the first hour, corresponding to approximately 600% ID/g of tumour; 2) localisation is specific for cell-surface Id; 3) optimal doses can overcome circulating Id; 4) circulating Id markedly increases the catabolism of IgG, thus impairing tumour localisation; 5) bivalent reagents are internalised by the target cells; 6) iodine covalently bound to bivalent antibodies [IgG, F(ab')2] is rapidly (T(1/2): 6-9 hr) released from the tumour; in contrast, the bivalent hapten is retained for a longer time (T(1/2): 25 hr); and 7) in the absence of bivalent hapten, the monovalent BsF(ab')2 is not rapidly internalised and dissociates from tumour cell-surface Id. Our results suggest that monovalent anti-Id, lacking Fc, can efficiently be targeted to the BCL1 tumour surface. For radioimmunotherapy, the intracellular targeting of catabolism-resistant 125I-labelled bivalent hapten provides optimal tissue selectivity.

Animals↗
PubMed1986

Bivalent orientation and behavior in crane-fly spermatocytes recovering from cold exposure.

At metaphase in crane-fly primary spermatocytes, the two sister kinetochores at the centromere of each homologue in a bivalent normally are adjacent and face the same pole; one homologue has all its kinetochore microtubules (kMTs) extending toward one pole and its partner has all its kMTs extending toward the opposite pole. In contrast, during recovery from exposure to 2 degrees C, one or both homologues in many metaphase bivalents had bipolar malorientations: all kMTs of one kinetochore extended toward one pole and some or all those of its sister extended toward the other. Metaphase sister kinetochores that had most of their kMTs extending toward the same pole were adjacent, and those with most extending toward opposite poles were separated from each other. Distances between homologous centromeres were similar to those in properly oriented bivalents. Maloriented bivalents were tilted relative to the spindle axis, and analysis of living cells showed that tilted configurations were rare during prometaphase in untreated cells but frequently arose in cold-recovering cells as initial configurations, then persisted through metaphase. This was in contrast to unipolar configurations of bivalents (configurations suggesting orientation of both homologous centromeres toward the same pole), which always reoriented shortly after the configuration arose. We conclude that in cold-recovering cells, bipolar malorientations are more stable than unipolar malorientations, and the orientation process is affected such that bipolar malorientations arise in bivalents upon initial interaction with the spindle and persist through metaphase.

Animals↗
PubMed2005

XY chromosomal bivalent: nucleolar attraction.

Nucleolar organization by autosomal bivalents occurs during male meiotic prophase in mammalian species. During late leptotene-early zygotene stages, several autosomal bivalents are engaged in ribosomal RNA synthesis. At pachytene stage, nucleolar masses detach from the sites of primary autosomal origin, relocate close to the XY chromosomal pair, and nucleolar components become segregated. In early pachytene, an extensive synaptonemal complex at the pseudoautosomal region, links X and Y chromosomes in close juxtaposition along most of the length of the Y chromosome, except for a terminal region of the Y that diverges from the pairing region. As meiotic prophase advances, X and Y chromosomes progressively desynapse and, at diplotene, the XY pair is associated end-to-end. Xmr (Xlr-related, meiosis regulated) is a protein component of the nucleolus associated to the XY pair and of the asynapsed portions of the X and Y axial cores. Xmr, like SCP3, is a component of the lateral element of the synaptonemal complex. Both share structural homology in their C-terminal region. This region contains several putative coiled-coil domains known to mediate heterodimeric protein-protein interactions and to provide binding sites to regulatory proteins. Like Xmr, the tumor repressor protein BRCA1 is present along the unsynapsed cores of the XY bivalent. Both Xmr and BRCA1 have been implicated in a mechanism leading to chromatin condensation and transcription inactivation of the XY bivalent. The BRCA1-ATR kinase complex, as recent research suggests, triggers the phosphorylation of histone H2AX, which predominates in the condensed chromatin of the XY chromosomal pair. Xmr is not present in the XY bivalent when the expression of histone H2AX is deficient. The role of Xmr in chromatin condensation of the XY bivalent has not been determined. The partial structural homology of SCP3 and Xmr, their distribution along the unsynapsed axial cores of the X and Y chromosomes, and the presence of Xmr in the XY pair-associated nucleolus raises the possibility that Xmr, and other proteins including protein kinases, may be recruited to the nucleolus to perform functions related to chromosomal synapsis, chromatin condensation and recombination processes, as well as cell cycle progression.

Animals↗
PubMed1982

Meiosis in Drosophila melanogaster. IV. The conjunctive mechanism of the XY bivalent.

Chromosome pairing during meiosis I in D. melanogaster males was investigated ultrastructurally by examining complete bivalents in electron micrographs of serial thin sections. The XY bivalent is characterized by the presence of the unique material located between the two half-bivalents at the site of synapsis. The material has a fibrillar appearance and is less electron dense than the surrounding chromatin. XY bivalents in XYY males and XY bivalents containing the X chromosome, In (1) sc4LSC8R, where the pairing sites of the X chromosome are inverted and partially deleted also possess this material. The material is not associated with autosomal bivalents and may represent a morphological manifestation of the hypothetical cohesive elements (collochores) which are thought to function in conjunction of the X and Y chromosomes (Cooper, 1964).

Animals↗
PubMedDate not supplied

Chlamydia trachomatis species specific serology: ImmunoComb Chlamydia bivalent versus microimmunofluorescence (MIF).

The ImmunoComb Chlamydia Bivalent IgG/IgA (Orgenics, Israel) is a new quantitative serologic test that employs LPS extracted Chlamydia trachomatis L2 and LPS extracted Chlamydia pneumoniae elementary bodies on two separate antigenic spots. The Bivalent C. trachomatis specific test results were compared with microimmunofluorescence (MIF), the gold standard of chlamydial species specific serology. For C. trachomatis IgG the Bivalent was highly concordant with the MIF: the rate of positive titres (IgG > or = 1:8) was 10% vs. 11% in 100 blood donors, 18% vs. 16% in 111 obstetric patients (6% antigen prevalence), 26% vs. 22% in sterile women with open (n = 54) and 86% vs. 84% with occluded (n = 51) tubes, and 88% vs. 85% in 103 women with C. trachomatis positive cervical smears. Surprisingly, the Bivalent differed considerably from the MIF in IgA prevalence: in obstetric patients (8% vs. 4%), sterile women with open (13% vs. 6%) and occluded (71% vs. 20%) tubes, and women with positive cervical smears (78% vs. 24%). Bivalent IgA appeared to be more sensitive than MIF IgA and showed a stronger correlation with positive cervical smears in obstetric patients (sensitivity 67% vs. 0%, specificity 95% vs. 96%, positive prediction 44% vs. 0%, negative prediction 98% vs. 94%) and with tubal occlusion in sterile women (sensitivity 71% vs. 20%, specificity 87% vs. 94%, positive prediction 84% vs. 77%, negative prediction 76% vs. 55%). MIF IgM was of little diagnostic help. Supplemental to the often difficult C. trachomatis antigen detection, the easily performed Bivalent IgG/IgA appears to be of great value in routine diagnosis of genital chlamydial infections.

Adult↗
PubMed2001

Colchicine promotes a change in chromosome structure without loss of sister chromatid cohesion in prometaphase I-arrested bivalents.

In somatic cells colchicine promotes the arrest of cell division at prometaphase, and chromosomes show a sequential loss of sister chromatid arm and centromere cohesion. In this study we used colchicine to analyse possible changes in chromosome structure and sister chromatid cohesion in prometaphase I-arrested bivalents of the katydid Pycnogaster cucullata. After silver staining we observed that in colchicine-arrested prometaphase I bivalents, and in contrast to what was found in control bivalents, sister kinetochores appeared individualised and sister chromatid axes were completely separated all along their length. However, this change in chromosome structure occurred without loss of sister chromatid arm cohesion. We also employed the MPM-2 monoclonal antibody against mitotic phosphoproteins on control and colchicine-treated spermatocytes. In control metaphase I bivalents this antibody labelled the tightly associated sister kinetochores and the interchromatid domain. By contrast, in colchicine-treated prometaphase I bivalents individualised sister kinetochores appeared labelled, but the interchromatid domain did not show labelling. These results support the notion that MPM-2 phosphoproteins, probably DNA topoisomerase IIalpha, located in the interchromatid domain act as "chromosomal staples" associating sister chromatid axes in metaphase I bivalents. The disappearance of these chromosomal staples would induce a change in chromosome structure, as reflected by the separation of sister kinetochores and sister axes, but without a concomitant loss of sister chromatid cohesion.

Animals↗
PubMed2005

Development and evaluation of a Shigella flexneri 2a and S. sonnei bivalent invasin complex (Invaplex) vaccine.

Over 160 million cases of shigellosis occur annually worldwide, with the two most prevalent species being Shigella flexneri and S. sonnei. Protective immunity against Shigella infection is primarily directed at the lipopolysaccharide (LPS) of the homologous serotype, so it may be necessary to combine monovalent vaccines for multiple Shigella serotypes to construct a multivalent vaccine against predominant serotypes. Recently, we described a subcellular vaccine isolated from virulent S. flexneri, consisting of proteins (including the invasins IpaB and IpaC) and LPS, that protected mice and guinea pigs from homologous challenge. In the present study, a bivalent Invaplex vaccine consisting of S. flexneri 2a and S. sonnei Invaplex was used to intranasally immunize mice and guinea pigs to determine the bivalent vaccine's immunogenicity and protective capacity against challenge with either strain. Mice and guinea pigs immunized with the bivalent S. flexneri 2a/S. sonnei Invaplex vaccine produced serum IgA and IgG antibodies to S. flexneri LPS, S. sonnei LPS, the homologous Invaplex and the water extract antigens (invasins) as determined by ELISA. The immune responses in animals immunized with the bivalent vaccine were similar to responses in animals immunized with the monovalent Invaplex vaccines. Mice and guinea pigs immunized with the bivalent vaccine were protected from a lethal lung challenge (mice, P<0.001) or severe keratoconjunctivitis (guinea pigs, P< or = 0.002) after challenge with either S. flexneri 2a or S. sonnei. Animals immunized with monovalent Invaplex vaccines were protected (P<0.001) against the homologous agent at levels comparable to the bivalent vaccine. After challenge, immunized animals demonstrated boosts in antibody titers to LPS, water extract antigens and Invaplex. These studies indicate that the subcellular Invaplex vaccine will be readily adaptable to a multivalent vaccine approach for shigellosis.

Animals↗