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PubMed1999

[Stable expression and immunogenicity in a attenuated Salmonella typhi strain of coli surface antigen-6 of enterotoxigenic Escherichia coli].

A gene fragment encoding for surface antigen CS6 of enterotoxigenic of Escherichia coli has been cloned into the plasmid pXL670, a new recombinant plasmid pSS64 was obtained by transforming E. coli X6097 with asd gene deletion. A safe and effective E. coli/S. typhi bivalent candidate vaccine was constructed by introducing pSS64 into delta aroA, delta aroC, delta asd Salmonella typhi. The vaccine strain is still stable in the absence of antibiotics. Animal tests demonstrated that this strain, when administered subcutaneously in mice, could provide significant protection against the intraperitoneal challenge from wild S. typhi Ty2. Immunization of rabbit with this strain raised specific antibody responses against CS6 and Vi antigen of S. typhi. This study lays the foundation for the construction of a new E. coli/S. typhi bivalent live oral vaccine.

Animals↗
PubMed1992

[Hirudin and hirudin fragments].

Hirudin is a potent and specific thrombin inhibitor: compared with heparin thrombin inhibition occurs directly and does not require the presence of plasma cofactors. Recombinant hirudin is well tolerated in animals and in healthy volunteers. Its clearance half-life after IV administration range from 1 to 2 hours and its bioavailability after subcutaneous administration reaches 75%. In most of the experimental models the ratio of the haemorrhagic side effect against the antithrombotic efficacy is satisfactory. Hirudin analogs are mono or bivalent according to their recognition site on thrombin. Bivalent derivatives (Hirulogs) have been mostly evaluated: they exhibit pharmacologic properties similar experimental to that of recombinant hirudin and have been successfully used in several thrombosis models and in healthy volunteers. Taking into account these data the most appropriate use for hirudin and hirudin derivatives should be clinical situations where the role of thrombin is important or which are only partially controlled by heparin therapy.

Animals↗
PubMed1992

Binding parameters and idiotypic profile of the whole immunoglobulin and Fab' fragments of murine monoclonal antibody to distinct determinants of the human high molecular weight-melanoma associated antigen.

The nonspecific accumulation of radioactivity in bone marrow, liver, and spleen in patients with melanoma injected with radiolabeled whole IgG of anti-high molecular weight-melanoma associated antigen (HMW-MAA) monoclonal antibody (mAb) hampers the application of immunoscintigraphy to visualize melanoma lesions. This nonspecific background can be reduced by utilizing fragments which do not contain the Fc portion of anti-HMW-MAA mAb. Since the in vivo targeting to melanoma lesions of radiolabeled F(ab')2 and Fab' fragments of anti-HMW-MAA mAb is critically dependent on their binding parameters, we have analyzed the effect of fragmentation on the binding characteristics of the anti-HMW-MAA mAbs 225.28, 763.74, and TP41.2. The three mAbs recognize distinct and spatially distant determinants with a heterogeneous distribution on the pool of HMW-MAA molecules synthesized by melanoma cells. The determinant recognized by mAb TP41.2 is detectable on a markedly smaller population of HMW-MAA molecules than those recognized by mAbs 225.28 and 763.74. 125I-labeled F(ab')2 fragments of the three mAbs displayed an immunoreactive fraction similar to that of the whole IgG, while Fab' fragments displayed a lower one. Fragmentation of mAbs 225.28 and TP41.2 to F(ab')2 produced a 2- and 1.5-fold reduction in their association constants but did not cause a significant change in that of mAb 763.74. Cleavage of F(ab')2 fragments to Fab' fragments produced 2-, 40-, and 7-fold reductions in the association constants of mAbs 225.28, 763.74, and TP41.2, respectively. These changes qualitatively fit the predictions of theory for univalent and bivalent mAb binding, since mAbs 763.74 and TP41.2 appear to show bivalent binding to melanoma cells and mAb 225.28 to show univalent binding. The affinity constant of IgG, F(ab')2 and Fab' fragments of mAbs 225.28, 763.74, and TP41.2 displays an inverse relationship with the extent of their time-dependent release from the membrane of melanoma cells. Since no endocytosis of mAb could be detected, the latter results suggest that radioactivity remains bound to melanoma cells in vivo for a longer time following injection of F(ab')2 fragments than following that of Fab' fragments of each of the anti-HMW-MAA mAb tested. Radiolabeled Fab' fragments of mAbs 763.74 and TP41.2 displayed a marked reduction in their reactivity with some of the antiidiotypic mAb tested. The loss of some idiotopes is likely to be caused by changes in the conformation of the molecules associated with the fragmentation of IgG and by damage during the iodination procedure.

Antibodies, Monoclonal↗
PubMed1992

Membrane IgM-mediated signaling of human B cells. Effect of increased ligand binding site valency on the affinity and concentration requirements for inducing diverse stages of activation.

The potential for ligand-initiated signal transduction through B cell membrane IgM is assessed in terms of ligand concentration, binding site valency, and binding site affinity for membrane Ig. Estimates of the physicochemical requirements for achieving G0* enhancement of class II MHC expression, G1 entry, and S phase entry in human B cells were made by comparing the stimulatory effects of three affinity-diverse anti-Cmu2 mAb when in bivalent (unconjugated) form, or as mAb-dextran conjugates with low binding site valency (oligovalent ligands) or high binding site valency (multivalent ligands). An increase in binding site number (and concomitant molecular mass) caused a profound reduction in both the minimal concentration and affinity requisites for B cell activation. The enhancing effect of increased binding site valency was most evident for the signaling of those most distal stages in B cell activation, i.e., G1 and S phase, which were difficult to induce with bivalent ligands. The results suggest that highly multimeric TI-2 Ag may be good immunogens because they are able to elicit a full activation response not only from infrequent high affinity B cells, but also from a substantial proportion of the many lower affinity Ag-specific B cells in virgin B cell populations. Interestingly, the activation of B cells by ligands with binding sites of high intrinsic affinity (Ka = 5 x 10(8) M-1) was less influenced by increases in binding site valency than was B cell activation by ligands with intermediate binding site affinity (Ka = 2 x 10(7) M-1). This suggests that the minimal epitope valency requirement for T cell-independent B cell activation by mIg cross-linking Ag may be dependent on the intrinsic affinity with which membrane Ig molecules on a given B cell interact with the redundantly expressed epitopes.

B-Lymphocytes↗
PubMedDate not supplied

An evaluation of inactivated infectious coryza vaccines containing a double-emulsion adjuvant system.

The efficacy of experimental inactivated infectious coryza vaccines produced by a commercial vaccine manufacturer was evaluated. The vaccines, containing as the adjuvant phase either a double-emulsion mineral oil system or aluminum-hydroxide gel, were administered to 6-week-old chickens as a single dose. Some vaccines were a monovalent product containing a Page serovar C Haemophilus paragallinarum strain, and others were a bivalent product containing both Page serovar A and serovar C strains. After 3 weeks, all chickens were challenged by infraorbital sinus inoculation of virulent H. paragallinarum, either Page serovar C (strain HP31) or Page serovar A (strain HP14). The monovalent serovar C double-emulsion-based vaccines gave significant protection against a serovar C challenge, with the level of protection varying from 60% to 100%. The monovalent serovar C aluminum-hydroxide-gel vaccine also gave significant protection (94%) against a serovar C challenge. The bivalent double-emulsion vaccine gave significant protection against challenge from both serovars (100% for serovar C and 83% for serovar A). Although no major adverse reactions were detected, some chickens receiving both the double-emulsion vaccines and the aluminum-hydroxide vaccine developed relatively minor granulomatous reactions at the site of injection.

Adjuvants, Immunologic↗
PubMed1992

[Electron microscopic analysis of synaptonemal complexes of male laboratory mice exposed during the period of embryogenesis in the vicinity of the Chernobyl Nuclear Power Station].

Four male mice were shown to have decreased fertility among 74 laboratory male mice exposed in the Chernobyl APP area during embryogenesis. Electron microscopic analysis of synaptonemal complexes (SC) of at zygotene-diplotene and light-optic analysis of chromosome aberrations at diakinesis-metaphase 1 demonstrated the presence of interchromosome translocations in autosomal chromosomes, and also intrachromosome translocations in two of four animals. The frequency of chromosome translocations in SC preparations was on the average 1.8 times higher than their frequency at the diakinesis-metaphase 1 stage. High percentage of cells in which associations of sex bivalent axes (XY) with the axes of autosomal bivalents were observed in the SC preparations and reduced fertility in the animals studied confirmed the Forejt's hypothesis that such associations caused the arrest of cells at pachytene and, as a consequence, disturbed the process of embryogenesis.

Accidents↗
PubMed1992

[Protection from virulent Salmonella groups B and D after the peroral immunization of chicks with a hybrid of Salmonella typhimurium and Salmonella dublin].

Chickens over 10 days old, infected orally with virulent salmonellae, were found to remain alive. Histologic investigation showed the development of mild enteritis and more pronounced, lasting for more than two weeks, inflammation of the cecum, dissemination and focal lesions in the liver (granulomas, necrosis). In experiments on the oral immunization of 3-day old chickens the bivalent hybrid of S. typhimurium vaccine strain 274 and S. dublin induced only pronounced blast transformation in lymphatic follicles of the cecum, hyperplasia of activated macrophages and formation of granulomas from these macrophages and lymphocytes. After oral challenge of the immunized chickens with virulent salmonellae of group B (S. typhimurium) and group D (S. enteritidis, S. gallinarum-pullorum) the chickens exhibited sharply pronounced protection against adhesion, colonization and invasion, and a few penetrating bacteria were rapidly destroyed by immune macrophages. Hybrid strain 274/O9 proved to be suitable for use as oral bivalent vaccine against salmonellosis in chickens.

Administration, Oral↗
PubMed1992

T cell receptor aggregation, but not dimerization, induces increased cytosolic calcium concentrations and reveals a lack of stable association between CD4 and the T cell receptor.

Exposure of T94, a CD4+ V beta 8-expressing murine Th cell clone, or immediately ex vivo CD4+ T cells to deaggregated, bivalent antibodies specific for either the TCR or CD3 failed to induce an increase in [Ca2+]i, or activation of phosphatidylinositol hydrolysis unless cross-linked with a secondary anti-Ig antibody. In contrast, we show that a combination of two mAb directed against different components of the TCR/CD3 complex (145.2C11, anti-CD3 epsilon and F23.1, anti-V beta 8) successfully induce second messenger formation, that is, without any requirement for a secondary antibody. This requirement for either a secondary antibody or two independent bivalent antibodies to activate second messenger production in T cells suggested that the signal transduction apparatus may be activated by multiple TCR/CD3 complexes being brought together on the T cell surface. This was supported by the observation that conditions inducing increased T cell [Ca2+]i through the TCR/CD3 complex also resulted in aggregation of the TCR/CD3 complex on the T cell surface. Conversely, binding of anti-TCR/CD3 antibodies to the T cell under conditions that did not induce increased [Ca2+]i also failed to induce surface TCR/CD3 redistribution. Cross-linking of the CD4 accessory molecule on T94 also resulted in increased [Ca2+]i, with kinetics similar to those observed after TCR/CD3 oligomerization. CD4 is involved in the recognition of invariant regions of MHC class II during Ag presentation and has been proposed to be associated with TCR/CD3 in the absence of Ag. Aggregation of TCR/CD3 and subsequent second messenger formation was achieved by combinations of mAb to distinct determinants within the complex due to the stable association of these determinants within the T cell membrane. We therefore assessed the functional association of CD4 with the TCR/CD3 complex by examining whether a combination of mAb directed against CD4 and CD3 or TCR induced second messenger formation. We found that anti-CD4 in combination with F23.1 or with 145.2C11 failed to induce increases in [Ca2+]i. Furthermore, mAb to CD4 failed to inhibit the increase in [Ca2+]i observed with the combination of 145.2C11 and F23.1. We therefore conclude that CD4 is not stably associated with TCR or CD3 in the absence of Ag/MHC class II composites.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2005

Cytology and fertility of viable hybrids of Nicotiana tabacum L. cv. TB-566 with N. alata Link et Otto.

A vigorous hybrid (N. tabacum cv. TB-566 tetra x N. alata) x N. alata was obtained by backcrossing a partly viable sesquidiploid hybrid N. tabacum cv. TB-566 tetra x N. alata to N. alata. The hybrid was a 35-chromosome near-amphihaploid with a pair of N. alata chromosomes in disomic condition. It was completely self- and cross-sterile and formed from 7 to 8 bivalents in pollen mother cells. By using stem pith culture, polyploidized regenerants were obtained from the 35-chromosome hybrid with somatic chromosome numbers from 65 to 70. These regenerants showed fairly regular meiosis with the number of bivalents in pollen mother cells ranging from 27.3 to 30.4. Irregularities in meiosis included a high number of univalents, aberrant tetrads, and a high frequency of micronuclei. The percentage of acetocarmine-stainable pollen ranged from 22.1 to 78.4. A 66-chromosome regenerant showed fairly regular meiosis and was self-fertile but could not be backcrossed to N. tabacum. This barrier seems to be caused by genic imbalance rather than irregularities of meiotic divisions. Hence transfer programs based on the introgression of entire linkage groups (sexual and somatic hybridization) seem to be of little use in the case of that species.

Chromosomes, Plant↗
PubMed2005

[Evidence of the unreduced diploid eggs generated from the diploid gynogenetic progeny of allotetraploid hybrids].

Following activation by UV-irradiated sperms from scatter scale common carp and without the treatment for doubling the chromosome number, the eggs generated by the diploid gynogenetic progeny (G1) with 100 chromosomes,developed into diploid gynogenetic progeny (G2) with 100 chromosomes. Both the males and females of the tetraploids with 200 chromosomes were obtained from the offsprings (G1 x AT) produced by mating the eggs of G1 with the diploid sperms from the allotetraploid hybrids. The results provided the evidence that diploid G1 is able to produce diploid eggs. In the oogonia of diploid six-month old G2, only the chromosomes in the metaphase of mitosis were observed in all slides, no bivalent chromosome being found, suggesting that the oogonia in six-month old G2 were not mature enough for meiosis I. The presence of the chromosome spreads with 100, 200 and 380 chromosomes observed in the metaphase indicated that the diploid G2 had the potential ability to generate diploid eggs with the probable mechanism of pre-meiotic endoreduplication. In contrast, the spermatocytes of G1 x AT allotetraploids had the normal chromosomal behavior with only 100 bivalents found in meiosis I. The one-year old G2 possessed the slowly developmental ovaries which stayed at the oogonium stage for a long time, in which no primary and mature oocyte was found, whereas both the females and males of one-year old G1 x AT allotetraploids had normal ovaries and testes which reached maturity and produced diploid eggs and diploid sperms, respectively. The formation of the diploid eggs generated from the diploid gynogenetic progeny makes it available to establish a diploid hybrid clonal line, and will become an important source of production of diploid eggs. In addition, the bisexual fertile G1 x AT allotetraploids enriched the types of the tetraploids.

Animals↗
PubMed2004

[Synthesis of 2-(4-dimethylaminophenyl)-5-fluoro-6-(morpholin-4-yl)-1H-benzimidazole and its spectroscopic research].

A new potential pharmaceutical compound, 2-(4-dimethylaminophenyl)-5-fluoro-6-(morpholin-4-yl)-1H-benzimidazole (4) was synthesized. The effect of the pH value of aqueous solution on the absorption spectrum of compound 4 and its interaction with beta-cyclodextrin (beta-CD) were investigated by UV-Vis spectrum, steady-state fluorescence and time-resolved spectroscopic measurements. The results indicate that compound 4 mainly exists in neutral molecular state when pH value of the aqueous phase is above 7.0. In the pH range from 7.0 to 3.8 the neutral molecular state and protonated univalent cationic form coexist. As the pH value decreases, the content of univalent cationic form increases. When 2.76 < pH < 3.8, the protonated univalent cationic form is the predominant species. With further decrease of the pH value, the univalent cation is protonated by another H+ to form a bivalent cation, and both univalent and bivalent cations coexist in the solution. The steady-state fluorescence and time-resolved spectroscopic measurements revealed that compound 4 is a sensitive molecular probe. The interaction of compound 4 and beta-CD is very strong. The guest:host ratio of inclusion complex between compound 4 and beta-CD formed in the aqueous solution (pH = 9.50) is 1:1, and the association constant was determined to be (1.02 +/- 0.04) x 10(3) mol x L(-1).

Absorption↗
PubMed2005

Changes in crossover distribution along a quadrivalent in a man carrier of a reciprocal translocation t(11;14).

A testicular biopsy from an infertile man carrying a heterozygous chromosome translocation t(11;14) was studied with synaptonemal complex analysis and immunolocalization of the protein MLH1 for crossover detection. A full blockage of spermatogenesis at the spermatocyte stage was related to the presence of the translocation quadrivalents at pachytene. Only 2% of the quadrivalents showed full synapsis. Most of the spermatocytes showed asynaptic free ends that frequently mingled with the XY pair. The average number of crossovers per cell was diminished from a mean of 52.7 in controls to a mean of 48 in the patient. The difference between the number of crossovers in the quadrivalent and the normal bivalents was highly significant. The distribution of crossovers over the segment of the quadrivalent corresponding to bivalent #14 was also very different from that of the control. It is concluded that in this translocation, the pattern of crossovers is changed, mainly due to a synaptic hindrance in the quadrivalent, and that the spermatogenesis arrest is mainly due to the quadrivalents that interact with the XY pair.

Chromosomes, Human, Pair 11↗
PubMed2005

[The comparison study on the preparation of chromosomes of the freshwater prawn Macrobrachraium nipponense (Crustacea, Decapoda)].

The Chromosomes of Macrobrachium nipponense had been prepared using the materials of testis or embryo with the chromosome low-osmosis method or cell low-osmosis method. After 5.5 h, the bivalents at meiotic diplotene were appeared. The comparison of the two methods for two different materials showed that the morpha of the chromosome of testis using the low-osmosis method was better than that of using the cell low-osmosis method. Contrarily, the low-osmosis was better than the cell low-osmosis for the morpha of the chromosome of embryo. The bivalents at meiotic diplotene were rod-shaped, and centromere position could be identified easily at that time. The diploid chromosomes numbers were 104. The chromosome formula was N=11M+26SM+4ST+11T. The technique of the chromosome preparation of Macrobrachium nipponense was preliminarily discussed as well.

Animals↗
PubMed1991

Recombinant 55-kDa tumor necrosis factor (TNF) receptor. Stoichiometry of binding to TNF alpha and TNF beta and inhibition of TNF activity.

The extracellular domain of the 55-kDa TNF receptor (rsTNFR beta) has been expressed as a secreted protein in baculovirus-infected insect cells and Chinese hamster ovary (CHO)/dhfr- cells. A chimeric fusion protein (rsTNFR beta-h gamma 3) constructed by inserting the extracellular part of the receptor in front of the hinge region of the human IgG C gamma 3 chain has been expressed in mouse myeloma cells. The recombinant receptor proteins were purified from transfected cell culture supernatants by TNF alpha- or protein G affinity chromatography and gel filtration. In a solid phase binding assay rsTNFR beta was found to bind TNF alpha with high affinity comparable with the membrane-bound full-length receptor. The affinity for TNF beta was slightly impaired. However, the bivalent rsTNFR beta-h gamma 3 fusion protein bound both ligands with a significantly higher affinity than monovalent rsTNFR beta reflecting most likely an increased avidity of the bivalent construct. A molecular mass of about 140 kDa for both rsTNFR beta.TNF alpha and rsTNFR beta.TNF beta complexes was determined in analytical ultracentrifugation studies strongly suggesting a stoichiometry of three rsTNFR beta molecules bound to one TNF alpha or TNF beta trimer. Sedimentation velocity and quasielastic light scattering measurements indicated an extended structure for rsTNFR beta and its TNF alpha and TNF beta complexes. Multiple receptor binding sites on TNF alpha trimers could also be demonstrated by a TNF alpha-induced agglutination of Latex beads coated with the rsTNFR beta-h gamma 3 fusion protein. Both rsTNFR beta and rsTNFR beta-h gamma 3 were found to inhibit binding of TNF alpha and TNF beta to native 55- and 75-kDa TNF receptors and to prevent TNF alpha and TNF beta bioactivity in a cellular cytotoxicity assay. Concentrations of rsTNFR beta-h gamma 3 equimolar to TNF alpha were sufficient to neutralize TNF activity almost completely, whereas a 10-100-fold excess of rsTNFR beta was needed for similar inhibitory effects. In view of their potent TNF antagonizing activity, recombinant soluble TNF receptor fragments might be useful as therapeutic agents in TNF-mediated disorders.

Animals↗
PubMed2006

The human papillomavirus vaccines.

Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) among sexually active couples. Its annual incidence is approximately 5.5 million. Overall, an estimated 75% of sexually active men and women have been exposed to HPV at some point in their lives. HPV-16 and -18 account for about 70% of cancers of the cervix, vagina and anus, and for about 30%-40% of cancers of the vulva, penis and orophaynx. Cancer of the cervix uteri is the second most cancer among women worldwide. Cancer of the penis is a rare cancer, accounting for less than 0.5% of cancers in men. Spontaneous clearance of HPV infection is accompanied by humoral and cellular immune response against virus-specific antigens. Two vaccines, prophylactic and therapeutic ones, are considered. Prophylactic vaccines use L1 and L2 capsid proteins to induce production of conformationally-specific antibodies. They block HPV infection. Lone L1 and L2 proteins self-assemble into a capsid that is identical to the complete virion. In this way, an antibody-mediated response is induced before the body actually comes into contact with the live virion. Therapeutic vaccines are being developed to protect HPV-positive persons against tumor development. For these vaccines, researchers are targeting the activity of the E6 and E7 oncoproteines.On June 8, 2006, the U.S. Food and Drug Administration (FDA) approved an HPV vaccine for clinical use. The HPV vaccine that has been approved is the quadrivalent vaccine that consists of recombinant viral-like particles (VLPs) of HPV 6, 11, 16, 18 mixed with an aluminum-containing adjuvant. It is manufactured by Merck & Co., Inc. and sold under the name of Gardasil?. The new vaccine is approved for use in females 9-26 years of age. The primary target population for vaccination should be females aged 11-12 years. However, vaccination can be given to girls as young as 9 years of age. Vaccination can receive women aged 13-26 years who have been sexually active. There are still no data on the vaccine efficacy in women older than 26, and currently no data to demonstrate the efficacy of vaccination in males; male subjects should not be vaccinated until such data become available. The vaccine is to be administered intramuscularly either into the deltoid muscle of the arm or the high anteriolateral area of the leg. Each patient receives three 0.5 mL doses given according to the following schedule: first dose is given at the elected date, second dose two months after the first dose, and third dose six months after the first dose. According to statements from Merck, the list price of the vaccine is 120 USD per dose. GlaxoSmithKline is now conducting a phase III trial of a bivalent (HPV 16, 18) vaccine, and it is going to be presented under the name of Cervarix. Similar results to those obtained with the quadrivalent HPV vaccine have been reported with the bivalent vaccine. It is expected to be released in June next year. Evaluation of the HPV vaccine efficiency in preventing dysplasia and cancer has been recommended as a globally accepted endpoint for population based studies.

Adolescent↗
PubMed1990

[Latrotoxin channels. Permeability for divalent cations].

The dependence of Ca2+ transport in synaptosomes along the channels formed by alpha-latrotoxin on [Ca2+]in and the feasibility of transport along these channels of other bivalent cations were studied. It was found that the concentration dependence of Ca2+ influx is nonlinear and is described by the Michaelis-Menten kinetics (Km = 1.07 +/- 0.19 mM). Mg2+, Ba2+, Sr2+, Mn2+ and Co2+ competitively inhibited the Ca2+ influx via latrotoxin channels. Studies with the use of the fluorescent Ca2+ probes, Quin-2 and Fura-2, revealed that these cations can also penetrate inside synaptosomes via latrotoxin channels. The bivalent cation influx via latrotoxin channels caused a decrease of the membrane potential of synaptosomes. The similarity of properties of latrotoxin and endogenous Ca2+ channels is discussed.

Aminoquinolines↗
PubMedDate not supplied

[Study of properties of the actomyosin complex using photo-cleavage of proteins by vanadates].

Study of myosin and actomyosin preparations photocleavage conditioned by polyvanadates confirmed the data on V1 and V2 centre cleavage independence of bivalent cations. Actin does not change sufficiently the reaction in V1 centre and considerably slows down the reaction in V2 centre. These actin properties do not depend on bivalent cation (Mg2+), nor on preliminary incubation with vanadate. It was also discovered that preincubation with vanadate in EDTA medium results in myosin molecule cleavage with producing light (M 18 kD) fragments in both cases: with myosin and actomyosin preparations. Besides vanadate-dependent photocleavage of myosin peptide bonds, there were discovered photocrosslinkings of polypeptide chains in myosin and actomyosin preparations also depending on the presence of vanadate. In actomyosin preparations they probably lead to crosslinking of heavy minor proteins to heavy myosin chains.

Actomyosin↗
PubMed1991

Enhanced modulation of antibodies coating guinea pig leukemic cells in vitro and in vivo. The role of Fc gamma R expressing cells.

We have investigated the antigenic modulation induced by a number of antibody fragments and derivatives directed against the idiotype of the surface Ig of the L2C guinea pig B lymphoblastic leukemia, and studied the effects upon such modulation of the simultaneous presence of cells expressing Fc gamma receptors (FcR). In vitro studies confirmed previous work showing that antibody bivalency is required to induce modulation in vitro in simple systems. However, in the presence of isolated Kupffer cells, Fc-containing univalent antibodies were found to induce significant antigenic modulation, and the modulation induced by intact IgG was also found to be more rapid and extensive. Fragments that did not contain Fc regions behaved similarly in the presence or absence of Kupffer cells. Further investigations demonstrated that all three classes of human FcR can mediate modulation enhancement, and suggest that the mechanism involves indirect cross-linking of cell surface Ag via the antibody and effector cell FcR. In vivo studies showed that univalent antibody derivatives containing Fc regions did induce antigenic modulation, but that this was significantly reduced in comparison with bivalent antibodies, confirming their potential advantage for immunotherapy.

Animals↗