Somatic hypermutation of T cell receptor α chain contributes to selection in nurse shark thymus.

Science.gov (United States)

Ott, Jeannine A; Castro, Caitlin D; Deiss, Thaddeus C; Ohta, Yuko; Flajnik, Martin F; Criscitiello, Michael F

2018-04-17

Since the discovery of the T cell receptor (TcR), immunologists have assigned somatic hypermutation (SHM) as a mechanism employed solely by B cells to diversify their antigen receptors. Remarkably, we found SHM acting in the thymus on α chain locus of shark TcR. SHM in developing shark T cells likely is catalyzed by activation-induced cytidine deaminase (AID) and results in both point and tandem mutations that accumulate non-conservative amino acid replacements within complementarity-determining regions (CDRs). Mutation frequency at TcRα was as high as that seen at B cell receptor loci (BcR) in sharks and mammals, and the mechanism of SHM shares unique characteristics first detected at shark BcR loci. Additionally, fluorescence in situ hybridization showed the strongest AID expression in thymic corticomedullary junction and medulla. We suggest that TcRα utilizes SHM to broaden diversification of the primary αβ T cell repertoire in sharks, the first reported use in vertebrates. © 2018, Ott et al.

AID to overcome the limitations of genomic information by introducing somatic DNA alterations.

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Honjo, Tasuku; Muramatsu, Masamichi; Nagaoka, Hitoshi; Kinoshita, Kazuo; Shinkura, Reiko

2006-05-01

The immune system has adopted somatic DNA alterations to overcome the limitations of the genomic information. Activation induced cytidine deaminase (AID) is an essential enzyme to regulate class switch recombination (CSR), somatic hypermutation (SHM) and gene conversion (GC) of the immunoglobulin gene. AID is known to be required for DNA cleavage of S regions in CSR and V regions in SHM. However, its molecular mechanism is a focus of extensive debate. RNA editing hypothesis postulates that AID edits yet unknown mRNA, to generate specific endonucleases for CSR and SHM. By contrast, DNA deamination hypothesis assumes that AID deaminates cytosine in DNA, followed by DNA cleavage by base excision repair enzymes. We summarize the basic knowledge for molecular mechanisms for CSR and SHM and then discuss the importance of AID not only in the immune regulation but also in the genome instability.

Analysis of immunoglobulin transcripts and hypermutation following SHIV(AD8) infection and protein-plus-adjuvant immunization.

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Francica, Joseph R; Sheng, Zizhang; Zhang, Zhenhai; Nishimura, Yoshiaki; Shingai, Masashi; Ramesh, Akshaya; Keele, Brandon F; Schmidt, Stephen D; Flynn, Barbara J; Darko, Sam; Lynch, Rebecca M; Yamamoto, Takuya; Matus-Nicodemos, Rodrigo; Wolinsky, David; Nason, Martha; Valiante, Nicholas M; Malyala, Padma; De Gregorio, Ennio; Barnett, Susan W; Singh, Manmohan; O'Hagan, Derek T; Koup, Richard A; Mascola, John R; Martin, Malcolm A; Kepler, Thomas B; Douek, Daniel C; Shapiro, Lawrence; Seder, Robert A

2015-04-10

Developing predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for the development of an HIV vaccine. Here we use two nonhuman primate models to compare the roles of antigen persistence, diversity and innate immunity. We perform longitudinal analyses of HIV Env-specific B-cell receptor responses to SHIV(AD8) infection and Env protein vaccination with eight different adjuvants. A subset of the SHIV(AD8)-infected animals with higher viral loads and greater Env diversity show increased neutralization associated with increasing somatic hypermutation (SHM) levels over time. The use of adjuvants results in increased ELISA titres but does not affect the mean SHM levels or CDR H3 lengths. Our study shows how the ontogeny of Env-specific B cells can be tracked, and provides insights into the requirements for developing neutralizing antibodies that should facilitate translation to human vaccine studies.

Somatic hypermutation of the new antigen receptor gene (NAR) in the nurse shark does not generate the repertoire: possible role in antigen-driven reactions in the absence of germinal centers.

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Diaz, M; Greenberg, A S; Flajnik, M F

1998-11-24

The new antigen receptor (NAR) gene in the nurse shark diversifies extensively by somatic hypermutation. It is not known, however, whether NAR somatic hypermutation generates the primary repertoire (like in the sheep) or rather is used in antigen-driven immune responses. To address this issue, the sequences of NAR transmembrane (Tm) and secretory (Sec) forms, presumed to represent the primary and secondary repertoires, respectively, were examined from the peripheral blood lymphocytes of three adult nurse sharks. More than 40% of the Sec clones but fewer than 11% of Tm clones contained five mutations or more. Furthermore, more than 75% of the Tm clones had few or no mutations. Mutations in the Sec clones occurred mostly in the complementarity-determining regions (CDR) with a significant bias toward replacement substitutions in CDR1; in Tm clones there was no significant bias toward replacements and only a low level of targeting to the CDRs. Unlike the Tm clones where the replacement mutational pattern was similar to that seen for synonymous changes, Sec replacements displayed a distinct pattern of mutations. The types of mutations in NAR were similar to those found in mouse Ig genes rather than to the unusual pattern reported for shark and Xenopus Ig. Finally, an oligoclonal family of Sec clones revealed a striking trend toward acquisition of glutamic/aspartic acid, suggesting some degree of selection. These data strongly suggest that hypermutation of NAR does not generate the repertoire, but instead is involved in antigen-driven immune responses.

Immunoglobulin class-switch recombination deficiencies.

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Durandy, Anne; Kracker, Sven

2012-07-30

Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches.

What do somatic hypermutation and class switch recombination teach us about chronic lymphocytic leukaemia pathogenesis?

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Oppezzo, P; Dighiero, G

2005-01-01

B-CLL cells express CD5 and IgM/IgD and thus have a mantle zone-like phenotype of naive cells, which, in normal conditions express unmutated Ig genes. However, recent studies have shown that 50%-70% of CLL harbour somatic mutations of VH genes, as if they had matured in a lymphoid follicle. Interestingly, the presence or absence of somatic hypermutation (SHM) process is associated with the use of particular VH genes. Particular alleles of the VH1-69 gene and the VH4-39 gene are preferentially expressed in an unmutated form, while VH4-34 or the majority of VH3 family genes frequently contain somatic mutations. The fact that some genes like VH1-69 and VH3-07 recombine this VH segment to particular JH segments and the restricted use of CDR3 sequences by CLLs expressing the VH4-39 gene suggest that the observed differences in BCR structure in B-CLL could result from selection by distinct antigenic epitopes. It is currently unclear whether this putative antigen-driven process could occur prior to leukaemic transformation and/or that the precursors were transformed into leukaemic cells at distinct maturational stages. The mutational profile of Ig genes has been shown to be associated with disease prognosis. These results could favour the idea that CLL could correspond to two different diseases that look alike in morphologic and phenotypic terms. In CLL with mutated Ig genes, the proliferating B cell may have transited through germinal centres, the physiologic site of hypermutation, whereas in CLL with unmutated Ig genes the malignant B cell may derive from a pre-germinal centre naïve B cell. Despite these clinical and molecular differences, recent studies on gene expression profiling of B-CLL cells showed that CLL is characterized by a common gene expression signature that is irrespective of Ig mutational status and differs from other lymphoid cancers and normal lymphoid subpopulations, suggesting that CLL cases share a common mechanism of transformation and/or cell of

Generation of Immunoglobulin diversity in human gut-associated lymphoid tissue.

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Spencer, Jo; Barone, Francesca; Dunn-Walters, Deborah

2009-06-01

The organised gut associated lymphoid tissue (GALT) exists adjacent to an extensive and diverse luminal flora. The follicle associated epithelium and associated dendritic cells and lymphocytes form a tightly fortified gateway between the flora and the host that permits connectivity between them and chronic activation of the lymphoid compartment. As a consequence, plasma cell precursors are generated continuously, and in abundance, in GALT by clonal proliferation. Clonal proliferation alone on this scale would reduce the spectrum of B cell specificity. To compensate, GALT also houses molecular machinery that diversifies the receptor repertoire by somatic hypermutation, class switch recombination and receptor revision. These three processes of enhancing the diversity of mature B cells ensure that although clonally related plasma cells may secrete immunoglobulin side by side in the mucosa they rarely have identical antigen binding sites.

Hypermutation In Pancreatic Cancer.

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Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

2017-01-01

Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Different Somatic Hypermutation Levels among Antibody Subclasses Disclosed by a New Next-Generation Sequencing-Based Antibody Repertoire Analysis

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Kazutaka Kitaura

2017-05-01

Full Text Available A diverse antibody repertoire is primarily generated by the rearrangement of V, D, and J genes and subsequent somatic hypermutation (SHM. Class-switch recombination (CSR produces various isotypes and subclasses with different functional properties. Although antibody isotypes and subclasses are considered to be produced by both direct and sequential CSR, it is still not fully understood how SHMs accumulate during the process in which antibody subclasses are generated. Here, we developed a new next-generation sequencing (NGS-based antibody repertoire analysis capable of identifying all antibody isotype and subclass genes and used it to examine the peripheral blood mononuclear cells of 12 healthy individuals. Using a total of 5,480,040 sequences, we compared percentage frequency of variable (V, junctional (J sequence, and a combination of V and J, diversity, length, and amino acid compositions of CDR3, SHM, and shared clones in the IgM, IgD, IgG3, IgG1, IgG2, IgG4, IgA1, IgE, and IgA2 genes. The usage and diversity were similar among the immunoglobulin (Ig subclasses. Clonally related sequences sharing identical V, D, J, and CDR3 amino acid sequences were frequently found within multiple Ig subclasses, especially between IgG1 and IgG2 or IgA1 and IgA2. SHM occurred most frequently in IgG4, while IgG3 genes were the least mutated among all IgG subclasses. The shared clones had almost the same SHM levels among Ig subclasses, while subclass-specific clones had different levels of SHM dependent on the genomic location. Given the sequential CSR, these results suggest that CSR occurs sequentially over multiple subclasses in the order corresponding to the genomic location of IGHCs, but CSR is likely to occur more quickly than SHMs accumulate within Ig genes under physiological conditions. NGS-based antibody repertoire analysis should provide critical information on how various antibodies are generated in the immune system.

Mutational pattern of the nurse shark antigen receptor gene (NAR) is similar to that of mammalian Ig genes and to spontaneous mutations in evolution: the translesion synthesis model of somatic hypermutation.

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Diaz, M; Velez, J; Singh, M; Cerny, J; Flajnik, M F

1999-05-01

The pattern of somatic mutations of shark and frog Ig is distinct from somatic hypermutation of Ig in mammals in that there is a bias to mutate GC base pairs and a low frequency of mutations. Previous analysis of the new antigen receptor gene in nurse sharks (NAR), however, revealed no bias to mutate GC base pairs and the frequency of mutation was comparable to that of mammalian IgG. Here, we analyzed 1023 mutations in NAR and found no targeting of the mechanism to any particular nucleotide but did obtain strong evidence for a transition bias and for strand polarity. As seen for all species studied to date, the serine codon AGC/T in NAR was a mutational hotspot. The NAR mutational pattern is most similar to that of mammalian IgG and furthermore both are strikingly akin to mutations acquired during the neutral evolution of nuclear pseudogenes, suggesting that a similar mechanism is at work for both processes. In yeast, most spontaneous mutations are introduced by the translesion synthesis DNA polymerase zeta (REV3) and in various DNA repair-deficient backgrounds transitions were more often REV3-dependent than were transversions. Therefore, we propose a model of somatic hypermutation where DNA polymerase zeta is recruited to the Ig locus. An excess of DNA glycosylases in germinal center reactions may further enhance the mutation frequency by a REV3-dependent mutagenic process known as imbalanced base excision repair.

Stage-specific hypermutability of the regA locus of Volvox, a gene regulating the germ-soma dichotomy

International Nuclear Information System (INIS)

Kirk, D.L.; Baran, G.J.; Harper, J.F.; Huskey, R.J.; Huson, K.S.; Zagris, N.

1987-01-01

Mutation at the regA locus confers on somatic cells of Volvox (which otherwise undergo programmed death) ability to redifferentiate as reproductive cells. Stable mutations at the regA locus, but not at other loci, were induced at high frequency when embryos at one particular stage were exposed to either UV irradiation, novobiocin, nalidixic acid, bleomycin, 4-hydroxyaminoquinoline-1-oxide, 5-bromodeoxyuridine, or 5-fluorouracil. All treatments led to some mutations that were not expressed until the second generation after treatment. The sensitive period was after somatic and reproductive cells of the next generation had been set apart, but before they had undergone cytodifferentiation. Hypermutability occurs in presumptive reproductive cells (in which regA is normally not expressed) somewhat before regA normally acts in somatic cells. We postulate that hypermutability of regA in the reproductive cells at this time reflects a change of state that the locus undergoes as it is inactivated

Assessing somatic hypermutation in Ramos B cells after overexpression or knockdown of specific genes.

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Upton, Dana C; Unniraman, Shyam

2011-11-01

B cells start their life with low affinity antibodies generated by V(D)J recombination. However, upon detecting a pathogen, the variable (V) region of an immunoglobulin (Ig) gene is mutated approximately 100,000-fold more than the rest of the genome through somatic hypermutation (SHM), resulting in high affinity antibodies. In addition, class switch recombination (CSR) produces antibodies with different effector functions depending on the kind of immune response that is needed for a particular pathogen. Both CSR and SHM are initiated by activation-induced cytidine deaminase (AID), which deaminates cytosine residues in DNA to produce uracils. These uracils are processed by error-prone forms of repair pathways, eventually leading to mutations and recombination. Our current understanding of the molecular details of SHM and CSR come from a combination of studies in mice, primary cells, cell lines, and cell-free experiments. Mouse models remain the gold standard with genetic knockouts showing critical roles for many repair factors (e.g. Ung, Msh2, Msh6, Exo1, and polymerase η). However, not all genes are amenable for knockout studies. For example, knockouts of several double-strand break repair proteins are embryonically lethal or impair B-cell development. Moreover, sometimes the specific function of a protein in SHM or CSR may be masked by more global defects caused by the knockout. In addition, since experiments in mice can be lengthy, altering expression of individual genes in cell lines has become an increasingly popular first step to identifying and characterizing candidate genes. Ramos - a Burkitt lymphoma cell line that constitutively undergoes SHM - has been a popular cell-line model to study SHM. One advantage of Ramos cells is that they have a built-in convenient semi-quantitative measure of SHM. Wild type cells express IgM and, as they pick up mutations, some of the mutations knock out IgM expression. Therefore, assaying IgM loss by fluorescence

Mutation Pattern of Paired Immunoglobulin Heavy and Light Variable Domains in Chronic Lymphocytic Leukemia B Cells

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Ghiotto, Fabio; Marcatili, Paolo; Tenca, Claudya; Calevo, Maria Grazia; Yan, Xiao-Jie; Albesiano, Emilia; Bagnara, Davide; Colombo, Monica; Cutrona, Giovanna; Chu, Charles C; Morabito, Fortunato; Bruno, Silvia; Ferrarini, Manlio; Tramontano, Anna; Fais, Franco; Chiorazzi, Nicholas

2011-01-01

B-cell chronic lymphocytic leukemia (CLL) patients display leukemic clones bearing either germline or somatically mutated immunoglobulin heavy variable (IGHV ) genes. Most information on CLL immunoglobulins (Igs), such as the definition of stereotyped B-cell receptors (BCRs), was derived from germline unmutated Igs. In particular, detailed studies on the distribution and nature of mutations in paired heavy- and light-chain domains of CLL clones bearing mutated Igs are lacking. To address the somatic hyper-mutation dynamics of CLL Igs, we analyzed the mutation pattern of paired IGHV–diversity-joining (IGHV-D-J ) and immunoglobulin kappa/lambda variable-joining (IGK/LV-J ) rearrangements of 193 leukemic clones that displayed ≥2% mutations in at least one of the two immunoglobulin variable (IGV ) genes (IGHV and/or IGK/LV ). The relationship between the mutation frequency in IGHV and IGK/LV complementarity determining regions (CDRs) and framework regions (FRs) was evaluated by correlation analysis. Replacement (R) mutation frequency within IGK/LV chain CDRs correlated significantly with mutation frequency of paired IGHV CDRs in λ but not κ isotype CLL clones. CDRs of IGKV-J rearrangements displayed a lower percentage of R mutations than IGHVs. The frequency/pattern of mutations in kappa CLL Igs differed also from that in κ-expressing normal B cells described in the literature. Instead, the mutation frequency within the FRs of IGHV and either IGKV or IGLV was correlated. Notably, the amount of diversity introduced by replaced amino acids was comparable between IGHVs and IGKVs. The data indicate a different mutation pattern between κ and λ isotype CLL clones and suggest an antigenic selection that, in κ samples, operates against CDR variation. PMID:21785810

Mutation Pattern of Paired Immunoglobulin Heavy and Light Variable Domains in Chronic Lymphocytic Leukemia B Cells

KAUST Repository

Ghiotto, Fabio; Marcatili, Paolo

2011-01-01

B-cell chronic lymphocytic leukemia (CLL) patients display leukemic clones bearing either germline or somatically mutated immunoglobulin heavy variable (IGHV ) genes. Most information on CLL immunoglobulins (Igs), such as the definition of stereotyped B-cell receptors (BCRs), was derived from germline unmutated Igs. In particular, detailed studies on the distribution and nature of mutations in paired heavy- and light-chain domains of CLL clones bearing mutated Igs are lacking. To address the somatic hyper-mutation dynamics of CLL Igs, we analyzed the mutation pattern of paired IGHV-diversity-joining (IGHV-D-J ) and immunoglobulin kappa/lambda variable-joining (IGK/LV-J ) rearrangements of 193 leukemic clones that displayed ≥ 2% mutations in at least one of the two immunoglobulin variable (IGV ) genes (IGHV and/or IGK/LV ). The relationship between the mutation frequency in IGHV and IGK/LV complementarity determining regions (CDRs) and framework regions (FRs) was evaluated by correlation analysis. Replacement (R) mutation frequency within IGK/LV chain CDRs correlated significantly with mutation frequency of paired IGHV CDRs in λ but not κ isotype CLL clones. CDRs of IGKV-J rearrangements displayed a lower percentage of R mutations than IGHVs. The frequency/pattern of mutations in kappa CLL Igs differed also from that in κ-expressing normal B cells described in the literature. Instead, the mutation frequency within the FRs of IGHV and either IGKV or IGLV was correlated. Notably, the amount of diversity introduced by replaced amino acids was comparable between IGHVs and IGKVs. The data indicate a different mutation pattern between κ and λ isotype CLL clones and suggest an antigenic selection that, in κ samples, operates against CDR variation.

Evolutionary immunology. A boost to immunity from nurse sharks.

Science.gov (United States)

Parham, P

1995-07-01

A study of the nurse shark has revealed a type of rearranging gene that has yet to be seen in mammals; it encodes a secreted 'new antigen receptor' which, unlike shark immunoglobulin, revels in somatic hypermutation.

Modulation of Pleurodeles waltl DNA polymerase mu expression by extreme conditions encountered during spaceflight.

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Véronique Schenten

Full Text Available DNA polymerase µ is involved in DNA repair, V(DJ recombination and likely somatic hypermutation of immunoglobulin genes. Our previous studies demonstrated that spaceflight conditions affect immunoglobulin gene expression and somatic hypermutation frequency. Consequently, we questioned whether Polμ expression could also be affected. To address this question, we characterized Polμ of the Iberian ribbed newt Pleurodeles waltl and exposed embryos of that species to spaceflight conditions or to environmental modifications corresponding to those encountered in the International Space Station. We noted a robust expression of Polμ mRNA during early ontogenesis and in the testis, suggesting that Polμ is involved in genomic stability. Full-length Polμ transcripts are 8-9 times more abundant in P. waltl than in humans and mice, thereby providing an explanation for the somatic hypermutation predilection of G and C bases in amphibians. Polμ transcription decreases after 10 days of development in space and radiation seem primarily involved in this down-regulation. However, space radiation, alone or in combination with a perturbation of the circadian rhythm, did not affect Polμ protein levels and did not induce protein oxidation, showing the limited impact of radiation encountered during a 10-day stay in the International Space Station.

Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig Loci in activated B cells

NARCIS (Netherlands)

Staszewski, Ori; Baker, Richard E.; Ucher, Anna J.; Martier, Raygene; Stavnezer, Janet; Guikema, Jeroen E. J.

2011-01-01

After immunization or infection, activation-induced cytidine deaminase (AID) initiates diversification of immunoglobulin (Ig) genes in B cells, introducing mutations within the antigen-binding V regions (somatic hypermutation, SHM) and double-strand DNA breaks (DSBs) into switch (S) regions, leading

Preferrential rearrangement in normal rabbits of the 3' VHa allotype gene that is deleted in Alicia mutants; somatic hypermutation/conversion may play a major role in generating the heterogeneity of rabbit heavy chain variable region sequences.

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Allegrucci, M; Young-Cooper, G O; Alexander, C B; Newman, B A; Mage, R G

1991-02-01

The rabbit is unique in having well-defined allotypes in the variable region of the heavy chain. Products of the VHa locus, (with alleles a1, a2, and a3), account for the majority of the serum immunoglobulins. A small percentage of the serum immunoglobulins are a-negative. In 1986, Kelus and Weiss described a mutation that depressed the expression of the Ig VH a2 genes in an a1/a2 rabbit. From this animal the Alicia rabbit strain was developed and the mutation was termed ali. We previously showed, using Southern analysis and the transverse alternating field electrophoresis technique, that the difference between the ali rabbit and normal is a relatively small deletion including some of the most 3' VH genes. The most JH proximal 3' VH1 genes in DNA from normal rabbits of a1, a2 and a3 haplotypes encode a1, a2 and a3 molecules respectively, and it has been suggested that these genes are responsible for allelic inheritance of VHa allotypes. The present study suggests that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression in rabbits because VH gene(s) in this region are the target(s) of preferential VDJ rearrangements. This raises the possibility that mechanisms such as somatic gene conversion and hypermutation are at work to generate the antibody repertoire in this species. Our data support the view that the 3' VH1 gene may be the preferred target for rearrangement in normal rabbits, and for the normal chromosome in heterozygous ali animals. However, homozygous ali rabbits with a deletion that removed the a2-encoding VH1 on both chromosomes do survive, rearrange other VH genes and produce normal levels of immunoglobulins as well as a significant percentage of B cells which bear the a2 allotype. This challenges the view that one VH gene, VH1, is solely responsible for the inheritance pattern of VHa allotypes.

Clonal relationships between thyroid-stimulating hormone receptor-stimulating antibodies illustrate the effect of hypermutation on antibody function

DEFF Research Database (Denmark)

Padoa, Carolyn J; Larsen, Sanne L; Hampe, Christiane S

2009-01-01

relationship and derivation from a single precursor B-cell clone. The IGHV-region genes of the two mAbs underwent high degrees of somatic hypermutation by sharing numerous mutations before diverging, while the IGLV genes evolved separately. Interestingly, the mutations were present in both the complementarity......, in experimentally immunized mice, multiple pathogenic antibodies to TSHR can arise from a single clone by a series of somatic mutations in the V-region genes and may give an insight into how such antibodies develop spontaneously in autoimmune Graves' disease....

Expression of activation-induced cytidine deaminase is confined to B-cell non-Hodgkin's lymphomas of germinal-center phenotype

NARCIS (Netherlands)

Smit, Laura A.; Bende, Richard J.; Aten, Jan; Guikema, Jeroen E. J.; Aarts, Wilhelmina M.; van Noesel, Carel J. M.

2003-01-01

Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation and class switch recombination of the immunoglobulin (IG) genes in B cells. It has recently been proposed that AID, as the newly identified DNA mutator in man, may be instrumental in initiation and progression of

Characterizing immunoglobulin repertoire from whole blood by a personal genome sequencer.

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Fan Gao

Full Text Available In human immune system, V(DJ recombination produces an enormously large repertoire of immunoglobulins (Ig so that they can tackle different antigens from bacteria, viruses and tumor cells. Several studies have demonstrated the utility of next-generation sequencers such as Roche 454 and Illumina Genome Analyzer to characterize the repertoire of immunoglobulins. However, these techniques typically require separation of B cell population from whole blood and require a few weeks for running the sequencers, so it may not be practical to implement them in clinical settings. Recently, the Ion Torrent personal genome sequencer has emerged as a tabletop personal genome sequencer that can be operated in a time-efficient and cost-effective manner. In this study, we explored the technical feasibility to use multiplex PCR for amplifying V(DJ recombination for IgH, directly from whole blood, then sequence the amplicons by the Ion Torrent sequencer. The whole process including data generation and analysis can be completed in one day. We tested the method in a pilot study on patients with benign, atypical and malignant meningiomas. Despite the noisy data, we were able to compare the samples by their usage frequencies of the V segment, as well as their somatic hypermutation rates. In summary, our study suggested that it is technically feasible to perform clinical monitoring of V(DJ recombination within a day by personal genome sequencers.

DNA polymerase η mutational signatures are found in a variety of different types of cancer.

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Rogozin, Igor B; Goncearenco, Alexander; Lada, Artem G; De, Subhajyoti; Yurchenko, Vyacheslav; Nudelman, German; Panchenko, Anna R; Cooper, David N; Pavlov, Youri I

2018-01-01

DNA polymerase (pol) η is a specialized error-prone polymerase with at least two quite different and contrasting cellular roles: to mitigate the genetic consequences of solar UV irradiation, and promote somatic hypermutation in the variable regions of immunoglobulin genes. Misregulation and mistargeting of pol η can compromise genome integrity. We explored whether the mutational signature of pol η could be found in datasets of human somatic mutations derived from normal and cancer cells. A substantial excess of single and tandem somatic mutations within known pol η mutable motifs was noted in skin cancer as well as in many other types of human cancer, suggesting that somatic mutations in A:T bases generated by DNA polymerase η are a common feature of tumorigenesis. Another peculiarity of pol ηmutational signatures, mutations in YCG motifs, led us to speculate that error-prone DNA synthesis opposite methylated CpG dinucleotides by misregulated pol η in tumors might constitute an additional mechanism of cytosine demethylation in this hypermutable dinucleotide.

Immunoglobulin gene usage in the human anti-pathogen response.

Science.gov (United States)

Newkirk, M M; Rioux, J D

1995-09-01

The human antibody response to foreign pathogens is generated to a relatively small number of target surface proteins and carbohydrates that nonetheless have an extensive array of epitopes. The study of human monoclonal antibodies to different pathogens shows that there are a diversity of mechanisms used to generate a sufficient repertoire of antibodies to combat the invading pathogens. Although many different immunoglobulin gene elements are used to construct the anti-pathogen response, some elements are used more often than would be expected if all elements were used randomly. For example, the immune response to Haemophilus influenzae polysaccharide appears to be quite narrow, being restricted primarily to a specific heavy-chain gene, 3-15, and a lambda light-chain family II member, 4A. In contrast, for the immune response to cytomegalovirus proteins, a wider group of gene elements is needed. It is also surprising that despite an investigator bias for IgG- rather than IgM-secreting immortal B cells (because of their high affinity and neutralizing abilities), 26% of light chains and 13% of heavy chains showed a very low level of somatic mutation, equivalent to an IgM molecule that has not undergone affinity maturation. Although some highly mutated IgG molecules are present in the anti-pathogen response, most of the monoclonal antibodies specific for viruses or bacteria have a level of somatic hypermutation similar to that of the adult IgM repertoire. A number of studies have shown that there are similarities in the antibody responses to pathogens and to self (autoantibodies).(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma

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Xiang Chen

2014-04-01

Full Text Available Pediatric osteosarcoma is characterized by multiple somatic chromosomal lesions, including structural variations (SVs and copy number alterations (CNAs. To define the landscape of somatic mutations in pediatric osteosarcoma, we performed whole-genome sequencing of DNA from 20 osteosarcoma tumor samples and matched normal tissue in a discovery cohort, as well as 14 samples in a validation cohort. Single-nucleotide variations (SNVs exhibited a pattern of localized hypermutation called kataegis in 50% of the tumors. We identified p53 pathway lesions in all tumors in the discovery cohort, nine of which were translocations in the first intron of the TP53 gene. Beyond TP53, the RB1, ATRX, and DLG2 genes showed recurrent somatic alterations in 29%–53% of the tumors. These data highlight the power of whole-genome sequencing for identifying recurrent somatic alterations in cancer genomes that may be missed using other methods.

Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination

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Nicolas, Laura; Cols, Montserrat; Choi, Jee Eun; Chaudhuri, Jayanta; Vuong, Bao

2018-01-01

Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig locus, DNA repair pathways are diverted from their canonical role in maintaining genomic integrity to permit AID-directed mutation and deletion of gene coding segments. Recently identified proteins, genes, and regulatory networks have provided new insights into the temporally and spatially coordinated molecular interactions that control the formation and repair of DSBs within the Ig locus. Unravelling the genetic program that allows B cells to selectively alter the Ig coding regions while protecting non-Ig genes from DNA damage advances our understanding of the molecular processes that maintain genomic integrity as well as humoral immunity. PMID:29744038

Comparison of identical and functional Igh alleles reveals a nonessential role for Eμ in somatic hypermutation and class-switch recombination.

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Li, Fubin; Yan, Yi; Pieretti, Joyce; Feldman, Danielle A; Eckhardt, Laurel A

2010-11-15

Somatic hypermutation (SHM), coupled with Ag selection, provides a mechanism for generating Abs with high affinity for invading pathogens. Class-switch recombination (CSR) ensures that these Abs attain pathogen-appropriate effector functions. Although the enzyme critical to both processes, activation-induced cytidine deaminase, has been identified, it remains unclear which cis-elements within the Ig loci are responsible for recruiting activation-induced cytidine deaminase and promoting its activity. Studies showed that Ig gene-transcription levels are positively correlated with the frequency of SHM and CSR, making the intronic, transcriptional enhancer Eμ a likely contributor to both processes. Tests of this hypothesis yielded mixed results arising, in part, from the difficulty in studying B cell function in mice devoid of Eμ. In Eμ's absence, V(H) gene assembly is dramatically impaired, arresting B cell development. The current study circumvented this problem by modifying the murine Igh locus through simultaneous insertion of a fully assembled V(H) gene and deletion of Eμ. The behavior of this allele was compared with that of a matched allele carrying the same V(H) gene but with Eμ intact. Although IgH transcription was as great or greater on the Eμ-deficient allele, CSR and SHM were consistently, but modestly, reduced relative to the allele in which Eμ remained intact. We conclude that Eμ contributes to, but is not essential for, these complex processes and that its contribution is not as a transcriptional enhancer but, rather, is at the level of recruitment and/or activation of the SHM/CSR machinery.

Expression of members of immunoglobulin gene family in somatic cell hybrids between human B and T cells

International Nuclear Information System (INIS)

Kozbor, D.; Burioni, R.; Ar-Rushdi, A.; Zmijewski, C.; Croce, C.M.

1987-01-01

Somatic cell hybrids were obtained between human T and B cells and tested for the expression of differentiated traits of both cell lineages. The T-cell parent SUP-T1 is CD3 - , CD4 + , CD1 + , CD8 + , is weakly positive for HLA class I determinants, and has an inversion of chromosome 14 due to a site-specific recombination event between an immunoglobulin heavy-chain variable gene and the joining segment of the T-cell receptor α chain. The B-cell parent, the 6-thioguanine- and ouabain-resistant mutant GM1500, is a lymphoblastoid cell line that secretes IgG2, K chains, and expresses B1, B532, and HLA class I and II antigens. All hybrids expressed characteristics of B cells (Ig + , B1 + , B532 + , EBNA + , HLA antigens), whereas only CD4 among the T-cell markers was expressed. The level of T-cell receptor β-chain transcript was greatly reduced and no RNA of the chimeric T-cell receptor α-chain joining segment-immunoglobulin heavy-chain variable region was detected. Southern blot analysis indicated that absence of T-cell differentiation markers in the hybrids was not due to chromosomal loss. Rather, some B-cell-specific factor present in the hybrids may account for the suppression

Activation-induced cytidine deaminase (AID)-dependent somatic hypermutation requires a splice isoform of the serine/arginine-rich (SR) protein SRSF1.

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Kanehiro, Yuichi; Todo, Kagefumi; Negishi, Misaki; Fukuoka, Junji; Gan, Wenjian; Hikasa, Takuya; Kaga, Yoshiaki; Takemoto, Masayuki; Magari, Masaki; Li, Xialu; Manley, James L; Ohmori, Hitoshi; Kanayama, Naoki

2012-01-24

Somatic hypermutation (SHM) of Ig variable region (IgV) genes requires both IgV transcription and the enzyme activation-induced cytidine deaminase (AID). Identification of a cofactor responsible for the fact that IgV genes are much more sensitive to AID-induced mutagenesis than other genes is a key question in immunology. Here, we describe an essential role for a splice isoform of the prototypical serine/arginine-rich (SR) protein SRSF1, termed SRSF1-3, in AID-induced SHM in a DT40 chicken B-cell line. Unexpectedly, we found that SHM does not occur in a DT40 line lacking SRSF1-3 (DT40-ASF), although it is readily detectable in parental DT40 cells. Strikingly, overexpression of AID in DT40-ASF cells led to a large increase in nonspecific (off-target) mutations. In contrast, introduction of SRSF1-3, but not SRSF1, into these cells specifically restored SHM without increasing off-target mutations. Furthermore, we found that SRSF1-3 binds preferentially to the IgV gene and inhibits processing of the Ig transcript, providing a mechanism by which SRSF1-3 makes the IgV gene available for AID-dependent SHM. SRSF1 not only acts as an essential splicing factor but also regulates diverse aspects of mRNA metabolism and maintains genome stability. Our findings, thus, define an unexpected and important role for SRSF1, particularly for its splice variant, in enabling AID to function specifically on its natural substrate during SHM.

Human cerebrospinal fluid monoclonal N-methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis.

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Kreye, Jakob; Wenke, Nina K; Chayka, Mariya; Leubner, Jonas; Murugan, Rajagopal; Maier, Nikolaus; Jurek, Betty; Ly, Lam-Thanh; Brandl, Doreen; Rost, Benjamin R; Stumpf, Alexander; Schulz, Paulina; Radbruch, Helena; Hauser, Anja E; Pache, Florence; Meisel, Andreas; Harms, Lutz; Paul, Friedemann; Dirnagl, Ulrich; Garner, Craig; Schmitz, Dietmar; Wardemann, Hedda; Prüss, Harald

2016-10-01

SEE ZEKERIDOU AND LENNON DOI101093/AWW213 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated with psychosis, dyskinesias, and seizures. Little is known about the cerebrospinal fluid autoantibody repertoire. Antibodies against the NR1 subunit of the NMDAR are thought to be pathogenic; however, direct proof is lacking as previous experiments could not distinguish the contribution of further anti-neuronal antibodies. Using single cell cloning of full-length immunoglobulin heavy and light chain genes, we generated a panel of recombinant monoclonal NR1 antibodies from cerebrospinal fluid memory B cells and antibody secreting cells of NMDAR encephalitis patients. Cells typically carried somatically mutated immunoglobulin genes and had undergone class-switching to immunoglobulin G, clonally expanded cells carried identical somatic hypermutation patterns. A fraction of NR1 antibodies were non-mutated, thus resembling 'naturally occurring antibodies' and indicating that tolerance induction against NMDAR was incomplete and somatic hypermutation not essential for functional antibodies. However, only a small percentage of cerebrospinal fluid-derived antibodies reacted against NR1. Instead, nearly all further antibodies bound specifically to diverse brain-expressed epitopes including neuronal surfaces, suggesting that a broad repertoire of antibody-secreting cells enrich in the central nervous system during encephalitis. Our functional data using primary hippocampal neurons indicate that human cerebrospinal fluid-derived monoclonal NR1 antibodies alone are sufficient to cause neuronal surface receptor downregulation and subsequent impairment of NMDAR-mediated currents, thus providing ultimate proof of antibody pathogenicity. The observed formation of immunological memory might be relevant for clinical relapses. © The Author (2016). Published by Oxford University Press on

Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer.

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Pritchard, Colin C; Morrissey, Colm; Kumar, Akash; Zhang, Xiaotun; Smith, Christina; Coleman, Ilsa; Salipante, Stephen J; Milbank, Jennifer; Yu, Ming; Grady, William M; Tait, Jonathan F; Corey, Eva; Vessella, Robert L; Walsh, Tom; Shendure, Jay; Nelson, Peter S

2014-09-25

A hypermutated subtype of advanced prostate cancer was recently described, but prevalence and mechanisms have not been well-characterized. Here we find that 12% (7 of 60) of advanced prostate cancers are hypermutated, and that all hypermutated cancers have mismatch repair gene mutations and microsatellite instability (MSI). Mutations are frequently complex MSH2 or MSH6 structural rearrangements rather than MLH1 epigenetic silencing. Our findings identify parallels and differences in the mechanisms of hypermutation in prostate cancer compared with other MSI-associated cancers.

Frequency patterns of T-cell exposed motifs in immunoglobulin heavy chain peptides presented by MHCs

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Robert D. Bremel

2014-10-01

Full Text Available Immunoglobulins are highly diverse protein sequences that are processed and presented to T-cells by B-cells and other antigen presenting cells. We examined a large dataset of immunoglobulin heavy chain variable regions (IGHV to assess the diversity of T-cell exposed motifs (TCEM. TCEM comprise those amino acids in a MHC-bound peptide which face outwards, surrounded by the MHC histotope, and which engage the T-cell receptor. Within IGHV there is a distinct pattern of predicted MHC class II binding and a very high frequency of re-use of the TCEMs. The re-use frequency indicates that only a limited number of different cognate T-cells are required to engage many different clonal B-cells. The amino acids in each outward-facing TCEM are intercalated with the amino acids of inward-facing MHC groove-exposed motifs (GEM. Different GEM may have differing, allele-specific, MHC binding affinities. The intercalation of TCEM and GEM in a peptide allows for a vast combinatorial repertoire of epitopes, each eliciting a different response. Outcome of T-cell receptor binding is determined by overall signal strength, which is a function of the number of responding T-cells and the duration of engagement. Hence, the frequency of T-cell exposed motif re-use appears to be an important determinant of whether a T-cell response is stimulatory or suppressive. The frequency distribution of TCEMs implies that somatic hypermutation is followed by clonal expansion that develop along repeated pathways. The observations of TCEM and GEM derived from immunoglobulins suggest a relatively simple, yet powerful, mechanism to correlate T-cell polyspecificity, through re-use of TCEMs, with a very high degree of specificity achieved by combination with a diversity of GEMs. The frequency profile of TCEMs also points to an economical mechanism for maintaining T-cell memory, recall, and self-discrimination based on an endogenously generated profile of motifs.

Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation.

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Delviks-Frankenberry, Krista A; Nikolaitchik, Olga A; Burdick, Ryan C; Gorelick, Robert J; Keele, Brandon F; Hu, Wei-Shau; Pathak, Vinay K

2016-05-01

Although the predominant effect of host restriction APOBEC3 proteins on HIV-1 infection is to block viral replication, they might inadvertently increase retroviral genetic variation by inducing G-to-A hypermutation. Numerous studies have disagreed on the contribution of hypermutation to viral genetic diversity and evolution. Confounding factors contributing to the debate include the extent of lethal (stop codon) and sublethal hypermutation induced by different APOBEC3 proteins, the inability to distinguish between G-to-A mutations induced by APOBEC3 proteins and error-prone viral replication, the potential impact of hypermutation on the frequency of retroviral recombination, and the extent to which viral recombination occurs in vivo, which can reassort mutations in hypermutated genomes. Here, we determined the effects of hypermutation on the HIV-1 recombination rate and its contribution to genetic variation through recombination to generate progeny genomes containing portions of hypermutated genomes without lethal mutations. We found that hypermutation did not significantly affect the rate of recombination, and recombination between hypermutated and wild-type genomes only increased the viral mutation rate by 3.9 × 10-5 mutations/bp/replication cycle in heterozygous virions, which is similar to the HIV-1 mutation rate. Since copackaging of hypermutated and wild-type genomes occurs very rarely in vivo, recombination between hypermutated and wild-type genomes does not significantly contribute to the genetic variation of replicating HIV-1. We also analyzed previously reported hypermutated sequences from infected patients and determined that the frequency of sublethal mutagenesis for A3G and A3F is negligible (4 × 10-21 and1 × 10-11, respectively) and its contribution to viral mutations is far below mutations generated during error-prone reverse transcription. Taken together, we conclude that the contribution of APOBEC3-induced hypermutation to HIV-1 genetic

POLE somatic mutations in advanced colorectal cancer.

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Guerra, Joana; Pinto, Carla; Pinto, Diana; Pinheiro, Manuela; Silva, Romina; Peixoto, Ana; Rocha, Patrícia; Veiga, Isabel; Santos, Catarina; Santos, Rui; Cabreira, Verónica; Lopes, Paula; Henrique, Rui; Teixeira, Manuel R

2017-12-01

Despite all the knowledge already gathered, the picture of somatic genetic changes in colorectal tumorigenesis is far from complete. Recently, germline and somatic mutations in the exonuclease domain of polymerase epsilon, catalytic subunit (POLE) gene have been reported in a small subset of microsatellite-stable and hypermutated colorectal carcinomas (CRCs), affecting the proofreading activity of the enzyme and leading to misincorporation of bases during DNA replication. To evaluate the role of POLE mutations in colorectal carcinogenesis, namely in advanced CRC, we searched for somatic mutations by Sanger sequencing in tumor DNA samples from 307 cases. Microsatellite instability and mutation analyses of a panel of oncogenes were performed in the tumors harboring POLE mutations. Three heterozygous mutations were found in two tumors, the c.857C>G, p.Pro286Arg, the c.901G>A, p.Asp301Asn, and the c.1376C>T, p.Ser459Phe. Of the POLE-mutated CRCs, one tumor was microsatellite-stable and the other had low microsatellite instability, whereas KRAS and PIK3CA mutations were found in one tumor each. We conclude that POLE somatic mutations exist but are rare in advanced CRC, with further larger studies being necessary to evaluate its biological and clinical implications. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

MLH1-Silenced and Non-Silenced Subgroups of Hypermutated Colorectal Carcinomas Have Distinct Mutational Landscapes

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Donehower, Lawrence A.; Creighton, Chad J.; Schultz, Nikolaus; Shinbrot, Eve; Chang, Kyle; Gunaratne, Preethi H.; Muzny, Donna; Sander, Chris; Hamilton, Stanley R.; Gibbs, Richard A.; Wheeler, David

2014-01-01

Approximately 15% of colorectal carcinomas (CRC) exhibit a hypermutated genotype accompanied by high levels of microsatellite instability (MSI-H) and defects in DNA mismatch repair. These tumors, unlike the majority of colorectal carcinomas, are often diploid, exhibit frequent epigenetic silencing of the MLH1 DNA mismatch repair gene, and have a better clinical prognosis. As an adjunct study to The Cancer Genome Atlas consortium that recently analyzed 224 colorectal cancers by whole exome sequencing, we compared the 35 CRC (15.6%) with a hypermutated genotype to those with a non-hypermutated genotype. We found that 22 (63%) of hypermutated CRC exhibited transcriptional silencing of the MLH1 gene, a high frequency of BRAF V600E gene mutations and infrequent APC and KRAS mutations, a mutational pattern significantly different from their non-hypermutated counterparts. However, the remaining 13 (37%) hypermutated CRC lacked MLH1 silencing, contained tumors with the highest mutation rates (“ultramutated” CRC), and exhibited higher incidences of APC and KRAS mutations, but infrequent BRAF mutations. These patterns were confirmed in an independent validation set of 250 exome-sequenced CRC. Analysis of mRNA and microRNA expression signatures revealed that hypermutated CRC with MLH1 silencing had greatly reduced levels of WNT signaling and increased BRAF signaling relative non-hypermutated CRC. Our findings suggest that hypermutated CRC include one subgroup with fundamentally different pathways to malignancy than the majority of CRC. Examination of MLH1 expression status and frequencies of APC, KRAS, and BRAF mutation in CRC may provide a useful diagnostic tool that could supplement the standard microsatellite instability assays and influence therapeutic decisions. PMID:22899370

Hypermutation in pancreatic cancer

OpenAIRE

Humphris, Jeremy L.; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J.; Johns, Amber L.; McKay, Skye; Chang, David K.; Miller, David K.; Pajic, Marina; Kassahn, Karin S.; Quinn, Michael C.J.; Bruxner, Timothy J.C.; Christ, Angelika N.; Harliwong, Ivon; Idrisoglu, Senel

2017-01-01

Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechan...

The Unusual Genetics and Biochemistry of Bovine Immunoglobulins.

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Stanfield, Robyn L; Haakenson, Jeremy; Deiss, Thaddeus C; Criscitiello, Michael F; Wilson, Ian A; Smider, Vaughn V

2018-01-01

Antibodies are the key circulating molecules that have evolved to fight infection by the adaptive immune system of vertebrates. Typical antibodies of most species contain six complementarity-determining regions (CDRs), where the third CDR of the heavy chain (CDR H3) has the greatest diversity and often makes the most significant contact with antigen. Generally, the process of V(D)J recombination produces a vast repertoire of antibodies; multiple V, D, and J gene segments recombine with additional junctional diversity at the V-D and D-J joints, and additional combinatorial possibilities occur through heavy- and light-chain pairing. Despite these processes, the overall structure of the resulting antibody is largely conserved, and binding to antigen occurs predominantly through the CDR loops of the immunoglobulin V domains. Bovines have deviated from this general paradigm by having few VH regions and thus little germline combinatorial diversity, but their antibodies contain long CDR H3 regions, with substantial diversity generated through somatic hypermutation. A subset of the repertoire comprises antibodies with ultralong CDR H3s, which can reach over 70 amino acids in length. Structurally, these unusual antibodies form a β-ribbon "stalk" and disulfide-bonded "knob" that protrude far from the antibody surface. These long CDR H3s allow cows to mount a particularly robust immune response when immunized with viral antigens, particularly to broadly neutralizing epitopes on a stabilized HIV gp140 trimer, which has been a challenge for other species. The unusual genetics and structural biology of cows provide for a unique paradigm for creation of immune diversity and could enable generation of antibodies against especially challenging targets and epitopes. © 2018 Elsevier Inc. All rights reserved.

Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

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Lohr, Jens G.; Stojanov, Petar; Lawrence, Michael S.; Auclair, Daniel; Chapuy, Bjoern; Sougnez, Carrie; Cruz-Gordillo, Peter; Knoechel, Birgit; Asmann, Yan W.; Slager, Susan L.; Novak, Anne J.; Dogan, Ahmet; Ansell, Stephen M.; Zou, Lihua; Gould, Joshua; Saksena, Gordon; Stransky, Nicolas; Rangel-Escareño, Claudia; Fernandez-Lopez, Juan Carlos; Hidalgo-Miranda, Alfredo; Melendez-Zajgla, Jorge; Hernández-Lemus, Enrique; Schwarz-Cruz y Celis, Angela; Imaz-Rosshandler, Ivan; Ojesina, Akinyemi I.; Jung, Joonil; Pedamallu, Chandra S.; Lander, Eric S.; Habermann, Thomas M.; Cerhan, James R.; Shipp, Margaret A.; Getz, Gad; Golub, Todd R.

2012-01-01

To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO, and TNFRSF14. Further, we show that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase–mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS, BRAF, and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease. PMID:22343534

Pathophysiology of B-cell intrinsic immunoglobulin class switch recombination deficiencies.

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Durandy, Anne; Taubenheim, Nadine; Peron, Sophie; Fischer, Alain

2007-01-01

B-cell intrinsic immunoglobulin class switch recombination (Ig-CSR) deficiencies, previously termed hyper-IgM syndromes, are genetically determined conditions characterized by normal or elevated serum IgM levels and an absence or very low levels of IgG, IgA, and IgE. As a function of the molecular mechanism, the defective CSR is variably associated to a defect in the generation of somatic hypermutations (SHMs) in the Ig variable region. The study of Ig-CSR deficiencies contributed to a better delineation of the mechanisms underlying CSR and SHM, the major events of antigen-triggered antibody maturation. Four Ig-CSR deficiency phenotypes have been so far reported: the description of the activation-induced cytidine deaminase (AID) deficiency (Ig-CSR deficiency 1), caused by recessive mutations of AICDA gene, characterized by a defect in CSR and SHM, clearly established the role of AID in the induction of the Ig gene rearrangements underlying CSR and SHM. A CSR-specific function of AID has, however, been detected by the observation of a selective CSR defect caused by mutations affecting the C-terminus of AID. Ig-CSR deficiency 2 is the consequence of uracil-N-glycosylase (UNG) deficiency. Because UNG, a molecule of the base excision repair machinery, removes uracils from DNA and AID deaminates cytosines into uracils, that observation indicates that the AID-UNG pathway directly targets DNA of switch regions from the Ig heavy-chain locus to induce the CSR process. Ig-CSR deficiencies 3 and 4 are characterized by a selective CSR defect resulting from blocks at distinct steps of CSR. A further understanding of the CSR machinery is expected from their molecular definition.

E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and stronger expression of the memory B-cell-associated miR-223: possible correlation with stage and treatment response.

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Liu, Ting-Yun; Chen, Shee-Uan; Kuo, Sung-Hsin; Cheng, Ann-Lii; Lin, Chung-Wu

2010-11-01

Extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach (gastric MALT lymphoma) is derived from memory B cells of the marginal zone. Normal memory B cells do not express markers of germinal-center B cells, such as E2A (immunoglobulin enhancer-binding factor E12/E47), B-cell chronic lymphocytic leukemia/lymphoma 6 (BCL6), or activation-induced cytidine deaminase (AID). E2A is a transcription factor that induces somatic hypermutations and blocks plasma cell differentiation. In 50 stage-I(E)/II(E1) gastric MALT lymphomas, we confirmed that all cases were BCL6(-)/AID(-), but a subset (50%, 25/50) was E2A(+). As E2A(-) and E2A(+) gastric MALT lymphomas had similar numbers of somatic hypermutations without intraclonal variations, which implied an origin from memory B cells, the expression of E2A was best regarded as a marker of aberrant follicular differentiation. Although the status of somatic hypermutation was not affected by E2A, E2A(+) gastric MALT lymphoma showed less plasmacytoid infiltrates and higher expressions of miRNA-223, a microRNA associated with memory B cells. Clinically, E2A(+) gastric MALT lymphomas were more likely to spread to perigastric lymph nodes and were less responsive to Helicobacter eradication therapy than were E2A(-) gastric MALT lymphomas. Taken together, aberrant E2A expression is a diagnostic feature of a subtype of gastric MALT lymphoma with weaker plasmacytoid infiltrates and stronger miR-223 expression. A prospective study would be necessary to verify the association between E2A expression and a poor response to Helicobacter eradication therapy.

Evidence for ADAR-induced hypermutation of the Drosophila sigma virus (Rhabdoviridae).

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Carpenter, Jennifer A; Keegan, Liam P; Wilfert, Lena; O'Connell, Mary A; Jiggins, Francis M

2009-11-26

ADARs are RNA editing enzymes that target double stranded RNA and convert adenosine to inosine, which is read by translation machinery as if it were guanosine. Aside from their role in generating protein diversity in the central nervous system, ADARs have been implicated in the hypermutation of some RNA viruses, although why this hypermutation occurs is not well understood. Here we describe the hypermutation of adenosines to guanosines in the genome of the sigma virus--a negative sense RNA virus that infects Drosophila melanogaster. The clustering of these mutations and the context in which they occur indicates that they have been caused by ADARs. However, ADAR-editing of viral RNA is either rare or edited viral RNA are rapidly degraded, as we only detected evidence for editing in two of the 104 viral isolates we studied. This is the first evidence for ADARs targeting viruses outside of mammals, and it raises the possibility that ADARs could play a role in the antiviral defences of insects.

Evidence for ADAR-induced hypermutation of the Drosophila sigma virus (Rhabdoviridae

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O'Connell Mary A

2009-11-01

Full Text Available Abstract Background ADARs are RNA editing enzymes that target double stranded RNA and convert adenosine to inosine, which is read by translation machinery as if it were guanosine. Aside from their role in generating protein diversity in the central nervous system, ADARs have been implicated in the hypermutation of some RNA viruses, although why this hypermutation occurs is not well understood. Results Here we describe the hypermutation of adenosines to guanosines in the genome of the sigma virus--a negative sense RNA virus that infects Drosophila melanogaster. The clustering of these mutations and the context in which they occur indicates that they have been caused by ADARs. However, ADAR-editing of viral RNA is either rare or edited viral RNA are rapidly degraded, as we only detected evidence for editing in two of the 104 viral isolates we studied. Conclusion This is the first evidence for ADARs targeting viruses outside of mammals, and it raises the possibility that ADARs could play a role in the antiviral defences of insects.

Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

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Puente, Xose S.; Pinyol, Magda; Quesada, Víctor; Conde, Laura; Ordóñez, Gonzalo R.; Villamor, Neus; Escaramis, Georgia; Jares, Pedro; Beà, Sílvia; González-Díaz, Marcos; Bassaganyas, Laia; Baumann, Tycho; Juan, Manel; López-Guerra, Mónica; Colomer, Dolors; Tubío, José M. C.; López, Cristina; Navarro, Alba; Tornador, Cristian; Aymerich, Marta; Rozman, María; Hernández, Jesús M.; Puente, Diana A.; Freije, José M. P.; Velasco, Gloria; Gutiérrez-Fernández, Ana; Costa, Dolors; Carrió, Anna; Guijarro, Sara; Enjuanes, Anna; Hernández, Lluís; Yagüe, Jordi; Nicolás, Pilar; Romeo-Casabona, Carlos M.; Himmelbauer, Heinz; Castillo, Ester; Dohm, Juliane C.; de Sanjosé, Silvia; Piris, Miguel A.; de Alava, Enrique; Miguel, Jesús San; Royo, Romina; Gelpí, Josep L.; Torrents, David; Orozco, Modesto; Pisano, David G.; Valencia, Alfonso; Guigó, Roderic; Bayés, Mónica; Heath, Simon; Gut, Marta; Klatt, Peter; Marshall, John; Raine, Keiran; Stebbings, Lucy A.; Futreal, P. Andrew; Stratton, Michael R.; Campbell, Peter J.; Gut, Ivo; López-Guillermo, Armando; Estivill, Xavier; Montserrat, Emili; López-Otín, Carlos; Campo, Elías

2012-01-01

Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution1,2. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes3,4. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer. PMID:21642962

Cell Cycle Regulates Nuclear Stability of AID and Determines the Cellular Response to AID.

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Quy Le

2015-09-01

Full Text Available AID (Activation Induced Deaminase deaminates cytosines in DNA to initiate immunoglobulin gene diversification and to reprogram CpG methylation in early development. AID is potentially highly mutagenic, and it causes genomic instability evident as translocations in B cell malignancies. Here we show that AID is cell cycle regulated. By high content screening microscopy, we demonstrate that AID undergoes nuclear degradation more slowly in G1 phase than in S or G2-M phase, and that mutations that affect regulatory phosphorylation or catalytic activity can alter AID stability and abundance. We directly test the role of cell cycle regulation by fusing AID to tags that destabilize nuclear protein outside of G1 or S-G2/M phases. We show that enforced nuclear localization of AID in G1 phase accelerates somatic hypermutation and class switch recombination, and is well-tolerated; while nuclear AID compromises viability in S-G2/M phase cells. We identify AID derivatives that accelerate somatic hypermutation with minimal impact on viability, which will be useful tools for engineering genes and proteins by iterative mutagenesis and selection. Our results further suggest that use of cell cycle tags to regulate nuclear stability may be generally applicable to studying DNA repair and to engineering the genome.

Analysis of IgV gene mutations in B cell chronic lymphocytic leukaemia according to antigen-driven selection identifies subgroups with different prognosis and usage of the canonical somatic hypermutation machinery.

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Degan, Massimo; Bomben, Riccardo; Bo, Michele Dal; Zucchetto, Antonella; Nanni, Paola; Rupolo, Maurizio; Steffan, Agostino; Attadia, Vincenza; Ballerini, Pier Ferruccio; Damiani, Daniela; Pucillo, Carlo; Poeta, Giovanni Del; Colombatti, Alfonso; Gattei, Valter

2004-07-01

Cases of B-cell chronic lymphocytic leukaemia (B-CLL) with mutated (M) IgV(H) genes have a better prognosis than unmutated (UM) cases. We analysed the IgV(H) mutational status of B-CLL according to the features of a canonical somatic hypermutation (SHM) process, correlating this data with survival. In a series of 141 B-CLLs, 124 cases were examined for IgV(H) gene per cent mutations and skewing of replacement/silent mutations in the framework/complementarity-determining regions as evidence of antigen-driven selection; this identified three B-CLL subsets: significantly mutated (sM), with evidence of antigen-driven selection, not significantly mutated (nsM) and UM, without such evidence and IgV(H) gene per cent mutations above or below the 2% cut-off. sM B-CLL patients had longer survival within the good prognosis subgroup that had more than 2% mutations of IgV(H) genes. sM, nsM and UM B-CLL were also characterized for the biased usage of IgV(H) families, intraclonal IgV(H) gene diversification, preference of mutations to target-specific nucleotides or hotspots, and for the expression of enzymes involved in SHM (translesion DNA polymerase zeta and eta and activation-induced cytidine deaminase). These findings indicate the activation of a canonical SHM process in nsM and sM B-CLLs and underscore the role of the antigen in defining the specific clinical and biological features of B-CLL.

Functional Versatility of AGY Serine Codons in Immunoglobulin Variable Region Genes

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Thiago Detanico

2016-11-01

Full Text Available In systemic autoimmunity, autoantibodies directed against nuclear antigens (Ag often arise by somatic hypermutation (SHM that converts AGT and AGC (AGY Ser codons into Arg codons. This can occur by three different single-base changes. Curiously, AGY Ser codons are far more abundant in complementarity-determining regions (CDRs of IgV-region genes than expected for random codon use or from species-specific codon frequency data. CDR AGY codons are also more abundant than TCN Ser codons. We show that these trends hold even in cartilaginous fishes. Because AGC is a preferred target for SHM by activation-induced cytidine deaminase (AID, we asked whether the AGY abundance was solely due to a selection pressure to conserve high mutability in CDRs regardless of codon context but found that this was not the case. Instead, AGY triplets were selectively enriched in the Ser codon reading frame. Motivated by reports implicating a functional role for poly/autoreactive specificities in anti-viral antibodies, we also analyzed mutations at AGY in antibodies directed against a number of different viruses, and found that mutations producing Arg codons in anti-viral antibodies were indeed frequent. Unexpectedly, however, we also found that AGY codons mutated often to encode nearly all of the amino acids that are reported to provide the most frequent contacts with antigen (Ag. In many cases, mutations producing codons for these alternative amino acids in anti-viral antibodies were more frequent than those producing Arg codons. Mutations producing each of these key amino acids required only single-base changes in AGY. AGY is the only codon group in which 2/3rds of random mutations generate codons for these key residues. Finally, by directly analyzing x-ray structures of immune complexes from the RCSB protein database, we found that Ag-contact residues generated via somatic hypermutation occurred more often at AGY than at any other codon group. Thus, preservation of

Germline and somatic polymerase ε and δ mutations define a new class of hypermutated colorectal and endometrial cancers.

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Briggs, Sarah; Tomlinson, Ian

2013-06-01

Polymerases ε and δ are the main enzymes that replicate eukaryotic DNA. Accurate replication occurs through Watson-Crick base pairing and also through the action of the polymerases' exonuclease (proofreading) domains. We have recently shown that germline exonuclease domain mutations (EDMs) of POLE and POLD1 confer a high risk of multiple colorectal adenomas and carcinoma (CRC). POLD1 mutations also predispose to endometrial cancer (EC). These mutations are associated with high penetrance and dominant inheritance, although the phenotype can be variable. We have named the condition polymerase proofreading-associated polyposis (PPAP). Somatic POLE EDMs have also been found in sporadic CRCs and ECs, although very few somatic POLD1 EDMs have been detected. Both the germline and the somatic DNA polymerase EDMs cause an 'ultramutated', apparently microsatellite-stable, type of cancer, sometimes leading to over a million base substitutions per tumour. Here, we present the evidence for POLE and POLD1 as important contributors to the pathogenesis of CRC and EC, and highlight some of the key questions in this emerging field. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Molecular analysis of immunoglobulin variable genes supports a germinal center experienced normal counterpart in primary cutaneous diffuse large B-cell lymphoma, leg-type.

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Pham-Ledard, Anne; Prochazkova-Carlotti, Martina; Deveza, Mélanie; Laforet, Marie-Pierre; Beylot-Barry, Marie; Vergier, Béatrice; Parrens, Marie; Feuillard, Jean; Merlio, Jean-Philippe; Gachard, Nathalie

2017-11-01

Immunophenotype of primary cutaneous diffuse large B-cell lymphoma, leg-type (PCLBCL-LT) suggests a germinal center-experienced B lymphocyte (BCL2+ MUM1+ BCL6+/-). As maturation history of B-cell is "imprinted" during B-cell development on the immunoglobulin gene sequence, we studied the structure and sequence of the variable part of the genes (IGHV, IGLV, IGKV), immunoglobulin surface expression and features of class switching in order to determine the PCLBCL-LT cell of origin. Clonality analysis with BIOMED2 protocol and VH leader primers was done on DNA extracted from frozen skin biopsies on retrospective samples from 14 patients. The clonal DNA IGHV sequence of the tumor was aligned and compared with the closest germline sequence and homology percentage was calculated. Superantigen binding sites were studied. Features of selection pressure were evaluated with the multinomial Lossos model. A functional monoclonal sequence was observed in 14 cases as determined for IGHV (10), IGLV (2) or IGKV (3). IGV mutation rates were high (>5%) in all cases but one (median:15.5%), with superantigen binding sites conservation. Features of selection pressure were identified in 11/12 interpretable cases, more frequently negative (75%) than positive (25%). Intraclonal variation was detected in 3 of 8 tumor specimens with a low rate of mutations. Surface immunoglobulin was an IgM in 12/12 cases. FISH analysis of IGHM locus, deleted during class switching, showed heterozygous IGHM gene deletion in half of cases. The genomic PCR analysis confirmed the deletions within the switch μ region. IGV sequences were highly mutated but functional, with negative features of selection pressure suggesting one or more germinal center passage(s) with somatic hypermutation, but superantigen (SpA) binding sites conservation. Genetic features of class switch were observed, but on the non functional allele and co-existing with primary isotype IgM expression. These data suggest that cell-of origin is

Hypermutation by intersegmental transfer of APOBEC3G cytidine deaminase.

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Nowarski, Roni; Britan-Rosich, Elena; Shiloach, Tamar; Kotler, Moshe

2008-10-01

Deamination of cytidine residues in single-stranded DNA (ssDNA) is an important mechanism by which apolipoprotein B mRNA-editing, catalytic polypeptide-like (APOBEC) enzymes restrict endogenous and exogenous viruses. The dynamic process underlying APOBEC-induced hypermutation is not fully understood. Here we show that enzymatically active APOBEC3G can be detected in wild-type Vif(+) HIV-1 virions, albeit at low levels. In vitro studies showed that single enzyme-DNA encounters result in distributive deamination of adjacent cytidines. Nonlinear translocation of APOBEC3G, however, directed scattered deamination of numerous targets along the DNA. Increased ssDNA concentrations abolished enzyme processivity in the case of short, but not long, DNA substrates, emphasizing the key role of rapid intersegmental transfer in targeting the deaminase. Our data support a model by which APOBEC3G intersegmental transfer via monomeric binding to two ssDNA segments results in dispersed hypermutation of viral genomes.

Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

International Nuclear Information System (INIS)

Takai, Atsushi; Marusawa, Hiroyuki; Chiba, Tsutomu

2011-01-01

Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis

Comparison of efficacies of bovine immune colostral antibody and each immunoglobulin class against verotoxin 2, flagellum and somatic cells of Escherichia coli O157:H7 in mice.

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Seita, Tetsurou; Kuribayashi, Takashi; Honjo, Toshio; Yamamoto, Shizuo

2013-04-01

The efficacy of bovine immune colostral (colostral) antibodies against verotoxin (VT) 2, flagellum and somatic cells of Escherichia coli (E. coli) O157:H7 in mice was determined. Three major immunoglobulin (Ig) classes were isolated from the colostral antibody against VT2 by affinity chromatography and were used for estimation. Mice inoculated with VT2 were administered each Ig class from the colostral antibody, colostral antibody (colostral whey containing antibody) or serum antibody against VT2 at 1 hour after VT2 inoculation. All control mice (20/20) died after administration of sterilized saline instead of the colostral antibody. The survival rate was 93.3% (14/15) after administration of S-IgA or IgM antibody, or colostral antibody. Survival rates for IgG antibody and serum antibody administration were 80% (12/15) and 60% (9/15), respectively. Serum concentrations of VT2, which was absorbed from the small intestine in mice after administration of VT2 and colostral antibody, were measured by fluorescence enzyme immunoassay (FEIA). Serum concentrations of VT2 after administration of colostral antibody were lower than those after administration of sterilized saline. Mice inoculated with VT2-producing E. coli 157:H7 were administered anti-flagellum or anti-somatic colostral antibodies. Survival rates for E. coli O157:H7-infected mice administered the anti-flagellum and anti-somatic colostral antibodies were 52.4% (11/21) and 22.2% (4/18), respectively. Furthermore, survival rates increased to 89.5% (17/19) with combined administration of anti-flagellum and anti-VT2 colostral antibodies. These results suggest that colostral antibodies against VT2, flagellum and somatic cells are effective against E. coli O157:H7 infection. Copyright © 2012. Published by Elsevier B.V.

MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils

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Campo, Vanina A.; Patenaude, Anne-Marie; Kaden, Svenja; Horb, Lori; Firka, Daniel; Jiricny, Josef; Di Noia, Javier M.

2013-01-01

The mammalian antibody repertoire is shaped by somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) loci of B lymphocytes. SHM and CSR are triggered by non-canonical, error-prone processing of G/U mismatches generated by activation-induced deaminase (AID). In birds, AID does not trigger SHM, but it triggers Ig gene conversion (GC), a ‘homeologous’ recombination process involving the Ig variable region and proximal pseudogenes. Because recombination fidelity is controlled by the mismatch repair (MMR) system, we investigated whether MMR affects GC in the chicken B cell line DT40. We show here that Msh6−/− and Pms2−/− DT40 cells display cell cycle defects, including genomic re-replication. However, although IgVλ GC tracts in MMR-deficient cells were slightly longer than in normal cells, Ig GC frequency, donor choice or the number of mutations per sequence remained unaltered. The finding that the avian MMR system, unlike that of mammals, does not seem to contribute towards the processing of G/U mismatches in vitro could explain why MMR is unable to initiate Ig GC in this species, despite initiating SHM and CSR in mammalian cells. Moreover, as MMR does not counteract or govern Ig GC, we report a rare example of ‘homeologous’ recombination insensitive to MMR. PMID:23314153

Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice

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Otani, Sanae [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan); Department of Pediatrics, Graduate School of Medicine, Osaka City University, Osaka (Japan); Ayata, Minoru, E-mail: maverick@med.osaka-cu.ac.jp [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan); Takeuchi, Kaoru [Laboratory of Environmental Microbiology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki (Japan); Takeda, Makoto [Department of Virology 3, National Institute of Infectious Diseases, Tokyo (Japan); Shintaku, Haruo [Department of Pediatrics, Graduate School of Medicine, Osaka City University, Osaka (Japan); Ogura, Hisashi [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan)

2014-08-15

Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency. - Highlights: • Wild-type MV can cause persistent infections in nude mice. • Biased hypermutation occurred in the M gene. • Biased hypermutation occurred in an inessential gene inserted between the leader and the N gene.

Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice

International Nuclear Information System (INIS)

Otani, Sanae; Ayata, Minoru; Takeuchi, Kaoru; Takeda, Makoto; Shintaku, Haruo; Ogura, Hisashi

2014-01-01

Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency. - Highlights: • Wild-type MV can cause persistent infections in nude mice. • Biased hypermutation occurred in the M gene. • Biased hypermutation occurred in an inessential gene inserted between the leader and the N gene

Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens.

Science.gov (United States)

Lin, Katherine I; Tam, Constantine S; Keating, Michael J; Wierda, William G; O'Brien, Susan; Lerner, Susan; Coombes, Kevin R; Schlette, Ellen; Ferrajoli, Alessandra; Barron, Lynn L; Kipps, Thomas J; Rassenti, Laura; Faderl, Stefan; Kantarjian, Hagop; Abruzzo, Lynne V

2009-04-02

Although immunoglobulin V(H) mutation status (IgV(H) MS) is prognostic in patients with chronic lymphocytic leukemia (CLL) who are treated with alkylating agents or single-agent fludarabine, its significance in the era of chemoimmunotherapy is not known. We determined the IgV(H) somatic mutation status (MS) in 177 patients enrolled in a phase 2 study of fludarabine, cyclophosphamide, and rituximab (FCR) and in 127 patients treated with subsequent chemoimmunotherapy protocols. IgV(H) MS did not impact significantly on the complete remission (CR) rate of patients receiving FCR or related regimens. However, CR duration was significantly shorter in patients with CLL that used unmutated IgV(H) than those whose CLL used mutated IgV(H) (TTP 47% vs 82% at 6 years, P IgV(H) MS emerged as the only determinant of remission duration (hazard ratio 3.8, P IgV(H) status.

Characterizing the Hypermutated Subtype of Advanced Prostate Cancer as a Predictive Biomarker for Precision Medicine

Science.gov (United States)

2016-10-01

instability, MSI, MLH1, MSH2, MSH6, PMS2 , metastasis, precision medicine 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...hypermutation, hyper-mutation, microsatellite instability, MSI, MLH1, MSH2, MSH6, PMS2 , metastasis, precision medicine Colin Pritchard MD, PhD 2015-2016 Year 2...BRCC3 BRIP1 CHEK1 CHEK2 FAM175A MLH1 MRE11A MSH2 MSH6 NBN PALB2 PMS2 PRSS1 PTEN RAD50 RAD51B RAD51C RAD51D RBBP8 TP53 TP53BP1 XRCC2 Additional

Antibody Affinity Maturation in Fishes—Our Current Understanding

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Brad G. Magor

2015-07-01

Full Text Available It has long been believed that fish lack antibody affinity maturation, in part because they were thought to lack germinal centers. Recent research done on sharks and bony fishes indicates that these early vertebrates are able to affinity mature their antibodies. This article reviews the functionality of the fish homologue of the immunoglobulin (Ig mutator enzyme activation-induced cytidine deaminase (AID. We also consider the protein and molecular evidence for Ig somatic hypermutation and antibody affinity maturation. In the context of recent evidence for a putative proto-germinal center in fishes we propose some possible reasons that observed affinity maturation in fishes often seems lacking and propose future work that might shed further light on this process in fishes.

Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles.

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Gadala-Maria, Daniel; Yaari, Gur; Uduman, Mohamed; Kleinstein, Steven H

2015-02-24

Individual variation in germline and expressed B-cell immunoglobulin (Ig) repertoires has been associated with aging, disease susceptibility, and differential response to infection and vaccination. Repertoire properties can now be studied at large-scale through next-generation sequencing of rearranged Ig genes. Accurate analysis of these repertoire-sequencing (Rep-Seq) data requires identifying the germline variable (V), diversity (D), and joining (J) gene segments used by each Ig sequence. Current V(D)J assignment methods work by aligning sequences to a database of known germline V(D)J segment alleles. However, existing databases are likely to be incomplete and novel polymorphisms are hard to differentiate from the frequent occurrence of somatic hypermutations in Ig sequences. Here we develop a Tool for Ig Genotype Elucidation via Rep-Seq (TIgGER). TIgGER analyzes mutation patterns in Rep-Seq data to identify novel V segment alleles, and also constructs a personalized germline database containing the specific set of alleles carried by a subject. This information is then used to improve the initial V segment assignments from existing tools, like IMGT/HighV-QUEST. The application of TIgGER to Rep-Seq data from seven subjects identified 11 novel V segment alleles, including at least one in every subject examined. These novel alleles constituted 13% of the total number of unique alleles in these subjects, and impacted 3% of V(D)J segment assignments. These results reinforce the highly polymorphic nature of human Ig V genes, and suggest that many novel alleles remain to be discovered. The integration of TIgGER into Rep-Seq processing pipelines will increase the accuracy of V segment assignments, thus improving B-cell repertoire analyses.

Molecular mechanism of immunoglobulin V-region diversification regulated by transcription and RNA metabolism in antigen-driven B cells.

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Sakaguchi, N; Maeda, K; Kuwahara, K

2011-06-01

The immune system produces specific antibodies (Ab) against any antigens (Ag) of exogenous and endogenous origins with a diverse repertoire of V-region specificities. The primary V-region repertoire is created by the rearrangement of immunoglobulin (Ig) V-region, D- and J-segments with the insertion of N- and P-sequences during early B cell differentiation. Recent studies revealed that secondary diversification of the IgV-region generated in the peripheral lymphoid organs plays a critical role in the generation of effective Ab production for protection from various pathogens. Naïve B cells that react with Ags initiate proliferation and differentiation in the follicular region and create the germinal centres (GCs), where activation-induced cytidine deaminase (AID)-dependent IgV-region somatic hypermutation (SHM) and class-switch recombination generate high-affinity and class-switched mature Ag-specific B cells. Our studies have discovered a 210-kDa nuclear protein, named GC-associated nuclear protein (GANP) that is up-regulated in GC B cells during the T cell-dependent (TD) immune responses. By studying mice with mutant forms of the ganp gene, we demonstrated that GANP is essential for the generation of high-affinity B cells against TD-Ag by affecting SHM at the IgV-regions. GANP is associated with AID in the cytoplasm and the GANP/AID complex is recruited to the nucleus, specifically, the chromatin, and targeted selectively to the IgV-region gene in B cells. GANP augments the access of AID towards IgV-regions in B cells. Here, we review the role of GANP in acquired immunity through the detailed analysis of the molecular mechanism generating SHM specifically at IgV-regions in B cells. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

Cloning and functional characterisation of avian transcription factor E2A

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Meyer Kerstin B

2004-06-01

Full Text Available Abstract Background During B lymphocyte development the E2A gene is a critical regulator of cell proliferation and differentiation. With regards to the immunoglobulin genes the E2A proteins contribute to the regulation of gene rearrangement, expression and class switch recombination. We are now using the chicken cell line DT40 as a model system to further analyse the function of E2A. Results Here we report the cloning and functional analysis of the transcription factor E2A from chicken. Using RACE PCR on the chicken lymphoma cell line DT40 we have isolated full-length clones for the two E2A splice variants E12 and E47. Sequence conservation between the human and chicken proteins is extensive: the basic-helix-loop-helix DNA binding domain of human and chicken E47 and E12 are 93% and 92% identical, respectively. In addition high levels of conservation are seen in activation domain I, the potential NLS and the ubiquitin ligase interaction domain. E2A is expressed in a variety of tissues in chicken, with higher levels of expression in organs rich in immune cells. We demonstrate that chicken E12 and E47 proteins are strong transcriptional activators whose function depends on the presence of activation domain I. As in mammals, the dominant negative proteins Id1 and Id3 can inhibit the function of chicken E47. Conclusions The potential for homologous recombination in DT40 allows the genetic dissection of biochemical pathways in somatic cells. With the cloning of avian E2A and the recent description of an in vitro somatic hypermutation assay in this cell line, it should now be possible to dissect the potential role of E2A in the regulation of somatic hypermutation and gene conversion.

APOBEC3G-induced hypermutation of human immunodeficiency virus type-1 is typically a discrete "all or nothing" phenomenon

DEFF Research Database (Denmark)

Armitage, Andrew E; Deforche, Koen; Chang, Chih-Hao

2012-01-01

The rapid evolution of Human Immunodeficiency Virus (HIV-1) allows studies of ongoing host-pathogen interactions. One key selective host factor is APOBEC3G (hA3G) that can cause extensive and inactivating Guanosine-to-Adenosine (G-to-A) mutation on HIV plus-strand DNA (termed hypermutation). HIV...... can inhibit this innate anti-viral defense through binding of the viral protein Vif to hA3G, but binding efficiency varies and hypermutation frequencies fluctuate in patients. A pivotal question is whether hA3G-induced G-to-A mutation is always lethal to the virus or if it may occur at sub......-lethal frequencies that could increase viral diversification. We show in vitro that limiting-levels of hA3G-activity (i.e. when only a single hA3G-unit is likely to act on HIV) produce hypermutation frequencies similar to those in patients and demonstrate in silico that potentially non-lethal G-to-A mutation rates...

A Public Database of Memory and Naive B-Cell Receptor Sequences.

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William S DeWitt

Full Text Available The vast diversity of B-cell receptors (BCR and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.

A Public Database of Memory and Naive B-Cell Receptor Sequences.

Science.gov (United States)

DeWitt, William S; Lindau, Paul; Snyder, Thomas M; Sherwood, Anna M; Vignali, Marissa; Carlson, Christopher S; Greenberg, Philip D; Duerkopp, Natalie; Emerson, Ryan O; Robins, Harlan S

2016-01-01

The vast diversity of B-cell receptors (BCR) and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.

Switch junction sequences in PMS2-deficient mice reveal a microhomology-mediated mechanism of Ig class switch recombination

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Ehrenstein, Michael R.; Rada, Cristina; Jones, Anne-Marie; Milstein, César; Neuberger, Michael S.

2001-01-01

Isotype switching involves a region-specific, nonhomologous recombinational deletion that has been suggested to occur by nonhomologous joining of broken DNA ends. Here, we find increased donor/acceptor homology at switch junctions from PMS2-deficient mice and propose that class switching can occur by microhomology-mediated end-joining. Interestingly, although isotype switching and somatic hypermutation show many parallels, we confirm that PMS2 deficiency has no major effect on the pattern of nucleotide substitutions generated during somatic hypermutation. This finding is in contrast to MSH2 deficiency. With MSH2, the altered pattern of switch recombination and hypermutation suggests parallels in the mechanics of the two processes, whereas the fact that PMS2 deficiency affects only switch recombination may reflect differences in the pathways of break resolution. PMID:11717399

IgV gene intraclonal diversification and clonal evolution in B-cell chronic lymphocytic leukaemia.

Science.gov (United States)

Bagnara, Davide; Callea, Vincenzo; Stelitano, Caterina; Morabito, Fortunato; Fabris, Sonia; Neri, Antonino; Zanardi, Sabrina; Ghiotto, Fabio; Ciccone, Ermanno; Grossi, Carlo Enrico; Fais, Franco

2006-04-01

Intraclonal diversification of immunoglobulin (Ig) variable (V) genes was evaluated in leukaemic cells from a B-cell chronic lymphocytic leukaemia (B-CLL) case over a 2-year period at four time points. Intraclonal heterogeneity was analysed by sequencing 305 molecular clones derived from polymerase chain reaction amplification of B-CLL cell IgV heavy (H) and light (C) chain gene rearrangements. Sequences were compared with evaluating intraclonal variation and the nature of somatic mutations. Although IgV intraclonal variation was detected at all time points, its level decreased with time and a parallel emergence of two more represented V(H)DJ(H) clones was observed. They differed by nine nucleotide substitutions one of which only caused a conservative replacement aminoacid change. In addition, one V(L)J(L) rearrangement became more represented over time. Analyses of somatic mutations suggest antigen selection and impairment of negative selection of neoplastic cells. In addition, a genealogical tree representing a model of clonal evolution of the neoplastic cells was created. It is of note that, during the period of study, the patient showed clinical progression of disease. We conclude that antigen stimulation and somatic hypermutation may participate in disease progression through the selection and expansion of neoplastic subclone(s).

Germline PMS2 and somatic POLE exonuclease mutations cause hypermutability of the leading DNA strand in biallelic mismatch repair deficiency syndrome brain tumours.

Science.gov (United States)

Andrianova, Maria A; Chetan, Ghati Kasturirangan; Sibin, Madathan Kandi; Mckee, Thomas; Merkler, Doron; Narasinga, Rao Kvl; Ribaux, Pascale; Blouin, Jean-Louis; Makrythanasis, Periklis; Seplyarskiy, Vladimir B; Antonarakis, Stylianos E; Nikolaev, Sergey I

2017-11-01

Biallelic mismatch repair deficiency (bMMRD) in tumours is frequently associated with somatic mutations in the exonuclease domains of DNA polymerases POLE or POLD1, and results in a characteristic mutational profile. In this article, we describe the genetic basis of ultramutated high-grade brain tumours in the context of bMMRD. We performed exome sequencing of two second-cousin patients from a large consanguineous family of Indian origin with early onset of high-grade glioblastoma and astrocytoma. We identified a germline homozygous nonsense variant, p.R802*, in the PMS2 gene. Additionally, by genome sequencing of these tumours, we found extremely high somatic mutation rates (237/Mb and 123/Mb), as well as somatic mutations in the proofreading domain of POLE polymerase (p.P436H and p.L424V), which replicates the leading DNA strand. Most interestingly, we found, in both cancers, that the vast majority of mutations were consistent with the signature of POLE exo - , i.e. an abundance of C>A and C>T mutations, particularly in special contexts, on the leading strand. We showed that the fraction of mutations under positive selection among mutations in tumour suppressor genes is more than two-fold lower in ultramutated tumours than in other glioblastomas. Genetic analyses enabled the diagnosis of the two consanguineous childhood brain tumours as being due to a combination of PMS2 germline and POLE somatic variants, and confirmed them as bMMRD/POLE exo - disorders. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Quantitative Analysis of Repertoire-Scale Immunoglobulin Properties in Vaccine-Induced B-Cell Responses

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Ilja V. Khavrutskii

2017-08-01

Full Text Available Recent advances in the next-generation sequencing of B-cell receptors (BCRs enable the characterization of humoral responses at a repertoire-wide scale and provide the capability for identifying unique features of immune repertoires in response to disease, vaccination, or infection. Immunosequencing now readily generates 103–105 sequences per sample; however, statistical analysis of these repertoires is challenging because of the high genetic diversity of BCRs and the elaborate clonal relationships among them. To date, most immunosequencing analyses have focused on reporting qualitative trends in immunoglobulin (Ig properties, such as usage or somatic hypermutation (SHM percentage of the Ig heavy chain variable (IGHV gene segment family, and on reducing complex Ig property distributions to simple summary statistics. However, because Ig properties are typically not normally distributed, any approach that fails to assess the distribution as a whole may be inadequate in (1 properly assessing the statistical significance of repertoire differences, (2 identifying how two repertoires differ, and (3 determining appropriate confidence intervals for assessing the size of the differences and their potential biological relevance. To address these issues, we have developed a technique that uses Wilcox’ robust statistics toolbox to identify statistically significant vaccine-specific differences between Ig repertoire properties. The advantage of this technique is that it can determine not only whether but also where the distributions differ, even when the Ig repertoire properties are non-normally distributed. We used this technique to characterize murine germinal center (GC B-cell repertoires in response to a complex Ebola virus-like particle (eVLP vaccine candidate with known protective efficacy. The eVLP-mediated GC B-cell responses were highly diverse, consisting of thousands of clonotypes. Despite this staggering diversity, we identified statistically

Biased Iglambda expression in hypermutated IgD multiple myelomas does not result from receptor revision

NARCIS (Netherlands)

van der Burg, M.; Bende, R. J.; Aarts, W. M.; Langerak, A. W.; van Dongen, J. J. M.; van Noesel, C. J. M.

2002-01-01

Normal IgM(-)IgD(+) CD38(+) B cells and IgM(-)IgD(+) multiple myelomas (MM) are characterized by Cmu deletion, biased Iglambda expression and hypermutated IgV regions. The predominant Iglambda usage has been proposed as resulting from secondary Ig gene rearrangements during extensive clonal

Site-Specific Gene Editing of Human Hematopoietic Stem Cells for X-Linked Hyper-IgM Syndrome

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Caroline Y. Kuo

2018-05-01

Full Text Available X-linked hyper-immunoglobulin M (hyper-IgM syndrome (XHIM is a primary immunodeficiency due to mutations in CD40 ligand that affect immunoglobulin class-switch recombination and somatic hypermutation. The disease is amenable to gene therapy using retroviral vectors, but dysregulated gene expression results in abnormal lymphoproliferation in mouse models, highlighting the need for alternative strategies. Here, we demonstrate the ability of both the transcription activator-like effector nuclease (TALEN and clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9 platforms to efficiently drive integration of a normal copy of the CD40L cDNA delivered by Adeno-Associated Virus. Site-specific insertion of the donor sequence downstream of the endogenous CD40L promoter maintained physiologic expression of CD40L while overriding all reported downstream mutations. High levels of gene modification were achieved in primary human hematopoietic stem cells (HSCs, as well as in cell lines and XHIM-patient-derived T cells. Notably, gene-corrected HSCs engrafted in immunodeficient mice at clinically relevant frequencies. These studies provide the foundation for a permanent curative therapy in XHIM.

Genome Analysis of a Transmissible Lineage of Pseudomonas aeruginosa Reveals Pathoadaptive Mutations and Distinct Evolutionary Paths of Hypermutators

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Marvig, Rasmus Lykke; Johansen, Helle Krogh; Molin, Søren

2013-01-01

Genome sequencing of bacterial pathogens has advanced our understanding of their evolution, epidemiology, and response to antibiotic therapy. However, we still have only a limited knowledge of the molecular changes in in vivo evolving bacterial populations in relation to long-term, chronic...... targeted by mutations to optimize pathogen fitness (pathoadaptive mutations). These genes were related to antibiotic resistance, the cell envelope, or regulatory functions, and we find that the prevalence of pathoadaptive mutations correlates with evolutionary success of co-evolving sub-lineages. The long...... likelihood to acquire mutations and identify two homopolymer-containing genes preferentially mutated in hypermutators. This homopolymer facilitated differential mutagenesis provides a novel genome-wide perspective on the different evolutionary trajectories of hypermutators, which may help explain...

Absence of A3Z3-Related Hypermutations in the env and vif Proviral Genes in FIV Naturally Infected Cats

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Lucía Cano-Ortiz

2018-05-01

Full Text Available Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3 proteins comprise an important family of restriction factors that produce hypermutations on proviral DNA and are able to limit virus replication. Vif, an accessory protein present in almost all lentiviruses, counteracts the antiviral A3 activity. Seven haplotypes of APOBEC3Z3 (A3Z3 were described in domestic cats (hap I–VII, and in-vitro studies have demonstrated that these proteins reduce infectivity of vif-defective feline immunodeficiency virus (FIV. Moreover, hap V is resistant to vif-mediated degradation. However, studies on the effect of A3Z3 in FIV-infected cats have not been developed. Here, the correlation between APOBEC A3Z3 haplotypes in domestic cats and the frequency of hypermutations in the FIV vif and env genes were assessed in a retrospective cohort study with 30 blood samples collected between 2012 and 2016 from naturally FIV-infected cats in Brazil. The vif and env sequences were analyzed and displayed low or undetectable levels of hypermutations, and could not be associated with any specific A3Z3 haplotype.

Immunoglobulins in Cerebrospinal Fluid

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Sellebjerg, Finn Thorup

2015-01-01

immunoglobulin synthesis. Intrathecally synthesised immunoglobulins are usually of restricted clonality, and electrophoresis-based methods can be used for detecting this in the form of oligoclonal bands. These methods depend on comparing paired CSF and blood samples. Qualitative analyses for the assessment......The assessment of intrathecally synthesised immunoglobulin is an important part of routine cerebrospinal fl uid (CSF) analysis. Immunoglobulins can be detected in normal CSF and are derived from plasma. The appearance of immunoglobulins in normal CSF is readily explained by size-dependent diffusion...

Effect of colostrum on gravity separation of milk somatic cells in skim milk.

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Geer, S R; Barbano, D M

2014-02-01

Our objective was to determine if immunoglobulins play a role in the gravity separation (rising to the top) of somatic cells (SC) in skim milk. Other researchers have shown that gravity separation of milk fat globules is enhanced by IgM. Our recent research found that bacteria and SC gravity separate in both raw whole and skim milk and that heating milk to >76.9 °C for 25s stopped gravity separation of milk fat, SC, and bacteria. Bovine colostrum is a good natural source of immunoglobulins. An experiment was designed where skim milk was heated at high temperatures (76 °C for 7 min) to stop the gravity separation of SC and then colostrum was added back to try to restore the gravity separation of SC in increments to achieve 0, 0.4, 0.8, 2.0, and 4.0 g/L of added immunoglobulins. The milk was allowed to gravity separate for 22 h at 4 °C. The heat treatment of skim milk was sufficient to stop the gravity separation of SC. The treatment of 4.0 g/L of added immunoglobulins was successful in restoring the gravity separation of SC as compared with raw skim milk. Preliminary spore data on the third replicate suggested that bacterial spores gravity separate the same way as the SC in heated skim milk and heated skim milk with 4.0 g/L of added immunoglobulins. Strong evidence exists that immunoglobulins are at least one of the factors necessary for the gravity separation of SC and bacterial spores. It is uncertain at this time whether SC are a necessary component for gravity separation of fat, bacteria, and spores to occur. Further research is needed to determine separately the role of immunoglobulins and SC in gravity separation of bacteria and spores. Understanding the mechanism of gravity separation may allow the development of a continuous flow technology to remove SC, bacteria, and spores from milk. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Differential programming of B cells in AID deficient mice.

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Marc A Hogenbirk

Full Text Available The Aicda locus encodes the activation induced cytidine deaminase (AID and is highly expressed in germinal center (GC B cells to initiate somatic hypermutation (SHM and class switch recombination (CSR of immunoglobulin (Ig genes. Besides these Ig specific activities in B cells, AID has been implicated in active DNA demethylation in non-B cell systems. We here determined a potential role of AID as an epigenetic eraser and transcriptional regulator in B cells. RNA-Seq on different B cell subsets revealed that Aicda(-/- B cells are developmentally affected. However as shown by RNA-Seq, MethylCap-Seq, and SNP analysis these transcriptome alterations may not relate to AID, but alternatively to a CBA mouse strain derived region around the targeted Aicda locus. These unexpected confounding parameters provide alternative, AID-independent interpretations on genotype-phenotype correlations previously reported in numerous studies on AID using the Aicda(-/- mouse strain.

The interaction between calreticulin and immunoglobulin G and immunoglobulin Y

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Møllegaard, Karen Mai; Duus, Karen; Træholt, Sofie Dietz

2011-01-01

accumulating in support of calreticulin as a polypeptide binding chaperone. In contrast to mammalian immunoglobulin G (IgG), which has complex type N-glycans, chicken immunoglobulin Y (IgY) possesses a monoglucosylated high mannose N-linked glycan, which is a ligand for calreticulin. Here, we have used solid...... and solution-phase assays to analyze the in vitro binding of calreticulin, purified from human placenta, to human IgG and chicken IgY in order to compare the interactions. In addition, peptides from the respective immunoglobulins were included to further probe the binding specificity of calreticulin....... The experiments demonstrate the ability of calreticulin to bind to denatured forms of both IgG and IgY regardless of the glycosylation state of the proteins. Furthermore, calreticulin exhibits binding to peptides (glycosylated and non-glycosylated) derived from trypsin digestion of both immunoglobulins...

Sequence similarities of protein kinase substrates and inhibitors with immunoglobulins and model immunoglobulin homologue: cell adhesion molecule from the living fossil sponge Geodia cydonium. Mapping of coherent database similarities and implications for evolution of CDR1 and hypermutation

Czech Academy of Sciences Publication Activity Database

Kubrycht, J.; Borecký, Jiří; Souček, P.; Ježek, Petr

2004-01-01

Roč. 49, č. 3 (2004), s. 219-246 ISSN 0015-5632 R&D Projects: GA MZd NJ6747 Institutional research plan: CEZ:AV0Z5011922 Keywords : CDR1 * immunoglobulin Subject RIV: EE - Microbiology, Virology Impact factor: 1.034, year: 2004

Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution

Science.gov (United States)

Senavirathne, Gayan; Bertram, Jeffrey G.; Jaszczur, Malgorzata; Chaurasiya, Kathy R.; Pham, Phuong; Mak, Chi H.; Goodman, Myron F.; Rueda, David

2015-12-01

Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using single-molecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles, while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an 8 nt model bubble. When unconstrained on single-stranded (ss) DNA, AID moves in random bidirectional short slides/hops over the entire molecule while remaining bound for ~5 min. Our analysis distinguishes dynamic scanning from static ssDNA creasing. That AID alone can track along with RNAP during transcription and scan within stalled transcription bubbles suggests a mechanism by which AID can initiate SHM and CSR when properly regulated, yet when unregulated can access non-Ig genes and cause cancer.

Diagnosis of Xeroderma pigmentosum variant in a young patient with two novel mutations in the POLH gene.

Science.gov (United States)

De Palma, Armando; Morren, Marie-Anne; Ged, Cécile; Pouvelle, Caroline; Taïeb, Alain; Aoufouchi, Said; Sarasin, Alain

2017-09-01

We describe the characterization of Xeroderma Pigmentosum variant (XPV) in a young Caucasian patient with phototype I, who exhibited a high sensitivity to sunburn and multiple cutaneous tumors at the age of 15 years. Two novel mutations in the POLH gene, which encodes the translesion DNA polymerase η, with loss of function due to two independent exon skippings, are reported to be associated as a compound heterozygous state in the patient. Western blot analysis performed on proteins from dermal fibroblasts derived from the patient and analysis of the mutation spectrum on immunoglobulin genes produced during the somatic hypermutation process in his memory B cells, show the total absence of translesion polymerase η activity in the patient. The total lack of Polη activity, necessary to bypass in an error-free manner UVR-induced pyrimidine dimers following sun exposure, explains the early unusual clinical appearance of this patient. © 2017 Wiley Periodicals, Inc.

Lysine residue 185 of Rad1 is a topological but not a functional counterpart of lysine residue 164 of PCNA.

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Niek Wit

Full Text Available Monoubiquitylation of the homotrimeric DNA sliding clamp PCNA at lysine residue 164 (PCNA(K164 is a highly conserved, DNA damage-inducible process that is mediated by the E2/E3 complex Rad6/Rad18. This ubiquitylation event recruits translesion synthesis (TLS polymerases capable of replicating across damaged DNA templates. Besides PCNA, the Rad6/Rad18 complex was recently shown in yeast to ubiquitylate also 9-1-1, a heterotrimeric DNA sliding clamp composed of Rad9, Rad1, and Hus1 in a DNA damage-inducible manner. Based on the highly similar crystal structures of PCNA and 9-1-1, K185 of Rad1 (Rad1(K185 was identified as the only topological equivalent of PCNA(K164. To investigate a potential role of posttranslational modifications of Rad1(K185 in DNA damage management, we here generated a mouse model with a conditional deletable Rad1(K185R allele. The Rad1(K185 residue was found to be dispensable for Chk1 activation, DNA damage survival, and class switch recombination of immunoglobulin genes as well as recruitment of TLS polymerases during somatic hypermutation of immunoglobulin genes. Our data indicate that Rad1(K185 is not a functional counterpart of PCNA(K164.

Uracil DNA glycosylase counteracts APOBEC3G-induced hypermutation of hepatitis B viral genomes: excision repair of covalently closed circular DNA.

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Kouichi Kitamura

Full Text Available The covalently closed circular DNA (cccDNA of the hepatitis B virus (HBV plays an essential role in chronic hepatitis. The cellular repair system is proposed to convert cytoplasmic nucleocapsid (NC DNA (partially double-stranded DNA into cccDNA in the nucleus. Recently, antiviral cytidine deaminases, AID/APOBEC proteins, were shown to generate uracil residues in the NC-DNA through deamination, resulting in cytidine-to-uracil (C-to-U hypermutation of the viral genome. We investigated whether uracil residues in hepadnavirus DNA were excised by uracil-DNA glycosylase (UNG, a host factor for base excision repair (BER. When UNG activity was inhibited by the expression of the UNG inhibitory protein (UGI, hypermutation of NC-DNA induced by either APOBEC3G or interferon treatment was enhanced in a human hepatocyte cell line. To assess the effect of UNG on the cccDNA viral intermediate, we used the duck HBV (DHBV replication model. Sequence analyses of DHBV DNAs showed that cccDNA accumulated G-to-A or C-to-T mutations in APOBEC3G-expressing cells, and this was extensively enhanced by UNG inhibition. The cccDNA hypermutation generated many premature stop codons in the P gene. UNG inhibition also enhanced the APOBEC3G-mediated suppression of viral replication, including reduction of NC-DNA, pre-C mRNA, and secreted viral particle-associated DNA in prolonged culture. Enhancement of APOBEC3G-mediated suppression by UNG inhibition was not observed when the catalytic site of APOBEC3G was mutated. Transfection experiments of recloned cccDNAs revealed that the combination of UNG inhibition and APOBEC3G expression reduced the replication ability of cccDNA. Taken together, these data indicate that UNG excises uracil residues from the viral genome during or after cccDNA formation in the nucleus and imply that BER pathway activities decrease the antiviral effect of APOBEC3-mediated hypermutation.

Cortisol and somatization.

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Rief, W; Auer, C

2000-05-01

Somatization symptoms are frequently associated with depression, anxiety, and feelings of distress. These features interact with the activity of the HPA-axis. Therefore we investigated relationships between somatization symptoms and cortisol. Seventy-seven participants were classified into three groups: somatization syndrome (at least eight physical symptoms from the DSM-IV somatization disorder list), somatization syndrome combined with major depression, and healthy controls. The following data were collected: salivary cortisol at three time points (morning, afternoon, evening), nighttime urinary cortisol, serum cortisol after the dexamethasone suppression test (DST), and psychological variables such as depression, anxiety, somatization, and hypochondriasis. Salivary cortisol showed typical diurnal variations. However, the groups did not differ on any of the cortisol variables. A possible explanation may be counteracting effects of somatization and depression. Exploratory correlational analyses revealed that associations between cortisol and psychopathological variables were time-dependent. DST results correlated with psychological aspects of somatization, but not with the number of somatoform symptoms per se.

Gravity separation of fat, somatic cells, and bacteria in raw and pasteurized milks.

Science.gov (United States)

Caplan, Z; Melilli, C; Barbano, D M

2013-04-01

The objective of experiment 1 was to determine if the extent of gravity separation of milk fat, bacteria, and somatic cells is influenced by the time and temperature of gravity separation or the level of contaminating bacteria present in the raw milk. The objective of experiment 2 was to determine if different temperatures of milk heat treatment affected the gravity separation of milk fat, bacteria, and somatic cells. In raw milk, fat, bacteria, and somatic cells rose to the top of columns during gravity separation. About 50 to 80% of the fat and bacteria were present in the top 8% of the milk after gravity separation of raw milk. Gravity separation for 7h at 12°C or for 22h at 4°C produced equivalent separation of fat, bacteria, and somatic cells. The completeness of gravity separation of fat was influenced by the level of bacteria in the milk before separation. Milk with a high bacterial count had less (about 50 to 55%) gravity separation of fat than milk with low bacteria count (about 80%) in 22h at 4°C. Gravity separation caused fat, bacteria, and somatic cells to rise to the top of columns for raw whole milk and high temperature, short-time pasteurized (72.6°C, 25s) whole milk. Pasteurization at ≥76.9°C for 25s prevented all 3 components from rising, possibly due to denaturation of native bovine immunoglobulins that normally associate with fat, bacteria, and somatic cells during gravity separation. Gravity separation can be used to produce reduced-fat milk with decreased bacterial and somatic cell counts, and may be a critical factor in the history of safe and unique traditional Italian hard cheeses produced from gravity-separated raw milk. A better understanding of the mechanism of this natural process could lead to the development of new nonthermal thermal technology (that does not involve heating the milk to high temperatures) to remove bacteria and spores from milk or other liquids. Copyright © 2013 American Dairy Science Association. Published by

Somatic Expression of Psychological Problems (Somatization: Examination with Structural Equation Model

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Tugba Seda Çolak

2014-09-01

Full Text Available The main purpose of the research is to define which psychological symptoms (somatization, depression, obsessive ‐ compulsive, hostility, interpersonal sensitivity, anxiety, phobic anxiety, paranoid ideation and psychoticism cause somatic reactions at most. Total effect of these psychological symptoms on somatic symptoms had been investigated. Study was carried out with structural equation model to research the relation between the psychological symptoms and somatization. The main material of the research is formed by the data obtained from 492 people. SCL‐90‐R scale was used in order to obtain the data. As a result of the structural equation analysis, it has been found that 1Psychoticism, phobic anxiety, and paranoid ideation do not predict somatic symptoms.2There is a negative relation between interpersonal sensitivity level mand somatic reactions.3Anxiety symptoms had been found as causative to occur the highest level of somatic reactions.

Enhancement of hypermutation frequency in the chicken B cell line DT40 for efficient diversification of the antibody repertoire

Energy Technology Data Exchange (ETDEWEB)

Magari, Masaki; Kanehiro, Yuichi; Todo, Kagefumi; Ikeda, Mika; Kanayama, Naoki, E-mail: nkanayama@cc.okayama-u.ac.jp; Ohmori, Hitoshi

2010-05-28

Chicken B cell line DT40 continuously accumulates mutations in the immunoglobulin variable region (IgV) gene by gene conversion and point mutation, both of which are mediated by activation-induced cytidine deaminase (AID), thereby producing an antibody (Ab) library that is useful for screening monoclonal Abs (mAbs) in vitro. We previously generated an engineered DT40 line named DT40-SW, whose AID expression can be reversibly switched on or off, and developed an in vitro Ab generation system using DT40-SW cells. To efficiently create an Ab library with sufficient diversity, higher hypermutation frequency is advantageous. To this end, we generated a novel cell line DT40-SW{Delta}C, which conditionally expresses a C-terminus-truncated AID mutant lacking the nuclear export signal. The transcription level of the mutant AID gene in DT40-SW{Delta}C cells was similar to that of the wild-type gene in DT40-SW cells. However, the protein level of the truncated AID mutant was less than that of the wild type. The mutant protein was enriched in the nuclei of DT40-SW{Delta}C cells, although the protein might be highly susceptible to degradation. In DT40-SW{Delta}C cells, both gene conversion and point mutation occurred in the IgV gene with over threefold higher frequency than in DT40-SW cells, suggesting that a lower level of the mutant AID protein was sufficient to increase mutation frequency. Thus, DT40-SW{Delta}C cells may be useful for constructing Ab libraries for efficient screening of mAbs in vitro.

Adaptive antibody diversification through N-linked glycosylation of the immunoglobulin variable region.

Science.gov (United States)

van de Bovenkamp, Fleur S; Derksen, Ninotska I L; Ooijevaar-de Heer, Pleuni; van Schie, Karin A; Kruithof, Simone; Berkowska, Magdalena A; van der Schoot, C Ellen; IJspeert, Hanna; van der Burg, Mirjam; Gils, Ann; Hafkenscheid, Lise; Toes, René E M; Rombouts, Yoann; Plomp, Rosina; Wuhrer, Manfred; van Ham, S Marieke; Vidarsson, Gestur; Rispens, Theo

2018-02-20

A hallmark of B-cell immunity is the generation of a diverse repertoire of antibodies from a limited set of germline V(D)J genes. This repertoire is usually defined in terms of amino acid composition. However, variable domains may also acquire N -linked glycans, a process conditional on the introduction of consensus amino acid motifs ( N -glycosylation sites) during somatic hypermutation. High levels of variable domain glycans have been associated with autoantibodies in rheumatoid arthritis, as well as certain follicular lymphomas. However, the role of these glycans in the humoral immune response remains poorly understood. Interestingly, studies have reported both positive and negative effects on antibody affinity. Our aim was to elucidate the role of variable domain glycans during antigen-specific antibody responses. By analyzing B-cell repertoires by next-generation sequencing, we demonstrate that N -glycosylation sites are introduced at positions in which glycans can affect antigen binding as a result of a specific clustering of progenitor glycosylation sites in the germline sequences of variable domain genes. By analyzing multiple human monoclonal and polyclonal (auto)antibody responses, we subsequently show that this process is subject to selection during antigen-specific antibody responses, skewed toward IgG4, and positively contributes to antigen binding. Together, these results highlight a physiological role for variable domain glycosylation as an additional layer of antibody diversification that modulates antigen binding.

Secondary immunization generates clonally related antigen-specific plasma cells and memory B cells.

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Frölich, Daniela; Giesecke, Claudia; Mei, Henrik E; Reiter, Karin; Daridon, Capucine; Lipsky, Peter E; Dörner, Thomas

2010-09-01

Rechallenge with T cell-dependent Ags induces memory B cells to re-enter germinal centers (GCs) and undergo further expansion and differentiation into plasma cells (PCs) and secondary memory B cells. It is currently not known whether the expanded population of memory B cells and PCs generated in secondary GCs are clonally related, nor has the extent of proliferation and somatic hypermutation of their precursors been delineated. In this study, after secondary tetanus toxoid (TT) immunization, TT-specific PCs increased 17- to 80-fold on days 6-7, whereas TT-specific memory B cells peaked (delayed) on day 14 with a 2- to 22-fold increase. Molecular analyses of V(H)DJ(H) rearrangements of individual cells revealed no major differences of gene usage and CDR3 length between TT-specific PCs and memory B cells, and both contained extensive evidence of somatic hypermutation with a pattern consistent with GC reactions. This analysis identified clonally related TT-specific memory B cells and PCs. Within clusters of clonally related cells, sequences shared a number of mutations but also could contain additional base pair changes. The data indicate that although following secondary immunization PCs can derive from memory B cells without further somatic hypermutation, in some circumstances, likely within GC reactions, asymmetric mutation can occur. These results suggest that after the fate decision to differentiate into secondary memory B cells or PCs, some committed precursors continue to proliferate and mutate their V(H) genes.

INTRAVENOUS IMMUNOGLOBULIN IN PEDIATRIC RHEUMATOLOGY PRACTICE

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E. I. Alexeeva

2015-01-01

Full Text Available Modern successful treatment of rheumatic diseases is impossible without the use of intravenous immunoglobulin. The use of intravenous immunoglobulin is based on strict indications developed as a result of long-term multicenter controlled studies. The article highlights the issues of using immunoglobulin in pediatric rheumatology practice, and provides the review of literature with the results from the evaluation of the efficiency of intravenous immunoglobulin confirming the efficiency of the drug only for certain rheumatic diseases. 

Characterization of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Shanghai, China: molecular and cytogenetic characteristics, IgV gene restriction and hypermutation patterns.

Science.gov (United States)

Irons, Richard D; Le, Anh; Bao, Liming; Zhu, Xiongzeng; Ryder, John; Wang, Xiao Qin; Ji, Meirong; Chen, Yan; Wu, Xichun; Lin, Guowei

2009-12-01

The clinical, cytogenetic and molecular features of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), a disease previously considered to be rare in Asia, were examined in consecutive series of 70 cases diagnosed by our laboratory over a 30-month period. Clonal abnormalities were observed in 80% of CLL/SLL cases using a combination of conventional cytogenetic and fluorescence in situ hybridization (FISH) analysis. Those involving 14q32/IGH were the most frequent (24 cases), followed by trisomy 12 and 11q abnormalities. IgV(H) gene usage was non-random with over-representation of V(H)4-34, V(H)3-23 and a previously unreported increase in V(H)3-48 gene use. Somatic hypermutation (SHM) of IgV(H) germline sequences was observed in 56.5% of cases with stereotyped patterns of SHM observed in V(H)4-34 heavy chain complimentary-determining (HCDR1) and framework region CFR2 sequences. These findings in a Chinese population suggest subtle geographical differences in IgV(H) gene usage while the remarkably specific pattern of SHM suggest that a relatively limited set of antigens may be involved in the development of this disease worldwide. IgV(H) gene mutation status was a significant predictor of initial survival in CLL/SLL. However, an influence of karyotype on prognosis was not observed.

Clinical applications of immunoglobulin: update

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Marcia Cristina Zago Novaretti

2011-06-01

Full Text Available Human immunoglobulin is the most used blood product in the clinical practice. Immunoglobulin applications have increased quickly since the elucidation of its immunomodulatory and antiinflammatory properties which turned this blood product into a precious tool in the treatment of numerous diseases that present with humoral immune deficiency or that cause immune system dysfunction. Currently, the approved indications for Ig are: primary immunodeficiencies, secondary immunodeficiencies (multiple myeloma or chronic lymphoid leukemia, Kawasaki syndrome, immune thrombocytopenic purpura, Guillain Barré syndrome, graft-versus-host disease following bone marrow transplantation and repeat infections in HIV children. On the other hand, there are numerous "off-label" indications of immunoglobulin, which represent 20-60% of all clinical applications of this drug. It is important to study all these indications and, above all, the scientific evidence for its use, in order to provide patients with a new therapeutic option without burdening the health system. This review results from a wide selection of papers identified in the Pubmed and Lilacs scientific electronic databases. A group of descriptors were used from human immunoglobulin to the names of each disease that immunoglobulin is clinically applied. Our main objective is to list the numerous indications of immunoglobulin, both authorized and "off-label" and to analyze these indications in the light of the most recent scientific evidence.

Immunoglobulins for preventing hepatitis A

DEFF Research Database (Denmark)

Liu, Jian Ping; Nikolova, Dimitrinka; Fei, Yutong

2009-01-01

Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention.......Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention....

SOMATIC EMBRYOGENESIS AND MORPHOANATOMY OF Ocotea porosa SOMATIC EMBRYOS

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Luciana Luiza Pelegrini

2013-01-01

Full Text Available Ocotea porosa seeds have strong tegument dormancy, recalcitrant behavior, low and irregular germination and that makes its natural propagation difficult. The aim of this study was to establish a protocol of regeneration of Ocotea porosa from somatic embryogenesis. Immature embryonic axes were inoculated on WPM culture medium supplemented with 2.4-D (200 μM combined or not with hydrolyzed casein or glutamine (0.5 or 1 g l-1, during 90 days. The repetitive embryogenesis was induced on medium with 2.4-D (22.62 μM combined with 2-iP (2.46 μM followed by transfer to culture medium with hydrolyzed casein or glutamine (1 g l-1 during 90 days. The maturation of somatic embryos was tested in culture medium containing NAA (0.5 μM and 2-iP (5; 10 and 20 μM. The highest percentage of somatic embryos induction (8.3% was observed in WPM culture medium containing 200 μM 2.4-D and 1 g L-1 hydrolyzed casein and the development of somatic embryos occurred indirectly. Repetitive somatic embryogenesis was promoted in WPM medium containing hydrolyzed casein or glutamine. However, the culture medium containing hydrolyzed casein promoted the maintenance of embryogenic capacity for more than two years. During the maturity phase, there was a low progression of globular embryos to cordiform and torpedo stages. The different ontogenetic stages of somatic embryos of Ocotea porosa were characterized by histological studies.

SOMATIC EMBRYOGENESIS AND MORPHOANATOMY OF Ocotea porosa SOMATIC EMBRYOS

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Luciana Luiza Pelegrini

2013-12-01

Full Text Available http://dx.doi.org/10.5902/1980509812343Ocotea porosa seeds have strong tegument dormancy, recalcitrant behavior, low and irregular germinationand that makes its natural propagation difficult. The aim of this study was to establish a protocol ofregeneration of Ocotea porosa from somatic embryogenesis. Immature embryonic axes were inoculatedon WPM culture medium supplemented with 2.4-D (200 μM combined or not with hydrolyzed casein orglutamine (0.5 or 1 g l-1, during 90 days. The repetitive embryogenesis was induced on medium with 2.4-D(22.62 μM combined with 2-iP (2.46 μM followed by transfer to culture medium with hydrolyzed caseinor glutamine (1 g l-1 during 90 days. The maturation of somatic embryos was tested in culture mediumcontaining NAA (0.5 μM and 2-iP (5; 10 and 20 μM. The highest percentage of somatic embryos induction(8.3% was observed in WPM culture medium containing 200 μM 2.4-D and 1 g L-1 hydrolyzed casein andthe development of somatic embryos occurred indirectly. Repetitive somatic embryogenesis was promotedin WPM medium containing hydrolyzed casein or glutamine. However, the culture medium containinghydrolyzed casein promoted the maintenance of embryogenic capacity for more than two years. Duringthe maturity phase, there was a low progression of globular embryos to cordiform and torpedo stages.The different ontogenetic stages of somatic embryos of Ocotea porosa were characterized by histologicalstudies.

Detection of inflammatory lesions with radiolabelled immunoglobulins

International Nuclear Information System (INIS)

Blok, D.; Rijksuniversiteit Leiden; Ogtrop, M. van; Arndt, J.W.; Camps, J.A.J.; Feitsma, R.I.J.; Pauwels, E.K.J.

1990-01-01

Previous reports on the use of radiolabelled immunoglobulins led us to undertake a pilot experiment in an animal model to investigate the potentials sodium pertechnate Tc 99m-immunoglobulin scintigraphy in the detection of infectious foci. Mice infected in one leg with staphylococcus infection in were injected with sodium pertechnote Tc 99m-immunoglobulin, albumin aggregated technetium Tc 99m or gallium citrate Ga 67. The results obtained by scintigraphy suggested a specific accumulation of radiolabelled immunoglobulin at the site of infection. Visualization of the infection and the image quality, especially the 6- and 24-h images, were clearly enhanced after the use of immunoglobulin preparations as compared with those labelled with gallium. (orig.)

Somatic symptom disorder

Science.gov (United States)

... related disorders; Somatization disorder; Somatiform disorders; Briquet syndrome; Illness anxiety disorder References American Psychiatric Association. Somatic symptom disorder. Diagnostic and Statistical Manual of Mental Disorders . ...

Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

DEFF Research Database (Denmark)

Hertel, Christina B; Zhou, Xiao-ge; Hamilton-Dutoit, Stephen J

2002-01-01

In classical Hodgkin lymphoma the malignant Hodgkin/Reed-Sternberg (HRS) cells characteristically constitute only a small minority of the tumour load. Their origin has been debated for decades, but on the basis of rearrangement and somatic hypermutations of their immunoglubulin (Ig) genes, HRS ce...

Management of somatic symptoms

DEFF Research Database (Denmark)

Schröder, Andreas; Dimsdale, Joel

2014-01-01

on the recognition and effective management of patients with excessive and disabling somatic symptoms. The clinical presentation of somatic symptoms is categorized into three groups of patients: those with multiple somatic symptoms, those with health anxiety, and those with conversion disorder. The chapter provides...

Further evidence for a broader concept of somatization disorder using the somatic symptom index.

Science.gov (United States)

Hiller, W; Rief, W; Fichter, M M

1995-01-01

Somatization syndromes were defined in a sample of 102 psychosomatic inpatients according to the restrictive criteria of DSM-III-R somatization disorder and the broader diagnostic concept of the Somatic Symptom Index (SSI). Both groups showed a qualitatively similar pattern of psychopathological comorbidity and had elevated scores on measures of depression, hypochondriasis, and anxiety. A good discrimination between mild and severe forms of somatization was found by using the SSI criterion. SSI use accounted for a substantial amount of comorbidity variance, with rates of 15%-20% for depression, 16% for hypochondriasis, and 13% for anxiety. The results provide further evidence for the validity of the SSI concept, which reflects the clinical relevance of somatization in addition to the narrow definition of somatization disorder.

Mechanisms behind functional avidity maturation in T cells

DEFF Research Database (Denmark)

von Essen, Marina Rode; Kongsbak, Martin; Geisler, Carsten

2012-01-01

During an immune response antigen-primed B-cells increase their antigen responsiveness by affinity maturation mediated by somatic hypermutation of the genes encoding the antigen-specific B-cell receptor (BCR) and by selection of higher-affinity B cell clones. Unlike the BCR, the T-cell receptor...

Is somatic comorbidity associated with more somatic symptoms, mental distress, or unhealthy lifestyle in elderly cancer survivors?

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Grov, Ellen Karine; Fosså, Sophie D; Dahl, Alv A

2009-06-01

The associations of lifestyle factors, somatic symptoms, mental distress, and somatic comorbidity in elderly cancer survivors have not been well studied. This study examines these associations among elderly cancer survivors (age >or=65 years) in a population-based sample. A cross-sectional comparative study of Norwegian elderly cancer survivors. Combining information from The Norwegian Cancer Registry, and by self-reporting, 972 elderly cancer survivors were identified, of whom 632 (65%) had somatic comorbidity and 340 did not. Elderly cancer survivors with somatic comorbidity had significantly higher BMI, more performed minimal physical activity, had more somatic symptoms, used more medication, and had more frequently seen a medical doctor than survivors without somatic comorbidity. In multivariable analyses, unhealthy lifestyle and higher somatic symptoms scores were significantly associated with cancer cases with somatic comorbidity. In univariate analyses those with somatic comorbidity were significantly older, had lower levels of education, higher proportions of BMI >or= 30, less physical activity, poorer self-rated health, higher somatic symptoms score, more mental distress, had more frequently seen a medical doctor last year, and more frequently used daily medication. Our outcome measures of lifestyle, somatic symptoms and mental distress were all significantly associated with somatic comorbidity in elderly cancer survivors, however only lifestyle and somatic symptoms were significant in multivariable analyses. In elderly cancer survivors not only cancer, but also somatic comorbidity, deserve attention. Such comorbidity is associated with unhealthy lifestyles, more somatic symptoms and mental distress which should be evaluated and eventually treated.

Pms2 and uracil-DNA glycosylases act jointly in the mismatch repair pathway to generate Ig gene mutations at A-T base pairs.

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Girelli Zubani, Giulia; Zivojnovic, Marija; De Smet, Annie; Albagli-Curiel, Olivier; Huetz, François; Weill, Jean-Claude; Reynaud, Claude-Agnès; Storck, Sébastien

2017-04-03

During somatic hypermutation (SHM) of immunoglobulin genes, uracils introduced by activation-induced cytidine deaminase are processed by uracil-DNA glycosylase (UNG) and mismatch repair (MMR) pathways to generate mutations at G-C and A-T base pairs, respectively. Paradoxically, the MMR-nicking complex Pms2/Mlh1 is apparently dispensable for A-T mutagenesis. Thus, how detection of U:G mismatches is translated into the single-strand nick required for error-prone synthesis is an open question. One model proposed that UNG could cooperate with MMR by excising a second uracil in the vicinity of the U:G mismatch, but it failed to explain the low impact of UNG inactivation on A-T mutagenesis. In this study, we show that uracils generated in the G1 phase in B cells can generate equal proportions of A-T and G-C mutations, which suggests that UNG and MMR can operate within the same time frame during SHM. Furthermore, we show that Ung -/- Pms2 -/- mice display a 50% reduction in mutations at A-T base pairs and that most remaining mutations at A-T bases depend on two additional uracil glycosylases, thymine-DNA glycosylase and SMUG1. These results demonstrate that Pms2/Mlh1 and multiple uracil glycosylases act jointly, each one with a distinct strand bias, to enlarge the immunoglobulin gene mutation spectrum from G-C to A-T bases. © 2017 Girelli Zubani et al.

Radioimmunoassay to quantitatively measure cell surface immunoglobulins

International Nuclear Information System (INIS)

Krishman, E.C.; Jewell, W.R.

1975-01-01

A radioimmunoassay techniques developed to quantitatively measure the presence of immunoglobulins on the surface of cells, is described. The amount of immunoglobulins found on different tumor cells varied from 200 to 1140 ng/10 6 cells. Determination of immunoglobulins on the peripheral lymphocytes obtained from different cancer patients varied between 340 to 1040 ng/10 6 cells. Cultured tumor cells, on the other hand, were found to contain negligible quantities of human IgG [pt

Hypochondriasis and somatization.

Science.gov (United States)

Kellner, R

1987-11-20

Between 60% and 80% of healthy individuals experience somatic symptoms in any one week. About 10% to 20% of a random sample of people worry intermittently about illness. A substantial proportion of patients present physicians with somatic complaints for which no organic cause can be found. Patients who are hypochondriacal do not understand the benign nature of functional somatic symptoms and interpret these as evidence of disease. Hypochondriacal concerns range from common short-lived worries to persistent and distressing fears or convictions of having a disease. Hypochondriasis can be secondary to other psychiatric disorders (eg, melancholia or panic disorder), and hypochondriacal attitudes remit when the primary disorder is successfully treated. Patients with primary hypochondriasis are also anxious or depressed, but the fear of disease, or the false belief of having a disease, persists and is the most important feature of their psychopathology. There are substantial differences among hypochondriacal patients in their personalities and psychopathologies. Psychotherapy as well as psychotropic drugs are effective in the treatment of functional somatic symptoms. There are no adequate controlled studies on the value of psychotherapy in hypochondriasis; the recommended guidelines are based on uncontrolled studies of hypochondriasis and on controlled studies of the psychotherapy in similar disorders. The prognosis of functional somatic symptoms as well as that of hypochondriasis is good in a substantial proportion of patients.

Immunoglobulin M

DEFF Research Database (Denmark)

Pleass, Richard J; Moore, Shona C; Stevenson, Liz

2016-01-01

Immunoglobulin M (IgM) is an ancient antibody class that is found in all vertebrates, with the exception of coelacanths, and is indispensable in both innate and adaptive immunity. The equally ancient human malaria parasite, Plasmodium falciparum, formed an intimate relationship with IgM with whic...

Red-shifted fluorescent proteins mPlum and mRaspberry and polynucleotides encoding the same

Science.gov (United States)

Tsien, Roger Y [La Jolla, CA; Wang, Lei [San Diego, CA

2008-07-01

Methods using somatic hypermutation (SHM) for producing polypeptide and nucleic acid variants, and nucleic acids encoding such polypeptide variants are disclosed. Such variants may have desired properties. Also disclosed are novel polypeptides, such as improved fluorescent proteins, produced by the novel methods, and nucleic acids, vectors, and host cells comprising such vectors.

[Production, specificity and structure of immunoglobulins].

Science.gov (United States)

Goujard, C; Delfraissy, J F

1991-03-21

Immunoglobulin is a key factor of the immune response resulting from B-cell activation and associated with T-cell stimulation. Because of its structure, this antibody has a dual function: it specifically recognizes the inducer antigen in the variable region and eliminates it by a constant portion which is responsible for effector properties. Surface immunoglobulin, therefore, is the B-cell antigen receptor; it differs from the T-cell receptor in that it recognizes the antigen unbound to the major istocompatibility complex; binding the antigen results in direct signal transduction first in the cytoplasm, then in the nucleus. This receptor can be secreted in the body: it is made up of circulating immunoglobulins. Human immunoglobulins are divided into 5 classes, each of them with its own response kinetics, distribution and functions. The variability of the antibody response accounts for a genetic organization involving numerous genes which may be associated with each other, or mutate, or recombine during maturation of the lymphocytes. Altogether, this system has a theoretical capacity of response to three hundred million different antigens.

Perspectives on Immunoglobulins in colostrum and milk

DEFF Research Database (Denmark)

Hurley, W L; Theil, Peter Kappel

2011-01-01

Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide...... a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases....... The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted...

[Somatization disorders of the urogenital tract].

Science.gov (United States)

Günthert, E A

2002-11-01

Diffuse symptoms in the urogenital region can frequently be explained by somatization disorders. Since they cannot be proven either by laboratory tests or with common technical diagnostic methods, somatization disorders should always be taken into consideration. Somatization disorders are to be considered functional disorders. Since somatization disorders due to muscular tension prevail in the urogenital region, the functional disturbance can be explained by the muscular tension. Subsequently, muscular tension causes the pathophysiological development of symptoms. As a rule they appear as myofascial pain or disorder. Muscular tension can have a psychic origin. The absence of urological findings is typical. Males and females between the ages of 16 and 75 can be affected by somatization disorders in the urogenital region. Somatization disorders due to muscular tension belong to the large group of symptoms due to tension. Diagnostic and therapeutic procedures as well as the pathophysiology of somatization disorders due to muscular tension are illustrated by two detailed case-reports.

Hypermutability of a UV-sensitive aphidicolin-resistant mutant of Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Liu, P.K.; Chang, C.; Trosko, J.E.

1982-01-01

An ultraviolet light (UV)-sensitive thymidine auxotroph of Chinese hamster V79 cells that exhibits pleiotropic effects such as a high level of deoxycytidine triphosphate, slow growth, sensitivity to cytidine, and high frequencies of site-specific bromodeoxyuridine-dependent chromosomal aberrations was selected by its resistance to aphidicolin. The UV-induced mutability of this mutant and one of its revertants, which retains some of the phenotypes listed above, was studied in 3 mutation assay systems. The results showed that the mutant was hypermutable for ouabain and diphtheria-toxin-resistant mutations compared to wild-type V79 cells at the same UV dose or the same survival level. The mutant exhibits a delayed expression of maximal frequency of induced 6-thioguanine-resistant mutants. When maximal frequencies are compared at the same UV dose, the mutant also has higher mutation frequencies at the hypoxanthine-guanine phosphoribosyl transferase locus. The revertant was similar to the wild-type in UV sensitivity and mutability. (orig./AJ)

A new high molecular weight immunoglobulin class from the carcharhine shark: implications for the properties of the primordial immunoglobulin.

Science.gov (United States)

Berstein, R M; Schluter, S F; Shen, S; Marchalonis, J J

1996-04-16

All immunoglobulins and T-cell receptors throughout phylogeny share regions of highly conserved amino acid sequence. To identify possible primitive immunoglobulins and immunoglobulin-like molecules, we utilized 3' RACE (rapid amplification of cDNA ends) and a highly conserved constant region consensus amino acid sequence to isolate a new immunoglobulin class from the sandbar shark Carcharhinus plumbeus. The immunoglobulin, termed IgW, in its secreted form consists of 782 amino acids and is expressed in both the thymus and the spleen. The molecule overall most closely resembles mu chains of the skate and human and a new putative antigen binding molecule isolated from the nurse shark (NAR). The full-length IgW chain has a variable region resembling human and shark heavy-chain (VH) sequences and a novel joining segment containing the WGXGT motif characteristic of H chains. However, unlike any other H-chain-type molecule, it contains six constant (C) domains. The first C domain contains the cysteine residue characteristic of C mu1 that would allow dimerization with a light (L) chain. The fourth and sixth domains also contain comparable cysteines that would enable dimerization with other H chains or homodimerization. Comparison of the sequences of IgW V and C domains shows homology greater than that found in comparisons among VH and C mu or VL, or CL thereby suggesting that IgW may retain features of the primordial immunoglobulin in evolution.

Monitoring Milk Somatic Cell Counts

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Gheorghe Şteţca

2014-11-01

Full Text Available The presence of somatic cells in milk is a widely disputed issue in milk production sector. The somatic cell counts in raw milk are a marker for the specific cow diseases such as mastitis or swollen udder. The high level of somatic cells causes physical and chemical changes to milk composition and nutritional value, and as well to milk products. Also, the mastitic milk is not proper for human consumption due to its contribution to spreading of certain diseases and food poisoning. According to these effects, EU Regulations established the maximum threshold of admitted somatic cells in raw milk to 400000 cells / mL starting with 2014. The purpose of this study was carried out in order to examine the raw milk samples provided from small farms, industrial type farms and milk processing units. There are several ways to count somatic cells in milk but the reference accepted method is the microscopic method described by the SR EN ISO 13366-1/2008. Generally samples registered values in accordance with the admissible limit. By periodical monitoring of the somatic cell count, certain technological process issues are being avoided and consumer’s health ensured.

Mediators between bereavement and somatic symptoms

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Konkolÿ Thege Barna

2012-06-01

Full Text Available Abstract Background In our research we examined the frequency of somatic symptoms among bereaved (N = 185 and non-bereaved men and women in a national representative sample (N = 4041 and investigated the possible mediating factors between bereavement status and somatic symptoms. Methods Somatic symptoms were measured by the Patient Health Questionnaire (PHQ-15, anxiety with a four-point anxiety rating scale, and depression with a nine-item shortened version of the Beck Depression Inventory. Results Among the bereaved, somatic symptoms proved to be significantly more frequent in both genders when compared to the non-bereaved, as did anxiety and depression. On the multivariate level, the results show that both anxiety and depression proved to be a mediator between somatic symptoms and bereavement. The effect sizes indicated that for both genders, anxiety was a stronger predictor of somatic symptoms than depression. Conclusions The results of our research indicate that somatic symptoms accompanying bereavement are not direct consequences of this state but they can be traced back to the associated anxiety and depression. These results draw attention to the need to recognize anxiety and depression looming in the background of somatic complaints in bereavement and to the importance of the dissemination of related information.

Use of intravenous immunoglobulins in clinical practice

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E.K. Donyush

2011-01-01

Full Text Available Immunoglobulins are main component of immune defense; they take part in anti-infectious resistance of organism and regulate processes of different immune reactions. Intravenous immunoglobulins are the most frequently used products made from donor blood plasma. The need in these drugs is steadily increasing during last 15–20 years, and indications are widening due to modern hightechnology methods of production and cleaning. The article presents modern data on formula, mechanisms of action and indications for different groups of intravenous immunoglobulins (standard, hyperimmune, fortified and description of possible adverse events.Key words: immuglobulines, prophylaxis, treatment, unfavorable reaction, children.

Osteoporosis and Somatization of Anxiety

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Maria Papanikou

2013-12-01

Full Text Available Chronic stress can now be physiologically traced as a significant player in the creation of osteoporotic bones. The present pilot study involved 100 women (N = 42 have been diagnosed with osteopenia, N = 21 have been diagnosed with osteoporosis, N = 37 had a non-osteoporotic condition who participated in the Hellenic Society of Osteoporosis Association Support. Correlations between somatic symptoms of anxiety and osteoporosis, and among medications and somatization in women were explored. Assessments were based on a self-report demographic questionnaire and on the Short Anxiety Screening Test (SAST administered for detection of anxiety disorder and somatization. Statistical analysis detected non-significant differences regarding the correlation between anxiety symptomatology or somatization due to osteoporosis and osteopenia diagnosis. The same pattern is observed among women’s age group, the occupational and marital status. Hypothesis that the osteoporosis and osteopenia group would manifest significant relationships with the age group and medicines was confirmed, as well as between somatization and medicines that women with osteoporosis and osteopenia undertake. The results suggest that women are not prone to manifest anxiety or somatization in relation to the osteoporosis condition. However, the majority of women with osteoporosis and osteopenia consume more than two medicines other than those for osteoporosis. This quantity and combination they undertake appear to contribute and deteriorate their anxiety/somatization symptomatology. Further research based on a larger sample would give more definite results.

Expression of Immunoglobulin Receptors with Distinctive Features Indicating Antigen Selection by Marginal Zone B Cells from Human Spleen

Science.gov (United States)

Colombo, Monica; Cutrona, Giovanna; Reverberi, Daniele; Bruno, Silvia; Ghiotto, Fabio; Tenca, Claudya; Stamatopoulos, Kostas; Hadzidimitriou, Anastasia; Ceccarelli, Jenny; Salvi, Sandra; Boccardo, Simona; Calevo, Maria Grazia; De Santanna, Amleto; Truini, Mauro; Fais, Franco; Ferrarini, Manlio

2013-01-01

Marginal zone (MZ) B cells, identified as surface (s)IgMhighsIgDlowCD23low/−CD21+CD38− B cells, were purified from human spleens, and the features of their V(D)J gene rearrangements were investigated and compared with those of germinal center (GC), follicular mantle (FM) and switched memory (SM) B cells. Most MZ B cells were CD27+ and exhibited somatic hypermutations (SHM), although to a lower extent than SM B cells. Moreover, among MZ B-cell rearrangements, recurrent sequences were observed, some of which displayed intraclonal diversification. The same diversifying sequences were detected in very low numbers in GC and FM B cells and only when a highly sensitive, gene-specific polymerase chain reaction was used. This result indicates that MZ B cells could expand and diversify in situ and also suggested the presence of a number of activation-induced cytidine deaminase (AID)-expressing B cells in the MZ. The notion of antigen-driven expansion/selection in situ is further supported by the VH CDR3 features of MZ B cells with highly conserved amino acids at specific positions and by the finding of shared (“stereotyped”) sequences in two different spleens. Collectively, the data are consistent with the notion that MZ B cells are a special subset selected by in situ antigenic stimuli. PMID:23877718

Hemoglobin promotes somatic embryogenesis in peanut cultures.

Science.gov (United States)

Jayabalan, N; Anthony, P; Davey, M R; Power, J B; Lowe, K C

2004-02-01

Critical parameters influencing somatic embryogenesis include growth regulators and oxygen supply. Consequently, the present investigation has focused on optimization of a somatic embryogenic system for peanut (Arachis hypogaea L.) through media supplementation with the auxin, picloram. The latter at 30 mg L(-1) was optimal for inducing regeneration of somatic embryos from cultured explants of zygotic embryos. In contrast, somatic embryogenesis did not occur in the absence of this growth regulator. An assessment has also been made of the beneficial effect on somatic embryogenesis and plant regeneration of the commercial hemoglobin (Hb) solution, Erythrogen. Hemoglobin at 1:50 and 1:100 (v:v) stimulated increases in mean fresh weight (up to a maximum of 57% over control), mean number of explants producing somatic embryos (15%) and mean number of somatic embryos per explant (29%).

The somatic symptom scale-8 (SSS-8): a brief measure of somatic symptom burden.

Science.gov (United States)

Gierk, Benjamin; Kohlmann, Sebastian; Kroenke, Kurt; Spangenberg, Lena; Zenger, Markus; Brähler, Elmar; Löwe, Bernd

2014-03-01

Somatic symptoms are the core features of many medical diseases, and they are used to evaluate the severity and course of illness. The 8-item Somatic Symptom Scale (SSS-8) was recently developed as a brief, patient-reported outcome measure of somatic symptom burden, but its reliability, validity, and usefulness have not yet been tested. To investigate the reliability, validity, and severity categories as well as the reference scores of the SSS-8. A national, representative general-population survey was performed between June 15, 2012, and July 15, 2012, in Germany, including 2510 individuals older than 13 years. The SSS-8 mean (SD), item-total correlations, Cronbach α, factor structure, associations with measures of construct validity (Patient Health Questionnaire-2 depression scale, Generalized Anxiety Disorder-2 scale, visual analog scale for general health status, 12-month health care use), severity categories, and percentile rank reference scores. The SSS-8 had excellent item characteristics and good reliability (Cronbach α = 0.81). The factor structure reflects gastrointestinal, pain, fatigue, and cardiopulmonary aspects of the general somatic symptom burden. Somatic symptom burden as measured by the SSS-8 was significantly associated with depression (r = 0.57 [95% CI, 0.54 to 0.60]), anxiety (r = 0.55 [95% CI, 0.52 to 0.58]), general health status (r = -0.24 [95% CI, -0.28 to -0.20]), and health care use (incidence rate ratio, 1.12 [95% CI, 1.10 to 1.14]). The SSS-8 severity categories were calculated in accordance with percentile ranks: no to minimal (0-3 points), low (4-7 points), medium (8-11 points), high (12-15 points), and very high (16-32 points) somatic symptom burden. For every SSS-8 severity category increase, there was a 53% (95% CI, 44% to 63%) increase in health care visits. The SSS-8 is a reliable and valid self-report measure of somatic symptom burden. Cutoff scores identify individuals with low, medium, high, and very high somatic

Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data.

Science.gov (United States)

Krøigård, Anne Bruun; Thomassen, Mads; Lænkholm, Anne-Vibeke; Kruse, Torben A; Larsen, Martin Jakob

2016-01-01

Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant callers creates a need for comparison and validation of the tools, as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported. We have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2 and Virmid for the detection of single nucleotide mutations and small deletions and insertions. We report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement. Sequencing depth had markedly diverse impact on individual callers, as for some callers, increased sequencing depth highly improved sensitivity. For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing. For indel calling, EBCall is superior due to high sensitivity and robustness to changes in sequencing depths.

Mutations in specific structural regions of immunoglobulin light chains are associated with free light chain levels in patients with AL amyloidosis.

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Tanya L Poshusta

Full Text Available BACKGROUND: The amyloidoses are protein misfolding diseases characterized by the deposition of amyloid that leads to cell death and tissue degeneration. In immunoglobulin light chain amyloidosis (AL, each patient has a unique monoclonal immunoglobulin light chain (LC that forms amyloid deposits. Somatic mutations in AL LCs make these proteins less thermodynamically stable than their non-amyloidogenic counterparts, leading to misfolding and ultimately the formation of amyloid fibrils. We hypothesize that location rather than number of non-conservative mutations determines the amyloidogenicity of light chains. METHODOLOGY/PRINCIPAL FINDINGS: We performed sequence alignments on the variable domain of 50 kappa and 91 lambda AL light chains and calculated the number of non-conservative mutations over total number of patients for each secondary structure element in order to identify regions that accumulate non-conservative mutations. Among patients with AL, the levels of circulating immunoglobulin free light chain varies greatly, but even patients with very low levels can have very advanced amyloid deposition. CONCLUSIONS: Our results show that in specific secondary structure elements, there are significant differences in the number of non-conservative mutations between normal and AL sequences. AL sequences from patients with different levels of secreted light chain have distinct differences in the location of non-conservative mutations, suggesting that for patients with very low levels of light chains and advanced amyloid deposition, the location of non-conservative mutations rather than the amount of free light chain in circulation may determine the amyloidogenic propensity of light chains.

Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data.

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Anne Bruun Krøigård

Full Text Available Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant callers creates a need for comparison and validation of the tools, as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported. We have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2 and Virmid for the detection of single nucleotide mutations and small deletions and insertions. We report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement. Sequencing depth had markedly diverse impact on individual callers, as for some callers, increased sequencing depth highly improved sensitivity. For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing. For indel calling, EBCall is superior due to high sensitivity and robustness to changes in sequencing depths.

Immunoglobulin concentration in blood serum of postcolostral calves: Ratio between immunoglobulin level and appearance of enzootic pneumonia

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Jonić Branko

2007-01-01

Full Text Available The timely supply of newborn calves with optimal quantities of colostrum has a key role in the process of immune protection in the early phase of their lives. Passively acquired antibodies can protect the digestive organs from infection caused by E.coli bacteria, and it seems also from the appearance of diseases of the respiratory tract. These examinations were performed on a cattle farm where bronchopneumonia was one of the most significant health problems, and a group of 39 calves were selected for the investigations. The calves were fed with their mothers’ colostrum after birth, and then with collective milk. Immunoglobulin concentration was determined in blood samples taken during the postcolostral period, with the method using zinc-sulphate. At the age of 40 days, the calves were administered a polyvalent inactivated vaccine, and revaccinated 20 days after that (Vibak, Veterinary Department Subotica. In 74.34% calves, the immunoglobulin G concentration ranged from 26 to 40 g/l. In 25.66% calves, the immunoglobulin concentration was lower, from 8 to 25 g/l. The calves found to have a lower concentration of immunoglobulin in blood contracted bronchopneumonia more frequently, and the outcome of the disease in some cases was mortality, even.

Improved purification of immunoglobulin G from plasma by mixed-mode chromatography.

Science.gov (United States)

Chai, Dong-Sheng; Sun, Yan; Wang, Xiao-Ning; Shi, Qing-Hong

2014-12-01

Efficient loading of immunoglobulin G in mixed-mode chromatography is often a serious bottleneck in the chromatographic purification of immunoglobulin G. In this work, a mixed-mode ligand, 4-(1H-imidazol-1-yl) aniline, was coupled to Sepharose Fast Flow to fabricate AN SepFF adsorbents with ligand densities of 15-64 mmol/L, and the chromatographic performances of these adsorbents were thoroughly investigated to identify a feasible approach to improve immunoglobulin G purification. The results indicate that a critical ligand density exists for immunoglobulin G on the AN SepFF adsorbents. Above the critical ligand density, the adsorbents showed superior selectivity to immunoglobulin G at high salt concentrations, and also exhibited much higher dynamic binding capacities. For immunoglobulin G purification, both the yield and binding capacity increased with adsorbent ligand density along with a decrease in purity. It is difficult to improve the binding capacity, purity, and yield of immunoglobulin G simultaneously in AN SepFF chromatography. By using tandem AN SepFF chromatography, a threefold increase in binding capacity as well as high purity and yield of immunoglobulin G were achieved. Therefore, the tandem chromatography demonstrates that AN SepFF adsorbent is a practical and feasible alternative to MEP HyperCel adsorbents for immunoglobulin G purification. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hydrometer test for estimation of immunoglobulin concentration in bovine colostrum.

Science.gov (United States)

Fleenor, W A; Stott, G H

1980-06-01

A practical field method for measuring immunoglobulin concentration in bovine colostrum has been developed from the linear relationship between colostral specific gravity and immunoglobulin concentration. Fourteen colostrums were collected within 24 h postpartum from nursed and unnursed cows and were assayed for specific gravity and major colostral constituents. Additionally, 15 colostrums were collected immediately postpartum prior to suckling and assayed for specific gravity and immunoglobulin concentration. Regression analysis provided an equation to estimate colostral immunoglobulin concentration from the specific gravity of fresh whole colostrum. From this, a colostrometer was developed for practical field use.

Comparison of techniques of detecting immunoglobulin-binding protein reactivity to immunoglobulin produced by different avian and mammalian species.

Science.gov (United States)

Justiz-Vaillant, A A; Akpaka, P E; McFarlane-Anderson, N; Smikle, M F

2013-01-01

The rationale of this study was to use several immunological assays to investigate the reactivity of immunoglobulin binding protein (IBP) to immunoglobulins from various avian and mammalian species. The IBP studied were Staphylococcal protein A (SpA), Streptococcal protein G (SpG), Peptostreptococcal protein L (SpL) and recombinant protein LA (SpLA). The various immunological techniques used were double immunodiffusion (Ouchterlony technique) that tested positive high protein reactivities, direct and competitive enzyme-linked immunosorbent assays (ELISAs) that tested moderate and low positive protein binding capacities, respectively. In addition to sandwich ELISAs, immunoblot analyses and Ig-purification by SpA-affinity chromatography, which were sensitive tests and helpful in the screening and confirmatory tests were also used. The Ouchterlony technique showed that compared to the other proteins, SpLA had the highest range of reactivity with animal sera and purified immunoglobulins while SpL was least reactive. With the direct ELISA, SpL reacted with the raccoon sera, rabbit IgG and with IgY from bantam hens and pigeons. While with the direct ELISA, SpA reacted with sera from skunk, coyote, raccoon, mule, donkey and human. The sandwich ELISA revealed high reactivity of both SpG and SpLA with mammalian sera titres ranging from 1:32 (raccoon serum) to 1:1024 (mule and donkey sera). These results suggest that IBP can be used for the detection of immunoglobulin using various immunological assays and this is important for the diagnosis of infectious diseases in animal and bird populations studied and in the purification of immunoglobulins.

Extending a structural model of somatization to South Koreans: Cultural values, somatization tendency, and the presentation of depressive symptoms.

Science.gov (United States)

Zhou, Xiaolu; Min, Seongho; Sun, Jiahong; Kim, Se Joo; Ahn, Joung-Sook; Peng, Yunshi; Noh, Samuel; Ryder, Andrew G

2015-05-01

Somatization refers to the tendency to emphasize somatic symptoms when experiencing a psychiatric disturbance. This tendency has been widely reported in patients from East Asian cultural contexts suffering from depression. Recent research in two Chinese samples have demonstrated that the local cultural script for depression, involving two aspects-the experience and expression of distress (EED) and conceptualization and communication of distress (CCD)-can be evoked to help explain somatization. Given the beliefs and practices broadly shared across Chinese and South Korean cultural contexts, the current study seeks to replicate this explanatory model in South Koreans. Our sample included 209 psychiatric outpatients from Seoul and Wonju, South Korea. Self-report questionnaires were used to assess somatization tendency, adherence to traditional values, and psychological and somatic symptoms of depression. Results from SEM showed that the EED and CCD factors of somatization tendency were differently associated with cultural values and somatic symptoms, replicating our previous findings in Chinese outpatients. The reliance on a brief self-report measure of somatization tendency, not originally designed to assess separate EED and CCD factors, highlights the need for measurement tools for the assessment of cultural scripts in cross-cultural depression research. The replication of the Chinese structural model of somatization in South Korea lends empirical support to the view that somatization can be understood as the consequence of specific cultural scripts. These scripts involve the experience and expression of distress as well as culturally meaningful ways in which this distress is conceptualized and communicated to others. Copyright © 2015 Elsevier B.V. All rights reserved.

Acute Inflammatory Demyelinating Neuropathy : Immunoglobulin And Immune Complex Profile

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Shripad A

2003-01-01

Full Text Available Serum immunoglobulins (IgG, IgA and IgM and immune complexes IgG (IcG were measured in 58 cases of acute inflammatory demyelinating neuropathy, popularly known as Guillian Barre′ syndrome, and in 30 healthy controls using single radial immunodiffusion assay. Immunoglobulin and immune complex levels were significantly elevated in patients as compared to controls. The increased levels of immunoglobulins and immune complexes may contribute to the pathogenesis of the disease and provide rationale for therapeutic plasmapheresis.

Somatic symptom profiles in the general population

DEFF Research Database (Denmark)

Eliasen, Marie; Jørgensen, Torben; Schröder, Andreas

2017-01-01

PURPOSE: The aim of this study was to identify and describe somatic symptom profiles in the general adult population in order to enable further epidemiological research within multiple somatic symptoms. METHODS: Information on 19 self-reported common somatic symptoms was achieved from a population...

Direct somatic embryogenesis in Swietenia macrophylla King

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Raúl Collado

2006-04-01

Full Text Available Swietenia macrophylla King is difficult to be propagated by tissue culture and there is not an efficient system via organogenesis, due to problems of microbial contamination, phenolic oxidation and death of tissue in the phase of in vitro establishment of explants. In order to establish a protocol for obtaining somatic embryos, zygotic embryos were used as initial plant material. Three combinations of 2,4-D with kinetin were studied, to obtain the formation of somatic embryos. After six weeks of culture, the number of explants with high and low somatic embryogenesis frequency were determined. So that the somatic embryos in globular stage reach the final stages of torpedo and cotyledonal, these were placed in three treatments with 6-BAP (0.2, 0.4 y 0.6 mg.l-1. The number of somatic embryos that reached the torpedo and cotyledonal stages were evaluated after 30 days of culture. Results demonstrated that direct somatic embryogenesis from immature zygotic embryos is obtained in the culture medium composed by MS salts with 4.0 mg.l-1 of 2,4-D and 1.0 mg.l-1 of kinetin. Higher percentage of somatic embryos in cotiledonal stage (91.7 %, was obtained with 0.4 mg.l-1 of 6-BAP. Key word: forestry, growth regulator, mahogany, somatic embryo, tissue culture

MMPI screening scales for somatization disorder.

Science.gov (United States)

Wetzel, R D; Brim, J; Guze, S B; Cloninger, C R; Martin, R L; Clayton, P J

1999-08-01

44 items on the MMPI were identified which appear to correspond to some of the symptoms in nine of the 10 groups on the Perley-Guze checklist for somatization disorder (hysteria). This list was organized into two scales, one reflecting the total number of symptoms endorsed and the other the number of organ systems with at least one endorsed symptom. Full MMPIs were then obtained from 29 women with primary affective disorder and 37 women with somatization disorder as part of a follow-up study of a consecutive series of 500 psychiatric clinic patients seen at Washington University. Women with the diagnosis of somatization disorder scored significantly higher on the somatization disorder scales created from the 44 items than did women with only major depression. These new scales appeared to be slightly more effective in identifying somatization disorder than the use of the standard MMPI scales for hypochondriasis and hysteria. Further development is needed.

Rapid Acquisition of Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus: Role of Hypermutation and Homologous Recombination.

Science.gov (United States)

Iguchi, Shigekazu; Mizutani, Tomonori; Hiramatsu, Keiichi; Kikuchi, Ken

2016-01-01

We previously reported the case of a 64-year-old man with mediastinitis caused by Staphylococcus aureus in which the infecting bacterium acquired linezolid resistance after only 14 days treatment with linezolid. We therefore investigated relevant clinical isolates for possible mechanisms of this rapid acquisition of linezolid resistance. Using clinical S. aureus isolates, we assessed the in vitro mutation rate and performed stepwise selection for linezolid resistance. To investigate homologous recombination, sequences were determined for each of the 23S ribosomal RNA (23S rRNA) loci; analyzed sequences spanned the entirety of each 23S rRNA gene, including domain V, as well as the 16S-23S intergenic spacer regions. We additionally performed next-generation sequencing on clinical strains to identify single-nucleotide polymorphisms compared to the N315 genome. Strains isolated from the patient prior to linezolid exposure (M5-M7) showed higher-level linezolid resistance than N315, and the pre-exposure strain (M2) exhibited more rapid acquisition of linezolid resistance than did N315. However, the mutation rates of these and contemporaneous clinical isolates were similar to those of N315, and the isolates did not exhibit any mutations in hypermutation-related genes. Sequences of the 23S rRNA genes and 16S-23S intergenic spacer regions were identical among the pre- and post-exposure clinical strains. Notably, all of the pre-exposure isolates harbored a recQ missense mutation (Glu69Asp) with respect to N315; such a lesion may have affected short sequence recombination (facilitating, for example, recombination among rrn loci). We hypothesize that this mechanism contributed to rapid acquisition of linezolid resistance. Hypermutation and homologous recombination of the ribosomal RNA genes, including 23S rRNA genes, appear not to have been sources of the accelerated acquisition of linezolid resistance observed in our clinical case. Increased frequency of short sequence

Personality characteristics in patients with somatized disorder

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Ekaterina Anatolyevna Tolkach

2010-01-01

Full Text Available Objective: to study personality characteristics, behavioral style, and modes of relations with their people in patients with somatized disorder. Subjects and methods. Eighty-six patients diagnosed as having somatized disorder were examined using Leary's interpersonal diagnosis system. Results. The author revealed the following personality characteristics and behavioral styles: a depressed need for authoritarianism, dominance, autonomy, aggressiveness, a display of qualities, such as superfriendliness, benevolence, submissiveness, dependency, and suspiciousness. These characteristics give an insight into the development of somatization in patients with somatized disorder.

Serum immunoglobulin G4 levels and Graves' disease phenotype.

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Martin, Carmen Sorina; Sirbu, Anca Elena; Betivoiu, Minodora Andreea; Florea, Suzana; Barbu, Carmen Gabriela; Fica, Simona Vasilica

2017-02-01

We investigated, at diagnosis, the relationship between serum immunoglobulin G4 levels and the main characteristics of Graves' disease: hyperthyroidism severity, goiter size, presence of active Graves' ophthalmopathy, antithyroid antibodies status, and titer. This prospective study included 80 newly diagnosed Graves' disease patients. The main parameters measured at diagnosis: thyroid-stimulating hormone, free thyroxine, free triiodothyronine, total triiodothyronine, thyroglobulin, antithyroid peroxidase antibodies, anti-thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, immunoglobulin G4. In Graves' disease patients, serum immunoglobulin G4 levels were higher than in general population (p = 0.028) and higher in men compared to women (p = 0.002). Only one female patient with intense hypoechoic goiter, high anti-thyroglobulin antibody, and antithyroid peroxidase antibody titers had an elevated serum immunoglobulin G4 level at diagnosis. Patients with immunoglobulin G4 levels above the 75th percentile (>237.52 mg/dl, N = 20) were younger at Graves' ophthalmopathy onset (p 286.28 mg/dl, N = 8) had lower total triiodothyronine values (p = 0.001) than patients with IgG below the 90th percentile. No significant correlations were found between smoking status (p = 0.58), goiter size (p = 0.50), the presence of ophthalmopathy (p = 0.42) or thyroid-stimulating hormone receptor antibody titers (p = 0.45) and the mean value of immunoglobulin G4 levels at diagnosis. Our data suggest that Graves' disease patients with elevated immunoglobulin G4 levels at diagnosis have a phenotype characterized by higher anti-thyroglobulin antibody and antithyroid peroxidase antibody titers, less severe T3 hyperthyroidism, younger age at ophthalmopathy onset and require a shorter duration of the first methimazole treatment cycle.

Somatic tinnitus prevalence and treatment with tinnitus retraining therapy.

Science.gov (United States)

Ostermann, K; Lurquin, P; Horoi, M; Cotton, P; Hervé, V; Thill, M P

2016-01-01

Somatic tinnitus originates from increased activity of the dorsal cochlear nucleus, a cross-point between the somatic and auditory systems. Its activity can be modified by auditory stimulation or somatic system manipulation. Thus, sound enrichment and white noise stimulation might decrease tinnitus and associated somatic symptoms. The present uncontrolled study sought to determine somatic tinnitus prevalence among tinnitus sufferers, and to investigate whether sound therapy with counselling (tinnitus retraining therapy; TRT) may decrease tinnitus-associated somatic symptoms. To determine somatic tinnitus prevalence, 70 patients following the TRT protocol completed the Jastreboff Structured Interview (JSI) with additional questions regarding the presence and type of somatic symptoms. Among 21 somatic tinnitus patients, we further investigated the effects of TRT on tinnitus-associated facial dysesthesia. Before and after three months of TRT, tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI), and facial dysesthesia was assessed with an extended JSI-based questionnaire. Among the evaluated tinnitus patients, 56% presented somatic tinnitus-including 51% with facial dysesthesia, 36% who could modulate tinnitus by head and neck movements, and 13% with both conditions. Self-evaluation indicated that TRT significantly improved tinnitus and facial dysesthesia in 76% of patients. Three months of TRT led to a 50% decrease in mean THI and JSI scores regarding facial dysesthesia. Somatic tinnitus is a frequent and underestimated condition. We suggest an extension of the JSI, including specific questions regarding somatic tinnitus. TRT significantly improved tinnitus and accompanying facial dysesthesia, and could be a useful somatic tinnitus treatment.

The association between immunoglobulin concentrations and prediabetes prevalence in a large Chinese cohort.

Science.gov (United States)

Wang, Honglei; Song, Yanqi; Sun, Shaomei; Gao, Li; Liu, Li; Meng, Ge; Wu, Hongmei; Xia, Yang; Bao, Xue; Gu, Yeqing; Shi, Hongbin; Su, Qian; Fang, Liyun; Yang, Huijun; Wang, Xing; Zhou, Ming; Jia, Qiyu; Song, Kun; Zhang, Qing; Niu, Kaijun

2017-08-01

Prediabetes has received public attention owing to the increasing prevalence worldwide. Mounting evidence has indicated that inflammation directly contributed to the etiology of glucose metabolism disorders. Although immunoglobulins play a crucial role in immune responses, little research has been done on the link between immunoglobulins and prediabetes in adults. Hence, the aim of the present study was to explore the associations between immunoglobulins levels and prevalence of prediabetes in a general adult population. A cross-sectional study was conducted among 8856 adults (mean±standard deviation age: 48.4±10.7years) in Tianjin, China. The serum immunoglobulins concentrations were measured by the immunonephelometric technique. Prediabetes was diagnosed using the following parameters in accordance with the American Diabetes Association: fasting plasma glucose, postprandial glucose and glycosylated hemoglobin. The associations between concentrations of immunoglobulins and the prevalence of prediabetes were assessed using multiple logistic regression models. Overall, the prevalence of prediabetes was 37.4% (3311/8856). After controlling for confounders, compared with the lowest quintile, the odds ratios (95% confidence interval) of prediabetes for the highest quintile of immunoglobulins (immunoglobulin G, immunoglobulin E, immunoglobulin M and immunoglobulin A) were as follows: 1.06 (0.91-1.23), 1.31 (1.13-1.52), 0.86 (0.74-1.01), and 1.19 (1.03-1.38) (P for trend were 0.35, prediabetes prevalence. There was also a trending association between immunoglobulin M concentrations and prediabetes prevalence. Further studies are necessary to clarify if there is a causal association of immunoglobulins in prediabetes or if they reflect early immunologic disturbances in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

The Role of Somatic Symptoms in Sexual Medicine: Somatization as Important Contextual Factor in Male Sexual Dysfunction.

Science.gov (United States)

Fanni, Egidia; Castellini, Giovanni; Corona, Giovanni; Boddi, Valentina; Ricca, Valdo; Rastrelli, Giulia; Fisher, Alessandra Daphne; Cipriani, Sarah; Maggi, Mario

2016-09-01

An important feature of somatic symptom disorder is the subjective perception of the physical symptoms and its maladaptive interpretation. Considering that psychological distress is often expressed through somatic symptoms, it is possible that they underlie at least a part of the symptoms in subjects complaining of sexual dysfunction. Nevertheless, studies on the impact of somatoform disorders in sexual dysfunction are scanty. To define the psychological, relational, and organic correlates of somatic symptoms in a large sample of patients complaining of sexual problems. A consecutive series of 2833 men (mean age 50.2 ± 13.5 years) was retrospectively studied. Somatic symptoms were assessed using the "somatized anxiety symptoms" subscale of the Middlesex Hospital Questionnaire (MHQ-S). Several clinical, biochemical, psychological, and relational parameters were studied. Patients were interviewed with the previously validated Structured Interview on Erectile Dysfunction (SIEDY), and ANDROTEST (a structured interview for the screening of hypogonadism in patients with sexual dysfunction). Among the 2833 patients studied, subjects scoring higher on somatic symptoms were older, more obese, reporting unhealthy lifestyle (current smoking, alcohol consumption), and a lower education (all P sexuality more often, including erectile problems (spontaneous or sexual-related), low sexual desire, decreased frequency of intercourse, and perceived reduction of ejaculate volume (all P sexual dysfunction. High levels of somatic symptoms in subjects with sexual dysfunction can be related to the sexual symptom itself. The consequences of this pattern have great clinical relevance in a sexual medicine setting, considering their severe impact on sexuality. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

[Somatic complaints, emotional awareness and maladjustment in schoolchildren].

Science.gov (United States)

Ordóñez, A; Maganto, C; González, R

2015-05-01

Somatic complaints are common in childhood. Research has shown their relationship with emotional awareness and maladjustment. The study had three objectives: 1) to analyze the prevalence of somatic complaints; 2) To explore the relationships between the variables evaluated: somatic complaints, differentiating emotions, verbal sharing of emotions, not hiding emotions, body awareness, attending to others' emotions, analysis of emotions, and personal, social, family, and school maladjustments; and 3) To identify predictors of somatic complaints. The study included a total of 1,134 randomly selected schoolchildren of both sexes between 10-12 years old (M=10.99; SD=0.88). The Somatic Complaint List, Emotional Awareness Questionnaire, and Self-reported Multifactor Test of Childhood Adaptation were used to gather information. The results showed that the prevalence of somatic complaints was 90.2%, with fatigue, headache and stomachache being the most frequently. Dizziness and headache were more common in girls, and the frequency of complaints decreases with age. Somatic complaints are negatively related to emotional awareness, and positively related to maladjustment. The variables that contribute the most to the prediction of somatic complaints are personal maladjustment (25.1%) and differentiating emotions (2.5%). The study shows that personal maladjustment is the best predictor of somatic complaints; the more emotional awareness and better adapted the child, the fewer somatic complaints they lodge. Childhood is a stage with significant physical discomfort. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Transcription factor YY1 can control AID-mediated mutagenesis in mice.

Science.gov (United States)

Zaprazna, Kristina; Basu, Arindam; Tom, Nikola; Jha, Vibha; Hodawadekar, Suchita; Radova, Lenka; Malcikova, Jitka; Tichy, Boris; Pospisilova, Sarka; Atchison, Michael L

2018-02-01

Activation-induced cytidine deminase (AID) is crucial for controlling the immunoglobulin (Ig) diversification processes of somatic hypermutation (SHM) and class switch recombination (CSR). AID initiates these processes by deamination of cytosine, ultimately resulting in mutations or double strand DNA breaks needed for SHM and CSR. Levels of AID control mutation rates, and off-target non-Ig gene mutations can contribute to lymphomagenesis. Therefore, factors that control AID levels in the nucleus can regulate SHM and CSR, and may contribute to disease. We previously showed that transcription factor YY1 can regulate the level of AID in the nucleus and Ig CSR. Therefore, we hypothesized that conditional knock-out of YY1 would lead to reduction in AID localization at the Ig locus, and reduced AID-mediated mutations. Using mice that overexpress AID (IgκAID yy1 f/f ) or that express normal AID levels (yy1 f/f ), we found that conditional knock-out of YY1 results in reduced AID nuclear levels, reduced localization of AID to the Sμ switch region, and reduced AID-mediated mutations. We find that the mechanism of YY1 control of AID nuclear accumulation is likely due to YY1-AID physical interaction which blocks AID ubiquitination. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wearing red for signaling: the heme-bach axis in heme metabolism, oxidative stress response and iron immunology.

Science.gov (United States)

Igarashi, Kazuhiko; Watanabe-Matsui, Miki

2014-04-01

The connection between gene regulation and metabolism is an old issue that warrants revisiting in order to understand both normal as well as pathogenic processes in higher eukaryotes. Metabolites affect the gene expression by either binding to transcription factors or serving as donors for post-translational modification, such as that involving acetylation and methylation. The focus of this review is heme, a prosthetic group of proteins that includes hemoglobin and cytochromes. Heme has been shown to bind to several transcription factors, including Bach1 and Bach2, in higher eukaryotes. Heme inhibits the transcriptional repressor activity of Bach1, resulting in the derepression of its target genes, such as globin in erythroid cells and heme oxygenase-1 in diverse cell types. Since Bach2 is important for class switch recombination and somatic hypermutation of immunoglobulin genes as well as regulatory and effector T cell differentiation and the macrophage function, the heme-Bach2 axis may regulate the immune response as a signaling cascade. We discuss future issues regarding the topic of the iron/heme-gene regulation network based on current understanding of the heme-Bach axis, including the concept of "iron immunology" as the synthesis of the iron metabolism and the immune response.

The Somatic Complaints List: Validation of a self-report questionnaire assessing somatic complaints in children

NARCIS (Netherlands)

Jellesma, F. C.; Rieffe, C.J.; Meerum Terwogt, M.

2007-01-01

Objective: To evaluate the Somatic Complaint List (SCL) in children. Method: At T1, 365 fourth and 352 fifth graders completed the SCL, the Children's Somatization Inventory (CSI-C), and the Mood Questionnaire. Parents (n=564) completed the parental form of the CSI-C (CSI-P). Six months later, the

Somatization in Parkinson's Disease

DEFF Research Database (Denmark)

Carrozzino, Danilo; Bech, Per; Patierno, Chiara

2017-01-01

The current systematic review study is aimed at critically analyzing from a clinimetric viewpoint the clinical consequence of somatization in Parkinson's Disease (PD). By focusing on the International Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we...... consequence of such psychiatric symptom should be further evaluated by replacing the clinically inadequate diagnostic label of psychogenic parkinsonism with the psychosomatic concept of persistent somatization as conceived by the Diagnostic Criteria for Psychosomatic Research (DCPR)....

Fish Immunoglobulins

OpenAIRE

Sara Mashoof; Michael F. Criscitiello

2016-01-01

The B cell receptor and secreted antibody are at the nexus of humoral adaptive immunity. In this review, we summarize what is known of the immunoglobulin genes of jawed cartilaginous and bony fishes. We focus on what has been learned from genomic or cDNA sequence data, but where appropriate draw upon protein, immunization, affinity and structural studies. Work from major aquatic model organisms and less studied comparative species are both included to define what is the rule for an immunoglob...

Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

Directory of Open Access Journals (Sweden)

Marković-Sovtić Gordana

2013-01-01

Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes

International Nuclear Information System (INIS)

Grayson, J.; Dooley, N.J.; Koski, I.R.; Blaese, R.M.

1981-01-01

The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [/sup 3/H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells

Immunoglobulin Concentration in Tears of Contact Lens Wearers

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Rajendra P Maurya

2014-01-01

Conclusion: The relation of immunoglobulin concentration with increasing duration of wear and material of contact lens shows that tear immunoglobulin rise accrues due to mechanical stimulation, hence contact lenses should not be used for a long period and lenses of hard nature should be discouraged. The maintenance, cleaning and deproteinization of the lenses are of high importance to avoid immunostimulation.

Somatization: a perspective from self psychology.

Science.gov (United States)

Rodin, G M

1991-01-01

Somatization is a complex phenomenon that occurs in many forms and diverse settings. It is not necessarily pathological and may be found in a variety of psychiatric disorders. Much of the psychiatric literature has focused on patients with conversion disorders and hypochondriasis. Psychoanalytic theories regarding such conditions were largely based upon concepts of drive, conflict, and defense. The perspective from self psychology, with its emphasis on subjective experience and the sense of self, may further enhance the psychoanalytic understanding of somatization. Individuals with disturbances in the stability and organization of the self may present with somatic symptoms and disturbances in emotional awareness. Somatization in such cases may be the experiential manifestation of a disturbance in the cohesion of the self and/or may result from defensive operations to ward off affect. The latter may be prominent when affective arousal triggers the psychological threat of fragmentation. Somatization may diminish in such individuals when a self-object relationship is formed that bolsters and consolidates the sense of self. The integration of affect into ongoing subjective experience may also be an important aspect of psychoanalytic treatment in such patients.

21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fab fragment specific... Test Systems § 866.5520 Immunoglobulin G (Fab fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fab fragment specific) immunological test system is a device that consists...

21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fd fragment specific... Test Systems § 866.5540 Immunoglobulin G (Fd fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fd fragment specific) immunological test system is a device that consists of...

21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fc fragment specific... Test Systems § 866.5530 Immunoglobulin G (Fc fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fc fragment specific) immunological test system is a device that consists of...

Levels of serum immunoglobulins in apparently healthy children and ...

African Journals Online (AJOL)

The results also confirm suggestions that levels of some immunoglobulin types seen amongst African adults may have possibly been attained during childhood. Our study could be of value since previous reports in this regard have been relatively scanty especially in this part of Nigeria. Keywords: Immunoglobulin, Immunity ...

Levels of serum immunoglobulins in apparently healthy children and ...

African Journals Online (AJOL)

olayemitoyin

suggestions that levels of some immunoglobulin types seen amongst African adults may have possibly been attained during childhood. Our study could be of value since previous reports in this regard have been relatively scanty especially in this part of Nigeria. Keywords: Immunoglobulin, Immunity, IgA, IgG, IgM.

Predictive factors for somatization in a trauma sample

DEFF Research Database (Denmark)

Elklit, Ask; Christiansen, Dorte M

2009-01-01

ABSTRACT: BACKGROUND: Unexplained somatic symptoms are common among trauma survivors. The relationship between trauma and somatization appears to be mediated by posttraumatic stress disorder (PTSD). However, only few studies have focused on what other psychological risk factors may predispose...... a trauma victim towards developing somatoform symptoms. METHODS: The present paper examines the predictive value of PTSD severity, dissociation, negative affectivity, depression, anxiety, and feeling incompetent on somatization in a Danish sample of 169 adult men and women who were affected by a series...... of incompetence significantly predicted somatization in the trauma sample whereas dissociation, depression, and anxiety were not associated with degree of somatization. PTSD as a risk factor was mediated by negative affectivity....

Somatic point mutation calling in low cellularity tumors.

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Karin S Kassahn

Full Text Available Somatic mutation calling from next-generation sequencing data remains a challenge due to the difficulties of distinguishing true somatic events from artifacts arising from PCR, sequencing errors or mis-mapping. Tumor cellularity or purity, sub-clonality and copy number changes also confound the identification of true somatic events against a background of germline variants. We have developed a heuristic strategy and software (http://www.qcmg.org/bioinformatics/qsnp/ for somatic mutation calling in samples with low tumor content and we show the superior sensitivity and precision of our approach using a previously sequenced cell line, a series of tumor/normal admixtures, and 3,253 putative somatic SNVs verified on an orthogonal platform.

Purification, characterization and ELISA detection of mink immunoglobulins

DEFF Research Database (Denmark)

Martel, Cyril Jean-Marie; Aasted, Bent

2008-01-01

the estimated molecular weights of the immunoglobulin gamma, alpha and mu heavy chains were found to be 54 kDa, 69 kDa and 83 kDa respectively. The purities of purified IgG, IgM and IgA were estimated by immunoglobulin class specific ELISAs to be more than 90% for IgG and IgM, and more than 80% for IgA....

Somatic embryogenesis of Carica Papaya

International Nuclear Information System (INIS)

Alvina Lindsay Mijen; Rusli Ibrahim

2006-01-01

This paper describes the somatic embryogenesis of Carica papaya. Culture medium used was1/2 strength MS basal medium supplemented with 6% sucrose, 0.27 % agar, glutamine and various concentrations of 2,4-Dichlorophenoxyacetic acid (2,4-D). After 8 weeks in culture, the best concentration of 2,4-D to induce somatic embryo is at 45.2 μM. (Author)

Induction of somatic embryogenesis in soybean: physicochemical factors influencing the development of somatic embryos

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Bonacin Gisele Aparecida

2000-01-01

Full Text Available The embryogenic capability of five soybean cultivars (Renascença, IAS-5, IAC-17, BR-16 and FT-Cometa was studied at different auxin concentrations (8, 10 and 12 mg/l naphthalene acetic acid, NAA, at different pHs (5.8 and 7.0 and at low (8-12 muEm-2 s-1 and high (27-33 mEm-2 s-1 light intensities. The experimental design was completely randomized with four replications. Immature cotyledons 4-6 mm in length were placed in the six induction mediums evaluated and submitted to two light intensities. Twenty immature cotyledons per cultivar were placed on each Petri dish, which was considered to be one replication. The number of somatic embryos per treatment per replication was counted. The results showed genotype influence on somatic embryogenic capability of each cultivar, with the most embryogenic cultivars being BR-16, FT-Cometa and IAS-5. Auxin concentration and pH value also influenced somatic embryo production, with 10 mg/l NAA being the best auxin concentration and 7.0 the best pH value. The interactions cultivar x auxin, auxin x pH and pH x light were significant, while other double interactions were not. All triple and quadruple interactions were significant, except cultivar x pH x light. No significant differences in somatic embryo production were observed in medium with different pHs or when the Petri dishes containing immature cotyledons were exposed to the two light intensities evaluated. However, a higher number of somatic embryos was produced when the medium pH was adjusted to 7.0.

Depression and hypochondriasis in family practice patients with somatization disorder.

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Oxman, T E; Barrett, J

1985-10-01

The relationships specified in DSM-III between somatization disorder and depression, and somatization disorder and hypochondriasis require further validation and easier methods of detection for use by primary care physicians. The authors investigated hypochondriacal and depressive symptoms in 13 family practice outpatients with somatization disorder. Pain complaints and depressive symptomatology were present in over 75% of this group, while hypochondriacal symptoms were present in 38%. The mean score on the somatization scale of the Hopkins Symptom Check List (HSCL-90) was greater than that reported for any other group. These findings support the separation of somatization disorder and hypochondriasis and suggest the need for better delineation of depressive subtypes in somatization disorder. The somatization scale of the HSCL-90 should be a useful screen for somatization disorder in future research.

Multicellularity makes somatic differentiation evolutionarily stable

Science.gov (United States)

Wahl, Mary E.; Murray, Andrew W.

2016-01-01

Many multicellular organisms produce two cell lineages: germ cells, whose descendants produce the next generation, and somatic cells, which support, protect, and disperse the germ cells. This germ-soma demarcation has evolved independently in dozens of multicellular taxa but is absent in unicellular species. A common explanation holds that in these organisms, inefficient intercellular nutrient exchange compels the fitness cost of producing nonreproductive somatic cells to outweigh any potential benefits. We propose instead that the absence of unicellular, soma-producing populations reflects their susceptibility to invasion by nondifferentiating mutants that ultimately eradicate the soma-producing lineage. We argue that multicellularity can prevent the victory of such mutants by giving germ cells preferential access to the benefits conferred by somatic cells. The absence of natural unicellular, soma-producing species previously prevented these hypotheses from being directly tested in vivo: to overcome this obstacle, we engineered strains of the budding yeast Saccharomyces cerevisiae that differ only in the presence or absence of multicellularity and somatic differentiation, permitting direct comparisons between organisms with different lifestyles. Our strains implement the essential features of irreversible conversion from germ line to soma, reproductive division of labor, and clonal multicellularity while maintaining sufficient generality to permit broad extension of our conclusions. Our somatic cells can provide fitness benefits that exceed the reproductive costs of their production, even in unicellular strains. We find that nondifferentiating mutants overtake unicellular populations but are outcompeted by multicellular, soma-producing strains, suggesting that multicellularity confers evolutionary stability to somatic differentiation. PMID:27402737

Somatically acquired structural genetic differences

DEFF Research Database (Denmark)

Magaard Koldby, Kristina; Nygaard, Marianne; Christensen, Kaare

2016-01-01

Structural genetic variants like copy number variants (CNVs) comprise a large part of human genetic variation and may be inherited as well as somatically acquired. Recent studies have reported the presence of somatically acquired structural variants in the human genome and it has been suggested t...... with age.European Journal of Human Genetics advance online publication, 20 April 2016; doi:10.1038/ejhg.2016.34....

Immunoassay of serum polypeptide hormones by using 125I-labelled anti(-immunoglobulin G) antibodies.

Science.gov (United States)

Beck, P; Nicholas, H

1975-03-01

1. A technique for indirectly labelling antibodies to polypeptide hormones, by combining them with radioactively labelled anti-(immunoglobulin G) is described. (a) 125I-labelled anti-(rabbit immunoglobulin G) and anti-(guinea-pig immunoglobulin G) antibodies with high specific radioactivity were prepared after purification of the antibodies on immunoadsorbents containing the respective antigens. (b) Rabbit immunoglobulin G antibodies to human growth hormone, porcine glucagon and guinea-pig immunoglobulin G antibodies to bovine insulin and bovine parathyroid hormone were combined with immunoadsorbents containing the respective polypeptide hormone antigen. (c) The immunoglobulin G antibodies to the polypeptide hormones were reacted with 125-I-labelled anti-(immunoglobulin G) antibodies directed against the appropriate species of immunoglobulin G,and the anti-hormone antibodies were combined with the hormone-containing immunoadsorbent. (d) 125I-labelled anti-(immunoglobulin G) antibodies and anti-hormone antibodies were simultaneously eluted from the hormone-containing immunoadsorbent by dilute HCl, pH 2.0. After elution the anti-(immunoglobulin G) antibodies and antihormone antibodies were allowed to recombine at pH 8.0 and 4 degrees C. 2. The resultant immunoglobulin G-anti-immunoglobulin G complex was used in immunoradiometric (labelled antibody) and two-site assays of the respective polypeptide hormone. 3. By using these immunoassays, concentrations down to 90pg of human growth hormone/ml, 100 pg of bovine insulin/ml, 80 pg of bovine parathyroid hormone/ml and 150 pg of glucagon/ml were readily detected. Assays of human plasma for growth hormone and insulin by these methods showed good agreement with results obtained by using a directly 125I-labelled anti-hormone antibody in an immunoradiometric assay of human growth hormone or by radioimmunoassay of human insulin. 4. The method described allows immunoradiometric or two-site assays to be performed starting with as

INTERACTION OF ALBUMIN AND IMMUNOGLOBULIN G WITH SYNTHETIC HYDROXYAPATITE

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E. Pylypchuk

2012-12-01

Full Text Available It was shown by X-ray phase analysis, IR spectra analysis and MALDI-ToF mass spectrometry methods that interaction of synthetic hydroxyapatite with a solution of immunoglobulin G leads to its partial dissolution due to leaching from the surface of calcium triphosphate which, in our opinion, forms complexes with immunoglobulin G.

Biological function of activation-induced cytidine deaminase (AID

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Ritu Kumar

2014-10-01

Full Text Available Activation-induced Cytidine Deaminase (AID is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

Dance and Somatic Inquiry in Studios and Community Dance Programs.

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Eddy, Martha Hart

2002-01-01

Addresses pragmatic aspects of somatics in the public sector, investigating the fit of somatics within various institutions and settings, including universities, professional schools, and community programs. The article explores issues such as somatic movement approaches, certification, academic degrees in somatic study, confusions within the…

Somatic embryogenesis in ferns: a new experimental system.

Science.gov (United States)

Mikuła, Anna; Pożoga, Mariusz; Tomiczak, Karolina; Rybczyński, Jan J

2015-05-01

Somatic embryogenesis has never been reported in ferns. The study showed that it is much easier to evoke the acquisition and expression of embryogenic competence in ferns than in spermatophytes. We discovered that the tree fern Cyathea delgadii offers an effective model for the reproducible and rapid formation of somatic embryos on hormone-free medium. Our study provides cyto-morphological evidence for the single cell origin and development of somatic embryos. Somatic embryogenesis (SE) in both primary and secondary explants was induced on half-strength micro- and macro-nutrients Murashige and Skoog medium without the application of exogenous plant growth regulators, in darkness. The early stage of SE was characterized by sequential perpendicular cell divisions of an individual epidermal cell of etiolated stipe explant. These resulted in the formation of a linear pro-embryo. Later their development resembled that of the zygotic embryo. We defined three morphogenetic stages of fern somatic embryo development: linear, early and late embryonic leaf stage. The transition from somatic embryo to juvenile sporophyte was quick and proceeded without interruption caused by dormancy. Following 9 weeks of culture the efficiency of somatic embryogenesis reached 12-13 embryos per responding explant. Spontaneous formation of somatic embryos and callus production, which improved the effectiveness of the process sevenfold in 10-month-long culture, occurred without subculturing. The tendency for C. delgadii to propagate by SE in vitro makes this species an excellent model for studies relating to asexual embryogenesis and the endogenous hormonal regulation of that process and opens new avenues of experimentation.

Pattern of somatic symptoms in anxiety and depression

International Nuclear Information System (INIS)

Shah, M.

2011-01-01

To determine the pattern of somatic symptoms in anxiety and depressive disorders. Design: Cross Sectional Comparative study Place of Study: Department of Psychiatry Military Hospital Rawalpindi. Duration of Study: From May to November 2002. Patients and Methods: Patients were divided in Group I of anxiety and group II of depression. Fifty patients considered in each group by convenience sampling. The organic basis of their symptoms was ruled out. The patterns of their somatic symptoms and other information like educational and economic status were recorded on Semi Structured Proforma. The patient's diagnosis was made on schedule based ICD-10 research criteria. The severity of anxiety and depression was assessed by using HARS and HDRS respectively. The pattern of somatic symptoms in both groups was then analyzed by the urdu version of Bradford Somatic Inventory. Patterns of somatic complaints were then analyzed by chi square test. Results: Out of 100 patients we placed 50 each in group I (anxiety) and group II (Depression). Males were higher in depression whereas females were higher in anxiety disorder group. P-value for headache was 0.017 while in rest of the somatic symptoms it was insignificant ranging from 0.4 to 1. Conclusion: We found that the patterns of somatic symptoms are present in both the groups of anxiety and depression like symptoms related to musculoskeletal and gastrointestinal system were commonly observed in cases of depression whereas symptoms related to autonomic nervous system and cardiovascular system is more significantly somatized in patients of anxiety. A larger sample is required for further studies to get better results. (author)

Immunoglobulin adsorption on modified surfaces

NARCIS (Netherlands)

Bremer, M.G.E.G.

2001-01-01

Preservation of biological functioning of proteins during immobilisation is of special interest in various biomedical and biotechnical applications. In industry physical adsorption of immunoglobulins (IgGs) onto solid surfaces is still the predominant immobilisation procedure because it is

Immunoglobulin and fatty acids

DEFF Research Database (Denmark)

2009-01-01

The present invention relates to a composition comprising 0.1-10 w/w % immunoglobulin (Ig), 4-14 w/w % saturated fatty acids, 4-14 w/w % mono-unsaturated fatty acids and 0-5 w/w % poly-unsaturated fatty acids, wherein the weight percentages are based on the content of dry matter in the composition...

Inhibition of neutrophil migration by aggregated immunoglobulin attached to micropore membranes.

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Kemp, A S; Brown, S

1980-01-01

The effect of substrate-bound immunoglobulin on neutrophil migration was examined. Immunoglobulin aggregates bound to micropore membranes inhibited the neutrophil response to a chemotactic stimulus. This inhibition was reversed by the presence of aggregates in suspension suggesting competition between substrate-bound and free aggregates for neutrophil surface binding sites. The immobilization of neutrophils by substrate-bound aggregated immunoglobulin suggests a mechanism for the accumulation of neutrophils at sites of immune complex deposition and tissue-bound antibodies in vivo. PMID:7380477

Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation.

Science.gov (United States)

Ueda, Masumi; Berger, Melvin; Gale, Robert Peter; Lazarus, Hillard M

2018-03-01

Immunoglobulins are used to prevent or reduce infection risk in primary immune deficiencies and in settings which exploit its anti-inflammatory and immune-modulatory effects. Rigorous proof of immunoglobulin efficacy in persons with lympho-proliferative neoplasms, plasma cell myeloma, and persons receiving hematopoietic cell transplants is lacking despite many clinical trials. Further, there are few consensus guidelines or algorithms for use in these conditions. Rapid development of new therapies targeting B-cell signaling and survival pathways and increased use of chimeric antigen receptor T-cell (CAR-T) therapy will likely result in more acquired deficiencies of humoral immunity and infections in persons with cancer. We review immunoglobulin formulations and discuss efficacy and potential adverse effects in the context of preventing infections and in graft-versus-host disease. We suggest an algorithm for evaluating acquired deficiencies of humoral immunity in persons with hematologic neoplasms and recommend appropriate use of immunoglobulin therapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Screening for congenital toxoplasmosis: accuracy of immunoglobulin M and immunoglobulin A tests after birth

DEFF Research Database (Denmark)

Gilbert, Ruth E; Thalib, Lukman; Tan, Hooi Kuan

2007-01-01

OBJECTIVES: To determine the accuracy of postnatal screening for toxoplasma-specific immunoglobulin (Ig) M and IgA. SETTING: Ten centres in three European countries. METHODS: We compared results of the first postnatal IgM or IgA test in infants with infected mothers identified by prenatal screeni...

Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data

DEFF Research Database (Denmark)

Krøigård, Anne Bruun; Thomassen, Mads; Lænkholm, Anne Vibeke

2016-01-01

a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2...

Hyper-immunoglobulin D syndrome with novel mutations in an afebrile infant.

Science.gov (United States)

Cadmus, Simi D; Green, Reid; Carrasco, Ruy; Levy, Moise L; Diaz, Lucia Z

2018-03-30

Hyper-immunoglobulin D syndrome is a rare autosomal-recessive autoinflammatory syndrome in which a mevalonate kinase deficiency results due to mutations of the mevalonate kinase gene. We report a case of an Asian male infant who was found to have hyper-immunoglobulin D syndrome in the absence of fever. His skin manifestations included cephalic pustulosis as well recurrent transient and fixed pink plaques and nodules on the face and extremities. Subsequent examination revealed hyper-immunoglobulin D syndrome with two novel allelic mutations in the mevalonate kinase gene: c.895G > A (p.D299N) and c.1168C > T (p.Q390). It is important for dermatologists to recognize the varied cutaneous presentations of hyper-immunoglobulin D syndrome because rapid diagnosis and treatment can significantly affect outcomes. © 2018 Wiley Periodicals, Inc.

The expanding polymerase universe.

Science.gov (United States)

Goodman, M F; Tippin, B

2000-11-01

Over the past year, the number of known prokaryotic and eukaryotic DNA polymerases has exploded. Many of these newly discovered enzymes copy aberrant bases in the DNA template over which 'respectable' polymerases fear to tread. The next step is to unravel their functions, which are thought to range from error-prone copying of DNA lesions, somatic hypermutation and avoidance of skin cancer, to restarting stalled replication forks and repairing double-stranded DNA breaks.

Solvent-Detergent Treatment of IgM-Enriched Immunoglobulin

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Mojgan Pourmokhtar

2003-08-01

Full Text Available Viral safety of human plasma products plays a key role in their safe uses. Solvent- detergent (SD virus-inactivation method has gained widespread popularity in the manufacture of biological products. This treatment which inactivates lipid-enveloped viruses effectively consists of incubation of a plasma protein solution in the presence of a non-volatile organic solvent and a detergent. In this study, IgM-enriched immunoglobulin was incubated at 24 °C for 6 h under slow stirring in the presence of tri(n-butyl phosphate (0.3% w/w as solvent and tween 80 (1% w/w as detergent. After completion of the inactivation process and removal of the solvent-detergent, the ability of SD-treatment to remove Infectious Bovine Rhinotracheitis (IBR virus (a lipid-enveloped virus and Foot-and-Mouth Disease virus (a non-enveloped virus were evaluated by "virus spiking studies" using a scaled down process. Reduction factor of 4 log was obtained for the SD-treatment of IgM-enriched immunoglobulin spiked with IBR virus. No virus inactivation was observed in the SD-treated IgM-enriched immunoglobulin, spiked with Foot-and-Mouth Disease virus. It was concluded that treatment of IgM-enriched immunoglobulin with TNBP-TWEEN 80 may be considered as an efficient lipid-enveloped virus inactivation step in the manufacture of this product.

Somatic embryogenesis in cassava: A tool for mutation breeding

International Nuclear Information System (INIS)

Lee, K.S.; Duren, M. Van; Morpurgo, R.

1997-01-01

Cassava is an important food and livestock feed crop. The effect of gamma radiation on somatic embryogenesis and plant regeneration in cassava clones of African origin was investigated. Explants from young leaves of cassava were cultured on MS medium, supplemented with 18.1 mM 2,4-D and 2 mM CuSO4, solidified with 0.3% Phytagel. Compact and friable calli were observed after 10-15 days of explant culture in dark, which produced somatic embryos in all but one clone. The somatic embryos showed morphological aberrations, such as fused cotyledons, lack of meristematic tip, epicotyl elongation, and had low germination rate; desiccation of embryos increased germination. Histological study showed that the somatic embryos were of multicellular origin. Leaf explants were irradiated with doses between 4 to 38 Gy of gamma rays, and cultured on somatic embryo induction medium. In addition, somatic embryos were irradiated with gamma ray doses from 10 to 18 Gy, and analyzed for germination. LD 50 for embryogenic response of leaf-explants was at around 20 Gy, while that for somatic embryo germination was ca. 10 Gy. (author). 7 refs, 2 tabs

Somatic embryogenesis in cassava: A tool for mutation breeding

Energy Technology Data Exchange (ETDEWEB)

Lee, K S; Duren, M Van; Morpurgo, R [Agriculture and Biotechnology Laboratory, International Atomic Energy Agency, Seibersdorf (Austria)

1997-07-01

Cassava is an important food and livestock feed crop. The effect of gamma radiation on somatic embryogenesis and plant regeneration in cassava clones of African origin was investigated. Explants from young leaves of cassava were cultured on MS medium, supplemented with 18.1 mM 2,4-D and 2 mM CuSO4, solidified with 0.3% Phytagel. Compact and friable calli were observed after 10-15 days of explant culture in dark, which produced somatic embryos in all but one clone. The somatic embryos showed morphological aberrations, such as fused cotyledons, lack of meristematic tip, epicotyl elongation, and had low germination rate; desiccation of embryos increased germination. Histological study showed that the somatic embryos were of multicellular origin. Leaf explants were irradiated with doses between 4 to 38 Gy of gamma rays, and cultured on somatic embryo induction medium. In addition, somatic embryos were irradiated with gamma ray doses from 10 to 18 Gy, and analyzed for germination. LD{sub 50} for embryogenic response of leaf-explants was at around 20 Gy, while that for somatic embryo germination was ca. 10 Gy. (author). 7 refs, 2 tabs.

Somatic Symptom Disorder in Semantic Dementia: The Role of Alexisomia.

Science.gov (United States)

Gan, Joanna J; Lin, Andrew; Samimi, Mersal S; Mendez, Mario F

Semantic dementia (SD) is a neurodegenerative disorder characterized by loss of semantic knowledge. SD may be associated with somatic symptom disorder due to excessive preoccupation with unidentified somatic sensations. To evaluate the frequency of somatic symptom disorder among patients with SD in comparison to comparably demented patients with Alzheimer׳s disease. A retrospective cohort study was conducted using clinical data from a referral-based behavioral neurology program. Fifty-three patients with SD meeting criteria for imaging-supported semantic variant primary progressive aphasia (another term for SD) were compared with 125 patients with clinically probable Alzheimer disease. Logistic regression controlled for sex, age, disease duration, education, overall cognitive impairment, and depression. The prevalence of somatic symptom disorder was significantly higher among patients with SD (41.5%) compared to patients with Alzheimer disease (11.2%) (odds ratio = 6:1; p Cotard syndrome or the delusion that unidentified somatic symptoms signify death or deterioration. SD, a disorder of semantic knowledge, is associated with somatic symptom disorder from impaired identification of somatic sensations. Their inability to read and name somatic sensations, or "alexisomia," results in disproportionate and persistent concern about somatic sensations with consequent significant disability. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Sulphur depletion altered somatic embryogenesis in Theobroma ...

African Journals Online (AJOL)

Somatic embryogenesis is a useful tool for Theobroma cacao improvement and propagation. Depending on culture medium composition, different morphogenetic structures (including somatic embryo) occur in response to alteration of genes expression patterns and biochemical changes. The effect of SO42- ion deficiency ...

21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

Science.gov (United States)

2010-04-01

... of antibody-forming cells), lymphocytic neoplasms (cancer of lymphoid tissue), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid... portions of immunoglobulin molecules in serum, other body fluids, and tissues. In some disease states, an...

Biased immunoglobulin light chain gene usage in the shark1

Science.gov (United States)

Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

2015-01-01

This study of a large family of kappa light (L) chain clusters in nurse shark completes the characterization of its classical immunoglobulin (Ig) gene content (two heavy chain classes, mu and omega, and four L chain isotopes, kappa, lambda, sigma, and sigma-2). The shark kappa clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over a ~500 bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ca. 39 kappa clusters are pre-rearranged in the germline (GL-joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, non-productive, and sterile transcripts of the kappa clusters compared to the other three L chain isotypes. Kappa cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and non-productive rearrangements. These results show that the individual activation of the spatially distant kappa clusters is non-random. Although both split and GL-joined kappa genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. PMID:26342033

Translocations affecting human immunoglobulin heavy chain locus

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Sklyar I. V.

2014-03-01

Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.

Characteristics of somatic tinnitus patients with and without hyperacusis.

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Massimo Ralli

Full Text Available Determine if somatic tinnitus patients with hyperacusis have different characteristics from those without hyperacusis.172 somatic tinnitus patients with (n = 82 and without (n = 90 hyperacusis referred to the Tinnitus Unit of Sapienza University of Rome between June 2012 and June 2016 were compared for demographic characteristics, tinnitus features, self-administered questionnaire scores, nature of somatic modulation and history.Compared to those without hyperacusis, patients with somatic tinnitus and hyperacusis: (a were older (43.38 vs 39.12 years, p = 0.05, (b were more likely to have bilateral tinnitus (67.08% vs 55.56%, p = 0.04, (c had a higher prevalence of somatic modulation of tinnitus (53.65% vs 36.66%, p = 0.02 and (d scored significantly worse on tinnitus annoyance (39.34 vs 22.81, p<0.001 and subjective hearing level (8.04 vs 1.83, p<0.001.Our study shows significantly higher tinnitus modulation and worse self-rating of tinnitus and hearing ability in somatic tinnitus patients with hyperacusis versus somatic tinnitus patients without hyperacusis. These differences could prove useful in developing a better understanding of the pathophysiology and establishing a course of treatment for these two groups of patients.

Studies on Somatic Embryogenesis in Sweetpotato

Science.gov (United States)

Bennett, J. Rasheed; Prakash, C. S.

1997-01-01

The purpose of this study was to improve the somatic embryo (SE) system for plant production of sweetpotato Ipomoea batatas L.(Lam)l. Explants isolated from SE-derived sweet potato plants were compared with control (non SE-derived) plants for their competency for SE production. Leaf explants were cultured on Murashige-Skoog (MS) medium with 2,4-dichlorophenoxy acetic acid (0.2 mg/L) and 6-benzylaminopurine (2.5 mg/L) for 2 weeks in darkness and transferred to MS medium with abscisic acid (2.5 Explants isolated from those plants developed through somatic embryo-genesis produced new somatic embryos rapidly and in higher frequency than those isolated from control plants. They also appeared to grow faster in tissue culture than the control plants. Current studies in the laboratory are examining whether plants derived from a cyclical embryogenesis system (five cycles) would have any further positive impact on the rapidity and frequency of somatic embryo development. More detailed studies using electron microscopy are expected to show the point of origin of the embryos and to allow determination of their quality throughout the cyclical process. This study may facilitate improved plant micropropagation, gene transfer and germplasm conservation in sweet potato.

Hypochondriacal concerns and somatization in panic disorder.

Science.gov (United States)

Furer, P; Walker, J R; Chartier, M J; Stein, M B

1997-01-01

To clarify the relationship between panic disorder and the symptoms of hypochondriasis and somatization, we evaluated these symptoms and diagnoses in patients attending an Anxiety Disorders Clinic. Structured clinical interviews, self-report measures, and symptom diaries were used to assess 21 patients with panic disorder, 23 patients with social phobia, and 22 control subjects with no psychiatric disorders. Ten of the patients with panic disorder (48%) also met DSM-IV criteria for hypochondriasis, whereas only one of the patients with social phobia and none of the healthy control subjects met the criteria for this diagnosis. None of the participants met DSM-IV criteria for somatization disorder, even though both anxiety groups reported high levels of somatic symptoms. The panic disorder group reported higher levels of fear about illness and disease conviction and endorsed more somatic symptoms than did the other groups. A higher proportion of panic disorder patients reported previously diagnosed medical conditions (48%) as compared with patients with social phobia (17%) or healthy control subjects (14%). The panic disorder patients with DSM-IV hypochondriasis obtained higher scores on measures of hypochondriacal concerns, somatization, blood-injury phobia, and general anxiety and distress than did the panic disorder patients without hypochondriasis. The results suggest a strong association between panic disorder and hypochondriasis.

Cryopreservation of Arachis pintoi (leguminosae) somatic embryos.

Science.gov (United States)

Rey, H Y; Faloci, M; Medina, R; Dolce, N; Engelmann, F; Mroginski, L

2013-01-01

In this study, we successfully cryopreserved cotyledonary somatic embryos of diploid and triploid Arachis pintoi cytotypes using the encapsulation-dehydration technique. The highest survival rates were obtained when somatic embryos were encapsulated in calcium alginate beads and precultured in agitated (80 rpm) liquid establishment medium (EM) with daily increasing sucrose concentration (0.50, 0.75, and 1.0 M). The encapsulated somatic embryos were then dehydrated with silica gel for 5 h to 20% moisture content (fresh weight basis) and cooled either rapidly (direct immersion in liquid nitrogen, LN) or slowly (1 degree C per min from 25 degree C to -30 degree C followed by immersion in LN). Beads were kept in LN for a minimum of 1 h and then were rapidly rewarmed in a 30 degree C water-bath for 2 min. Finally, encapsulated somatic embryos were post-cultured in agitated (80 rpm) liquid EM with daily decreasing sucrose concentration (0.75 and 0.5 M) and transferred to solidified EM. Using this protocol, we obtained 26% and 30% plant regeneration from cryopreserved somatic embryos of diploid and triploid cytotypes. No morphological abnormalities were observed in any of the plants regenerated from cryopreserved embryos and their genetic stability was confirmed with 10 isozyme systems and nine RAPD profiles.

Mortality in unipolar depression preceding and following chronic somatic diseases

DEFF Research Database (Denmark)

Koyanagi, A; Köhler-Forsberg, O; Benros, M E

2018-01-01

-varying covariates were constructed to assess the risk for all-cause and non-suicide deaths for individual somatic diseases. RESULTS: For all somatic diseases, prior and/or subsequent depression conferred a significantly higher mortality risk. Prior depression was significantly associated with a higher mortality......OBJECTIVE: It is largely unknown how depression prior to and following somatic diseases affects mortality. Thus, we examined how the temporal order of depression and somatic diseases affects mortality risk. METHOD: Data were from a Danish population-based cohort from 1995 to 2013, which included...... all residents in Denmark during the study period (N = 4 984 912). Nineteen severe chronic somatic disorders from the Charlson Comorbidity Index were assessed. The date of first diagnosis of depression and somatic diseases was identified. Multivariable Cox proportional Hazard models with time...

Recent advancements in cloning by somatic cell nuclear transfer.

Science.gov (United States)

Ogura, Atsuo; Inoue, Kimiko; Wakayama, Teruhiko

2013-01-05

Somatic cell nuclear transfer (SCNT) cloning is the sole reproductive engineering technology that endows the somatic cell genome with totipotency. Since the first report on the birth of a cloned sheep from adult somatic cells in 1997, many technical improvements in SCNT have been made by using different epigenetic approaches, including enhancement of the levels of histone acetylation in the chromatin of the reconstructed embryos. Although it will take a considerable time before we fully understand the nature of genomic programming and totipotency, we may expect that somatic cell cloning technology will soon become broadly applicable to practical purposes, including medicine, pharmaceutical manufacturing and agriculture. Here we review recent progress in somatic cell cloning, with a special emphasis on epigenetic studies using the laboratory mouse as a model.

Recent advancements in cloning by somatic cell nuclear transfer

Science.gov (United States)

Ogura, Atsuo; Inoue, Kimiko; Wakayama, Teruhiko

2013-01-01

Somatic cell nuclear transfer (SCNT) cloning is the sole reproductive engineering technology that endows the somatic cell genome with totipotency. Since the first report on the birth of a cloned sheep from adult somatic cells in 1997, many technical improvements in SCNT have been made by using different epigenetic approaches, including enhancement of the levels of histone acetylation in the chromatin of the reconstructed embryos. Although it will take a considerable time before we fully understand the nature of genomic programming and totipotency, we may expect that somatic cell cloning technology will soon become broadly applicable to practical purposes, including medicine, pharmaceutical manufacturing and agriculture. Here we review recent progress in somatic cell cloning, with a special emphasis on epigenetic studies using the laboratory mouse as a model. PMID:23166393

Masked depression: its interrelations with somatization, hypochondriasis and conversion.

Science.gov (United States)

Fisch, R Z

1987-01-01

Masked depression appears to be a common clinical phenomenon. Most depressions present with some somatic complaints in addition to affective and cognitive ones. About one half of all depressions seen by primary care physicians initially present predominantly or exclusively with somatic symptoms. Many of these depressions are not recognized or are misdiagnosed and mistreated. The possible reasons for this are discussed here. The phenomenon of somatization in depressions and other conditions is reviewed and the interface with other related clinical problems like hypochondriasis and conversion is delineated. It is hypothesized that the proportion of depressions that are masked is positively correlated to the patients' tendency to somatize and negatively correlated to the doctors' ability to recognize depressions that hide behind somatic complaints. Suggestions for the diagnosis and treatment of masked depressions are given.

Optimization of somatic embryogenesis procedure for commercial ...

African Journals Online (AJOL)

The first objective of this study was to assess and optimize somatic embryo production in a genetically diverse range of cacao genotypes. The primary and secondary somatic embryogenesis response of eight promising cacao clones and a positive control was evaluated using modified versions of standard protocols.

Bacteriostatic enterochelin-specific immunoglobulin from normal human serum

Energy Technology Data Exchange (ETDEWEB)

Moore, D.G.; Yancey, R.J.; Lankford, C.E.; Earhart, C.F.

1980-02-01

Heat-inactivated normal human serum produces iron-reversible bacteriostasis of a number of microorganisms. This inhibitory effect was abolished by adsorption of serum with ultraviolet-killed cells of species that produce the siderophore enterochelin. Bacteriostasis also was alleviated by asorption of serum with 2,3-dihydroxy-N-benzoyl-L-serine, a degradation product of enterochelin, bound to the insoluble matrix AH-Sepharose 4B. Our results indicate that enterochelin-specific immunoglobulins exist in normal human serum. These immunoglobulins may act synergistically with transferrin to effect bacteriostasis of enterochelin-producing pathogens.

Bovine somatic cell nuclear transfer.

Science.gov (United States)

Ross, Pablo J; Cibelli, Jose B

2010-01-01

Somatic cell nuclear transfer (SCNT) is a technique by which the nucleus of a differentiated cell is introduced into an oocyte from which its genetic material has been removed by a process called enucleation. In mammals, the reconstructed embryo is artificially induced to initiate embryonic development (activation). The oocyte turns the somatic cell nucleus into an embryonic nucleus. This process is called nuclear reprogramming and involves an important change of cell fate, by which the somatic cell nucleus becomes capable of generating all the cell types required for the formation of a new individual, including extraembryonic tissues. Therefore, after transfer of a cloned embryo to a surrogate mother, an offspring genetically identical to the animal from which the somatic cells where isolated, is born. Cloning by nuclear transfer has potential applications in agriculture and biomedicine, but is limited by low efficiency. Cattle were the second mammalian species to be cloned after Dolly the sheep, and it is probably the most widely used species for SCNT experiments. This is, in part due to the high availability of bovine oocytes and the relatively higher efficiency levels usually obtained in cattle. Given the wide utilization of this species for cloning, several alternatives to this basic protocol can be found in the literature. Here we describe a basic protocol for bovine SCNT currently being used in our laboratory, which is amenable for the use of the nuclear transplantation technique for research or commercial purposes.

Somatic delusions and obsessive-compulsive disorder in ...

African Journals Online (AJOL)

The patient was later referred to the psychiatry department of the same hospital and diagnosed with schizophrenia with somatic delusions and OCS according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. He was screened for schizophrenia, OCS and olfactory and somatic delusions by ...

Body image and self-esteem in somatizing patients.

Science.gov (United States)

Sertoz, Ozen O; Doganavsargil, Ozge; Elbi, Hayriye

2009-08-01

The aim of the present study was to determine dissatisfaction with body appearance and bodily functions and to assess self-esteem in somatizing patients. Body image and self-esteem were investigated in 128 women; 34 of those had diagnosed somatoform disorders, 50 were breast cancer patients with total mastectomy surgery alone, and 44 were healthy subjects. Body image and self-esteem were assessed using the Body Cathexis Scale and Rosenberg Self-Esteem Scale. The two clinical groups did not differ from one another (z = -1.832, P = 0.067), but differed from healthy controls in terms of body image (somatizing patients vs healthy controls, z = -3.628, P self-esteem (z = -0.936, P = 0.349) when depressive symptoms were controlled. No statistically significant difference was observed between total mastectomy patients and healthy controls in terms of self-esteem (z = -1.727, P = 0.084). The lower levels of self-esteem in somatizing patients were largely mediated by depressive symptoms. Depressed and non-depressed somatizing patients differed significantly from healthy controls with respect to their self-esteem and body image. Somatizing patients who were dissatisfied with their bodily functions and appearance had lower levels of self-esteem and high comorbidity of depression. In clinical practice it is suggested that clinicians should take into account psychiatric comorbidity, self-esteem, and body image in somatizing patients when planning treatment approaches.

Somatic Embryogenesis: Still a Relevant Technique in Citrus Improvement.

Science.gov (United States)

Omar, Ahmad A; Dutt, Manjul; Gmitter, Frederick G; Grosser, Jude W

2016-01-01

The genus Citrus contains numerous fresh and processed fruit cultivars that are economically important worldwide. New cultivars are needed to battle industry threatening diseases and to create new marketing opportunities. Citrus improvement by conventional methods alone has many limitations that can be overcome by applications of emerging biotechnologies, generally requiring cell to plant regeneration. Many citrus genotypes are amenable to somatic embryogenesis, which became a key regeneration pathway in many experimental approaches to cultivar improvement. This chapter provides a brief history of plant somatic embryogenesis with focus on citrus, followed by a discussion of proven applications in biotechnology-facilitated citrus improvement techniques, such as somatic hybridization, somatic cybridization, genetic transformation, and the exploitation of somaclonal variation. Finally, two important new protocols that feature plant regeneration via somatic embryogenesis are provided: protoplast transformation and Agrobacterium-mediated transformation of embryogenic cell suspension cultures.

Fragments of the constant region of immunoglobulin light chains are constituents of AL-amyloid proteins

DEFF Research Database (Denmark)

Olsen, K E; Sletten, K; Westermark, Per

1998-01-01

Immunoglobulin light chains are the precursor proteins of AL-amyloidosis. In the fibril formation process properties of the variable part of the immunoglobulin light chains are believed to be of major importance. In this work it is shown that fragments of the constant part of the immunoglobulin l...... light chain are a constituent of the AL-amyloid proteins of kappa type. A specific antiserum has identified these fragments in gel filtration fractions where the absorbance approached the base line after the main retarded peak. The fragments are small and have been overlooked previously......Immunoglobulin light chains are the precursor proteins of AL-amyloidosis. In the fibril formation process properties of the variable part of the immunoglobulin light chains are believed to be of major importance. In this work it is shown that fragments of the constant part of the immunoglobulin...... in the purification process. The significance of the constant part in AL-proteins is unclear, but adds new aspects to the discussion of pre- or post-fibrillogenic cleavage of the immunoglobulin light chains....

An evaluation of serum and tissue bound immunoglobulins in prostatic diseases.

Directory of Open Access Journals (Sweden)

Gahankari D

1993-04-01

Full Text Available In forty-four patients with different prostatic lesions serum immunoglobulins and tissue deposited immunoglobulins were studied by single radial immunodiffusion technique, and direct immunofluorescence and immunoperoxidase (PAP methods respectively. Serum IgM levels were found reduced only in patients with prostatic carcinomas (80% of cases as compared to controls. Serum IgA levels showed stage dependence in prostatic carcinoma being more raised in advanced malignancy (stage C and D than in localized ones (stage B. Localization of immunoglobulins particularly IgM, was characteristically found in stroma and lumen along with intracellular localization in prostatic carcinoma; while normal and benign lesions of prostate only showed characteristic ′necklace′ pattern. Also the intensity of deposits of immunoglobulins in poorly differentiated prostatic carcinomas was markedly low as compared to well differentiated carcinomas indicating lowered local immunological response in former. In prostatitis, IgA was also found localized in lumen indicating the immunological defence against infection by secretory antibody (IgA.

The visceromotor and somatic afferent nerves of the penis.

Science.gov (United States)

Diallo, Djibril; Zaitouna, Mazen; Alsaid, Bayan; Quillard, Jeanine; Ba, Nathalie; Allodji, Rodrigue Sètchéou; Benoit, Gérard; Bedretdinova, Dina; Bessede, Thomas

2015-05-01

Innervation of the penis supports erectile and sensory functions. This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment. © 2015 International Society for Sexual Medicine.

Anxiety, depression, and somatization in DSM-III hypochondriasis.

Science.gov (United States)

Kellner, R; Abbott, P; Winslow, W W; Pathak, D

1989-01-01

To assess the severity of distress and of somatization in hypochondriasis, the authors administered several validated self-rating scales of depression, anxiety, somatic symptoms, and anger/hostility to 21 psychiatric outpatients with the DSM-III diagnosis of hypochondriasis and to matched groups of other nonpsychotic psychiatric patients, family practice patients, and employees. Anxiety and somatic symptoms were highest in hypochondriacal patients; depression and anger/hostility did not differ from those of other psychiatric patients but were higher than in the other groups. The findings do not support the theory that hypochondriasis is a defense against anxiety or that it is a masked depression or depressive equivalent. The findings are consistent with the view that the interaction of severe anxiety and severe somatic symptoms is a common feature of the psychopathology of hypochondriasis.

Cognitive aspects of hypochondriasis and the somatization syndrome.

Science.gov (United States)

Rief, W; Hiller, W; Margraf, J

1998-11-01

The aim of this study was to evaluate whether specific cognitive aspects are present in patients suffering from somatoform disorders. With a sample of 493 patients from a center for behavioral medicine, the authors evaluated a questionnaire assessing typical cognitions concerning body perception, illness behavior, and health. The authors further examined 225 participants, including patients with a somatization syndrome, patients with somatization syndrome and additional hypochondriasis, patients with hypochondriasis, patients with other mental disorders (clinical control group), and nonclinical controls. The results showed that not only patients with hypochondriasis but also patients with somatization syndrome had cognitive concerns and assumptions that were specific for the disorder. These patients had a self-concept of being weak and unable to tolerate stress. A catastrophizing interpretation of minor bodily complaints found in hypochondriacal patients in earlier studies was also found for patients with multiple somatization symptoms.

Germline contamination and leakage in whole genome somatic single nucleotide variant detection.

Science.gov (United States)

Sendorek, Dorota H; Caloian, Cristian; Ellrott, Kyle; Bare, J Christopher; Yamaguchi, Takafumi N; Ewing, Adam D; Houlahan, Kathleen E; Norman, Thea C; Margolin, Adam A; Stuart, Joshua M; Boutros, Paul C

2018-01-31

The clinical sequencing of cancer genomes to personalize therapy is becoming routine across the world. However, concerns over patient re-identification from these data lead to questions about how tightly access should be controlled. It is not thought to be possible to re-identify patients from somatic variant data. However, somatic variant detection pipelines can mistakenly identify germline variants as somatic ones, a process called "germline leakage". The rate of germline leakage across different somatic variant detection pipelines is not well-understood, and it is uncertain whether or not somatic variant calls should be considered re-identifiable. To fill this gap, we quantified germline leakage across 259 sets of whole-genome somatic single nucleotide variant (SNVs) predictions made by 21 teams as part of the ICGC-TCGA DREAM Somatic Mutation Calling Challenge. The median somatic SNV prediction set contained 4325 somatic SNVs and leaked one germline polymorphism. The level of germline leakage was inversely correlated with somatic SNV prediction accuracy and positively correlated with the amount of infiltrating normal cells. The specific germline variants leaked differed by tumour and algorithm. To aid in quantitation and correction of leakage, we created a tool, called GermlineFilter, for use in public-facing somatic SNV databases. The potential for patient re-identification from leaked germline variants in somatic SNV predictions has led to divergent open data access policies, based on different assessments of the risks. Indeed, a single, well-publicized re-identification event could reshape public perceptions of the values of genomic data sharing. We find that modern somatic SNV prediction pipelines have low germline-leakage rates, which can be further reduced, especially for cloud-sharing, using pre-filtering software.

[Correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma].

Science.gov (United States)

Xue, Yi-Nan; Zou, Xian-De; Wu, Jia-Ling

2006-02-01

This study examined the changes of serum levels of interleukin (IL)-16, IL-18 and immunoglobulins and the correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma and aimed to explore the role of IL-16, IL-18 and immunoglobulins in the pathogenesis of asthma. Thirty-four children with asthma and 21 age and gender-matched healthy children were enrolled in this study. The levels of IL-16, IL-18 and immunoglobulin E (IgE) were determined using ELISA. Immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) were detected by immunoturbidimetry. The levels of IL-16, IL-18 and IgE in patients with asthma at both acute attack and convalescence stages were significantly higher than those in healthy controls. An increased IgG and a decreased IgA levels were found in asthmatic patients at the acute attack stage. There was a positive correlation between the IL-16 and IL-18 levels at both acute attack and convalescence stages of asthma (r=0.70, P attack stage of asthma (r=0.624, P asthma. The immunologic imbalance exists in children with asthma at both acute attack and convalescence stages. Anti-allergic therapy should be administered through the acute attack to the convalescence stages of asthma.

Is chronic pain associated with somatization/hypochondriasis? An evidence-based structured review.

Science.gov (United States)

Fishbain, David A; Lewis, John E; Gao, Jinrun; Cole, Brandly; Steele Rosomoff, R

2009-01-01

This is an evidence-based structured review. The objectives of this review were to answer the following questions: (1) Are somatization/hypochondriasis associated with chronic pain? (2) Is the degree of somatization/hypochondriasis related to pain levels? (3) Does pain treatment improve somatization/hypochondriasis? (4) Are some pain diagnoses differentially associated with somatization/hypochondriasis? Fifty-seven studies which fulfilled inclusion criteria and had high quality scores were sorted by the above-mentioned objectives. Agency for health care policy and research guidelines were utilized to type and characterize the strength/consistency of the study evidence within each objective. Somatization and hypochondriasis were both consistently associated with chronic pain (consistency ratings B and A, respectively). Study evidence indicated a correlation between pain intensity and presence of somatization and hypochondriasis (consistency rating A and B, respectively). Pain treatment improved somatization and hypochondriasis (consistency rating B and A, respectively). Some chronic pain diagnostic groups somatized more (consistency rating B). Somatization is commonly associated with chronic pain and may relate to pain levels.

Facilitated subcutaneous immunoglobulin administration (fSCIg)

DEFF Research Database (Denmark)

Blau, Igor-Wolfgang; Conlon, Niall; Petermann, Robert

2016-01-01

and diverse medical needs that treatments for SID management should strive to meet. In this special report, we study the opportunities provided by facilitated subcutaneous immunoglobulin administration (fSCIg) to treat patients for whom the conventional routes (intravenous and subcutaneous) are sub...

Personality traits influencing somatization symptoms and social inhibition in the elderly

Directory of Open Access Journals (Sweden)

Wongpakaran T

2014-01-01

Full Text Available Tinakon Wongpakaran, Nahathai WongpakaranFaculty of Medicine, Chiang Mai University, Chiang Mai, ThailandPurpose: Somatization is a common symptom among the elderly, and even though personality disorders have been found to be associated with somatization, personality traits have not yet been explored with regard to this symptom. The aim of this study is to investigate the relationship between personality traits and somatization, and social inhibition.Patients and methods: As part of a cross-sectional study of a community sample, 126 elderly Thais aged 60 years or over completed self-reporting questionnaires related to somatization and personality traits. Somatization was elicited from the somatization subscale when using the Symptom Checklist SCL-90 instrument. Personality traits were drawn from the 16 Personality Factor Questionnaire and social inhibition was identified when using the inventory of interpersonal problems. In addition, path analysis was used to establish the influence of personality traits on somatization and social inhibition.Results: Of the 126 participants, 51% were male, 55% were married, and 25% were retired. The average number of years in education was 7.6 (standard deviation =5.2. “Emotional stability” and “dominance” were found to have a direct effect on somatization, as were age and number of years in education, but not sex. Also, 35% of the total variance could be explained by the model, with excellent fit statistics. Dominance was found to have an indirect effect, via vigilance, on social inhibition, which was also influenced by number of years in education and emotional stability. Social inhibition was not found to have any effect on somatization, although hypothetically it should.Conclusion: “Emotional stability”, “dominance”, and “vigilance”, as well as age and the number of years in education, were found to have an effect on somatization. Attention should be paid to these factors in the elderly

Cerebrospinal fluid aquaporin-4-immunoglobulin G disrupts blood brain barrier

DEFF Research Database (Denmark)

Asgari, Nasrin; Berg, Carsten Tue; Mørch, Marlene Thorsen

2015-01-01

associated with blood-borne horseradish peroxidase leakage indicating blood-brain barrier breakdown. The cerebrospinal fluid aquaporin-4-immunoglobulin G therefore distributes widely in brain to initiate astrocytopathy and blood-brain barrier breakdown....... was evaluated. A distinct distribution pattern of aquaporin-4-immunoglobulin G deposition was observed in the subarachnoid and subpial spaces where vessels penetrate the brain parenchyma, via a paravascular route with intraparenchymal perivascular deposition. Perivascular astrocyte-destructive lesions were...

Optimization of somatic embryogenesis induction in Iranian melon ...

African Journals Online (AJOL)

Jane

2011-07-11

Jul 11, 2011 ... embryo induction and the combination of 0.1 mg/l BA and 5 mg/l 2,4-D had significant effect on somatic ... such as genotype, growth regulator, explant and culture ... different stages of somatic embryos development. (globular ...

Induction of somatic embryogenesis by polyethylene glycol and ...

African Journals Online (AJOL)

VIJI

2012-06-05

Jun 5, 2012 ... supplemented with 2,4-D (2 µM), abscisic acid (3 µM) and glutamine (0.03 mM). The somatic embryos ... essential amino acids of seed proteins, shortened vegetative ... or somatic embryo maturation in diverse plants such as.

Practice Guidelines for Treatment of Somatic Pain and Depression

OpenAIRE

Sonali Sarkar

2017-01-01

Background: Somatic pain is often associated with depression. Patients presenting with this combination can be difficult to treat and create a significant financial burden on the medical system. The mechanisms of action linking somatic pain and the myriad of depression are not clearly understood thus highlighting a gap in knowledge between the scientific mechanism, pathogenesis, and psychiatry involved in depression and somatic pain. The objective of this review article is to address etiolog...

Effect of light quality on somatic embryogenesis of quince leaves

International Nuclear Information System (INIS)

D'Onofrio, C.; Morini, S.; Bellocchi, G.

1998-01-01

The effect of light quality on somatic embryogenesis in quince BA 29 was investigated. 2,4-D induced leaves were exposed for 25 days to the following light quality treatments: dark, far-red, far-red+blue, far-red+red, blue, white, red+blue, red. After a further 20 days of white light exposure, somatic embryo production was recorded. Somatic embryogenesis was highest in cultures subjected to red light treatment, and decreased progressively with the transition to red+blue and to white. Overall, embryogenic competence showed a correlation with photoequilibrium. Phytochrome appeared to be inductive although this effect was adversely influenced by the blue absorbing photoreceptor, in particular at low photoequilibrium. Independently of light treatments applied, somatic embryos frequently showed severe morphological abnormalities. Conversion of somatic embryos to plantlets was not observed. (author)

THE ROLE OF IgM-ENRICHED INTRAVENOUS IMMUNOGLOBULIN IN TRANSPLANTATION

Directory of Open Access Journals (Sweden)

Szabó Judit

2014-04-01

Full Text Available After organ transplantation, gamma globulin and intravenous immunoglobulin enriched with IgM are most frequently used in septic shock as early immune-support. If the explanted organ is infected, the transplantation, as a life-saving operation, can be performed if there is no systemic inflammation and the patient receives IgM enriched immunoglobulin prophylaxis during surgery. The period after transplantation can be divided into three parts from the infection point of view: the first month after transplantation, the first sixth months and the following six months. Infections within the first month are basically related to the surgical procedure. Because of the immunosuppressive therapy, the opportunistic and fungal infections are more common during the first sixth months. After this period, the occurrence and the type of infections are similar to that of the non-transplant population except for pulmonary infections. The latter is two to three times more frequent. This is explained by the secondary hypogammaglobulinaemia (lower blood levels of IgM and IgG which is caused by the steroids but most of mycophenolate mofetil by inhibition of the T and B lymphocyte proliferation. Septic shock develops with a continuing fall of IgM levels. Under these circumstances additional intravenous immunoglobulin therapy with IgM can be lifesaving. Besides, immunoglobulin concentrates with IgM may also be used in the case of viral infections without prophylaxis and/or without etiological therapy such as in the case of West Nile virus infection. As a result of the increase in antibiotic resistance, the application of immunotherapy, including immunoglobulins may become the mainstream in the treatment of septic shock.

Parental Criticism is an Environmental Influence on Adolescent Somatic Symptoms

Science.gov (United States)

Horwitz, BN; Marceau, K; Narusyte, J; Ganiban, J; Spotts, EL; Reiss, D; Lichtenstein, P; Neiderhiser, JM

2015-01-01

Previous studies have suggested that parental criticism leads to more somatic symptoms in adolescent children. Yet this research has not assessed the direction of causation or whether genetic and/or environmental influences explain the association between parental criticism and adolescent somatic symptoms. As such, it is impossible to understand the mechanisms that underlie this association. The current study uses the Extended Children of Twins design to examine whether parents’ genes, adolescents’ genes, and/or environmental factors explain the relationship between parental criticism and adolescent somatic symptoms. Participants came from two twin samples, including the Twin and Offspring Study in Sweden (N = 868 pairs of adult twins and each twin’s adolescent child) and from the Twin Study of Child and Adolescent Development (N = 690 pairs of twin children and their parents). Findings showed that environmental influences account for the association between parental criticism and adolescent somatic symptoms. This suggests that parents’ critical behaviors exert a direct environmental effect on somatic symptoms in adolescent children. Results support the use of intervention programs focused on parental criticism to help reduce adolescents’ somatic symptoms. PMID:25844495

Analyse des génomes à la recherche de répétitions en tandem polymorphes : outils d?épidémiologie bactérienne et locus hypermutables humains

OpenAIRE

Denoeud , France

2003-01-01

thèse soutenue par la DGA; Tandem repeats are consecutive occurrences of a DNA unit. Such structures are found in all organisms, prokaryotes as well as eukaryotes. Although their biological function is not fully understood, they have diverse practical applications. In bacteria, polymorphic tandem repeats (with varying copy numbers), are powerful tools for strain identification in bacterial epidemiology. In humans, some tandem repeats mutate at a very high rate: hypermutable minisatellites are...

A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

International Nuclear Information System (INIS)

Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing; Li, Liping; Li, Wuxian; Dai, Yong

2012-01-01

Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH 2 -CH = O), L5 lipids (-CH 2 -C = O), and L3 lipids (-CH 2 -CH 2 -C = O) as well as lower levels of β-glucose, α-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high-risk groups in our research

A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

Energy Technology Data Exchange (ETDEWEB)

Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing [181st Hospital Guangxi, Central Laboratory, Laboratory of Metabolic Diseases Research, Guangxi Province (China); Li, Liping [Guangxi Normal University, The Life Science College, Guangxi Province (China); Li, Wuxian [Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqiong Medical University, Chongqing (China); Dai, Yong [Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People' s Hospital), Shenzhen, Guangdong Province (China)

2012-07-01

Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH{sub 2}-CH = O), L5 lipids (-CH{sub 2}-C = O), and L3 lipids (-CH{sub 2}-CH{sub 2}-C = O) as well as lower levels of {beta}-glucose, {alpha}-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high

Three forms of somatization in primary care: prevalence, co-occurrence, and sociodemographic characteristics.

Science.gov (United States)

Kirmayer, L J; Robbins, J M

1991-11-01

Three definitions of somatization were operationalized: (a) high levels of functional somatic distress, measured by the Somatic Symptom Index (SSI) of the Diagnostic Interview Schedule; (b) hypochondriasis measured by high scores on a measure of illness worry in the absence of evidence for serious illness; and (c) exclusively somatic clinical presentations among patients with current major depression or anxiety. Of 685 patients attending two family medicine clinics, 26.3% met criteria for one or more forms of somatization. While DSM-III somatization disorder had a prevalence of only 1% in this population, 16.6% of the patients met abridged criteria for subsyndromal somatization disorder (SSI 4,6). Hypochondriacal worry had a prevalence of 7.7% in the clinic sample. Somatized presentations of current major depression or anxiety disorder had a prevalence of 8%. The three forms of somatization were associated with different sociodemographic and illness behavior characteristics. A majority of patients met criteria for only one type of somatization, suggesting that distinct pathogenic processes may be involved in each of the three types.

Development of direct somatic embryogenesis and regeneration on citrus sinesis

International Nuclear Information System (INIS)

Chong Saw Peng; Alvina Lindsay Mijen; Rusli Ibrahim

2004-01-01

The plant regeneration processes in Citrus sinensis involves direct somatic embryogenesis. Culture medium used was MS basal supplemented with 50 mg/L sucrose, 0.27% agar and 0.1% vitamin at pH 5.8. Sucrose is the major carbon source for the induction of somatic embryo and also the maturation and germination of somatic embryo. (Author)

Children of people with somatization disorder.

Science.gov (United States)

Livingston, R

1993-05-01

The author investigated psychopathology, suicidal behavior, child abuse, somatization, and health care utilization in 34 children with a parent who has somatization disorder (SD-P) and two comparison groups: 41 children with a somatizing parent (SOM) (fewer symptoms than required for diagnosis of SD-P), and 30 pediatrically ill controls (CON). Child and parent versions of the Diagnostic Interview for Children and Adolescents were scored for diagnosis and symptom counts in specified categories. Medical records were obtained and abstracted. Children of SD-P had significantly more psychiatric disorders and suicide attempts than did children of SOM or the CON. SD-P and CON had significantly more unexplained physical symptoms than SOM. SD-P showed a trend toward more hospitalizations and experienced significantly more maltreatment. Children of SD-P are at significant risk in several respects. Clinical implications of these findings include a need for awareness and cooperation among general psychiatrists, primary care physicians, and child and adolescent psychiatrists to facilitate detection and treatment of these children's problems.

An immunoenzymatic assay for the diagnosis of hepatitis A utilising immunoglobulin Y

Directory of Open Access Journals (Sweden)

Alexandre dos Santos da Silva

2012-11-01

Full Text Available The detection of anti-hepatitis A virus (HAV antibody levels by diagnostic kits in the convalescent period of disease generally use immunoglobulin G (IgG, which is expensive. An alternative to IgG is immunoglobulin Y (IgY, an immunoglobulin antibody encountered in birds and reptiles. The aim of this study was to develop a competitive immunoenzymatic assay to measure total anti-HAV antibody levels using anti-HAV IgY as the capture and conjugated immunoglobulins. For this purpose, anti-HAV IgY was conjugated to horseradish peroxidase (HRP and the optimal dilution of HRP-conjugated antibodies was evaluated to establish the competitive immuneenzymatic assay. The results obtained from our "in-house" assay were plotted on a receiver operator curve, which showed a sensitivity of 95% and a specificity of 98.8%, demonstrating that a competitive anti-HAV IgY immunoenzymatic assay developed "in house" could be used as an alternative to commercial assays that utilise IgG.

Delusional disorder-somatic type (or body dysmorphic disorder) and ...

African Journals Online (AJOL)

to distinguish cases of delusional disorder of somatic subtype from severe somatization .... features suggestive of a paranoid schizophrenia. Paranoid schizophrenia ... Of note is that the patient's personality and psychosocial functioning were ...

Somatic surveillance: corporeal control through information networks

OpenAIRE

Monahan, Torin; Wall, Tyler

2007-01-01

Somatic surveillance is the increasingly invasive technological monitoring of and intervention into body functions. Within this type of surveillance regime, bodies are recast as nodes on vast information networks, enabling corporeal control through remote network commands, automated responses, or self-management practices. In this paper, we investigate three developments in somatic surveillance: nanotechnology systems for soldiers on the battlefield, commercial body-monitoring systems for hea...

Intravenous immunoglobulin and Alzheimer's disease immunotherapy.

Science.gov (United States)

Solomon, Beka

2007-02-01

Amyloid-beta peptide (Abeta) contributes to the acute progression of Alzheimer's disease (AD) and has become the main target for therapeutics. Active immunization with Abeta in individuals with AD has been efficacious; however, some patients developed side effects, possibly related to an autoimmune response. Evidence that intravenous immunoglobulin (IVIg), an FDA-approved purified immunoglobulin fraction from normal human donor blood, shows promise of passive immunotherapy for AD is reviewed. Investigations into the molecular effects of IVIg on Abeta clearance, using the BV-2 cellular microglia line, demonstrate that IVIg dissolves Abeta fibrils in vitro, increases cellular tolerance to Abeta, enhances microglial migration toward Abeta deposits, and mediates phagocytosis of Abeta. Preliminary clinical results indicate that IVIg, which contains natural antibodies against the Abeta, warrants further study into its potential to deliver a controlled immune attack on the peptide, avoiding the immune toxicities that have had a negative impact on the first clinical trials of vaccine against Abeta.

Somatic embryogenesis for efficient micropropagation of guava (Psidium guajava L.).

Science.gov (United States)

Akhtar, Nasim

2013-01-01

Guava (Psidium guajava L.) is well known for edible fruit, environment friendly pharmaceutical and commercial products for both national and international market. The conventional propagation and in vitro organogenesis do not meet the demand for the good quality planting materials. Somatic embryogenesis for efficient micropropagation of guava (P. guajava L.) has been developed to fill up the gap. Somatic embryogenesis and plantlets regeneration are achieved from 10-week post-anthesis zygotic embryo explants by 8-day inductive treatment with different concentrations of 2,4-dichlorophenoxy acetic acid (2,4-D) on MS agar medium containing 5% sucrose. Subsequent development and maturation of somatic embryos occur after 8 days on MS basal medium supplemented with 5% sucrose without plant growth regulator. The process of somatic embryogenesis shows the highest relative efficiency in 8-day treatment of zygotic embryo explants with 1.0 mg L(-1) 2,4-D. High efficiency germination of somatic embryos and plantlet regeneration takes place on half strength semisolid MS medium amended with 3% sucrose within 2 weeks of subculture. Somatic plantlets are grown for additional 2 weeks by subculturing in MS liquid growth medium containing 3% sucrose. Well-grown plantlets from liquid medium have survived very well following 2-4 week hardening process. The protocol of somatic embryogenesis is optimized for high efficiency micropropagation of guava species.

Plant regeneration of Michelia champaca L., through somatic ...

African Journals Online (AJOL)

STORAGESEVER

2010-05-03

May 3, 2010 ... as a basic material for perfume, cosmetic, and medicine. The development of an ... Plant regeneration systems of M. champaca through somatic ... The embryogenic cells proliferated and formed somatic embryos (30%) after four to six .... by using MS excel program and Duncan's new multiple range test.

Mutator/hypermutable fetal/juvenile metakaryotic stem cells and human colorectal carcinogenesis.

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Lohith G. Kini

2013-10-01

Full Text Available Adult age-specific colorectal cancer incidence rates increase exponentially from maturity, reach a maximum, then decline in extreme old age. Armitage and Doll (1957 postulated that the exponential increase resulted from n mutations occurring throughout adult life in normal cells at risk that initiated the growth of a preneoplastic colony in which subsequent m mutations promoted one of the preneoplastic cells at risk to form a lethal neoplasia. We have reported cytologic evidence that these cells at risk are fetal/juvenile organogenic, then preneoplastic metakaryotic stem cells. Metakaryotic cells display stem-like behaviors of both symmetric and asymmetric nuclear divisions and peculiarities such as bell shaped nuclei and amitotic nuclear fission that distinguish them from embryonic, eukaryotic stem cells. Analyses of mutant colony sizes and numbers in adult lung epithelia supported the inferences that the metakaryotic organogenic stem cells are constitutively mutator/hypermutable and that their contributions to cancer initiation are limited to the fetal/juvenile period. We have amended the two-stage model of Armitage and Doll and incorporated these several inferences in a computer program CancerFit v.5.0. We compared the expectations of the amended model to adult (15-104 yr age-specific colon cancer rates for European American males born 1890-99 and observed remarkable concordance. When estimates of normal colonic fetal/juvenile APC and OAT gene mutation rates (~2-5 x 10-5 per stem cell doubling and preneoplastic colonic gene loss rates (~ 8 x 10-3 were applied, the model was in accordance only for the values of n = 2 and m = 4 or 5.

File list: Pol.Gon.50.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Gon.50.AllAg.Testicular_somatic_cells mm9 RNA polymerase Gonad Testicular somat...ic cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Gon.50.AllAg.Testicular_somatic_cells.bed ...

Immunoglobulin Concentration in Tears of Contact Lens Wearers

Science.gov (United States)

Maurya, Rajendra P.; Bhushan, Prashant; Singh, Virendra P.; Singh, Mahendra K.; Kumar, Prakash; Bhatia, Ravindra P.S.; Singh, Usha

2014-01-01

Purpose: To evaluate changes in the concentration of tear immunoglobulins in contact lens wearers. Methods: A total of 45 cases including 23 contact lens wearers (43 eyes) and 22 age and sex matched healthy controls having no ocular pathology were studied for immunoglobulins (IgA, IgG, IgM) in their tears by single radial immunodiffusion method. Results: Most of the cases used soft (56.6%) and semi-soft gas permeable (30.4%) contact lenses. Tear IgM was detected in only 17.4% and tear IgG in 43.6% of contact lens wearers, while in controls IgG was detected in 9.1% but none of the controls had IgM. There was a significant rise in total tear IgA (13.17 ± 4.44 mg/dl) in contact lens wearer as compared to controls (8.93 ± 3.79 mg/dl). Rise of tear IgA was more in symptomatic patients (15.38 ± 5.28 mg/dl) and in those wearing hard (19.73 ± 5.43 mg/dl) and semi-soft contact lenses (13.31 ± 5.43 mg/dl). A significant increase in tear IgA was noticed in subjects wearing lenses for >3 years (15.69 ± 5.39 mg/dl). About 43.4% of lens wearers were symptomatic and 80% of their lenses showed deposits and/or haziness. All cases with IgM in tear were symptomatic. Conclusion: The relation of immunoglobulin concentration with increasing duration of wear and material of contact lens shows that tear immunoglobulin rise accrues due to mechanical stimulation, hence contact lenses should not be used for a long period and lenses of hard nature should be discouraged. The maintenance, cleaning and deproteinization of the lenses are of high importance to avoid immunostimulation. PMID:25667732

File list: Oth.Gon.50.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Gon.50.AllAg.Testicular_somatic_cells mm9 TFs and others Gonad Testicular somat...ic cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Gon.50.AllAg.Testicular_somatic_cells.bed ...

File list: Oth.Gon.05.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Gon.05.AllAg.Testicular_somatic_cells mm9 TFs and others Gonad Testicular somat...ic cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Gon.05.AllAg.Testicular_somatic_cells.bed ...

Intravenous immunoglobulin to treat hyperbilirubinemia in neonates with isolated Glucose-6-Phosphate dehydrogenase deficiency

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Wadah Khriesat

2017-04-01

Full Text Available Background Glucose-6-phosphate dehydrogenase deficiency alone or concomitant with ABO isoimmunisation is a widespread indication for neonatal exchange transfusion. Aims To evaluate the effectiveness of Intravenous Immunoglobulin in the treatment of neonatal hyperbilirubinemia due to glucose-6-phosphate dehydrogenase deficiency. Methods A retrospective cohort study was conducted between 2006 and 2014 at the Jordan University of Science and technology. The medical records of 43 infants admitted to the neonatal intensive care unit for isolated glucose-6- phosphate dehydrogenase deficiency hemolytic disease of the newborns were reviewed. Patients were divided into two groups. Group I, a historical cohort, included newborns born between 2006 and 2010, Treatment included phototherapy and exchange transfusion. Group II included newborns born between 2011 and 2014, where, in addition to phototherapy, intravenous immunoglobulin was administered. The duration of phototherapy and number of exchange transfusions were evaluated. Results Of 412 newborns that were admitted with neonatal hyperbilirubinemia, Glucose-6-phosphate dehydrogenase deficiency was present in 43. Of these, 22, did not receive intravenous immunoglobulin and served as a control group. The other 21 newborns received intravenous immunoglobulin. There was no difference in the demographic characteristics between the two groups. Infants in the control group were significantly more likely to receive exchange blood transfusion than infants in the immunoglobulin treatment group, but were significantly less likely to need phototherapy. Conclusion Intravenous immunoglobulin is an effective alternative to exchange transfusion in infants with glucose-6-phosphate dehydrogenase deficiency hemolytic disease of the newborn. It is suggested that intravenous immunoglobulin may be beneficial as a prophylaxis for infants with hyperbilirubinemia.

Optimized localization of bacterial infections with technetium-99m labelled human immunoglobulin after protein charge selection

International Nuclear Information System (INIS)

Welling, M.; Feitsma, H.I.J.; Calame, W.; Ensing, G.J.; Goedemans, W.; Pauwels, E.K.J.

1994-01-01

To improve the scintigraphic detection of bacterial infections a protein charge-purified fraction of polyclonal human immunoglobulin was applied as a radiopharmaceutical. This purification was achieved by attaching the immunoglobulin to an anion-exchanger column and by obtaining the column-bound fraction with buffer. The binding to bacteria in vitro and the target to non-target ratios of an experimental thigh infection with Staphylococcus aureus or Klebsiella pneumoniae in mice were evaluated to compare the purified and the unpurified immunoglobulin. The percentage of binding to all gram-positive and gram-negative bacteria used in this study was significantly (P 99m Tc-labelled protein charge-purified polyclonal human immunoglobulin was administered intravenously. At all time intervals the target (infected thighs) to non-target (non-infected thighs) ratios for both infections were significantly higher (P 99m Tc-labelled protein charge-purified immunoglobulin localizes both a gram-positive and a gram-negative thigh infection more intensely and faster than 99m Tc-labelled unpurified immunoglobulin. (orig.)

Somatic Embryogenesis Induction and Plant Regeneration in Strawberry Tree (Arbutus unedo L.).

Science.gov (United States)

Martins, João F; Correia, Sandra I; Canhoto, Jorge M

2016-01-01

Somatic embryogenesis is a powerful tool both for cloning and studies of genetic transformation and embryo development. Most protocols for somatic embryogenesis induction start from zygotic embryos or embryonic-derived tissues which do not allow the propagation of elite trees. In the present study, a reliable protocol for somatic embryogenesis induction from adult trees of strawberry tree is described. Leaves from in vitro proliferating shoots were used to induce somatic embryo formation on a medium containing an auxin and a cytokinin. Somatic embryos germinated in a plant growth regulator-free medium.

Somatic hybridization of sexually incompatible petunias: Petunia parodii, Petunia parviflora.

Science.gov (United States)

Power, J B; Berry, S F; Chapman, J V; Cocking, E C

1980-01-01

Somatic hybrid plants were regenerated following the fusion of leaf mesophyll protoplasts of P. parodii with those isolated from a nuclear-albino mutant of P. parviflora. Attempts at sexual hybridization of these two species repeatedly failed thus confirming their previously established cross-incompatibility. Selection of somatic hybrid plants was possible since protoplasts of P. parodii would not develop beyond the cell colony stage, whilst those of the somatic hybrid and albino P. parviflora produced calluses. Green somatic hybrid calluses were visible against a background of albino cells/calluses, and upon transfer to regeneration media gave rise to shoots. Shoots and the resultant flowering plants were confirmed as somatic hybrids based on their growth habit, floral pigmentation and morphology, leaf hair structure, chromosome number and Fraction 1 protein profiles. The relevance of such hybrid material for the development of new, and extensively modified cultivars, is discussed.

A database of immunoglobulins with integrated tools: DIGIT.

KAUST Repository

Chailyan, Anna; Tramontano, Anna; Marcatili, Paolo

2011-01-01

The DIGIT (Database of ImmunoGlobulins with Integrated Tools) database (http://biocomputing.it/digit) is an integrated resource storing sequences of annotated immunoglobulin variable domains and enriched with tools for searching and analyzing them. The annotations in the database include information on the type of antigen, the respective germline sequences and on pairing information between light and heavy chains. Other annotations, such as the identification of the complementarity determining regions, assignment of their structural class and identification of mutations with respect to the germline, are computed on the fly and can also be obtained for user-submitted sequences. The system allows customized BLAST searches and automatic building of 3D models of the domains to be performed.

A database of immunoglobulins with integrated tools: DIGIT.

KAUST Repository

Chailyan, Anna

2011-11-10

The DIGIT (Database of ImmunoGlobulins with Integrated Tools) database (http://biocomputing.it/digit) is an integrated resource storing sequences of annotated immunoglobulin variable domains and enriched with tools for searching and analyzing them. The annotations in the database include information on the type of antigen, the respective germline sequences and on pairing information between light and heavy chains. Other annotations, such as the identification of the complementarity determining regions, assignment of their structural class and identification of mutations with respect to the germline, are computed on the fly and can also be obtained for user-submitted sequences. The system allows customized BLAST searches and automatic building of 3D models of the domains to be performed.

Somatic seeds of Plantago asiatica L.

Directory of Open Access Journals (Sweden)

Emilia Andrzejewska-Golec

2011-01-01

Full Text Available Somatic seeds of Plantago asiatica L. were produced for the first time. Shoot-tips isolated from in vitro obtained 4-week shoots were encapsulated using sodium alginate and calcium chloride. Capsules with or without sucrose and with and without cytokinin - indole-3-butyric acid (IBA were used. Sucrose presence in capsules very distinctly influences somatic seeds of Plantago asiatica germination and their conversion into plants. However, addition of IBA to capsules has not clear influence on the ability of plant regrowth. Plantlets transplanted to soil grew to phenotypically normal plants.

Plasma vitamin D-binding protein (GC) factors, immunoglobulin G heavy chain (GM) allotypes and immunoglobulin kappa light chain (KM1) allotype in patients with sarcoidosis and in healthy control subjects

DEFF Research Database (Denmark)

Milman, Nils; Thymann, Mariann; Graudal, Niels

2002-01-01

BACKGROUND AND AIM: Sarcoidosis is an immune disease with abnormalities in the production of vitamin D and immunoglobulins. The aim was to examine whether the distribution of plasma vitamin D-binding protein = group-specific component (GC) allotypes, immunoglobulin G heavy chain (GM) allotypes an...

The Effectiveness of Somatization in Communicating Distress in Korean and American Cultural Contexts

Science.gov (United States)

Choi, Eunsoo; Chentsova-Dutton, Yulia; Parrott, W. Gerrod

2016-01-01

Previous research has documented that Asians tend to somatize negative experiences to a greater degree than Westerners. It is posited that somatization may be a more functional communication strategy in Korean than American context. We examined the effects of somatization in communications of distress among participants from the US and Korea. We predicted that the communicative benefits of somatic words used in distress narratives would depend on the cultural contexts. In Study 1, we found that Korean participants used more somatic words to communicate distress than US participants. Among Korean participants, but not US participants, use of somatic words predicted perceived effectiveness of the communication and expectations of positive reactions (e.g., empathy) from others. In Study 2, we found that when presented with distress narratives of others, Koreans (but not Americans) showed more sympathy in response to narratives using somatic words than narratives using emotional words. These findings suggest that cultural differences in use of somatization may reflect differential effectiveness of somatization in communicating distress across cultural contexts. PMID:27047414

The Effectiveness of Somatization in Communicating Distress in Korean and American Cultural Contexts

Directory of Open Access Journals (Sweden)

Eunsoo eChoi

2016-03-01

Full Text Available Previous research has documented that Asians tend to somatize negative experiences to a greater degree than Westerners. It is posited that somatization may be a more functional communication strategy in Korean than American context. We examined the effects of somatization in communications of distress among participants from the US and Korea. We predicted that the communicative benefits of somatic words used in distress narratives would depend on the cultural contexts. In Study 1, we found that Korean participants used more somatic words to communicate distress than US participants. Among Korean participants, but not US participants, use of somatic words predicted perceived effectiveness of the communication and expectations of positive reactions (e.g., empathy from others. In study 2, we found that when presented with distress narratives of others, Koreans (but not Americans showed more sympathy in response to narratives using somatic words than narratives using emotional words. These findings suggest that cultural differences in use of somatization may reflect differential effectiveness of somatization in communicating distress across cultural contexts.

Evaluation of immunoglobulin G synthesizing plasma cells in periapical granuloma and cyst.

OpenAIRE

Grover N; Rao N; Kotian M

2001-01-01

Immunoglobulin synthesizing plasma cells for IgG were quantitated in 20 periapical granulomas and 20 periapical cysts, using unlabelled antibody peroxidase-antiperoxidase complex method. Result showed that immunoglobulin G producing plasma cells were predominant in periapical cyst as compared with periapical granuloma. A statistical significant relation was observed between these two lesions.

Human placental immunoglobulins show unique re-association ...

African Journals Online (AJOL)

Objective: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. Design: Laboratory based experimentation. Setting: Biological Sciences Department and Discipline for Reproductive Medicine University of ...

Studies for Somatic Embryogenesis in Sweet Potato

Science.gov (United States)

Bennett, J. Rasheed; Prakash, C. S.

1997-01-01

The purpose of this study was to improve the somatic embryo (SE) system for plant production of sweet potato (Ipomoea batatas L(Lam)). Explants isolated from SE-derived sweet potato plants were compared with control (non SE-derived) plants for their competency for SE production. Leaf explants were cultured on Murashige-Skoog (MS) medium with 2,4-dichlorophenoxy acetic acid (0.2 mg/L) and 6-benzylaminopurine (2.5 mg/L) for 2 weeks in darkness and transferred to MS medium with abscisic acid (2.5 mg/L). Explants isolated from those plants developed through somatic embryogenesis produced new somatic embryos rapidly and in higher frequency than those isolated from control plants They also appeared to grow faster in tissue culture than the control plants. Current studies in the laboratory are examining whether plants derived from a cyclical embryogenesis system (five cycles) would have any further positive impact on the rapidity and frequency of somatic embryo development. More detailed studies using electron microscopy are expected to show the point of origin of the embryos and to allow determination of their quality throughout the cyclical process. This study may facilitate improved plant micropropagation, gene transfer and germplasm conservation in sweet potato.

METHODOLOGICAL APPROACHES TO EXPERT EVALUATION OF PRECLINICAL AND CLINICAL TRIALS OF HUMAN IMMUNOGLOBULIN PRODUCTS

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V. B. Ivanov

2017-01-01

Full Text Available The article considers the experience of Russian and leading foreign regulatory agencies in organisation and conduction of preclinical and clinical trials of human immunoglobulin products. The authors suggest a classification of human immunoglobulins and provide updated information on authorization of these products in Russia. The article summarizes methodological approaches, basic scientific principles and criteria relating to expert evaluation of preclinical and clinical trials of blood products. The authors further define the expert body’s requirements for data on preclinical and clinical trials of human normal immuniglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases which are submitted as part of applications for marketing authorization or marketing authorization variation. The article suggests programs of preclinical and clinical trials for human normal immunoglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases that are aligned with the Russian legislation and Eurasian Economic Union’s regulations on medicines circulation, and have been elaborated with respect to the guidelines of the European Medicines Agency.

Production of non-stimulatory immunoglobulins that inhibit TSH binding in Graves' disease after radioiodine administration

International Nuclear Information System (INIS)

Bech, K.; Bliddal, H.; Siersbaek-Nielsen, K.; Friis, T.

1982-01-01

The effect of single dose of 131 I upon thyroid stimulating immunoglobulins has been studied in twenty-two patients with Graves' disease. The thyroid stimulating immunoglobulins were assessed by parallel measurements of thyrotrophin receptor binding inhibitory immunoglobulins (TBII) and of thyroid adenylate cyclase stimulating immunoglobulins (TACSI) in serum by radioreceptor assay and stimulation of adenylate cyclase respectively. The present study thus confirms that radioiodine therapy is followed by an increase of TBII and TACSI in most patients with Graves' disease. The level of TBII can probably provide a marker for development of hypothyroidism following 131 I therapy and might be involved in its pathogenesis. (author)

Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody

International Nuclear Information System (INIS)

Stewart, J.S.; Sivolapenko, G.B.; Hird, V.; Davies, K.A.; Walport, M.; Ritter, M.A.; Epenetos, A.A.

1990-01-01

Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment

Importance of neonatal immunoglobulin transfer for hippocampal development and behaviour in the newborn pig.

Directory of Open Access Journals (Sweden)

Kateryna Goncharova

Full Text Available Neurological disorders are among the main clinical problems affecting preterm children and often result in the development of communication and learning disabilities later in life. Several factors are of importance for brain development, however the role of immunoglobulins (passive immunity transfer has not yet been investigated. Piglets are born agammaglobulinemic, as a result of the lack of transfer of maternal immunoglobulins in utero, thus, they serve as an ideal model to mimic the condition of immunoglobulin deficiency in preterm infants. Thirty six, unsuckled newborn piglets were fed an infant formula or colostrum and supplemented orally or intravenously with either species-specific or foreign immunoglobulin and then compared to both newborn and sow-reared piglets. Two days after the piglets were born behavioural tests (novel recognition and olfactory discrimination of conspecifics scent were performed, after which the piglets were sacrificed and blood, cerebrospinal fluid and hippocampi samples were collected for analyses. Both parameters of neuronal plasticity (neuronal maturation and synapse-associated proteins and behavioural test parameters appeared to be improved by the appearance of species-specific porcine immunoglulin in the circulation and cerebrospinal fluid of the piglets. In conclusion, we postulate possible positive clinical effects following intravenous infusion of human immunoglobulin in terms of neuronal plasticity and cognitive function in preterm infants born with low blood immunoglobulin levels.

Germinal and somatic mutations in cancer

International Nuclear Information System (INIS)

Knudson, A.G. Jr.

1977-01-01

The role of germinal and somatic mutations in carcinogenesis leads to the conclusion that environmental carcinogens probably exert their effects via somatic mutations. Susceptibility to this process may itself be genetically determined, so we may deduce that two groups, one genetic and one non-genetic, are included in the 'environmental' class. Other individuals seem to acquire cancer even in the absence of such environmental agents, and these too may be classified into a genetic and a non-genetic group. It has been estimated that in industrial countries, the environmental groups include 70-80% of all cancer cases, but we are only beginning to know how to separate the genetic and non-genetic subgroups. The genetic subgroup of the 'non-environmental' group is very small, probably of the order of magnitude of 1-2% for cancer as a whole. The remainder, about 25%, comprises a non-genetic, non-environmental subgroup that seems to arise as a consequence of 'spontaneous' somatic mutations. The incidence of these 'background' cancers is what we should combat with preventive and therapeutic measures

Serum immunoglobulin levels predict fibrosis in patients with non-alcoholic fatty liver disease.

Science.gov (United States)

McPherson, Stuart; Henderson, Elsbeth; Burt, Alastair D; Day, Christopher P; Anstee, Quentin M

2014-05-01

A third of the population are estimated to have NAFLD of varying severity. Serum immunoglobulins are frequently elevated in patients with chronic liver disease, but little is known about serum immunoglobulin levels in patients with NAFLD. Aim of this study was to evaluate serum immunoglobulin levels (IgA, IgG, and IgM) in a large cohort of patients with biopsy-proven NAFLD and determine if immunoglobulin levels are associated with clinical or histological features. Patients seen in a tertiary fatty liver clinic between 1999 and 2009 were included. Liver biopsies were assessed using the Kleiner score. Immunoglobulin levels and other blood tests were taken at time of biopsy. 285 patients (110 simple steatosis and 175 NASH) had serum immunoglobulins measured within 6months of liver biopsy. 130 (46%) patients had elevated (>1× upper limit of normal) serum IgA levels, 28 (10%) patients had elevated IgG and 22 (8%) raised IgM. Serum IgA levels were elevated more frequently in patients with NASH compared with subjects with simple steatosis (55% vs. 31%, pliver fibrosis (Kleiner stage 3-4). There was a significant positive association between serum IgA levels and the stage of fibrosis (pfibrosis following multivariate analysis. A model constructed from these independent predictors accurately predicted advanced fibrosis (AUROC 0.87). The serum IgA level was frequently elevated in patients with NAFLD and was an independent predictor of advanced fibrosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Somatic Embryogenesis in Two Orchid Genera (Cymbidium, Dendrobium).

Science.gov (United States)

da Silva, Jaime A Teixeira; Winarto, Budi

2016-01-01

The protocorm-like body (PLB) is the de facto somatic embryo in orchids. Here we describe detailed protocols for two orchid genera (hybrid Cymbidium Twilight Moon 'Day Light' and Dendrobium 'Jayakarta', D. 'Gradita 31', and D. 'Zahra FR 62') for generating PLBs. These protocols will most likely have to be tweaked for different cultivars as the response of orchids in vitro tends to be dependent on genotype. In addition to primary somatic embryogenesis, secondary (or repetitive) somatic embryogenesis is also described for both genera. The use of thin cell layers as a sensitive tissue assay is outlined for hybrid Cymbidium while the protocol outlined is suitable for bioreactor culture of D. 'Zahra FR 62'.

Monitoring somatic symptoms in patients with mental disorders: Sensitivity to change and minimal clinically important difference of the Somatic Symptom Scale - 8 (SSS-8).

Science.gov (United States)

Gierk, Benjamin; Kohlmann, Sebastian; Hagemann-Goebel, Marion; Löwe, Bernd; Nestoriuc, Yvonne

2017-09-01

The SSS-8 is a brief questionnaire for the assessment of somatic symptom burden. This study examines its sensitivity to change and the minimal clinically important difference (MCID) in patients with mental disorders. 55 outpatients with mental disorders completed the SSS-8 and measures of anxiety, depression, and disability before and after receiving treatment. Effect sizes and correlations between the change scores were calculated. The MCID was estimated using a one standard error of measurement threshold and the change in disability as an external criterion. There was a medium decline in somatic symptom burden for the complete sample (n=55, d z =0.53) and a large decline in a subgroup with very high somatic symptom burden at baseline (n=11, d z =0.94). Decreases in somatic symptom burden were associated with decreases in anxiety (r=0.68, pSSS-8 is sensitive to change. A 3-point decrease reflects a clinically important improvement. Due to its brevity and sound psychometric properties, the SSS-8 is useful for monitoring somatic symptom burden. Copyright © 2017 Elsevier Inc. All rights reserved.

A randomized trial of treatments for high-utilizing somatizing patients.

Science.gov (United States)

Barsky, Arthur J; Ahern, David K; Bauer, Mark R; Nolido, Nyryan; Orav, E John

2013-11-01

Somatization and hypochondriacal health anxiety are common sources of distress, impairment, and costly medical utilization in primary care practice. A range of interventions is needed to improve the care of these patients. To determine the effectiveness of two cognitive behavioral interventions for high-utilizing, somatizing patients, using the resources found in a routine care setting. Patients were randomly assigned to a two-step cognitive behavioral treatment program accompanied by a training seminar for their primary care physicians, or to relaxation training. Providers routinely working in these patients' primary care practices delivered the cognitive behavior therapy and relaxation training. A follow-up assessment was completed immediately prior to treatment and 6 and 12 months later. Eighty-nine medical outpatients with elevated levels of somatization, hypochondriacal health anxiety, and medical care utilization. Somatization and hypochondriasis, overall psychiatric distress, and role impairment were assessed with well-validated, self-report questionnaires. Outpatient visits and medical care costs before and after the intervention were obtained from the encounter claims database. At 6 month and 12 month follow-up, both intervention groups showed significant improvements in somatization (p somatization, hypochondriacal symptoms, overall psychiatric distress, and role function. They also reduced the ambulatory visits and costs of these high utilizing outpatients.

Characterization of immunoglobulin A kappa autoantibodies to human lactate dehydrogenase isoenzyme-3

NARCIS (Netherlands)

Weijers, R. N.; Oude Elferink, R. P.; Mulder, J.; Kruijswijk, H.

1987-01-01

We have purified with a cumulative recovery of 48% from the serum of a patient the immunoglobulin A kappa subunit of the lactate dehydrogenase-immunoglobulin A kappa (LD-IgA kappa) complex. It appears that the pI range of the complex is 5.4-5.8. The Ig part of the complex showed a monoclonal

Polyphenols distributions and reserve substances analysis in cacao somatic embryogenesis

OpenAIRE

Adriana María Gallego Rúa; Ana María Henao Ramírez; Aura Inés Urrea Trujillo; Lucía Atehortúa Garcés

2016-01-01

ABSTRACTIn order to understand the causes of lack of regeneration in cacao somatic embryos, two cacao varieties with different responses to regeneration potential were described based on their capacity to store different compounds. It is well known that seed reserves play a central role in the regenerative capability of somatic embryos; thus, we followed histochemical changes and reserve fluctuations of proteins, polysaccharides and polyphenols during somatic embryogenesis (SE) in the two cac...

POLYPHENOLS DISTRIBUTION AND RESERVE SUBSTANCES ANALYSIS IN CACAO SOMATIC EMBRYOGENESIS

OpenAIRE

GALLEGO RÚA, Adriana María; HENAO RAMÍREZ, Ana María; URREA TRUJILLO, Aura Inés; ATEHORTÚA GARCÉS, Lucía

2016-01-01

In order to understand the causes of lack of regeneration in cacao somatic embryos, two cacao varieties with different responses to regeneration potential were described based on their capacity to store different compounds. It is well known that seed reserves play a central role in the regenerative capability of somatic embryos; thus, we followed histochemical changes and reserve fluctuations of proteins, polysaccharides and polyphenols during somatic embryogenesis (SE) in the two cacao varie...

In vitro somatic embryogenesis and plant regeneration of cassava.

Science.gov (United States)

Szabados, L; Hoyos, R; Roca, W

1987-06-01

An efficient and reproducible plant regeneration system, initiated in somatic tissues, has been devised for cassava (Manihot esculenta Crantz). Somatic embryogenesis has been induced from shoot tips and immature leaves of in vitro shoot cultures of 15 cassava genotypes. Somatic embryos developed directly on the explants when cultured on a medium containing 4-16 mg/l 2,4-D. Differences were observed with respect to the embryogenic capacity of the explants of different varieties. Secondary embryogenesis has been induced by subculture on solid or liquid induction medium. Long term cultures were established and maintained for up to 18 months by repeated subculture of the proliferating somatic embryos. Plantlets developed from primary and secondary embryos in the presence of 0.1 mg/l BAP, 1mg/l GA3, and 0.01 mg/l 2,4-D. Regenerated plants were transferred to the field, and were grown to maturity.

An inherited immunoglobulin class-switch recombination deficiency associated with a defect in the INO80 chromatin remodeling complex.

Science.gov (United States)

Kracker, Sven; Di Virgilio, Michela; Schwartzentruber, Jeremy; Cuenin, Cyrille; Forveille, Monique; Deau, Marie-Céline; McBride, Kevin M; Majewski, Jacek; Gazumyan, Anna; Seneviratne, Suranjith; Grimbacher, Bodo; Kutukculer, Necil; Herceg, Zdenko; Cavazzana, Marina; Jabado, Nada; Nussenzweig, Michel C; Fischer, Alain; Durandy, Anne

2015-04-01

Immunoglobulin class-switch recombination defects (CSR-D) are rare primary immunodeficiencies characterized by impaired production of switched immunoglobulin isotypes and normal or elevated IgM levels. They are caused by impaired T:B cooperation or intrinsic B cell defects. However, many immunoglobulin CSR-Ds are still undefined at the molecular level. This study's objective was to delineate new causes of immunoglobulin CSR-Ds and thus gain further insights into the process of immunoglobulin class-switch recombination (CSR). Exome sequencing in 2 immunoglobulin CSR-D patients identified variations in the INO80 gene. Functional experiments were performed to assess the function of INO80 on immunoglobulin CSR. We identified recessive, nonsynonymous coding variations in the INO80 gene in 2 patients affected by defective immunoglobulin CSR. Expression of wild-type INO80 in patients' fibroblastic cells corrected their hypersensitivity to high doses of γ-irradiation. In murine CH12-F3 cells, the INO80 complex accumulates at Sα and Eμ regions of the IgH locus, and downregulation of INO80 as well as its partners Reptin and Pontin impaired CSR. In addition, Reptin and Pontin were shown to interact with activation-induced cytidine deaminase. Finally, an abnormal separation of sister chromatids was observed upon INO80 downregulation in CH12-F3 cells, pinpointing its role in cohesin activity. INO80 deficiency appears to be associated with defective immunoglobulin CSR. We propose that the INO80 complex modulates cohesin function that may be required during immunoglobulin switch region synapsis. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The Immunobiology of Immunoglobulin G4

NARCIS (Netherlands)

Lighaam, Laura C.; Rispens, Theo

2016-01-01

Human immunoglobulin G4 (IgG4) antibodies are in many ways unusual. In this review, an overview is given of the structural and functional aspects of IgG4 antibodies, the consequences of IgG4 antibody formation in various disease settings, and the factors involved in the regulation of IgG4 responses.

Somatic syndromes, insomnia, anxiety, and stress among sleep disordered breathing patients.

Science.gov (United States)

Amdo, Tshering; Hasaneen, Nadia; Gold, Morris S; Gold, Avram R

2016-05-01

We tested the hypothesis that the prevalence of somatic syndromes, anxiety, and insomnia among sleep disordered breathing (SDB) patients is correlated with their levels of somatic arousal, the symptoms of increased sympathetic nervous system tone under conditions of stress. We administered the Body Sensation Questionnaire (BSQ; a 17-item questionnaire with increasing levels of somatic arousal scored 17-85) to 152 consecutive upper airway resistance syndrome (UARS) patients and 150 consecutive obstructive sleep apnea/hypopnea (OSA/H) patients. From medical records, we characterized each patient in terms of the presence of syndromes and symptoms into three categories: somatic syndromes (six syndromes), anxiety (anxiety disorders, nightmares, use of benzodiazepines), and insomnia (sleep onset, sleep maintenance, and use of hypnotics). For the pooled sample of SDB patients, we modeled the correlation of the BSQ score with the presence of each syndrome/symptom parameter within each of the three categories, with adjustment for male vs. female. Mean BSQ scores in females were significantly higher than those in males (32.5 ± 11.1 vs. 26.9 ± 8.2; mean ± SD). Increasing BSQ scores significantly correlated with increasing prevalence rates of somatic syndromes (p insomnia (p ≤ 0.0001). In general, females had higher prevalence rates of somatic syndromes and symptoms of anxiety than males at any BSQ score while rates of insomnia were similar. In patients with SDB, there is a strong association between the level of somatic arousal and the presence of stress-related disorders like somatic syndromes, anxiety, and insomnia.

Effects of spaceflight on the immunoglobulin repertoire of unimmunized C57BL/6 mice

Science.gov (United States)

Ward, Claire; Rettig, Trisha A.; Hlavacek, Savannah; Bye, Bailey A.; Pecaut, Michael J.; Chapes, Stephen K.

2018-02-01

Spaceflight has been shown to suppress the adaptive immune response, altering the distribution and function of lymphocyte populations. B lymphocytes express highly specific and highly diversified receptors, known as immunoglobulins (Ig), that directly bind and neutralize pathogens. Ig diversity is achieved through the enzymatic splicing of gene segments within the genomic DNA of each B cell in a host. The collection of Ig specificities within a host, or Ig repertoire, has been increasingly characterized in both basic research and clinical settings using high-throughput sequencing technology (HTS). We utilized HTS to test the hypothesis that spaceflight affects the B-cell repertoire. To test this hypothesis, we characterized the impact of spaceflight on the unimmunized Ig repertoire of C57BL/6 mice that were flown aboard the International Space Station (ISS) during the Rodent Research One validation flight in comparison to ground controls. Individual gene segment usage was similar between ground control and flight animals, however, gene segment combinations and the junctions in which gene segments combine was varied among animals within and between treatment groups. We also found that spontaneous somatic mutations in the IgH and Igκ gene loci were not increased. These data suggest that space flight did not affect the B cell repertoire of mice flown and housed on the ISS over a short period of time.

PARTIAL PURIFICATION AND IMMUNE-BIOCHEMICAL CHARACTERIZATION OF DOG SERUM IMMUNOGLOBULIN G

Directory of Open Access Journals (Sweden)

Manoj Kumar

2013-06-01

Full Text Available In the present study Immunoglobulin G was purified from serum of dog by gel filtration chromatography on Sephacryl S-200. SDS- PAGE analysis of purified dog IgG showed major polypeptides of 66 kDa, 52.40 kDa and 20.72 kDa. The purified Immunoglobulin has been found to be immune-reactive by DID test and Western Blot analysis when treated against hyperimmune sera which was raised in rabbit.

Alcohol dependence and risk of somatic diseases and mortality

DEFF Research Database (Denmark)

Holst, Charlotte; Tolstrup, Janne Schurmann; Sørensen, Holger Jelling

2017-01-01

AIMS: To (1) estimate sex-specific risks of a comprehensive spectrum of somatic diseases in alcohol-dependent individuals versus a control population, and in the same population to (2) estimate sex-specific risks of dying from the examined somatic diseases. DESIGN: Register-based matched cohort...

Estimation of serum, salivary immunoglobulin G, immunoglobulin A levels and total protein, hemoglobin in smokeless tobacco chewers and oral submucous fibrosis patients

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Chandrakanth Balakrishnan

2015-01-01

Full Text Available Background: Oral submucous fibrosis (OSMF is a debilitating, potentially cancerous oral condition. Although areca nut is the most important causative agent, it is also considered that the disease is immunologically mediated. Aim of the Study: To establish that autoimmunity and nutritional deficiency play a role in the etiopathogenesis of OSMF. Objectives of the Study: To show that serum immunoglobulin markers (immunoglobulin-G [IgG], immunoglobulin-A [IgA] and nutritional parameters such as total serum protein (TSP, Hemoglobin (Hb play a role in causing OSMF and also to correlate serum, salivary IgG, IgA levels in OSMF patients. Settings and Design: A case-control study was done with 50 patients (25 patients who were provisionally diagnosed as OSMF - Group I, and 25 patients who were chronic smokeless tobacco chewers and who did not have any intraoral lesion - Group II. Materials and Methods: Five milliliters of blood and saliva were collected from both the groups. Quantitative analysis of serum, and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hemoglobin (Hb were estimated by spectrophotometry. Statistical Analysis: Results were analyzed by independent samples t-test and one-way analysis of variance (ANOVA. Results: All patients of OSMF showed significant (P < 0.01 increase in serum IgG, IgA, and salivary IgG levels as compared to smokeless tobacco chewers. The salivary IgA levels showed a significant decrease in OSMF patients (P < 0.05. TSP and Hb levels showed significant (P < 0.01 decrease in OSMF patients as compared to smokeless tobacco chewers. Conclusion: The elevation of immunoglobulin levels supports the concept of autoimmunity. The decrease in TSP and Hb suggests that nutritional deficiency plays a defined role in the occurrence as well as a further progression of OSMF.

Mouse cloning and somatic cell reprogramming using electrofused blastomeres.

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Riaz, Amjad; Zhao, Xiaoyang; Dai, Xiangpeng; Li, Wei; Liu, Lei; Wan, Haifeng; Yu, Yang; Wang, Liu; Zhou, Qi

2011-05-01

Mouse cloning from fertilized eggs can assist development of approaches for the production of "genetically tailored" human embryonic stem (ES) cell lines that are not constrained by the limitations of oocyte availability. However, to date only zygotes have been successfully used as recipients of nuclei from terminally differentiated somatic cell donors leading to ES cell lines. In fertility clinics, embryos of advanced embryonic stages are usually stored for future use, but their ability to support the derivation of ES cell lines via somatic nuclear transfer has not yet been proved. Here, we report that two-cell stage electrofused mouse embryos, arrested in mitosis, can support developmental reprogramming of nuclei from donor cells ranging from blastomeres to somatic cells. Live, full-term cloned pups from embryonic donors, as well as pluripotent ES cell lines from embryonic or somatic donors, were successfully generated from these reconstructed embryos. Advanced stage pre-implantation embryos were unable to develop normally to term after electrofusion and transfer of a somatic cell nucleus, indicating that discarded pre-implantation human embryos could be an important resource for research that minimizes the ethical concerns for human therapeutic cloning. Our approach provides an attractive and practical alternative to therapeutic cloning using donated oocytes for the generation of patient-specific human ES cell lines.

Characterization of somatic embryo attached structures in Feijoa sellowiana Berg. (Myrtaceae).

Science.gov (United States)

Correia, Sandra M; Canhoto, Jorge M

2010-06-01

The presence of an attached organ to somatic embryos of angiosperms connecting the embryo to the supporting tissue has been a subject of controversy. This study shows that 67% of the morphologically normal somatic embryos of Feijoa sellowiana possess this type of organ and that its formation was not affected by culture media composition. Histological and ultrastructural analysis indicated that the attached structures of somatic embryos displayed a great morphological diversity ranging from a few cells to massive and columnar structures. This contrast with the simple suspensors observed in zygotic embryos which were only formed by five cells. As well as the suspensor of zygotic embryos, somatic embryo attached structures undergo a process of degeneration in later stages of embryo development. Other characteristic shared by zygotic suspensors and somatic embryo attached structures was the presence of thick cell walls surrounding the cells. Elongated thin filaments were often associated with the structures attached to somatic embryos, whereas in other cases, tubular cells containing starch grains connected the embryo to the supporting tissue. These characteristics associated with the presence of plasmodesmata in the cells of the attached structures seem to indicate a role on embryo nutrition. However, cell proliferation in the attached structures resulting into new somatic embryos may also suggest a more complex relationship between the embryo and the structures connecting it to the supporting tissue.

Improving somatic health of outpatients with severe mental illness

NARCIS (Netherlands)

Van Hasselt, Fenneke M.; Oud, Marian J. T.; Krabbe, Paul F. M.; Postma, Maarten J.; Loonen, A.J.M.

2014-01-01

Background: Patients with severe mental illness (SMI) experience a 13-to 30-year reduction in life expectancy compared with the general population. The majority of these deaths can be attributed to somatic health problems. The risk on somatic health problems is partly increased due to a reduced

Somatic embryogenesis and plant regeneration from leaf explants of ...

African Journals Online (AJOL)

An attempt was made to study the somatic embryogenesis and plant regeneration from the in vitro leaf explants of Rumex vesicarius L. a renowned medicinal plant, which belongs to polygonaceae family. Effective in vitro regeneration of R. vesicarius was achieved via young leaf derived somatic embryo cultures.

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Somatic mutations in histiocytic sarcoma identified by next generation sequencing.

Science.gov (United States)

Liu, Qingqing; Tomaszewicz, Keith; Hutchinson, Lloyd; Hornick, Jason L; Woda, Bruce; Yu, Hongbo

2016-08-01

Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20-72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 "Hotspot" oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6 %] and G466R (VF of 29.6 %) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4 %), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities.

Hypochondriasis and somatization: two distinct aspects of somatoform disorders?

Science.gov (United States)

Leibbrand, R; Hiller, W; Fichter, M M

2000-01-01

We investigated boundaries and overlap between somatization and hypochondriasis on different levels of psychopathology: (1) comorbidity between hypochondriasis and somatization on the level of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association, 1994): (2) comorbidity with other mental disorders; (3) differences in clinical characteristics: and (4) overlap on the level of psychometric measures. The sample consisted of 120 psycho somatic inpatients. Somatoform, hypochondriacal, and depressive symptomatology, cognitions about body and health, and further aspects of general symptomatology were investigated. Diagnoses of Axis I and II were based on DSM-IV Our results suggest a large overlap on the level of DSM-IV-diagnoses: only 3 of 31 hypochondriacal patients had no multiple somatoform symptoms, while 58 of 86 patients with multiple somatoform symptoms had no hypochondriasis. However, the overlap between hypochondriacal and somatization symptomatology on the level of psychometric measurement is only moderate, indicating that hypochondriasis is a markedly distinct aspect of somatoform disorders.

Zygotic and somatic embryo morphogenesis in Pinus pinaster: comparative histological and histochemical study.

Science.gov (United States)

Tereso, Susana; Zoglauer, Kurt; Milhinhos, Ana; Miguel, Célia; Oliveira, M Margarida

2007-05-01

We compared morphogenesis and accumulation of storage proteins and starch in Pinus pinaster Ait. zygotic embryos with those in somatic embryos grown with different carbohydrate sources. The maturation medium for somatic embryos included 80 microM abscisic acid (ABA), 9 g l(-1) gellam gum and either glucose, sucrose or maltose at 44, 88, 175 or 263 mM in the presence or absence of 6% (w/v) polyethylene glycol (PEG) 4000 MW. Maturation medium containing 44 or 88 mM of a carbohydrate source produced only one or no cotyledonary somatic embryos per 0.6 g fresh mass of culture. The addition of PEG to the basal maturation medium resulted in a low yield of cotyledonary somatic embryos that generally showed incomplete development and anatomical abnormalities such as large intercellular spaces and large vacuoles. High concentrations of maltose also induced large intercellular spaces in the somatic embryonic cells, and 263 mM sucrose produced fewer and less developed cotyledonary somatic embryos compared with 175 mM sucrose, indicating that the effect of carbohydrate source is partially osmotic. Zygotic embryos had a lower dry mass than somatic embryos at the same stage of development. Starch granules followed a similar accumulation pattern in zygotic and somatic embryos. A low starch content was found in cotyledonary zygotic embryos and in somatic embryos developed in the presence of 175 mM maltose or 263 mM glucose. In zygotic embryos and in PEG-treated somatic embryos, protein bodies appeared later and were smaller and fewer than in well-developed somatic embryos grown without PEG. We propose that storage protein concentration might be a marker of embryo quality.

Behavioral Variability and Somatic Mosaicism: A Cytogenomic Hypothesis.

Science.gov (United States)

Vorsanova, Svetlana G; Zelenova, Maria A; Yurov, Yuri B; Iourov, Ivan Y

2018-04-01

Behavioral sciences are inseparably related to genetics. A variety of neurobehavioral phenotypes are suggested to result from genomic variations. However, the contribution of genetic factors to common behavioral disorders (i.e. autism, schizophrenia, intellectual disability) remains to be understood when an attempt to link behavioral variability to a specific genomic change is made. Probably, the least appreciated genetic mechanism of debilitating neurobehavioral disorders is somatic mosaicism or the occurrence of genetically diverse (neuronal) cells in an individual's brain. Somatic mosaicism is assumed to affect directly the brain being associated with specific behavioral patterns. As shown in studies of chromosome abnormalities (syndromes), genetic mosaicism is able to change dynamically the phenotype due to inconsistency of abnormal cell proportions. Here, we hypothesize that brain-specific postzygotic changes of mosaicism levels are able to modulate variability of behavioral phenotypes. More precisely, behavioral phenotype variability in individuals exhibiting somatic mosaicism might correlate with changes in the amount of genetically abnormal cells throughout the lifespan. If proven, the hypothesis can be used as a basis for therapeutic interventions through regulating levels of somatic mosaicism to increase functioning and to improve overall condition of individuals with behavioral problems.

Restriction endonuclease analysis of chloroplast DNA in interspecies somatic Hybrids of Petunia.

Science.gov (United States)

Kumar, A; Cocking, E C; Bovenberg, W A; Kool, A J

1982-12-01

Restriction endonuclease cleavage pattern analysis of chloroplast DNA (cpDNA) of three different interspecific somatic hybrid plants revealed that the cytoplasms of the hybrids contained only cpDNA of P. parodii. The somatic hybrid plants analysed were those between P. parodii (wild type) + P. hybrida (wild type); P. parodii (wild type)+P. inflata (cytoplasmic albino mutant); P. parodii (wild type) + P. parviflora (nuclear albino mutant). The presence of only P. parodii chloroplasts in the somatic hybrid of P. parodii + P. inflata is possibly due to the stringent selection used for somatic hybrid production. However, in the case of the two other somatic hybrids P. parodii + P. hybrida and P. parodii + P. parviflora it was not possible to determine whether the presence of only P. parodii chloroplasts in these somatic hybrid plants was due to the nature of the selection schemes used or simply occurred by chance. The relevance of such somatic hybrid material for the study of genomic-cytoplasmic interaction is discussed, as well as the use of restriction endonuclease fragment patterns for the analysis of taxonomic and evolutionary inter-relationships in the genus Petunia.

Evaluation of adsorption selectivity of immunoglobulins M, A and G and purification of immunoglobulin M with mixed-mode resins.

Science.gov (United States)

Luo, Ying-Di; Zhang, Qi-Lei; Yao, Shan-Jing; Lin, Dong-Qiang

2018-01-19

This study investigated adsorption selectivity of immunoglobulin M (IgM), immunoglobulin A (IgA) and immunoglobulin (IgG) on four mixed-mode resins with the functional ligands of 4-mercatoethyl-pyridine (MEP), 2-mercapto-1-methylimidazole (MMI), 5-aminobenzimidazole (ABI) and tryptophan-5-aminobenzimidazole (W-ABI), respectively. IgM purification processes with mixed-mode resins were also proposed. All resins showed typical pH-dependent adsorption, and high adsorption capacity was found at pH 5.0-8.0 with low adsorption capacity under acidic conditions. Meanwhile, high selectivity of IgM/IgA and IgM/IgG was obtained with ABI-4FF and MMI-4FF resins at pH 4.0-5.0, which was used to develop a method for IgM, IgA and IgG separation by controlling loading and elution pH. Capture of monoclonal IgM from cell culture supernatant with ABI-4FF resins was studied and high purity (∼99%) and good recovery (80.8%) were obtained. Moreover, IgM direct separation from human serum with combined two-step chromatography (ABI-4FF and MMI-4FF) was investigated, and IgM purity of 65.2% and a purification factor of 28.3 were obtained after optimization. The antibody activity of IgM was maintained after purification. The results demonstrated that mixed-mode chromatography with specially-designed ligands is a promising way to improve adsorption selectivity and process efficiency of IgM purification from complex feedstock. Copyright © 2017 Elsevier B.V. All rights reserved.

Cellular Mechanisms of Somatic Stem Cell Aging

Science.gov (United States)

Jung, Yunjoon

2014-01-01

Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

From culture to symptom: Testing a structural model of "Chinese somatization".

Science.gov (United States)

Zhou, Xiaolu; Peng, Yunshi; Zhu, Xiongzhao; Yao, Shuqiao; Dere, Jessica; Chentsova-Dutton, Yulia E; Ryder, Andrew G

2016-02-01

"Chinese somatization" has been frequently discussed over the past three decades of cultural psychiatry, and has more recently been demonstrated in cross-national comparisons. Empirical studies of potential explanations are lacking, however. Ryder and Chentsova-Dutton (2012) proposed that Chinese somatization can be understood as a cultural script for depression, noting that the literature is divided on whether this script primarily involves felt bodily experience or a stigma-avoiding communication strategy. Two samples from Hunan province, China-one of undergraduate students (n = 213) and one of depressed psychiatric outpatients (n = 281)-completed the same set of self-report questionnaires, including a somatization questionnaire developed in Chinese. Confirmatory factor analysis demonstrated that Chinese somatization could be understood as two correlated factors: one focusing on the experience and expression of distress, the other on its conceptualization and communication. Structural equation modeling demonstrated that traditional Chinese cultural values are associated with both of these factors, but only bodily experience is associated with somatic depressive symptoms. This study takes a first step towards directly evaluating explanations for Chinese somatization, pointing the way to future multimethod investigations of this cultural script. © The Author(s) 2015.

Perceived social support and life satisfaction in persons with somatization disorder

Directory of Open Access Journals (Sweden)

Arif Ali

2010-01-01

Full Text Available Background: Life satisfaction and perceived social support been shown to improve the well-being of a person and also affect the outcome of treatment in somatization disorder. The phenomenon of somatization was explored in relation to the perceived social support and life satisfaction. Aim: This study aimed at investigating perceived social support and life satisfaction in people with somatization disorder. Materials and Methods: The study was conducted on persons having somatization disorder attending the outpatient unit of LGB Regional Institute of Mental Health, Tezpur, Assam. Satisfaction with life scale and multidimensional scale of perceived social support were used to assess life satisfaction and perceived social support respectively. Results: Women reported more somatic symptoms than men. Family perceived social support was high in the patient in comparison to significant others′ perceived social support and friends′ perceived social support. Perceived social support showed that a significant positive correlation was found with life satisfaction. Conclusion: Poor social support and low life satisfaction might be a stress response with regard to increased distress severity and psychosocial stressors rather than a cultural response to express psychological problems in somatic terms.

Cloning animals by somatic cell nuclear transfer – biological factors

Science.gov (United States)

Tian, X Cindy; Kubota, Chikara; Enright, Brian; Yang, Xiangzhong

2003-01-01

Cloning by nuclear transfer using mammalian somatic cells has enormous potential application. However, somatic cloning has been inefficient in all species in which live clones have been produced. High abortion and fetal mortality rates are commonly observed. These developmental defects have been attributed to incomplete reprogramming of the somatic nuclei by the cloning process. Various strategies have been used to improve the efficiency of nuclear transfer, however, significant breakthroughs are yet to happen. In this review we will discuss studies conducted, in our laboratories and those of others, to gain a better understanding of nuclear reprogramming. Because cattle are a species widely used for nuclear transfer studies, and more laboratories have succeeded in cloning cattle than any other specie, this review will be focused on somatic cell cloning of cattle. PMID:14614770

Characterization of a Broadly Reactive Anti-CD40 Agonistic Monoclonal Antibody for Potential Use as an Adjuvant.

Directory of Open Access Journals (Sweden)

Cameron Martin

Full Text Available Lack of safe and effective adjuvants is a major hindrance to the development of efficacious vaccines. Signaling via CD40 pathway leads to enhanced antigen processing and presentation, nitric oxide expression, pro-inflammatory cytokine expression by antigen presenting cells, and stimulation of B-cells to undergo somatic hypermutation, immunoglobulin class switching, and proliferation. Agonistic anti-CD40 antibodies have shown promising adjuvant qualities in human and mouse vaccine studies. An anti-CD40 monoclonal antibody (mAb, designated 2E4E4, was identified and shown to have strong agonistic effects on primary cells from multiple livestock species. The mAb recognize swine, bovine, caprine, and ovine CD40, and evoked 25-fold or greater proliferation of peripheral blood mononuclear cells (PBMCs from these species relative to cells incubated with an isotype control (p<0.001. In addition, the mAb induced significant nitric oxide (p<0.0001 release by bovine macrophages. Furthermore, the mAb upregulated the expression of MHC-II by PBMCs, and stimulated significant (p<0.0001 IL-1α, IL6, IL-8, and TNF-α expression by PBMCs. These results suggest that the mAb 2E4E4 can target and stimulate cells from multiple livestock species and thus, it is a potential candidate for adjuvant development. This is the first study to report an anti-swine CD40 agonistic mAb that is also broadly reactive against multiple species.

DNA/RNA hybrid substrates modulate the catalytic activity of purified AID.

Science.gov (United States)

Abdouni, Hala S; King, Justin J; Ghorbani, Atefeh; Fifield, Heather; Berghuis, Lesley; Larijani, Mani

2018-01-01

Activation-induced cytidine deaminase (AID) converts cytidine to uridine at Immunoglobulin (Ig) loci, initiating somatic hypermutation and class switching of antibodies. In vitro, AID acts on single stranded DNA (ssDNA), but neither double-stranded DNA (dsDNA) oligonucleotides nor RNA, and it is believed that transcription is the in vivo generator of ssDNA targeted by AID. It is also known that the Ig loci, particularly the switch (S) regions targeted by AID are rich in transcription-generated DNA/RNA hybrids. Here, we examined the binding and catalytic behavior of purified AID on DNA/RNA hybrid substrates bearing either random sequences or GC-rich sequences simulating Ig S regions. If substrates were made up of a random sequence, AID preferred substrates composed entirely of DNA over DNA/RNA hybrids. In contrast, if substrates were composed of S region sequences, AID preferred to mutate DNA/RNA hybrids over substrates composed entirely of DNA. Accordingly, AID exhibited a significantly higher affinity for binding DNA/RNA hybrid substrates composed specifically of S region sequences, than any other substrates composed of DNA. Thus, in the absence of any other cellular processes or factors, AID itself favors binding and mutating DNA/RNA hybrids composed of S region sequences. AID:DNA/RNA complex formation and supporting mutational analyses suggest that recognition of DNA/RNA hybrids is an inherent structural property of AID. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular mechanism for generation of antibody memory.

Science.gov (United States)

Shivarov, Velizar; Shinkura, Reiko; Doi, Tomomitsu; Begum, Nasim A; Nagaoka, Hitoshi; Okazaki, Il-Mi; Ito, Satomi; Nonaka, Taichiro; Kinoshita, Kazuo; Honjo, Tasuku

2009-03-12

Activation-induced cytidine deaminase (AID) is the essential enzyme inducing the DNA cleavage required for both somatic hypermutation and class switch recombination (CSR) of the immunoglobulin gene. We originally proposed the RNA-editing model for the mechanism of DNA cleavage by AID. We obtained evidence that fulfils three requirements for CSR by this model, namely (i) AID shuttling between nucleus and cytoplasm, (ii) de novo protein synthesis for CSR, and (iii) AID-RNA complex formation. The alternative hypothesis, designated as the DNA-deamination model, assumes that the in vitro DNA deamination activity of AID is representative of its physiological function in vivo. Furthermore, the resulting dU was removed by uracil DNA glycosylase (UNG) to generate a basic site, followed by phosphodiester bond cleavage by AP endonuclease. We critically examined each of these provisional steps. We identified a cluster of mutants (H48A, L49A, R50A and N51A) that had particularly higher CSR activities than expected from their DNA deamination activities. The most striking was the N51A mutant that had no ability to deaminate DNA in vitro but retained approximately 50 per cent of the wild-type level of CSR activity. We also provide further evidence that UNG plays a non-canonical role in CSR, namely in the repair step of the DNA breaks. Taking these results together, we favour the RNA-editing model for the function of AID in CSR.

Autoantibodies and immunoglobulins in alcoholic steatosis and cirrhosis

DEFF Research Database (Denmark)

Gluud, C; Tage-Jensen, Ulrik Viggo

1983-01-01

increased (p less than 0.005) concentrations of immunoglobulins G, A, and M when compared to patients with steatosis. These results indicate that the degree of liver damage has more effect than chronic alcoholism on the humoral immune system. Whether this influence is direct or indirect remains......Antinuclear antibodies were significantly more prevalent (p less than 0.01) in 143 patients with alcoholic cirrhosis than in 64 patients with alcoholic steatosis and in 94 controls. Smooth muscle antibodies were significantly more prevalent (p less than 0.05) in patients with alcoholic steatosis...... and cirrhosis than in controls. The prevalence of antimitochondrial antibodies and IgG liver membrane antibodies did not differ significantly between the three groups. Immunoglobulin G, A, and M concentrations were only occasionally increased in patients with steatosis. Patients with cirrhosis had significantly...

Preparation of γ-immunoglobulins coupled with DTPA and their labelling with trivalent metal radionuclides for radiotherapy

International Nuclear Information System (INIS)

Rekova, M.; Miler, V.; Budsky, F.; Malek, Z.; Prokop, J.; Prazak, Z.

2007-06-01

The scope of the report is as follows: immunoglobulin coupling with cDTPAA and labelling of the conjugate with 90 Y; Acid-base and complexation equilibria in the coupled immunoglobulin solution; Theory of the complex equilibrium of yttrium between coupled immunoglobulin and EDTA; and Procedures and results of recent experiments. The following was achieved: (i) The dependence of the bovine immunoglobulin on the cDTPAA/IgG coupling ratio and immunoglobulin concentration was obtained; (ii) A procedure aimed to free phosphate buffer from ubiquitous trivalent cations was tested; (iii) The procedure of lyophilization of coupled bovine IgG-DTPA in a phosphate buffer at pH 7.34 and I = 0.16 mol.l -1 .was elaborated. (iv) A procedure for lyophilization of the coupled CD20 monoclonal antibody in the same phosphate buffer was elaborated. (v) Acid-base and complexation equilibria were calculated for citrate and phosphate buffer solutions in the presence of coupled immunoglobulin. ( vi) A theory of the complexation equilibrium of yttrium between coupled immunoglobulin and EDTA was developed. (vii) Experiments were performed leading to the determination of a so far unknown constant of complexity of yttrium to DTPA coupled to immunoglobulin; its 3rd and 4th dissociation constants. (viii) The method sub (vii) can be applied to the determination of the complexity constants of other radionuclides with DTPA coupled to immunoglobulin; the 3rd and 4th dissociation constants of IgG-DTPA will not have to be sought any more. (ix) Samples of lyophilizate of the Y-CD20-DTPA complex can be sent to the biochemical laboratory for immunoreactivity determination. (x) Lyophilizates from experiments (iv-vi) are stored in a refrigerator at 4 deg C to be used for labelling with 177 Lu. (xi) The results obtained can be used to plan an experiment with CD20 in which a specific radioactivity of 400 MBq 177 Lu per mg CD20 will be achieved. (P.A.)

Human somatic cell nuclear transfer and cloning.

Science.gov (United States)

2012-10-01

This document presents arguments that conclude that it is unethical to use somatic cell nuclear transfer (SCNT) for infertility treatment due to concerns about safety; the unknown impact of SCNT on children, families, and society; and the availability of other ethically acceptable means of assisted reproduction. This document replaces the ASRM Ethics Committee report titled, "Human somatic cell nuclear transfer (cloning)," last published in Fertil Steril 2000;74:873-6. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A novel IgA-like immunoglobulin in the reptile Eublepharis macularius.

Science.gov (United States)

Deza, Francisco Gambón; Espinel, Christian Sánchez; Beneitez, Julio Valdueza

2007-01-01

The appearance of antibody genes over evolution coincided with the origin of the vertebrates. Reptiles are of great interest in evolution since they are the link between the amphibians, birds, and mammals. This work describes the presence of a gene in the reptile leopard gecko (Eublepharis macularius) where phylogenetic studies suggest that it is the gene orthologue of immunoglobulin A (IgA) and immunoglobulin X (IgX) in Xenopus. Messenger RNA samples taken from different tissues showed expression of this antibody in intestinal tissue. Data on the structure deduced from the sequence of nucleotides showed an antibody with four domains in the constant region. There is a sequence of 20 amino acids in the C terminus similar to the secretory tail of immunoglobulin M (IgM) and IgA. A detailed analysis of the sequence of amino acids displayed a paradox, i.e., domains CH1 and CH2 showed a clear homology with domains CH1 and CH2 of immunoglobulin Y (IgY) while domains CH3 and CH4 were homologous with domains CH3 and CH4 of IgM. This homology pattern is also seen in Xenopus IgX and bird IgA. The most logical explanation for this phenomenon is that a recombination between the IgM and IgY gave rise to the IgA.

Repair of U/G and U/A in DNA by UNG2-associated repair complexes takes place predominantly by short-patch repair both in proliferating and growth-arrested cells

DEFF Research Database (Denmark)

Akbari, Mansour; Otterlei, Marit; Pena Diaz, Javier

2004-01-01

Nuclear uracil-DNA glycosylase UNG2 has an established role in repair of U/A pairs resulting from misincorporation of dUMP during replication. In antigen-stimulated B-lymphocytes UNG2 removes uracil from U/G mispairs as part of somatic hypermutation and class switch recombination processes. Using......, PCNA and DNA ligase, the latter detected as activity. Short-patch repair was the predominant mechanism both in extracts and UNG2-ARC from proliferating and less BER-proficient growth-arrested cells. Repair of U/G mispairs and U/A pairs was completely inhibited by neutralizing UNG...

File list: Unc.Gon.50.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

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Full Text Available Unc.Gon.10.AllAg.Testicular_somatic_cells mm9 Unclassified Gonad Testicular somatic... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Gon.10.AllAg.Testicular_somatic_cells.bed ...

Flow cytometric and morphological analyses of Pinus pinaster somatic embryogenesis.

Science.gov (United States)

Marum, Liliana; Loureiro, João; Rodriguez, Eleazar; Santos, Conceição; Oliveira, M Margarida; Miguel, Célia

2009-09-25

An approach combining morphological profiling and flow cytometric analysis was used to assess genetic stability during the several steps of somatic embryogenesis in Pinus pinaster. Embryogenic cell lines of P. pinaster were established from immature zygotic embryos excised from seeds obtained from open-pollinated trees. During the maturation stage, phenotype of somatic embryos was characterized as being either normal or abnormal. Based upon the prevalent morphological traits, different types of abnormal embryos underwent further classification and quantification. Nuclear DNA content of maritime pine using the zygotic embryos was estimated to be 57.04 pg/2C, using propidium iodide flow cytometry. According to the same methodology, no significant differences (P< or =0.01) in DNA ploidy were detected among the most frequently observed abnormal phenotypes, embryogenic cell lines, zygotic and normal somatic embryos, and somatic embryogenesis-derived plantlets. Although the differences in DNA ploidy level do not exclude the occurrence of a low level of aneuploidy, the results obtained point to the absence of major changes in ploidy level during the somatic embryogenesis process of this economically important species. Therefore, our primary goal of true-to-typeness was assured at this level.

Immunoglobulins and their fragments on solid surfaces

NARCIS (Netherlands)

Buijs, J.A.G.

1995-01-01

Summary

Adsorption of immunoglobulin G (IgG) is a common step in the production of immunological tests and biosensors. The use of IgG in these applications stems from its ability to specifically bind all kinds of molecules (antigens). In these tests the IgG

File list: Pol.Gon.05.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

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Immunoparesis and polyclonal immunoglobulin recovery after auto-SCT for patients with multiple myeloma treated at a single institution.

Science.gov (United States)

Jimenez-Zepeda, Victor H; Duggan, Peter; Neri, Paola; Chaudhry, Ahsan; Tay, Jason; Bahlis, Nizar

2017-11-21

Immunoparesis and polyclonal immunoglobulin recovery have been recently described as common indicators of immune dysfunction in patients with multiple myeloma. In the present study, we aimed to assess the impact of immunoparesis and polyclonal immunoglobulin recovery at day-100 post autologous stem cell transplant (auto-SCT) on clinical outcomes. A total of 302 patients were included for the analysis of immunoparesis, and 197 were evaluable for polyclonal immunoglobulin recovery evaluation. Immunoparesis was observed in 93.5% of cases, with 47% of cases having polyclonal immunoglobulin recovery at 12 months post auto-SCT. Median overall and progression-free survival were longer in the group of patients with complete or partial normalization of polyclonal immunoglobulins. Patients receiving consolidation had a lower level of polyclonal reconstitution. In conclusion, polyclonal immunoglobulin recovery by 12 months post-auto-SCT is associated with superior overall and progression free survival in patients with MM. Efforts to better enhance polyclonal recovery deserve further investigation.

Water relations in culture media influence maturation of avocado somatic embryos.

Science.gov (United States)

Márquez-Martín, Belén; Sesmero, Rafael; Quesada, Miguel A; Pliego-Alfaro, Fernando; Sánchez-Romero, Carolina

2011-11-15

Application of transformation and other biotechnological tools in avocado (Persea americana Mill.) is hampered by difficulties in obtaining mature somatic embryos capable of germination at an acceptable rate. In this work, we evaluated the effect of different compounds affecting medium water relations on maturation of avocado somatic embryos. Culture media were characterized with respect to gel strength, water potential and osmotic potential. Improved production of mature somatic embryos was achieved with gelling agent concentrations higher than those considered standard. The osmotic agents such as sorbitol and PEG did not have positive effects on embryo maturation. The number of w-o mature somatic embryos per culture was positively correlated with medium gel strength. Gel strength was significantly affected by gelling agent type as well as by gelling agent and PEG concentration. Medium water potential was influenced by sorbitol concentration; incorporation of PEG to a culture medium did not affect medium water potential. The highest maturation results were achieved on a medium gelled with 10 gl(-1) agar. Moreover, these somatic embryos had improved germination rates. These results corroborate the role of water restriction as a key factor controlling maturation of somatic embryos. Copyright © 2011 Elsevier GmbH. All rights reserved.

The somatic mutation landscape of premalignant colorectal adenoma.

Science.gov (United States)

Lin, Shu-Hong; Raju, Gottumukkala S; Huff, Chad; Ye, Yuanqing; Gu, Jian; Chen, Jiun-Sheng; Hildebrandt, Michelle A T; Liang, Han; Menter, David G; Morris, Jeffery; Hawk, Ernest; Stroehlein, John R; Futreal, Andrew; Kopetz, Scott; Mishra, Lopa; Wu, Xifeng

2017-06-12

There are few studies which characterised the molecular alterations in premalignant colorectal adenomas. Our major goal was to establish colorectal adenoma genome atlas and identify molecular markers of progression from colorectal adenoma to adenocarcinoma. Whole-exome sequencing and targeted sequencing were carried out in 149 adenoma samples and paired blood from patients with conventional adenoma or sessile serrated adenoma to characterise the somatic mutation landscape for premalignant colorectal lesions. The identified somatic mutations were compared with those in colorectal cancer (CRC) samples from The Cancer Genome Atlas. A supervised random forest model was employed to identify gene panels differentiating adenoma from CRC. Similar somatic mutation frequencies, but distinctive driver mutations, were observed in sessile serrated adenomas and conventional adenomas. The final model included 20 genes and was able to separate the somatic mutation profile of colorectal adenoma and adenocarcinoma with an area under the curve of 0.941. The findings of this project hold potential to better identify patients with adenoma who may be candidates for targeted surveillance programmes and preventive interventions to reduce the incidence of CRC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Buffalo milk: proteins electrophoretic profile and somatic cell count

Directory of Open Access Journals (Sweden)

S. Mattii

2011-03-01

Full Text Available Water buffalo milk differs from the cow’s milk for greater fat and protein content, very important features in cheese making. Proteins, casein and whey-proteins in particular, are the most important factors determining cheese yield. Several previous research discussed the rule of SCC in cow milk production (Varisco, 1999 and the close relationship existing between cow’s milk cheese yield and somatic cell count (Barbano, 2000. In particular the inverse correlation between cheese yields and somatic cells’content have been demonstrated. In Italy the regulation in force DPR 54/97 acknowledges what expressed in EEC 46/92 Directive (Tripodi, 1999 without fixing the limit threshold of somatic cells for buffalo’s milk....

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Somatic perception, cultural differences and immigration: results from administration of the Modified Somatic Perception Questionnaire (MSPQ to a sample of immigrants

Directory of Open Access Journals (Sweden)

Bragazzi NL

2014-06-01

Full Text Available Nicola Luigi Bragazzi, Giovanni Del Puente, Werner Maria NattaDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, ItalyAbstract: The number of immigrants in Italy has doubled every 10 years from 1972 and Genoa hosts two large communities of immigrants from South America and Africa. We investigated differences in the somatic perception between immigrants and Italians and between South Americans and Africans living in the city of Genoa. During a 7 month period, an anonymous questionnaire asking for sociodemographic information and the Modified Somatic Perception Questionnaire (MSPQ were administered to all immigrants accessing an outpatient clinic or the general practitioners offices. MSPQ mean scores were significantly higher in immigrant patients than in Italian patients, after adjusting for sex and age differences. We found no differences between South Americans and Africans in MSPQ score. The tendency to express discomfort through physical symptoms appears to be related to being a foreigner who arrived in Italy through a migratory trip and also to being a person who comes from a cultural context that is very different from the one of developed countries.Keywords: immigrants, Modified Somatic Perception Questionnaire (MSPQ, somatization, transcultural psychiatry

Somatic Diseases and Conditions Before the First Diagnosis of Schizophrenia

DEFF Research Database (Denmark)

Sørensen, Holger J; Nielsen, Philip Finn Rising; Benros, Michael E

2015-01-01

OBJECTIVE: Schizophrenia is associated with excess physical comorbidity. Yet, to our knowledge, large studies are lacking on the associations with somatic diseases before the onset of schizophrenia. The authors conducted a nationwide study of the full spectrum of treated somatic diseases before t...

A single-strand specific lesion drives MMS-induced hyper-mutability at a double-strand break in yeast.

Science.gov (United States)

Yang, Yong; Gordenin, Dmitry A; Resnick, Michael A

2010-08-05

Localized hyper-mutability (LHM) can be important in evolution, immunity, and genetic diseases. We previously reported that single-strand DNA (ssDNA) can be an important source of damage-induced LHM in yeast. Here, we establish that the generation of LHM by methyl methanesulfonate (MMS) during repair of a chromosomal double-strand break (DSB) can result in over 0.2 mutations/kb, which is approximately 20,000-fold higher than the MMS-induced mutation density without a DSB. The MMS-induced mutations associated with DSB repair were primarily due to substitutions via translesion DNA synthesis at damaged cytosines, even though there are nearly 10 times more MMS-induced lesions at other bases. Based on this mutation bias, the promutagenic lesion dominating LHM is likely 3-methylcytosine, which is single-strand specific. Thus, the dramatic increase in mutagenesis at a DSB is concluded to result primarily from the generation of non-repairable lesions in ssDNA associated with DSB repair along with efficient induction of highly mutagenic ssDNA-specific lesions. These findings with MMS-induced LHM have broad biological implications for unrepaired damage generated in ssDNA and possibly ssRNA. Published by Elsevier B.V.

Journeying as Amateur and Professional – A Somatic Movement Approach

Directory of Open Access Journals (Sweden)

Martha Eddy

2016-07-01

Full Text Available This account is an interactive case study co-authored by a teacher and her student on the topic of moving from amateur to professional. It highlights the role of somatic education in equalizing the experience of amateurs and professionals as well as pointing to specific curricula, public performances, participatory events and volunteer work that are made uniquely available to students of programs related to Dynamic EmbodimentTM Somatic Movement Therapy (known as the Somatic Movement Therapy Training – SMTT from 1991-2005. Written in first-person narrative style (Powdermaker 1966, this inquiry supports the primary methodology of somatic education – the process of self-discovery “from within” (Hanna 1976 emphasizing the physical body with a focus on bodily proprioception and kinesthetic awareness – as well as the humanistic nature of the student-teacher relationship and the value of each in performance and education.

Hypochondriasis and somatization related to personality and attitudes toward self.

Science.gov (United States)

Hollifield, M; Tuttle, L; Paine, S; Kellner, R

1999-01-01

Better definition of the boundary between hypochondriasis and somatization was determined by measuring attitudes to self and personality dimensions associated with these syndromes. In this study, the primary care patients with hypochondriacal responses (HR) on the Illness Attitudes Scales or high somatic concern (HSC) on the Symptom Questionnaire had more negative attitudes to self and more psychological distress than the matched group of primary care control subjects. The HR subjects were different from the non-HR subjects on two of five personality domains on the NEO Personality Inventory (NEO)-Five-Factor Inventory, and the HSC subjects were different from the non-HSC subjects on four of five NEO domains. Analysis of variance demonstrated that somatization explained most of the variance in attitudes, personality, and psychological distress, but hypochondriasis uniquely contributed only to thanatophobia. The authors discuss the boundary between hypochondriasis and somatization and offer a descriptive model of this relationship.

Solid-phase radioimmunoassay of immunoglobulins G, A and M: applicability in analysis of sucrose gradients

Energy Technology Data Exchange (ETDEWEB)

Eriksen, E F; Danielsen, H [Aarhus Kommunehospital (Denmark). Medical Department C; Johansen, A S [Aarhus Univ. (Denmark). Institute of Medical Biochemistry; Larsson, L I [Unit of Histochemistry, University Institute of Pathology, Copenhagen, Denmark

1984-01-01

A simple and sensitive solid-phase radioimmunoassay for the detection of immunoglobulins G, A and M in sucrose gradients is described. The solid-phase consisted of immunoglobulins adsorbed to polystyrene tubes. Using buffers without detergent and /sup 125/I-labeled sheep anti-rabbit IgA as radioligand, the assay was able to detect 0.8 ng per tube in the IgG assay and 1.6 ng per tube in the IgA and IgM assays. Standard curves with antigen dissolved in 10% and 32% sucrose were superimposable and did not deviate from standard curves with antigen dissolved in buffer without sucrose. Using these techniques on ultracentrifugation samples from patients with systemic lupus erythematosus, Schoenlein-Henoch nephritis and IgA glorulonephritis is was possible to detect both immunoglobulin fragments and immunoglobulin aggregates at the same time without prior dialysis of the samples.

When Whole(ness is more than the Sum of the Parts: somatics as contemporary epistemological field

Directory of Open Access Journals (Sweden)

Ciane

2014-12-01

Full Text Available In the text, it is discussed some aspects on somatics in contemporary times, from the starting point of its technical and conceptual basis, clarifying premises and applications, as well as misunderstandings and restrictions. Some aspects include: conceptual, historical, and technical origins; common premises and principles developed by diverse somatic techniques; the difference between somatic technique, method, and approach; transculturality, decolonization, and repatterning; Somatic Attunement and Wisdom; institutionalization in technical and/or academic courses; somatics as autonomous field of therapy, education, aesthetics, and research; somatics as practice as research; somatic-performative research.

Hypochondriasis, somatization, and perceived health and utilization of health care services.

Science.gov (United States)

Hollifield, M; Paine, S; Tuttle, L; Kellner, R

1999-01-01

The authors determined the different effects of hypochondriasis and somatization on health perceptions, health status, and service utilization in a primary care population. The subjects with hypochondriacal responses (HR) on the Illness Attitudes Scales or high somatic concern (HSC) on the Symptom Questionnaire had a worse perception of health and variably used more health services than the control subjects, even though the HR and HSC subjects had the same level of chronic medical disorders. Regression analyses determined that somatization contributed more to negative health perception and service utilization than did hypochondriasis, although an interaction between the two contributed to the use of psychiatric care. The authors discuss the boundary between hypochondriasis and somatization for its implications for research and clinical practice.

Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment.

Science.gov (United States)

Löwe, Bernd; Spitzer, Robert L; Williams, Janet B W; Mussell, Monika; Schellberg, Dieter; Kroenke, Kurt

2008-01-01

To determine diagnostic overlap of depression, anxiety and somatization as well as their unique and overlapping contribution to functional impairment. Two thousand ninety-one consecutive primary care clinic patients participated in a multicenter cross-sectional survey in 15 primary care clinics in the United States (participation rate, 92%). Depression, anxiety, somatization and functional impairment were assessed using validated scales from the Patient Health Questionnaire (PHQ) (PHQ-8, eight-item depression module; GAD-7, seven-item Generalized Anxiety Disorder Scale; and PHQ-15, 15-item somatic symptom scale) and the Short-Form General Health Survey (SF-20). Multiple linear regression analyses were used to investigate unique and overlapping associations of depression, anxiety and somatization with functional impairment. In over 50% of cases, comorbidities existed between depression, anxiety and somatization. The contribution of the commonalities of depression, anxiety and somatization to functional impairment substantially exceeded the contribution of their independent parts. Nevertheless, depression, anxiety and somatization did have important and individual effects (i.e., separate from their overlap effect) on certain areas of functional impairment. Given the large syndrome overlap, a potential consideration for future diagnostic classification would be to describe basic diagnostic criteria for a single overarching disorder and to optionally code additional diagnostic features that allow a more detailed classification into specific depressive, anxiety and somatoform subtypes.

File list: ALL.Gon.05.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Gon.05.AllAg.Testicular_somatic_cells mm9 All antigens Gonad Testicular somatic... cells SRX591729,SRX591728,SRX591717,SRX591716 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Gon.05.AllAg.Testicular_somatic_cells.bed ...

File list: ALL.Gon.20.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Gon.20.AllAg.Testicular_somatic_cells mm9 All antigens Gonad Testicular somatic... cells SRX591728,SRX591729,SRX591717,SRX591716 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Gon.20.AllAg.Testicular_somatic_cells.bed ...

File list: ALL.Gon.50.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Gon.50.AllAg.Testicular_somatic_cells mm9 All antigens Gonad Testicular somatic... cells SRX591728,SRX591729,SRX591717,SRX591716 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Gon.50.AllAg.Testicular_somatic_cells.bed ...

Somatic radiation risk in case of irradiation of the brain

Energy Technology Data Exchange (ETDEWEB)

Nocken, U.; Ewen, K.; Makoski, H.B.

1983-09-01

The somatic dose index for irradiation of the brain was determined for the 10 MeV bremsstrahlung of a linear electron-accelerator. A small volume rotation technique and the irradiation of the total neurocranium were chosen as extreme conditions for the radiation exposure of the skull. On the basis of a target volume dose of 50 Gy for the total irradiation series, the somatic dose index of the small volume technique is within the scope of coronarography. In case of irradiation of the total neurocranium, however, the somatic dose index largely exceeds the maximum values of X-ray diagnosis.

Somatization as a core symptom of melancholic type depression. Evidence from a cross-cultural study.

Science.gov (United States)

Ebert, D; Martus, P

1994-12-01

The study questions whether different types of somatization may be a core symptom of melancholia, thus, being invariable across cultures and being a candidate for neurobiological research and diagnostic criteria. 51 Turkish patients and 51 education-matched German patients with melancholic depression were compared for two types of somatization. Turkish patients had higher frequencies of somatic preoccupation and hypochondriasis but they were not different in the perception and experience of somatic symptoms. It is concluded that: (1) somatization has to be differentiated psychopathologically; (2) it may be a neurobiological core symptom of melancholia in the well-defined sense of 'perceiving abnormal somatic symptoms'; and (3) it may be a culture-bound symptom in the sense of 'being abnormally concerned with somatic symptoms or hypochondrial fears'.

Mind-Body Interactions in Anxiety and Somatic Symptoms.

Science.gov (United States)

Mallorquí-Bagué, Núria; Bulbena, Antonio; Pailhez, Guillem; Garfinkel, Sarah N; Critchley, Hugo D

2016-01-01

Anxiety and somatic symptoms have a high prevalence in the general population. A mechanistic understanding of how different factors contribute to the development and maintenance of these symptoms, which are highly associated with anxiety disorders, is crucial to optimize treatments. In this article, we review recent literature on this topic and present a redefined model of mind-body interaction in anxiety and somatic symptoms, with an emphasis on both bottom-up and top-down processes. Consideration is given to the role played in this interaction by predisposing physiological and psychological traits (e.g., interoception, anxiety sensitivity, and trait anxiety) and to the levels at which mindfulness approaches may exert a therapeutic benefit. The proposed model of mind-body interaction in anxiety and somatic symptoms is appraised in the context of joint hypermobility syndrome, a constitutional variant associated with autonomic abnormalities and vulnerability to anxiety disorders.

Anatomy of somatic embryogenesis in Carica papaya L.

Directory of Open Access Journals (Sweden)

Juliana A. Fernando

2001-09-01

Full Text Available Mature zygotic embryos of Carica papaya L. ‘Sunrise Solo’ were used as explants for embryogenesis induction. The explants were inoculated on Murashige and Skoog culture medium supplemented with 2 mg.L-1 2,4-dichlorophenoxyacetic acid and incubated in darkness at 25+2°C. Histological analysis of callogenesis and somatic embryogenesis indicated occurrence of direct and indirect somatic embryogenesis development. Direct somatic embryo formation was observed from hypocotyledonary epidermic cells only from explant 18 days after inoculation. Somatic embryos formed indirectly were originated from embryogenic superficial cells of pre-embryonic complexes located on peripherical and on internal cell layers of callus 49 days after inoculation. Diverse morphological differences including disformed embryos were observed among the somatic embryos.Embriões zigóticos maduros de Carica papaya L. ‘Sunrise Solo’ foram utilizados como explantes para indução da embriogênese. Estes explantes foram inoculados em meio de cultura de Murashige & Skoog suplementado com 2,0 mg.L-1 de 2,4 ácido diclorofenoxiacético (2,4-D e mantidos no escuro em câmara de crescimento à temperatura de 21°C por período de tempo variável. Através da análise histológica foi possível verificar que os primeiros embriões somáticos formaram-se diretamente a partir de células únicas da epiderme hipocotiledonar do explante após o 18º dia de cultura. Porém, os demais embriões somáticos originaram-se indiretamente a partir de células superficiais de complexos pré-embriônicos presentes nas camadas periféricas e internas do calo após o 49º dia de cultura. Foram detectadas algumas diferenças morfológicas entre os embriões somáticos obtidos.

Number and importance of somatic cells in goat’s milk

Directory of Open Access Journals (Sweden)

Lidija Kozačinski

2001-04-01

Full Text Available Goat’s milk samples were examined on mastitis using stable procedure (California-mastitis test. 427 of the examined milk samples (46.82% had positive reaction from 1 to 3 while other 485 samples (53.18% had negative reaction on the mastitis test, indicating that no illness of mammary gland occurred. Number of somatic cells, counted using “Fossomatic” counter, was 1.3x106/ml average. By comparing the results of mastitis-test evaluation (CMT with the number of somatic cells and findings of mastitis agents in milk showed that higher number of somatic cells is not the only indication of goat’s mammary gland illness. Mastitis-test is method that can exclude inflammation of goat’s mammary gland, but every positive reaction should be confirmed or eliminate with bacteriological examination. Based on the results of this research, it has been shown that the limit for somatic cells number in goat's milk can be over 1 000 000/ml.

Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

NARCIS (Netherlands)

de Jager, AEJ; van der Hoeven, JH

Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually

Autoantibodies and immunoglobulins among atomic-bomb survivors

International Nuclear Information System (INIS)

Fujiwara, Saeko; Carter, R.L.; Akiyama, Mitoshi

1993-06-01

The purpose of this study was to determine if exposure to atomic-bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody, and immunoglobulin levels (IgG, IgM, IgA, and IgE) were measured among 2061 Adult Health Study participants in Hiroshima and Nagasaki from December 1987 to November 1989. The prevalence and titers of rheumatoid factor increased in a statistically significant manner with increasing radiation dose. No radiation effect was found on the prevalence of antinuclear antibody, antithyroglobulin antibody, and anti-thyroid-microsomal antibody. A statistically significant relationship was also found between radiation exposure and the IgA level in females and the IgM levels in both sexes-both levels increased as radiation dose increased. However, the effects of radiation exposure were not large and accounted for less than 10% of the total variation in each measurement. Levels of IgG and IgE were not affected by radiation exposure. (author)

Determination of organ doses during radiological examinations and calculation of somatically significant dose

International Nuclear Information System (INIS)

Steiner, H.

1980-01-01

Examples are used to demonstrate that a shift in the point of emphasis is necessary with regard to radiation hazard in medicinal X-ray diagnosis. The parameters employed in this study to calculate somatic dose (SD) and somatically significant dose (SSD) may well be in need of modification; nevertheless the numerical estimation of SSD arrived at here appears to reflect the right order of magnitude for the estimation of somatic risk. The consideration of the threshold dose for somatic injury remains a problem. (orig./MG) [de

[Disease at any price: psychological challenge and the financial costs of somatization].

Science.gov (United States)

Matalon, A

1996-01-01

In clinical medicine we sometimes deal with patients with unexplained somatic complaints. In a 45-year-old woman with multiple somatic complaints, 2 years of medical examinations in search of a disease diagnosis cost almost 250,000 shekels (about +84,000). The differential diagnosis between somatization, hypochondriasis and psychosomatic pain, and the reasons why physicians are tempted to participate in the "investigation dance" are presented.

Pathological narcissism and somatic symptoms among men and women attending an outpatient mental health clinic.

Science.gov (United States)

Kealy, David; Tsai, Michelle; Ogrodniczuk, John S

2016-09-01

To explore the relationship between types of pathological narcissism and somatic symptoms among psychiatric outpatients. Patients (N = 95) completed measures of somatic symptoms, narcissistic grandiosity and vulnerability, and psychiatric symptoms. Relationships among variables were analysed using t-tests and correlations, controlling for psychiatric distress. Somatic symptoms were positively associated with two types of narcissistic dysfunction. Among women there was a positive association between somatic symptoms and narcissistic vulnerability, but not grandiosity. Among men, somatic symptoms were positively associated with narcissistic grandiosity, but not vulnerability. The connection between narcissistic pathology and somatic symptom severity appears to differ based on gender. Further research is needed to confirm and extend this preliminary finding.

Somatic cell counts in bulk milk and their importance for milk processing

Science.gov (United States)

Savić, N. R.; Mikulec, D. P.; Radovanović, R. S.

2017-09-01

Bulk tank milk somatic cell counts are the indicator of the mammary gland health in the dairy herds and may be regarded as an indirect measure of milk quality. Elevated somatic cell counts are correlated with changes in milk composition The aim of this study was to assess the somatic cell counts that significantly affect the quality of milk and dairy products. We examined the somatic cell counts in bulk tank milk samples from 38 farms during the period of 6 months, from December to the May of the next year. The flow cytometry, Fossomatic was used for determination of somatic cell counts. In the same samples content of total proteins and lactose was determined by Milcoscan. Our results showed that average values for bulk tank milk samples were 273,605/ml from morning milking and 292,895/ml from evening milking. The average values for total proteins content from morning and evening milking are 3,31 and 3,34%, respectively. The average values for lactose content from morning and evening milking are 4,56 and 4,63%, respectively. The highest somatic cell count (516,000/ml) was detected in bulk tank milk sample from evening milk in the Winter and the lowest content of lactose was 4,46%. Our results showed that obtained values for bulk tank milk somatic cell counts did not significantly affected the content of total proteins and lactose.

Swine plasma immunoglobulins for prevention and treatment of post-weaning diarrhoea: Safety and Preliminary results

DEFF Research Database (Denmark)

Hedegaard, Chris Juul; Strube, Mikael Lenz; Bendix Hansen, Marie

. coli F4+ induced PWD, we observed that piglets given IgG as a feed supplement cleared the E coli infection significantly faster than control weaner piglets not receiving an immunoglobulin feed supplement. Furthermore, deep sequencing of the ileal microbiota showed a significantly lowered colonization...... their adhesion to porcine epithelial cells in vitro. As the immunoglobulin fraction is intended for oral use as a feed supplement, we also tested the safety of feeding 4 grams of natural immunoglobulins to 4-5 week old weaner piglets for 14 days and observed no adverse effects. In an experimental model of E...

Epilepsy as a systemic condition: Link with somatic comorbidities.

Science.gov (United States)

Novy, J; Bell, G S; Peacock, J L; Sisodiya, S M; Sander, J W

2017-10-01

People with epilepsy have more concomitant medical conditions than the general population; these comorbidities play an important role in premature mortality. We sought to generate explanatory hypotheses about the co-occurrence of somatic comorbidities and epilepsy, avoiding causal and treatment-resultant biases. We collected clinical, demographic and somatic comorbidity data for 2016 consecutive adults with epilepsy undergoing assessment at a tertiary centre and in 1278 people with epilepsy in the community. Underlying causes of epilepsy were not classed as comorbidities. Somatic comorbidities were more frequent in the referral centre (49%) where people more frequently had active epilepsy than in the community (36%). Consistent risk factors for comorbidities were found in both cohorts. Using multivariable ordinal regression adjusted for age, longer epilepsy duration and an underlying brain lesion were independently associated with a smaller burden of somatic conditions. The treatment burden, measured by the number of drugs to which people were exposed, was not an independent predictor. Shorter epilepsy duration was a predictor for conditions that conceivably harbour significant mortality risks. Somatic comorbidities do not occur randomly in relation to epilepsy; having more severe epilepsy seems to be a risk factor. Independently from age, the early period after epilepsy onset appears to be at particular risk, although it is not clear whether this relates to an early mortality or to a later decrease in the burden of comorbidities. These results suggest that, for some people, epilepsy should be considered a systemic condition not limited to the CNS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pattern of intravenous immunoglobulins (IVIG) use in a pediatric ...

African Journals Online (AJOL)

Pattern of intravenous immunoglobulins (IVIG) use in a pediatric intensive care facility in a resource limited setting. ... Journal Home > Vol 13, No 2 (2013) > ... Results: The clinical diagnoses included neurology (35%), neonatology (16%), ...

Relationship of milking rate to somatic cell count.

Science.gov (United States)

Brown, C A; Rischette, S J; Schultz, L H

1986-03-01

Information on milking rate, monthly bucket somatic cell counts, mastitis treatment, and milk production was obtained from 284 lactations of Holstein cows separated into three lactation groups. Significant correlations between somatic cell count (linear score) and other parameters included production in lactation 1 (-.185), production in lactation 2 (-.267), and percent 2-min milk in lactation 2 (.251). Somatic cell count tended to increase with maximum milking rate in all lactations, but correlations were not statistically significant. Twenty-nine percent of cows with milking rate measurements were treated for clinical mastitis. Treated cows in each lactation group produced less milk than untreated cows. In the second and third lactation groups, treated cows had a shorter total milking time and a higher percent 2-min milk than untreated cows, but differences were not statistically significant. Overall, the data support the concept that faster milking cows tend to have higher cell counts and more mastitis treatments, particularly beyond first lactation. However, the magnitude of the relationship was small.

[Product safety analysis of somatic cell cloned bovine].

Science.gov (United States)

Hua, Song; Lan, Jie; Song, Yongli; Lu, Chenglong; Zhang, Yong

2010-05-01

Somatic cell cloning (nuclear transfer) is a technique through which the nucleus (DNA) of a somatic cell is transferred into an enucleated oocyte for the generation of a new individual, genetically identical to the somatic cell donor. It could be applied for the enhancement of reproduction rate and the improvement of food products involving quality, yield and nutrition. In recent years, the United States, Japan and Europe as well as other countries announced that meat and milk products made from cloned cattle are safe for human consumption. Yet, cloned animals are faced with a wide range of health problems, with a high death rate and a high incidence of disease. The precise causal mechanisms for the low efficiency of cloning remain unclear. Is it safe that any products from cloned animals were allowed into the food supply? This review focuses on the security of meat, milk and products from cloned cattle based on the available data.

The Use of Light Microscopy for Detection of Somatic Embryos

African Journals Online (AJOL)

usuario

2014-02-05

Feb 5, 2014 ... 2,4-D. After four weeks of culture of explants on the callus induction medium, globular structures were obtained. At the end of 20 days in maturation medium, somatic embryos were observed. Histological analysis showed somatic embryos with caulinar and root apex, protodermal tissue, and the vascular ...

On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events

OpenAIRE

Sp?th, Peter J.; Granata, Guido; La Marra, Fabiola; Kuijpers, Taco W.; Quinti, Isabella

2015-01-01

Abstract to the dark side of therapies with human immunoglobulin G concentratesTherapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A p...

Monitoring Genetic Stability in Quercus serrata Thunb. Somatic Embryogenesis Using RAPD Markers

OpenAIRE

Ramesh C., Thakur; Susumu, Goto; Katsuaki, Ishii; S. Mohan, Jain; Forestry and Forest Products Research Institute; Fukuoka Prefecture Forest Research and Extension Center; Forestry and Forest Products Research Institute; University of Helsinki

1999-01-01

Genetic stability of propagules regenerated via somatic embryogenesis is of paramount importance for its application to clonal forestry. Random amplified polymorphic DNA (RAPD) markers were used to determine the genetic stability in somatic embryogenesis of Quercus serrata Thunb. (Japanese white oak). Forty samples from an embryogenic line, consisting of regenerated plantlets, somatic embryos, and embryogenic calli, were examined using 54 decanucleotide primers. A total of 6520 clear reproduc...

Depression, Anxiety and Somatic Complaints in Colombian Children Living in Rural Communities

Directory of Open Access Journals (Sweden)

Ruby C. Castilla Puentes

2013-08-01

Full Text Available Introduction: In Colombia, children are frequently exposed to traumatic events; however, there are no data regarding the impact on depression, anxiety and somatic correlates of such exposure in children living in rural communities. Objective: To investigate the somatic complaints and symptoms of depression and anxiety among children exposed to traumatic events in a rural community of Colombia. Methods: Design: Cross-Sectional study. Participants: Two hundred and ninety-three Colombian children aged eight to 18 years. Main Outcome Measures: Standardized measures were administered to assess children's depression, anxiety, physical symptoms and exposure to traumatic events. Depression: CDI (Children's Depression Inventory; anxiety: SCARED (The Screen for Child Anxiety Related Emotional Disorders; somatic complaints: CBCL (Child Behavior Checklist, Somatic Complaints scale and reporting traumatic events during the K-SADS-PL (Diagnostic Interview for Children and Adolescents. Results: Ninety-one of the 293 children (31.1% reported somatic complaints. The most common somatic complaint was in the gastrointestinal category (35/91. One hundred and seventy eight children (60.5% had observed traumatic events, including homicides during the last month. Two hundred five (69.9% of the children showed depressive symptom profiles above established norms, and 239 (81.6% exhibited anxiety symptoms according to their own reports. The correlation between depression and traumatic events, anxiety and somatic complaints, and between anxiety and depression were statistically significant (p<0.005. Conclusions: As the first study of its kind in children living in rural communities in Colombia, it demonstrates a clear impact of traumatic events on mental health. Information that somatic complaints are commonly an expression of underlying depression and anxiety may facilitate the treatment and thereby help avoid unnecessary medical workups and sequelae from traumatized

File list: NoD.Gon.10.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Gon.10.AllAg.Testicular_somatic_cells mm9 No description Gonad Testicular somatic... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Gon.10.AllAg.Testicular_somatic_cells.bed ...

Somatic embryogenesis in plantain cultivar 'FHIA - 25' (AAB from meristem tips

Directory of Open Access Journals (Sweden)

Dayana Rodríguez González

2015-07-01

Full Text Available Plantain cultivar 'FHIA – 25' (AAB shows high yielding qualities and high resistance to Black Sigatoka disease, but its sugar content in the fruit is low, so a regeneration method at cell level is necessary, such as somatic embryogenesis supported by biotechnological tools to improve fruit quality. This work was performed with the aim of establishing a plant regeneration method via somatic embryogenesis using initial explants of shoot apices from axillary buds in liquid culture medium. Homogenous embryogenic cell suspensions were obtained from mentioned explants. The highest cellular multiplication rates were achieved at 3,0% density. The incubation of somatic embryos during 30 days in the maturation culture medium permitted to increase germination. During the acclimatization stage, plants regenerated from somatic embryos, as well as plants from organogenesis, showed a high survival percentage (98 and 97 respectively, without somaclonal variation.

Serum immunoglobulin levels in humans exposed to therapeutic total-body gamma irradiation

International Nuclear Information System (INIS)

Chaskes, S.; Kingdon, G.C.; Balish, E.

1975-01-01

Reduced serum immunoglobulin (IgA, IgG, IgM) levels developed in the majority of 27 patients with hematologic disorders after treatment with 100 to 350 R total-body gamma-ray exposures at a dose rate of either 1.5 R/min to 1.5 R/hr. A reduction in IgA of 20 percent or more was found in 66 percent of the cases, while 56 percent showed an IgM decrease, and 49 percent an IgG decrease of 20 percent. The severity of immunoglobulin depression was influenced by the total radiation dose and the patient's primary disease. The occurrence of IgG and IgM depression was greater when the radiation was given at 1.5 R/hr than when the dose rate was 1.5 R/min. Substantial but incomplete recovery toward preirradiation immunoglobulin levels was found for most patients by 7 wk after total-body irradiation (TBI). (U.S.)

Intravenous Immunoglobulin therapy for anti-E hemolytic disease in the newborn.

Science.gov (United States)

Onesimo, Roberta; Rizzo, Daniela; Ruggiero, Antonio; Valentini, Piero

2010-09-01

Anti-E alloimmunisation is a less common cause of haemolytic disease in the newborn (HDN) and is usually associated with mild to moderate clinical manifestations, that are often less severe than anti-D immunisation. Conventional treatments for HDN are phototherapy and exchange transfusion, the latter still representing a high-risk procedure. Currently, intravenous immunoglobulin has been used as alternative treatment for HDN to reduce the need for exchange transfusion, as well as the length of phototherapy and hospitalisation. We report a case of anti-E HDN treated successfully with intravenous immunoglobulin, as adjuvant treatment to phototherapy.

Further studies of immunoglobulin synthesis by guinea-pig leukaemic lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Hough, D W; Chapple, J C; Stevenson, F K; Stevenson, G T [Southampton General Hospital (UK)

1978-05-01

The L/sub 2/C leukemia is a B-lymphocytic neoplasm of strain 2 guinea pigs maintained by passaging in vivo. It synthesizes ..mu.. and lambda immunoglobulin chains. These combine to form monomeric (7S) IgM molecules which are inserted into the plasma membrane. From here they are shed as monomeric IgM and as a species of higher molecular weight which has not been further defined. The synthesis of lambda chain is in excess of that required for the IgM molecule, the surplus being exported directly from the cell without any intervening phase in the plasma membrane. Quantitative estimates of synthetic rates and pool sizes for these immunoglobulin species are presented.

Bacteremia and immunoglobulin classes in Nigerian women with ...

African Journals Online (AJOL)

Apart from antiphospholipid- and thyroid- autoantibodies which were reported as underlying causes of recurrent pregnancy loss, specific IgG to patermal MHC and Rh was proposed. This raises the possibility of other classes of immunoglobulin in recurrent abortion. Twenty-four pregnant women with recurrent abortion ...

Quantitation of Fc receptors and surface immunoglobulin is affected by cell isolation procedures using plasmagel and ficoll-hypaque.

Science.gov (United States)

Alexander, E L; Titus, J A; Segal, D M

1978-01-01

When mononuclear leukocytes are isolated directly from whole human blood using Ficoll-Hypaque or Plasmagel, cytophilic immunoglobulin is detected on cell surfaces. Upon incubation at 37 degrees C, this cell-associated immunoglobulin is shed slowly into the medium. However, when cells are prewashed in phosphate-buffered saline prior to isolation, they appear to be free of cytophilic immunoglobulin. Compared to prewashed cells, populations retaining cytophilic immunoglobulin on their surfaces demonstrate a decreased binding of soluble immune complexes and radiolabelled trimeric rabbit IgG. The data suggest that Ficoll-Hypaque and Plasmagel cause serum IgG to bind with abnormally high affinity to human mononuclear leukocytes, probably via Fc receptors. This artifact of preparation can lead to erroneous estimates of the numbers of cells bearing Fc receptors or intrinsic membrane immunoglobulin within a given population of cells and to an inaccurate assessment of the average number of Fc receptors per cell.

[Hypochondriac symptoms in late-onset depression: the relationship between hypochondria and somatic state of patients].

Science.gov (United States)

Ivanets, N N; Avdeeva, T I; Kinkul'kina, M A

2013-01-01

Authors studied 276 women with late-onset depression. Concomitant chronic somatic diseases were identified in 90%. The presence of disease and its nosological definition did not impact on the development of hypochondriac symptoms in patients with late-onset depression. Patients with hypochondriac late-onset depression more often had disability pension due to somatic disease because they more often referred to internists in case of similar objective severity of somatic pathology. It was singled out three variants of the relationship between hypochondria and somatic state: hypernosognostic (a complete coincidence of hypochondria content with actual somatic pathology; anosognostic (a lack of coincidence) and disharmonic (a partial coincidence). The themes of hypochondria in late-nset depressions were correlated with a total number of somatic diseases and their severity. At the same time, there was no correlation between the content of hypochondria and the character of somatic disease.

Dogs cloned from adult somatic cells.

Science.gov (United States)

Lee, Byeong Chun; Kim, Min Kyu; Jang, Goo; Oh, Hyun Ju; Yuda, Fibrianto; Kim, Hye Jin; Hossein, M Shamim; Shamim, M Hossein; Kim, Jung Ju; Kang, Sung Keun; Schatten, Gerald; Hwang, Woo Suk

2005-08-04

Several mammals--including sheep, mice, cows, goats, pigs, rabbits, cats, a mule, a horse and a litter of three rats--have been cloned by transfer of a nucleus from a somatic cell into an egg cell (oocyte) that has had its nucleus removed. This technology has not so far been successful in dogs because of the difficulty of maturing canine oocytes in vitro. Here we describe the cloning of two Afghan hounds by nuclear transfer from adult skin cells into oocytes that had matured in vivo. Together with detailed sequence information generated by the canine-genome project, the ability to clone dogs by somatic-cell nuclear transfer should help to determine genetic and environmental contributions to the diverse biological and behavioural traits associated with the many different canine breeds.

Detection and purification of rat and goat immunoglobulin G antibodies using protein G-based solid phase radioimmunoassays

International Nuclear Information System (INIS)

Nilson, B.; Aakerstroem, B.; Bjoerck, L.

1986-01-01

Using the newly described streptococcal surface protein, protein G, which has powerful immunoglobulin G binding properties, solid-phase radioimmunoassays were developed for the quantitation of goat and rat immunoglobulin G bound to the plastic surface of microtiter plates. The binding of goat immunoglobulin G to the surface via a specific antigen (guinea pig alpha 1 -microglobulin) permitted the determination of antigen-specific antibodies with a detection limit of 50-100 ng. Optimum assay conditions were established and the whole assay procedure could be brought to completion at room temperature in less than a working day. The value of the assays was illustrated by monitoring rat and goat immunoglobulin G antibodies during their purification from whole sera by classical chromatographic procedures. (Auth.)

File list: InP.Gon.20.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Gon.20.AllAg.Testicular_somatic_cells mm9 Input control Gonad Testicular somatic... cells SRX591728,SRX591716 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Gon.20.AllAg.Testicular_somatic_cells.bed ...

File list: InP.Gon.50.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Gon.50.AllAg.Testicular_somatic_cells mm9 Input control Gonad Testicular somatic... cells SRX591728,SRX591716 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Gon.50.AllAg.Testicular_somatic_cells.bed ...

Cognitive-affective depression and somatic symptoms clusters are differentially associated with maternal parenting and coparenting.

Science.gov (United States)

Lamela, Diogo; Jongenelen, Inês; Morais, Ana; Figueiredo, Bárbara

2017-09-01

Both depressive and somatic symptoms are significant predictors of parenting and coparenting problems. However, despite clear evidence of their co-occurrence, no study to date has examined the association between depressive-somatic symptoms clusters and parenting and coparenting. The current research sought to identify and cross-validate clusters of cognitive-affective depressive symptoms and nonspecific somatic symptoms, as well as to test whether clusters would differ on parenting and coparenting problems across three independent samples of mothers. Participants in Studies 1 and 3 consisted of 409 and 652 community mothers, respectively. Participants in Study 2 consisted of 162 mothers exposed to intimate partner violence. All participants prospectively completed self-report measures of depressive and nonspecific somatic symptoms and parenting (Studies 1 and 2) or coparenting (Study 3). Across studies, three depression-somatic symptoms clusters were identified: no symptoms, high depression and low nonspecific somatic symptoms, and high depression and nonspecific somatic symptoms. The high depression-somatic symptoms cluster was associated with the highest levels of child physical maltreatment risk (Study 1) and overt-conflict coparenting (Study 3). No differences in perceived maternal competence (Study 2) and cooperative and undermining coparenting (Study 3) were found between the high depression and low somatic symptoms cluster and the high depression-somatic symptoms cluster. The results provide novel evidence for the strong associations between clusters of depression and nonspecific somatic symptoms and specific parenting and coparenting problems. Cluster stability across three independent samples suggest that they may be generalizable. The results inform preventive approaches and evidence-based psychotherapeutic treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

Serum immunoglobulin levels in the ABCC-JNIH adult health study: Hiroshima and Nagasaki

Energy Technology Data Exchange (ETDEWEB)

King, R A; Milton, R C; Hamilton, H B

1973-05-31

Immunoglobulin levels (IgG, IgA, and IgM) were determined on 2043 individuals in the ABCC-JNIH Adult Health Study population, and levels were compared to disease states and the dose of radiation ATB. Mean levels for both cities and sexes combined were IgG = 1577 mg%, IgA = 312 mg%, and IgM = 127 mg%. Differences between these mean levels and those reported in other studies are thought secondary to racial and environmental factors, and technical differences with the methods used for quantitation. Females had higher IgM levels that tended to go down with advancing age. Of the diseases evaluated, rheumatoid arthritis, cirrhosis, and pulmonary tuberculosis affected immunoglobulin levels the greatest. There was no apparent relationship between radiation dose from the atomic bomb and immunoglobulin levels determined more than 25 years after exposure. (6 tables)

CYTOLOGICAL QUALITY OF GOAT MILK ON THE BASIS OF THE SOMATIC CELL COUNT

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Henryka BERNACKA

2007-07-01

Full Text Available The aim of the present paper was to evaluate the cytological quality of goat milk based on the somatic cell count in respective months of lactation. Besides there was defined the effect of somatic cell on the milk production and chemical composition of milk. The research covered goats of color improved breed in the 2nd and 3rd lactation. Daily milk yield, chemical composition of milk and its somatic cell count were defined based on monthly morning and evening control milkings from both teats, following the A4 method applied in District Animal Evaluation Stations. The research indicated that the greater the somatic cell count in milk, the lower the daily milk yield, however the greater the somatic cell count, the greater the percentage content of fat and dry matter and the lower the content of lactose.

Somatic embryogenesis from leaf explants of Australian fan flower, Scaevola aemula R. Br.

Science.gov (United States)

Wang, Y-H; Bhalla, P L

2004-01-01

Somatic embryogenesis from leaf explants of Scaevola aemula R. Br. was achieved. Somatic embryos were induced from explants cultured on MS medium supplemented with 0.2 mg/ 2,4-dichlorophenoxyacetic acid and 0.2-0.5 mg/l 6-benzylaminopurine (BAP). Various developmental stages of somatic embryos were found on this medium-from globular embryos to germinated embryos. The transfer of globular embryos to MS medium containing 0.5 mg/l BAP resulted in a high frequency of shoot regeneration. Leaf explants cultured on MS medium containing different combinations of BAP and alpha-naphthaleneacetic acid formed adventitious shoots and roots. Histological examination confirmed the process of somatic embryogenesis. Induction of somatic embryogenesis in Scaevola provides a system for studying embryogenesis in Australian native plants and will facilitate the improvement of these plants using genetic transformation techniques.

Somatic PI3K activity regulates transition to the spermatocyte stages ...

Indian Academy of Sciences (India)

Samir Gupta

2017-04-22

Apr 22, 2017 ... like growth factor (IGF) families, control the tissue homeosta- sis (Biteau et al. 2011 ... A breach in the somatic encapsulation due to the loss of somatic cyst cells .... populations at the apical region of testes of 4-days-old adults.

Somatic PI3K activity regulates transition to the spermatocyte stages ...

Indian Academy of Sciences (India)

Spermatogenesis, involving multiple transit amplification divisions and meiosis, occurs within an enclosure formed bytwo somatic cells. As the cohort of germline cells divide and grow, the surface areas of the somatic cells expandmaintaining a tight encapsulation throughout the developmental period. Correlation between ...

File list: InP.Gon.10.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Gon.10.AllAg.Testicular_somatic_cells mm9 Input control Gonad Testicular somati...c cells SRX591728,SRX591716 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Gon.10.AllAg.Testicular_somatic_cells.bed ...

Acute phase proteins and immunoglobulin classes in newly ...

African Journals Online (AJOL)

Background: No single organic cause has been found for schizophrenia and its management has been difficult. More so, there are few data on the immune parameters of Nigerian schizophrenic patients on drug treatment and those that are not on treatment. Methodology: This study determines the levels of immunoglobulin

Mechanism of immunoglobulin G4 Fab-arm exchange

NARCIS (Netherlands)

Rispens, Theo; Ooijevaar-de Heer, Pleuni; Bende, Onno; Aalberse, Rob C.

2011-01-01

Immunoglobulin G (IgG) antibodies are symmetrical molecules that may be regarded as covalent dimers of 2 half-molecules, each consisting of a light chain and a heavy chain. Human IgG4 is an unusually dynamic antibody, with half-molecule exchange ("Fab-arm exchange") resulting in asymmetrical,

IMMUNOGLOBULINS IN COLOSTRUM OF SOWS WITH PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME - PRRS

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Michal ROLINEC

2012-06-01

Full Text Available The aim of this study was to examine the effect of PRRS occurrence on sow colostrum immunological quality. We realised the experiment on 20 sows (breed: Large white. From farm without presences of PRRS were 10 sows and other 10 sows were from farm with presence of PRRS. We took the samples of sows colostrums during sucking. We detected concentration of immunoglobulins (IgG, IgA, IgM in sows colostrum in time of 0 hours to 12 hours after beginning of farrowing with pig Ig ELISA quantitation kits. We determined statistically significant (P<0.01 higher concentration of IgG at the beginning of farrowing, 3 hours, 6 hours and 12 hours from beginning of farrowing in favour of farm without presence of PRRS. We determined statistically significant (P<0.01 higher concentration of IgA at 6 and 12 hours from beginning of farrowing in favour of farm without presence of PRRS. We determined statistically significant (P<0.01 higher concentration of IgM at 6 and 12 hours from beginning of farrowing in favour of farm without presence of PRRS. Lower concentrations of colostral immunoglobulins in group with PRRS can be caused of presence of PRRS. Virus PRRS can evocate synthesis of cytokine IL-10, which inhibited the function of macrophages and lymphocytes and so PRRS decrease the production of immunoglobulins and their concentration in blood of sows and consequently also concentration of immunoglobulins in sows colostrum.

Teaching at the interface of dance science and somatics.

Science.gov (United States)

Geber, Pamela; Wilson, Margaret

2010-01-01

This article introduces a combined scientific and somatic approach to teaching and learning about the body, and explains how it can be of benefit to dancers and dance educators. The study of the science of movement (kinesiology) and a somatic approach to teaching are initially defined and described as distinct entities; following this, a model for integration of the two is presented. The authors advocate for such a combination in order to enhance dancing.

Comparative proteomic analysis of off-type and normal phenotype somatic plantlets derived from somatic embryos of Feijoa (Acca sellowiana (O. Berg) Burret).

Science.gov (United States)

Fraga, Hugo Pacheco de Freitas; Agapito-Tenfen, Sarah Zanon; Caprestano, Clarissa Alves; Nodari, Rubens Onofre; Guerra, Miguel Pedro

2013-09-01

Morphological disorders in a relevant portion of emerged somatic embryos have been a limiting factor in the true-to-type plantlet formation in Acca sellowiana. In this sense, the present study undertook a comparison between normal phenotype and off-type somatic plantlets protein profiles by means of the 2-D DIGE proteomics approach. Off-type and normal phenotype somatic plantlets obtained at 10 and 20 days conversion were evaluated. Results indicated 12 exclusive spots between normal and off-type plantlets at 10 days conversion, and 17 exclusive spots at 20 days conversion. Also at 20 days conversion, 4 spots were differentially expressed, up- or down-regulated. Two proteins related to carbohydrate metabolism were only expressed in off-types at 10 days conversion, suggesting a more active respiratory pathway. A vicilin-like storage protein was only found in off-types at 20 days conversion, indicating that plantlets may present an abnormality in the mobilization of storage compounds, causing reduced vigor in the development of derived plantlets. The presence of heat shock proteins were only observed during formation of normal phenotype somatic plantlets, indicating that these proteins may be involved in normal morphogenesis of plantlets formed. These new findings shed light on possible genetic or epigenetic mechanisms governing A. sellowiana morphogenesis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

HETEROGENEITY OF POLYCLONAL IMMUNOGLOBULINS NUCLEASE ACTIVITY IN RHEUMATOID AND REACTIVE ARTHRITIS

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M. V. Volkova

2017-01-01

Full Text Available Catalytic properties of immunoglobulins are widely studied within recent years. It was found that nuclease activity of immunoglobulins is increased in systemic autoimmune diseases. Given some pathogenetic features of rheumatoid arthritis and reactive arthritis, it is appropriate to clarify the nature of nuclease activity in these diseases. Determination of DNAse activity of immunoglobulins with different DNA substrates, and search for specific substrates for distinct clinical entities could serve these purposes. The aim of present work is to determine DNase activity of the polyclonal class G immunoglobulins in rheumatoid and reactive arthritis using various methods.Different methods are used to evaluate nuclease activity. In this paper we present newly developed and modified techniques for determination of DNAse activity of polyclonal IgGs. Particular attention was paid to the electrophoretic method of DNase activity assessment. Polyclonal IgG isolated from blood serum of patients with rheumatoid arthritis and reactive arthritis were used for assays. In this study, we demonstrated the presence of an inhomogeneous DNase activity of immunoglobulins in relation to different substrates.Along with calf thymus DNA, we used bacterial plasmid DNA and PCR products based on bacterial gene sequences. Levels of DNase activity by rivanol clot method with calf thymus DNA as substrate proved to be higher in patients with rheumatoid arthritis than the control values (p < 0.01. DNase abzyme activity in patients with rheumatoid arthritis was elevated, as compared to the patients with reactive arthritis (p < 0.01.When examining ability of the IgG to hydrolyze procaryotic DNA (bacterial plasmid DNA and PCR products, based on bacterial genes, we obtained heterogeneous results. Different Ig samples showed varying degrees of DNA hydrolysis. Abzyme hydrolysis of DNA substrates longer than 700 bp was more pronounced, as compared to short DNA substrates (100 base pairs

Are There Mutator Polymerases?

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Miguel Garcia-Diaz

2003-01-01

Full Text Available DNA polymerases are involved in different cellular events, including genome replication and DNA repair. In the last few years, a large number of novel DNA polymerases have been discovered, and the biochemical analysis of their properties has revealed a long list of intriguing features. Some of these polymerases have a very low fidelity and have been suggested to play mutator roles in different processes, like translesion synthesis or somatic hypermutation. The current view of these processes is reviewed, and the current understanding of DNA polymerases and their role as mutator enzymes is discussed.

Serum immunoglobulin and complement levels in prematures with parenteral feeding--preliminary results.

Science.gov (United States)

Tamaro, G; Morena, C; Uxa, F; Candusso, M; Trappan, A; de Vonderweid, U

1993-01-01

Immunoglobulins IgA, IgG and IgM and complement factors C3 and C4 have been measured in a population of premature infants to evaluate their degree of immunological maturity. All the infants were receiving complete parenteral nutrition. In parallel, the same parameters were measured in twenty two full term, healthy neonates. To explore maturation and liver function, the authors used other proteins as nutritional markers. Differences in the immunoglobulins, but not in the complement fractions were seen between the two groups. Two applications are suggested: incidence of infections and post partum maturation.

Serum-derived bovine immunoglobulin/ protein isolate: postulated mechanism of action for management of enteropathy

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Petschow BW

2014-05-01

Full Text Available Bryon W Petschow, Bruce Burnett, Audrey L Shaw, Eric M Weaver, Gerald L Klein Entera Health, Inc., Cary, NC, USA Abstract: The health and performance of the gastrointestinal tract is influenced by the interaction of a variety of factors, including diet, nutritional status, genetics, environment, stress, the intestinal microbiota, immune status, and gut barrier. Disruptions in one or more of these factors can lead to enteropathy or intestinal disorders that are known to occur in concert with certain disease states or conditions such as irritable bowel syndrome or human immunodeficiency virus (HIV infection. Nutritional support in the form of a medical food along with current therapies could help manage the adverse effects of enteropathy, which include effects on nutrient digestion, absorption, and metabolism, as well as utilization of nutrients from foodstuffs. Numerous studies have demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight management, normalize gut barrier function, and reduce the severity of enteropathy in animals. Recent trials in humans provide preliminary evidence that a serum-derived bovine immunoglobulin/protein isolate is safe and improves symptoms, nutritional status, and various biomarkers associated with enteropathy in patients with HIV infection or diarrhea-predominant irritable bowel syndrome. This review summarizes data from preclinical and clinical studies with immunoglobulin-containing plasma/serum protein concentrates, with a focus on the postulated mode of action of serum-derived bovine immunoglobulin/protein isolate for patients with enteropathy. Keywords: bovine immunoglobulins, nutrient, gut barrier, microbiota

Serology and immunoglobulin profile in rheumatoid arthritis.

Science.gov (United States)

Adhya, S; Chakraborty, G; Hajra, B; Bhattacharya, S; Sikdar, P K; Sinha, S; Banerjee, P P; Ghosh, E; Chakraborty, P

1998-01-01

One hundred and twenty cases of clinically diagnosed rheumatoid arthritis, 80 non-rheumatoid cases suffering from various other diseases and 40 healthy individuals were investigated for the presence of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of ANA and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor showed 56.6% positivity in rheumatoid group and 3.7% positivity in non-rheumatoid group. All three serum immunoglobulins (IgG, IgM, IgA) were raised in serum in significant titre in cases of rheumatoid arthritis, whereas only IgA lever was elevated in the group of non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 11.7% and 4.4% cases of rheumatoid arthritis who had severe underlying disease. In non-rheumatoid group, only one of 6 cases of systemic lupus erythematosus showed rheumatoid factor and that too in an insignificant titre (less than 1:20). Synovium and synovial fluid contained plenty of plasma cells and lymphocytes. It has been observed that RF appears first in synovial fluid and it may take several months to a year to attain detectable level in serum.

Hypermutability of CpG dinucleotides in the propeptide-encoding sequence of the human albumin gene

International Nuclear Information System (INIS)

Brennan, S.O.; Peach, R.; Myles, T.; George, P.; Arai, Kunio; Madison, J.; Watkins, S.; Putnam, F.W.; Laurell, C.B.; Galliano, M.

1990-01-01

An electrophoretically slow albumin variant was detected with a phenotype frequency of about 1:1,000 in Sweden and was also found in a family of Scottish descent from Kaikoura, New Zealand, and in five families in Tradate, Italy. Structural study established that the major variant component was arginyl-albumin, in which arginine at the -1 position of the propeptide is still attached to the processed albumin. A minor component with the amino-terminal sequence of proalbumin was also present as 3-6% of the total albumin. After amplification of the gene segment encoding the prepro sequence of albumin, specific hybridization of DNA to an oligonucleotide probe encoding cysteine at position -2 indicated the mutation of arginine at the -2 position to cysteine (-2 Arg → Cys). This produced the propeptide sequence Arg-Gly-Val-Phe-Cys-Arg. This was confirmed by sequence analysis after pyridylethylation of the cysteine. This mutation produces an alternate signal peptidase cleavage site in the variant proalbumin precursor of arginyl-albumin giving rise to two possible products, arginyl-albumin and the variant proalbumin. Another plasma from Bremen had an alloalbumin with a previously described substitution (1 Asp → Val), which also affects propeptide cleavage. Hypermutability of two CpG dinucleotides in the codons for the diarginyl sequence may account for the frequency of mutations in the propeptide. Mutation at these two sites results in a series of recurrent proalbumin variants that have arisen independently in diverse populations

The relationship of age, anxiety, and serum immunoglobulins with crystallized and fluid intelligence.

Science.gov (United States)

Cohen, D; Eisdorfer, C; Vitaliano, P P; Bloom, V

1980-10-01

Serum immunoglobulin concentrations (IgG, IgA, and IgM), cognitive performance (crystallized and fluid intelligence), and self-reports of anxiety were evaluated in 24 men and women 60-75 years, and 50 men and women, 30-45 years. Trait anxiety was an important factor relating to performance differences between the young and old on crystallized and fluid subtests. IgM was inversely related to performance in the older age groups. Anxiety was not related to serum immunoglobulin levels.

Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

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Akiko Sano

Full Text Available Therapeutic human polyclonal antibodies (hpAbs derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc cattle carrying a human artificial chromosome (HAC comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH and kappa-chain (hIGK germline loci (named as κHAC are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO. However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ in the pre-B cell receptor (pre-BCR complex, we partially replaced (bovinized the hIgM constant domain with the counterpart of bovine IgM (bIgM that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO, the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG can be produced from such Tc cattle.

WPMSD: A Malicious Script Detection Method Inspired by the Process of Immunoglobulin Secretion

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Hui Zhao

2011-10-01

Full Text Available Inspired by the process of immunoglobulin secretion in biological body, we present a Web Page Malicious Script Detection Method (WPMSD. In this paper, Firstly, the basic definitions of artificial immune items are given. Secondly, according to the spreading range of malicious script, the immunoglobulin number is changed as the detector clone proliferation is stimulated by malicious scripts. Further more, the nonlinear dynamics of antibody number is discussed. Thirdly, we propose a probability approach to trigger alarms to inform that the detected scripts are harmful. Finally, the WPMSD collects the effective immunoglobulin set based on Hidden Markov Model (HMM to update the detector gene library. Compared with the traditional immune based detection methods, such as Negative Selection Algorithm (NSA, Dynamic Colonel Selection (DynamiCS, and Variable size Detector (Vdetector, the false alarm rate of WPMSD has been reduced by 18.09%, 12.6%, and 7.47% respectively.

Contrastive Study of Somatisms Distinctive Features in Phraseology of Different Languages

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Sharbat Muhamedzhanova

2013-01-01

Full Text Available The article analyzes semantic transformations of phraseologically active somatisms, based on contrastive study of fixed combinations in Kazakh and French languages. The prospects for the study of fixed combinations, having somatic vocabulary as a semantic kernel in conceptualization of idioethnic anthropological paradigm was studied

Changes in serum immunoglobulin levels during radiotherapy for carcinoma of the uterine cervix

International Nuclear Information System (INIS)

Kaneta, Osamu

1978-01-01

We have, studied the effect of radiation on humoral immunity in patients with carcinoma of the cervix by measuring variations in serum immunoglobulins (IgA, IgG, IgM) during radiotherapy. Of 81 patients with untreated cancer of the cervix (at stages Ib-IIIb), those at stage III had a significantly lower IgG level (P < 0.05) compared with control patients (94 in number). There was a significant fall (P < 0.05) in the mean serum IgA and IgG levels during radiation therapy in group A (36 patients who received this modality of treatment alone). However, in group B (26 patients who underwent pelvic lymphadenectomy prior to radiotherapy) and in group C (9 patients subjected to hysterectomy with pelvic lymphadenectomy before irradiation) there was no significant fall in the mean serum IgA and IgG levels. There were two distinct patterns of variation in serum immunoglobulins seen during external irradiation: type a) in which serum immunoglobulin levels tended to decline with the increase in radiation dose, and type b) in which serum immunoglobulin levels either remained the same as those prior to irradiation or varied in an irregular fashion during irradiation. There was a significant difference (P < 0.05) in the incidence of either type a) or b) for IgG and IgM between group A and groups B and C. The type a) pattern of serum immunoglobulin variation was more common in patients with stage 1 carcinoma, and was gradually superceded by type b) in more advanced cases. Thus it would appear that lymph nodes retain the ability to respond to radiation in most cases of early stage carcinoma, but lose this capacity with more advanced carcinoma, a finding which is suggestive of lowered ability for antibody production of the most bearing advanced carcinoma. (author)

Health Anxiety in Panic Disorder, Somatization Disorder and Hypochondriasis

OpenAIRE

Özgün Karaer KARAPIÇAK; Selçuk ASLAN; Çisem UTKU

2012-01-01

Objective: Health anxiety is the fear of being or getting seriously sick due to the misinterpretation of physical symptoms. Severe health anxiety is also named as hypochondriasis. Belief of having a disease due to the misinterpretation of physical symptoms is also seen in panic disorder and somatization disorder. The aim of this study is to search the health anxiety in panic disorder, somatization disorder and hypochondriasis and compare it with healthy volunteers. Method: SCID-I was used ...

Somatic VHL gene alterations in MEN2-associated medullary thyroid carcinoma

International Nuclear Information System (INIS)

Koch, Christian A; Brouwers, Frederieke M; Vortmeyer, Alexander O; Tannapfel, Andrea; Libutti, Steven K; Zhuang, Zhengping; Pacak, Karel; Neumann, Hartmut PH; Paschke, Ralf

2006-01-01

Germline mutations in RET are responsible for multiple endocrine neoplasia type 2 (MEN2), an autosomal dominantly inherited cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia/adenoma. Recent studies suggest a 'second hit' mechanism resulting in amplification of mutant RET. Somatic VHL gene alterations are implicated in the pathogenesis of MEN2 pheochromocytomas. We hypothesized that somatic VHL gene alterations are also important in the pathogenesis of MEN2-associated MTC. We analyzed 6 MTCs and 1 C-cell hyperplasia (CCH) specimen from 7 patients with MEN2A and RET germline mutations in codons 609, 618, 620, or 634, using microdissection, microsatellite analysis, phosphorimage densitometry, and VHL mutation analysis. First, we searched for allelic imbalance between mutant and wild-type RET by using the polymorphic markers D10S677, D10S1239, and RET on thyroid tissue from these patients. Evidence for RET amplification by this technique could be demonstrated in 3 of 6 MTCs. We then performed LOH analysis using D3S1038 and D3S1110 which map to the VHL gene locus at 3p25/26. VHL gene deletion was present in 3 MTCs. These 3 MTCs also had an allelic imbalance between mutant and wild-type RET. Mutation analysis of the VHL gene showed a somatic frameshift mutation in 1 MTC that also demonstrated LOH at 3p25/26. In the 2 other MTCs with allelic imbalance of RET and somatic VHL gene deletion, no somatic VHL mutation could be detected. The CCH specimen did neither reveal RET imbalance nor somatic VHL gene alterations. These data suggest that a RET germline mutation is necessary for development of CCH, that allelic imbalance between mutant and wild-type RET may set off tumorigenesis, and that somatic VHL gene alterations may not play a major role in tumorigenesis of MEN2A-associated MTC

Somatic embryogenesis and plant regeneration of Capsicum baccatum L.

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Peddaboina Venkataiah

2016-06-01

Full Text Available A plant regeneration protocol via somatic embryogenesis was achieved in cotyledon and leaf explants of Capsicum baccatum, when cultured on MS medium supplemented with various concentrations of 2,4-dichlorophenoxy acetic acid (2,4-D, 0.5–5.0 mg l−1 in combination with Kinetin (Kn, 0.5 mg l−1 and 3% sucrose. Various stages were observed during the development of somatic embryos, including globular, heart, and torpedo-stages. Torpedo stage embryos were separated from the explants and subcultured on medium supplemented with various concentrations of different plant growth regulators for maturation. Maximum percentage (55% of somatic embryo germination and plantlet formation was found at 1.0 mg l−1 BA. Finally, about 68% of plantlets were successfully established under field conditions. The regenerated plants were morphologically normal, fertile and able to set viable seeds.

A pathway-centric survey of somatic mutations in Chinese patients with colorectal carcinomas.

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Chao Ling

Full Text Available Previous genetic studies on colorectal carcinomas (CRC have identified multiple somatic mutations in four candidate pathways (TGF-β, Wnt, P53 and RTK-RAS pathways on populations of European ancestry. However, it is under-studied whether other populations harbor different sets of hot-spot somatic mutations in these pathways and other oncogenes. In this study, to evaluate the mutational spectrum of novel somatic mutations, we assessed 41 pairs of tumor-stroma tissues from Chinese patients with CRC, including 29 colon carcinomas and 12 rectal carcinomas. We designed Illumina Custom Amplicon panel to target 43 genes, including genes in the four candidate pathways, as well as several known oncogenes for other cancers. Candidate mutations were validated by Sanger sequencing, and we further used SIFT and PolyPhen-2 to assess potentially functional mutations. We discovered 3 new somatic mutations in gene APC, TCF7L2, and PIK3CA that had never been reported in the COSMIC or NCI-60 databases. Additionally, we confirmed 6 known somatic mutations in gene SMAD4, APC, FBXW7, BRAF and PTEN in Chinese CRC patients. While most were previously reported in CRC, one mutation in PTEN was reported only in malignant endometrium cancer. Our study confirmed the existence of known somatic mutations in the four candidate pathways for CRC in Chinese patients. We also discovered a number of novel somatic mutations in these pathways, which may have implications for the pathogenesis of CRC.

Persistent Graves' hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report.

Science.gov (United States)

Ohara, Nobumasa; Kaneko, Masanori; Kitazawa, Masaru; Uemura, Yasuyuki; Minagawa, Shinichi; Miyakoshi, Masashi; Kaneko, Kenzo; Kamoi, Kyuzi

2017-02-06

Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism. A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism. The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid

Long-Term Follow-Up of Individuals Undergoing Sex-Reassignment Surgery: Somatic Morbidity and Cause of Death.

Science.gov (United States)

Simonsen, Rikke Kildevæld; Hald, Gert Martin; Kristensen, Ellids; Giraldi, Annamaria

2016-03-01

Studies of mortality and somatic well-being after sex-reassignment surgery (SRS) of transsexual individuals are equivocal. Accordingly, the present study investigated mortality and somatic morbidity using a sample of transsexual individuals who comprised 98% (n = 104) of all surgically reassigned transsexual individuals in Denmark. To investigate somatic morbidity before and after SRS and cause of death and its relation to somatic morbidity after SRS in Danish individuals who underwent SRS from 1978 through 2010. Somatic morbidity and mortality in 104 sex-reassigned individuals were identified retrospectively by data from the Danish National Health Register and the Cause of Death Register. Somatic morbidity and cause of death. Overall, 19.2% of the sample were registered with somatic morbidity before SRS and 23.1% after SRS (P = not significant). In total, 8.6% had somatic morbidity before and after SRS. The most common diagnostic category was cardiovascular disease, affecting 18 individuals, 9 before and 14 after SRS, and 5 of those 14 who were affected after SRS had cardiovascular disease before and after SRS. Ten individuals died after SRS at an average age of 53.5 ± 7.9 years (male to female) and 53.5 ± 7.3 years (female to male). Of 98% of all Danish transsexuals who officially underwent SRS from 1978 through 2010, one in three had somatic morbidity and approximately 1 in 10 had died. No significant differences in somatic morbidity or mortality were found between male-to-female and female-to-male individuals. Despite the young average age at death and the relatively larger number of individuals with somatic morbidity, the present study design does not allow for determination of casual relations between, for example, specific types of hormonal or surgical treatment received and somatic morbidity and mortality. Copyright © 2016. Published by Elsevier Inc.

Immunoglobulin superfamily members encoded by viruses and their multiple roles in immune evasion.

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Farré, Domènec; Martínez-Vicente, Pablo; Engel, Pablo; Angulo, Ana

2017-05-01

Pathogens have developed a plethora of strategies to undermine host immune defenses in order to guarantee their survival. For large DNA viruses, these immune evasion mechanisms frequently rely on the expression of genes acquired from host genomes. Horizontally transferred genes include members of the immunoglobulin superfamily, whose products constitute the most diverse group of proteins of vertebrate genomes. Their promiscuous immunoglobulin domains, which comprise the building blocks of these molecules, are involved in a large variety of functions mediated by ligand-binding interactions. The flexible structural nature of the immunoglobulin domains makes them appealing targets for viral capture due to their capacity to generate high functional diversity. Here, we present an up-to-date review of immunoglobulin superfamily gene homologs encoded by herpesviruses, poxviruses, and adenoviruses, that include CD200, CD47, Fc receptors, interleukin-1 receptor 2, interleukin-18 binding protein, CD80, carcinoembryonic antigen-related cell adhesion molecules, and signaling lymphocyte activation molecules. We discuss their distinct structural attributes, binding properties, and functions, shaped by evolutionary pressures to disarm specific immune pathways. We include several novel genes identified from extensive genome database surveys. An understanding of the properties and modes of action of these viral proteins may guide the development of novel immune-modulatory therapeutic tools. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Somatic gene mutation in the human in relation to radiation risk

International Nuclear Information System (INIS)

Mendelsohn, M.L.

1992-01-01

This report discusses the measurement of somatic gene-mutation frequencies in the human. We ask the following questions. How well can they be measured? Do they respond to radiation? Can they also function as a dosimeter? What do they tell us about the somatic mutation theory of carcinogenesis?

Somatic Markers and Explicit Knowledge Are both Involved in Decision-Making

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Guillaume, Sebastien; Jollant, Fabrice; Jaussent, Isabelle; Lawrence, Natalia; Malafosse, Alain; Courtet, Philippe

2009-01-01

In 1994, it was proposed that decision-making requires emotion-related signals, known as somatic markers. In contrast, some authors argued that conscious knowledge of contingencies is sufficient for advantageous decision-making. We aimed to investigate the respective roles of somatic markers and explicit knowledge in decision-making. Thirty…

Production of immunoglobulins in gingival tissue explant cultures from juvenile periodontitis patients

International Nuclear Information System (INIS)

Hall, E.R.; Falkler, W.A. Jr.; Suzuki, J.B.

1990-01-01

B lymphocytes and plasma cells are histologically observed in granulomatous periodontal tissues of juvenile periodontitis (JP) patients. Local immune processes may participate in protective or immunopathologic roles in the pathogenesis of this disease. An in vitro explant culture system was utilized to demonstrate the production of immunoglobulins by diseased JP tissues. Immunodiffusion studies using goat anti-human gamma, alpha, or mu chain serum revealed IgG to be the major immunoglobulin present in 92% of the day 1 supernatant fluids (SF) of the 47 JP gingival tissue explant cultures. IgA was present in 15% of the SF; however, no IgM was detected. Staph Protein A isolated 14C-labeled IgG from the SF, when allowed to react with goat anti-human gamma chain serum, formed lines of precipitation. Positive autoradiographs confirmed the biosynthesis of IgG by the explant cultures. The in vitro gingival tissue explant culture system described provides a useful model for the study of localized immunoglobulins produced by diseased tissues of JP patients

Production of immunoglobulins in gingival tissue explant cultures from juvenile periodontitis patients

Energy Technology Data Exchange (ETDEWEB)

Hall, E.R.; Falkler, W.A. Jr.; Suzuki, J.B. (Univ. of Maryland Dental School, Baltimore (USA))

1990-10-01

B lymphocytes and plasma cells are histologically observed in granulomatous periodontal tissues of juvenile periodontitis (JP) patients. Local immune processes may participate in protective or immunopathologic roles in the pathogenesis of this disease. An in vitro explant culture system was utilized to demonstrate the production of immunoglobulins by diseased JP tissues. Immunodiffusion studies using goat anti-human gamma, alpha, or mu chain serum revealed IgG to be the major immunoglobulin present in 92% of the day 1 supernatant fluids (SF) of the 47 JP gingival tissue explant cultures. IgA was present in 15% of the SF; however, no IgM was detected. Staph Protein A isolated 14C-labeled IgG from the SF, when allowed to react with goat anti-human gamma chain serum, formed lines of precipitation. Positive autoradiographs confirmed the biosynthesis of IgG by the explant cultures. The in vitro gingival tissue explant culture system described provides a useful model for the study of localized immunoglobulins produced by diseased tissues of JP patients.

Pattern of intravenous immunoglobulins (IVIG) use in a pediatric ...

African Journals Online (AJOL)

EB

Abstract. Background: Intravenous Immunoglobulin (IVIG) preparations are scarce biological products used for replacement or immunomodulatory effects. Guidelines have been issued by regulatory health authorities to ensure provision of the products for patients who are in severe need. Objectives: The study aimed at ...

Somatic symptoms of anxiety and nonadherence to statin therapy.

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Korhonen, Maarit Jaana; Pentti, Jaana; Hartikainen, Juha; Kivimäki, Mika; Vahtera, Jussi

2016-07-01

The association between anxiety and nonadherence to preventive therapies remains unclear. We investigated whether somatic symptoms of anxiety predict statin nonadherence. This is a prospective cohort study of 1924 individuals who responded to a questionnaire survey on health status and initiated statin therapy after the survey during 2008-2010. We followed the cohort for nonadherence, defined as the proportion of days covered pain upon anger or emotion, sweating without exercise, flushing, tremor of hands or voice, muscle twitching) before the statin initiation, and 16% had experienced at least one symptom on average weekly to daily. 49% of respondents were nonadherent. Weekly to daily occurrence of these symptoms predicted a 33% increase in the risk of nonadherence (risk ratio [RR] 1.33, 95% confidence interval, CI, 1.13-1.57) compared to no symptoms when adjusted for sociodemographics, lifestyle risks, cardiovascular comorbidities, and depression. Particularly, chest pain upon anger or emotion (RR 1.21, 95% CI 1.01-1.46) and muscle twitching (RR 1.24, 95% CI 1.08-1.42) predicted an increased risk of nonadherence to statin therapy. Psychological symptoms of anxiety were not associated with nonadherence when adjusted for somatic symptoms. Somatic anxiety-related symptoms predicted nonadherence to statin therapy. Information on pre-existing somatic symptoms may help identifying patients at increased risk of statin nonadherence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Central crosstalk for somatic tinnitus: abnormal vergence eye movements.

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Qing Yang

Full Text Available BACKGROUND: Frequent oulomotricity problems with orthoptic testing were reported in patients with tinnitus. This study examines with objective recordings vergence eye movements in patients with somatic tinnitus patients with ability to modify their subjective tinnitus percept by various movements, such as jaw, neck, eye movements or skin pressure. METHODS: Vergence eye movements were recorded with the Eyelink II video system in 15 (23-63 years control adults and 19 (36-62 years subjects with somatic tinnitus. FINDINGS: 1 Accuracy of divergence but not of convergence was lower in subjects with somatic tinnitus than in control subjects. 2 Vergence duration was longer and peak velocity was lower in subjects with somatic tinnitus than in control subjects. 3 The number of embedded saccades and the amplitude of saccades coinciding with the peak velocity of vergence were higher for tinnitus subjects. Yet, saccades did not increase peak velocity of vergence for tinnitus subjects, but they did so for controls. 4 In contrast, there was no significant difference of vergence latency between these two groups. INTERPRETATION: The results suggest dysfunction of vergence areas involving cortical-brainstem-cerebellar circuits. We hypothesize that central auditory dysfunction related to tinnitus percept could trigger mild cerebellar-brainstem dysfunction or that tinnitus and vergence dysfunction could both be manifestations of mild cortical-brainstem-cerebellar syndrome reflecting abnormal cross-modality interactions between vergence eye movements and auditory signals.

Characterisation of up-regulated immunoglobulins in patients with chronic rhinosinusitis

International Nuclear Information System (INIS)

Madani, S.A.; Hashemi, S.A

2014-01-01

To evaluate the role of immunoglobulins in patients of chronic rhinosinusitis. Methods: Patients were recruited from the Ear, Nose, Throat, Head And Neck Surgery section of Mazandaran University of Medical Sciences, Sari, Iran, from December 2011 to August 2012. Immunoglobulin G, IgG1, IgG2, IgG3, IgG4 were evaluated. Salivary IgA was assessed by direct immunoenzymatic determination. The quantifications of serum IgG, IgG1, IgG2, IgG3, IgG4 and salivary IgA was performed through nephelometric procedure. Serum IgE was measured by enzyme-linked immunoabsorbent assay. SPSS 15 was used for statistical analysis. Results: Of the 50 patients, 22 (44%) were males and 28(56%) were females. The overall age ranged from 1 to 67 years with a mean of 28.06+-15.49. There was significant changes in levels of IgG, IgG1, salivary IgA and IgE (p=0.001). Significant difference was noted for IgG2 (p=0.03) and in IgG4 (p=0.01). There was no significant alteration in IgG3 level (p=0.3). Conclusion: There was high prevalence of humoral immune alterations both in local and systemic response to chronic inflammation in the patients, which suggests that assessment of immunoglobulin before clinical evaluation and management could be important. (author)

Label-Free Quantitative Proteomics of Embryogenic and Non-Embryogenic Callus during Sugarcane Somatic Embryogenesis.

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Angelo Schuabb Heringer

Full Text Available The development of somatic cells in to embryogenic cells occurs in several stages and ends in somatic embryo formation, though most of these biochemical and molecular changes have yet to be elucidated. Somatic embryogenesis coupled with genetic transformation could be a biotechnological tool to improve potential crop yields potential in sugarcane cultivars. The objective of this study was to observe somatic embryo development and to identify differentially expressed proteins in embryogenic (E and non-embryogenic (NE callus during maturation treatment. E and NE callus were cultured on maturation culture medium supplemented with different concentrations (0.0, 0.75, 1.5 and 2.0 g L(-1 of activated charcoal (AC. Somatic embryo formation and differential protein expression were evaluated at days 0 and 21 using shotgun proteomic analyses. Treatment with 1.5 g L(-1 AC resulted in higher somatic embryo maturation rates (158 somatic embryos in 14 days in E callus but has no effect in NE callus. A total of 752 co-expressed proteins were identified through the SUCEST (The Sugarcane EST Project, including many housekeeping proteins. E callus showed 65 exclusive proteins on day 0, including dehydrogenase, desiccation-related protein, callose synthase 1 and nitric oxide synthase. After 21 days on maturation treatment, 14 exclusive proteins were identified in E callus, including catalase and secreted protein. NE callus showed 23 exclusive proteins on day 0 and 10 exclusive proteins after 21 days on maturation treatment, including many proteins related to protein degradation. The induction of maturation leads to somatic embryo development, which likely depends on the expression of specific proteins throughout the process, as seen in E callus under maturation treatment. On the other hand, some exclusive proteins can also specifically prevent of somatic embryos development, as seen in the NE callus.

Decision-making, somatic markers and emotion processing in opiate users.

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Biernacki, Kathryn; Terrett, Gill; McLennan, Skye N; Labuschagne, Izelle; Morton, Phoebe; Rendell, Peter G

2018-01-01

Opiate use is associated with deficits in decision-making. A possible explanation for these deficits is provided by the somatic marker hypothesis, which suggests that substance users may experience abnormal emotional responses during decision-making involving reward and punishment. This in turn may interfere with the brief physiological arousal, i.e. somatic markers that normally occur in anticipation of risky decisions. To date, the applicability of the somatic marker hypothesis to explain decision-making deficits has not been investigated in opiate users. This study assessed whether decision-making deficits in opiate users were related to abnormal emotional responses and reduced somatic markers. Opiate users enrolled in an opiate substitute treatment program (n = 28) and healthy controls (n = 32) completed the Iowa Gambling Task (IGT) while their skin conductance responses (SCRs) were recorded. Participants' emotional responses to emotion-eliciting videos were also recorded using SCRs and subjective ratings. Opiate users displayed poorer decision-making on the IGT than did controls. However, there were no differences between the groups in SCRs; both groups displayed stronger SCRs following punishment than following reward, and both groups displayed stronger anticipatory SCRs prior to disadvantageous decisions than advantageous decisions. There were no group differences in objective or subjective measures of emotional responses to the videos. The results suggest that deficits in emotional responsiveness are not apparent in opiate users who are receiving pharmacological treatment. Thus, the somatic marker hypothesis does not provide a good explanation for the decision-making deficits in this group.

Computational study on the interactions and orientation of monoclonal human immunoglobulin G on a polystyrene surface

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Javkhlantugs N

2013-07-01

Full Text Available Namsrai Javkhlantugs,1,2 Hexig Bayar,3 Chimed Ganzorig,1 Kazuyoshi Ueda2 1Center for Nanoscience and Nanotechnology and Department of Chemical Technology, School of Chemistry and Chemical Engineering, National University of Mongolia, Ulaanbaatar, Mongolia; 2Department of Advanced Materials Chemistry, Graduate School of Engineering, Yokohama National University, Yokohama, Japan; 3The Key Laboratory of Mammalian Reproductive Biology and Biotechnology of the Ministry of Education, Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, People's Republic of China Abstract: Having a theoretical understanding of the orientation of immunoglobulin on an immobilized solid surface is important in biomedical pathogen-detecting systems and cellular analysis. Despite the stable adsorption of immunoglobulin on a polystyrene (PS surface that has been applied in many kinds of immunoassays, there are many uncertainties in antibody-based clinical and biological experimental methods. To understand the binding mechanism and physicochemical interactions between immunoglobulin and the PS surface at the atomic level, we investigated the binding behavior and interactions of the monoclonal immunoglobulin G (IgG on the PS surface using the computational method. In our docking simulation with the different arrangement of translational and rotational orientation of IgG onto the PS surface, three typical orientation patterns of the immunoglobulin G on the PS surface were found. We precisely analyzed these orientation patterns and clarified how the immunoglobulin G interacts with the PS surface at atomic scale in the beginning of the adsorption process. Major driving forces for the adsorption of IgG onto the PS surface come from serine (Ser, aspartic acid (Asp, and glutamic acid (Glu residues. Keywords: bionano interface, immunoassay, polystyrene, IgG, physical adsorption, simulation

Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome.

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Dowdell, Kennichi C; Niemela, Julie E; Price, Susan; Davis, Joie; Hornung, Ronald L; Oliveira, João Bosco; Puck, Jennifer M; Jaffe, Elaine S; Pittaluga, Stefania; Cohen, Jeffrey I; Fleisher, Thomas A; Rao, V Koneti

2010-06-24

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by childhood onset of lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias, elevated numbers of double-negative T (DNT) cells, and increased risk of lymphoma. Most cases of ALPS are associated with germline mutations of the FAS gene (type Ia), whereas some cases have been noted to have a somatic mutation of FAS primarily in their DNT cells. We sought to determine the proportion of patients with somatic FAS mutations among a group of our ALPS patients with no detectable germline mutation and to further characterize them. We found more than one-third (12 of 31) of the patients tested had somatic FAS mutations, primarily involving the intracellular domain of FAS resulting in loss of normal FAS signaling. Similar to ALPS type Ia patients, the somatic ALPS patients had increased DNT cell numbers and elevated levels of serum vitamin B(12), interleukin-10, and sFAS-L. These data support testing for somatic FAS mutations in DNT cells from ALPS patients with no detectable germline mutation and a similar clinical and laboratory phenotype to that of ALPS type Ia. These findings also highlight the potential role for somatic mutations in the pathogenesis of nonmalignant and/or autoimmune hematologic conditions in adults and children.

CD11b regulates antibody class switching via induction of AID.

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Park, Seohyun; Sim, Hyunsub; Kim, Hye-In; Jeong, Daecheol; Wu, Guang; Cho, Soo Young; Lee, Young Seek; Kwon, Hyung-Joo; Lee, Keunwook

2017-07-01

The integrin CD11b, which is encoded by the integrin subunit alpha M (ITGAM), is primarily expressed on the surface of innate immune cells. Genetic variations in ITGAM are among the strongest risk factors for systemic lupus erythematosus, an autoimmune disease characterized by the presence of autoantibodies. However, the regulatory function of CD11b in the antibody responses remains unclear. Here, we report the induction of CD11b in activated B2 B cells and define its unexpected role in immunoglobulin heavy chain class switch recombination (CSR). LPS-activated B cells lacking CD11b yielded fewer IgG subtypes such as IgG1 and IgG2a in vitro, and immunization-dependent CSR and affinity maturation of antibodies were severely impaired in CD11b-deficient mice. Notably, we observed the reduced expression of activation-induced cytidine deaminase (AID), an enzyme that initiates CSR and somatic hypermutation, and ectopic expression of AID was sufficient to rescue the defective CSR of CD11b-deficient B cells. LPS-induced phosphorylation of NF-κB p65 and IκBα was attenuated in CD11b-deficient B cells, and hyperactivation of IκB kinase 2 restored the defective AID expression and CSR, which implied that CD11b regulates the NF-κB-dependent induction of AID. Overall, our experimental evidence emphasized the function of CD11b in antibody responses and the role of CD11b as a vital regulator of CSR. Copyright © 2017 Elsevier Ltd. All rights reserved.

B-Cell Dysregulation in Crohn's Disease Is Partially Restored with Infliximab Therapy.

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Wilhelmina M C Timmermans

Full Text Available B-cell depletion can improve a variety of chronic inflammatory diseases, but does not appear beneficial for patients with Crohn's disease.To elucidate the involvement of B cells in Crohn's disease, we here performed an 'in depth' analysis of intestinal and blood B-cells in this chronic inflammatory disease.Patients with Crohn's disease were recruited to study B-cell infiltrates in intestinal biopsies (n = 5, serum immunoglobulin levels and the phenotype and molecular characteristics of blood B-cell subsets (n = 21. The effects of infliximab treatment were studied in 9 patients.Granulomatous tissue showed infiltrates of B lymphocytes rather than Ig-secreting plasma cells. Circulating transitional B cells and CD21low B cells were elevated. IgM memory B cells were reduced and natural effector cells showed decreased replication histories and somatic hypermutation (SHM levels. In contrast, IgG and IgA memory B cells were normally present and their Ig gene transcripts carried increased SHM levels. The numbers of transitional and natural effector cells were normal in patients who responded clinically well to infliximab.B cells in patients with Crohn's disease showed signs of chronic stimulation with localization to granulomatous tissue and increased molecular maturation of IgA and IgG. Therapy with TNFα-blockers restored the defect in IgM memory B-cell generation and normalized transitional B-cell levels, making these subsets candidate markers for treatment monitoring. Together, these results suggest a chronic, aberrant B-cell response in patients with Crohn's disease, which could be targeted with new therapeutics that specifically regulate B-cell function.

Generation of “LYmph Node Derived Antibody Libraries” (LYNDAL) for selecting fully human antibody fragments with therapeutic potential.

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Diebolder, Philipp; Keller, Armin; Haase, Stephanie; Schlegelmilch, Anne; Kiefer, Jonathan D; Karimi, Tamana; Weber, Tobias; Moldenhauer, Gerhard; Kehm, Roland; Eis-Hübinger, Anna M; Jäger, Dirk; Federspil, Philippe A; Herold-Mende, Christel; Dyckhoff, Gerhard; Kontermann, Roland E; Arndt, Michaela A E; Krauss, Jürgen

2014-01-01

The development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. Here, we present a methodology for recovering such antibodies from antigen-encountered human B cell repertoires. As the source for variable antibody genes, we cloned immunoglobulin G (IgG)-derived B cell repertoires from lymph nodes of 20 individuals undergoing surgery for head and neck cancer. Sequence analysis of unselected “LYmph Node Derived Antibody Libraries” (LYNDAL) revealed a naturally occurring distribution pattern of rearranged antibody sequences, representing all known variable gene families and most functional germline sequences. To demonstrate the feasibility for selecting antibodies with therapeutic potential from these repertoires, seven LYNDAL from donors with high serum titers against herpes simplex virus (HSV) were panned on recombinant glycoprotein B of HSV-1. Screening for specific binders delivered 34 single-chain variable fragments (scFvs) with unique sequences. Sequence analysis revealed extensive somatic hypermutation of enriched clones as a result of affinity maturation. Binding of scFvs to common glycoprotein B variants from HSV-1 and HSV-2 strains was highly specific, and the majority of analyzed antibody fragments bound to the target antigen with nanomolar affinity. From eight scFvs with HSV-neutralizing capacity in vitro,the most potent antibody neutralized 50% HSV-2 at 4.5 nM as a dimeric (scFv)2. We anticipate our approach to be useful for recovering fully human antibodies with therapeutic potential.

IgV H mutations in blastoid mantle cell lymphoma characterize a subgroup with a tendency to more favourable clinical outcome.

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Cogliatti, Sergio B; Bertoni, Francesco; Zimmermann, Dieter R; Henz, Samuel; Diss, Tim C; Ghielmini, Michele; Schmid, Ulrico

2005-07-01

Mantle cell lymphoma (MCL) is associated with a very unfavourable clinical course. This is particularly true for mantle cell lymphoma of the blastoid subtype (MCL-b). In order to define prognostic factors, we analysed the impact of immunoglobulin heavy chain variable (IgV H) gene somatic hypermutations on clinical outcome in a series of 21 cases of morphologically, phenotypically, and genotypically well-characterized MCL-b. Testing and estimation were performed using log-rank statistics and displayed on Kaplan-Meier graphs. Thirteen of 21 cases of MCL-b revealed a homology rate of > or = 99% compared to IgV H germ-line sequences in the databases and were scored as non-mutated. Eight of 21 cases (38%) of MCL-b were mutated. In MCL-b the mutation frequency was usually low and the mutation pattern was only rarely antigen-selected, in contrast to a control group of 11 cases with morphologically almost identical, but phenotypically and genotypically clearly distinguishable, diffuse large B cell lymphoma, derived, most likely, from germinal centre B cells. In our series of 21 MCL-b, positive IgV H mutational status, irrespective of varying homology thresholds, had no statistically significant prognostic impact on event-free or overall survival. However, mutated MCL-b tended to present more frequently at an earlier stage and without bone marrow involvement and to show lower rates of relapse and death, resulting in a more favourable clinical outcome. Copyright 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Ectopic expression of AID in a non-B cell line triggers A:T and G:C point mutations in non-replicating episomal vectors.

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Tihana Jovanic

Full Text Available Somatic hypermutation (SHM of immunoglobulin genes is currently viewed as a two step process initiated by the deamination of deoxycytidine (C to deoxyuridine (U, catalysed by the activation induced deaminase (AID. Phase 1 mutations arise from DNA replication across the uracil residue or the abasic site, generated by the uracil-DNA glycosylase, yielding transitions or transversions at G:C pairs. Phase 2 mutations result from the recognition of the U:G mismatch by the Msh2/Msh6 complex (MutS Homologue, followed by the excision of the mismatched nucleotide and the repair, by the low fidelity DNA polymerase eta, of the gap generated by the exonuclease I. These mutations are mainly focused at A:T pairs. Whereas in activated B cells both G:C and A:T pairs are equally targeted, ectopic expression of AID was shown to trigger only G:C mutations on a stably integrated reporter gene. Here we show that when using non-replicative episomal vectors containing a GFP gene, inactivated by the introduction of stop codons at various positions, a high level of EGFP positive cells was obtained after transient expression in Jurkat cells constitutively expressing AID. We show that mutations at G:C and A:T pairs are produced. EGFP positive cells are obtained in the absence of vector replication demonstrating that the mutations are dependent only on the mismatch repair (MMR pathway. This implies that the generation of phase 1 mutations is not a prerequisite for the expression of phase 2 mutations.

High levels of immunoglobulin E and a continuous increase in immunoglobulin G and immunoglobulin M by age in children with newly diagnosed type 1 diabetes

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Svensson, Jannet; Eising, Stefanie; Mortensen, Henrik Bindesbøl

2012-01-01

The incidence of type 1 diabetes (T1D) is increasing, either because of environmental factors accelerating onset of the disease or because of inducement of autoimmune diabetes in children who previously were at lower risk. High levels of immunoglobulin (Ig), specifically, IgM and IgA, and a low...... level of IgG were reported in adult patients; however no studies have analyzed the increasing incidence in relation to Ig levels. Our aim was to describe Ig in children newly diagnosed with diabetes and in their healthy siblings. Children with T1D expressed significantly lower IgG (p

In vitro regeneration of some Iranian alfalfa (Medicago sativa L. genotypes via somatic embryogenesis

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Majid Shokrpour

2014-12-01

Full Text Available An effective in vitro regeneration system is one of the prerequisites for genetic manipulation of alfalfa (Medicago sativa L. varieties and genotypes. In this research, somatic embryogenesis of four alfalfa genotypes, 6-18 (synthetic, 4-14 (Kara Yonje- Karakozlu, 3-27 (Kara Yonje Maraghe and y-6 (Regen-SY, were investigated using leaf and petiole explants. Formation of callus and somatic embryogenesis was significantly influenced by the explant type and interaction of genotype and culture medium. Petiole explants of genotype 4-14 produced the highest yield of callus (0.406 gr fresh weight of callus. Percentage of somatic embryogenesis and the number of embryos per callus in petiole explants of genotype 4-14 was higher than those of other genotypes and explants. In genotype 6-18, the highest percentage of somatic embryogenesis was achieved on MS medium containing 5 mg/L 2,4-D and 2 mg/L kinetin. There was no significant differences between genotypes and explants in terms of embryo conversion to plantlet, and on average, 58% of somatic embryos converted to plantlet on MS medium. The petiole explants of genotype 6-18 did not exhibit somatic embryogenesis response in medium containing low ratio of 2,4-D:Kinetin (5 mg/L 2,4-D and 2 mg/L kinetin. While, these explants showed somatic embryogenesis in higher ratio of 2,4-D:Kinetin (5:1. The plantlet conversion efficiency of somatic embryos produced through this study was relatively higher and therefore, the method presented in this study could be used in alfalfa genetic manipulation and molecular studies.

Comparison of Excretory-Secretory and Somatic Antigens of Ornithobilharzia turkestanicum in Agar Gel Diffusion Test

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H Miranzadeh

2008-12-01

Full Text Available Background: Ornithobilharziosis as one of the parasitic infections may give rise to serious economic problems in animal husbandry. The Aim of the study was to prepare and compare the somatic and excretory-secretory (ES antigens of O. tur­kestanicum in gel diffusion test. Methods: Excretory-secretory (ES and somatic antigens of Ornithobilharzia turkestanicum were prepared from collected worms from mesentric blood vessels of infected sheep. The laboratory bred rabbits were immunized with antigens and then antisera were prepared. The reaction of antigens and antisera was observed in gel diffusion test. Results: ES antigens of this species showed positive reaction with antisera raised against ES and also somatic antigens. Somatic antigens also showed positive reaction with antisera raised against somatic and also ES antigens. Conclusion: The antigenicity of O. turkestanicum ES and somatic antigens is the same in gel diffusion test.

Somatic comorbidity among migrants with posttraumatic stress disorder and depression

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Lolk, Mette; Byberg, Stine; Carlsson, Jessica

2016-01-01

BACKGROUND: In a cohort of migrants in Denmark, we compared somatic disease incidence among migrants diagnosed with posttraumatic stress disorder (PTSD) and depression with migrants without a diagnosed psychiatric disorder. METHODS: The study builds on a unique cohort of migrants who obtained...... for the implementation of the project (No 2012-41-0065). RESULTS: Our results showed that migrants diagnosed with PTSD and depression had significantly higher rates of somatic diseases compared with migrants without diagnosed psychiatric disorders - especially, infectious disease (IRR, 1.89; 95% CI, 1.45-2.48; p ... with migrants without a diagnosed psychiatric disorder. The rates were especially high for infectious, neurological and pulmonary diseases. Our results further suggest difference in the rates of somatic comorbidity according to region of. Preventive and treatment services should pay special attention to improve...

Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer

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Adam Shlien

2016-08-01

Full Text Available Disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription, coordinated secondary pathway alterations, and increased transcriptional noise. To catalog the rules governing how somatic mutation exerts direct transcriptional effects, we developed an exhaustive pipeline for analyzing RNA sequencing data, which we integrated with whole genomes from 23 breast cancers. Using X-inactivation analyses, we found that cancer cells are more transcriptionally active than intermixed stromal cells. This is especially true in estrogen receptor (ER-negative tumors. Overall, 59% of substitutions were expressed. Nonsense mutations showed lower expression levels than expected, with patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusions, and premature polyadenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data reveals the rules by which transcriptional machinery interprets somatic mutation.

Sexual Victimization and Somatic Complaints in Pregnancy: Examination of Depression as a Mediator.

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Littleton, Heather

2015-01-01

Research suggests that women with histories of sexual victimization are more likely to experience somatic complaints in pregnancy. However, prior studies have been limited by homogenous samples, have primarily only examined the relationship of childhood sexual abuse (CSA) to somatic complaints, and have not examined potential mechanisms explaining this association. Thus, the current study examined the relationship between lifetime sexual victimization history and somatic complaints in pregnancy in an ethnically diverse sample of pregnant women. Additionally, depressive symptoms were examined as a mediator of the sexual victimization-somatic complaints relationship. Women were recruited from the waiting room of a university-affiliated obstetrics-gynecology clinic to complete a study of psychological health and negative sexual experiences. The 407 currently pregnant participants who completed measures of their sexual victimization history, depressive symptoms, and somatic complaints were primarily African American (53.6%), low to middle income (75.4%), and reported an unplanned pregnancy (72%). A total of 27.7% of women had a history of CSA and/or adolescent/adult sexual assault. Mediation analyses using bootstrapping supported depression as a significant mediator of the relationship between sexual victimization and somatic complaints, with a medium-sized effect (κ(2) = .09). Having a history of sexual victimization is associated with risk for poor mental and physical health during pregnancy. There are likely multiple mechanisms explaining the association between sexual victimization and somatic complaints in pregnancy, which should be investigated in future research. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Fibroblast growth factor signaling is required for early somatic gonad development in zebrafish.

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Leerberg, Dena M; Sano, Kaori; Draper, Bruce W

2017-09-01

The vertebrate ovary and testis develop from a sexually indifferent gonad. During early development of the organism, primordial germ cells (the gamete lineage) and somatic gonad cells coalesce and begin to undergo growth and morphogenesis to form this bipotential gonad. Although this aspect of development is requisite for a fertile adult, little is known about the genetic regulation of early gonadogenesis in any vertebrate. Here, we provide evidence that fibroblast growth factor (Fgf) signaling is required for the early growth phase of a vertebrate bipotential gonad. Based on mutational analysis in zebrafish, we show that the Fgf ligand 24 (Fgf24) is required for proliferation, differentiation, and morphogenesis of the early somatic gonad, and as a result, most fgf24 mutants are sterile as adults. Additionally, we describe the ultrastructural elements of the early zebrafish gonad and show that distinct somatic cell populations can be identified soon after the gonad forms. Specifically, we show that fgf24 is expressed in an epithelial population of early somatic gonad cells that surrounds an inner population of mesenchymal somatic gonad cells that are in direct contact with the germ cells, and that fgf24 is required for stratification of the somatic tissue. Furthermore, based on gene expression analysis, we find that differentiation of the inner mesenchymal somatic gonad cells into functional cell types in the larval and early juvenile-stage gonad is dependent on Fgf24 signaling. Finally, we argue that the role of Fgf24 in zebrafish is functionally analogous to the role of tetrapod FGF9 in early gonad development.

The relationship of PTSD to key somatic complaints and cultural syndromes among Cambodian refugees attending a psychiatric clinic: the Cambodian Somatic Symptom and Syndrome Inventory (CSSI).

Science.gov (United States)

Hinton, Devon E; Kredlow, M Alexandra; Pich, Vuth; Bui, Eric; Hofmann, Stefan G

2013-06-01

This article describes a culturally sensitive questionnaire for the assessment of the effects of trauma in the Cambodian refugee population, the Cambodian Somatic Symptom and Syndrome Inventory (CSSI), and gives the results of a survey with the instrument. The survey examined the relationship of the CSSI, the two CSSI subscales, and the CSSI items to posttraumatic stress disorder (PTSD) severity and self-perceived functioning. A total of 226 traumatized Cambodian refugees were assessed at a psychiatric clinic in Lowell, MA, USA. There was a high correlation of the CSSI, the CSSI somatic and syndrome scales, and all the CSSI items to the PTSD Checklist (PCL), a measure of PTSD severity. All the CSSI items varied greatly across three levels of PTSD severity, and patients with higher levels of PTSD had very high scores on certain CSSI-assessed somatic items such as dizziness, orthostatic dizziness (upon standing), and headache, and on certain CSSI-assessed cultural syndromes such as khyâl attacks, "fear of fainting and dying upon standing up," and "thinking a lot." The CSSI was more highly correlated than the PCL to self-perceived disability assessed by the Short Form-12 Health Survey (SF-12). The study demonstrates that the somatic symptoms and cultural syndromes described by the CSSI form a central part of the Cambodian refugee trauma ontology. The survey indicates that locally salient somatic symptoms and cultural syndromes need be profiled to adequately assess the effects of trauma.

symptomatology and comorbidity of somatization disorder amongst

African Journals Online (AJOL)

underlying mental disorder, manifesting solely as somatic symptoms or with ... unsatisfactory visit and seemingly ineffective treatment plan. ... patients of all ages and both gender with various ..... identity and physical health: Interdisciplinary.

Immunoglobulin transfusion in hemolytic disease of the newborn: place in therapy

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Mundy CA

2015-06-01

Full Text Available Cynthia A Mundy, Jatinder Bhatia Department of Pediatrics, Division of Neonatology, Georgia Regents University, Children's Hospital of Georgia, GA, USA Abstract: Hemolytic disease of the newborn continues to be a common neonatal disorder that requires a comprehensive understanding on the part of those caring for infants. Common treatments include hydration and phototherapy. Exchange transfusion is used in severe hemolytic disease, but infants undergoing this treatment are exposed to many adverse effects. Intravenous immunoglobulin is a newer strategy that is showing promise in the treatment of the disease. This review discusses the current use and future expectations of intravenous immunoglobulin therapy in newborns. Keywords: hyperbilirubinemia, ABO incompatibility, neonatal jaundice 

A study of immunoglobulins and complements (C3 &C4 in alopecia areata

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Sharma R

1995-01-01

Full Text Available Estimation of serum Immunoglobulins (IgG, IgM and IgA and complements (C3 and C4 was carried out in 100 cases of alopecia areata as per method described by Mancini (1965.[1] Clinically patients were divided in two groups, alopecia areata circumscribed (group I and severe alopecia areata (group II. Significant decrease in levels of one or more Immunoglobulins were observed in most of the patients. However, Serum complements (C3 and C4 were within range of normal control values

Replication of somatic micronuclei in bovine enucleated oocytes

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Canel Natalia

2012-11-01

Full Text Available Abstract Background Microcell-mediated chromosome transfer (MMCT was developed to introduce a low number of chromosomes into a host cell. We have designed a novel technique combining part of MMCT with somatic cell nuclear transfer, which consists of injecting a somatic micronucleus into an enucleated oocyte, and inducing its cellular machinery to replicate such micronucleus. It would allow the isolation and manipulation of a single or a low number of somatic chromosomes. Methods Micronuclei from adult bovine fibroblasts were produced by incubation in 0.05 μg/ml demecolcine for 46 h followed by 2 mg/ml mitomycin for 2 h. Cells were finally treated with 10 μg/ml cytochalasin B for 1 h. In vitro matured bovine oocytes were mechanically enucleated and intracytoplasmatically injected with one somatic micronucleus, which had been previously exposed [Micronucleus- injected (+] or not [Micronucleus- injected (−] to a transgene (50 ng/μl pCX-EGFP during 5 min. Enucleated oocytes [Enucleated (+] and parthenogenetic [Parthenogenetic (+] controls were injected into the cytoplasm with less than 10 pl of PVP containing 50 ng/μl pCX-EGFP. A non-injected parthenogenetic control [Parthenogenetic (−] was also included. Two hours after injection, oocytes and reconstituted embryos were activated by incubation in 5 μM ionomycin for 4 min + 1.9 mM 6-DMAP for 3 h. Cleavage stage and egfp expression were evaluated. DNA replication was confirmed by DAPI staining. On day 2, Micronucleus- injected (−, Parthenogenetic (− and in vitro fertilized (IVF embryos were karyotyped. Differences among treatments were determined by Fisher′s exact test (p≤0.05. Results All the experimental groups underwent the first cell divisions. Interestingly, a low number of Micronucleus-injected embryos showed egfp expression. DAPI staining confirmed replication of micronuclei in most of the evaluated embryos. Karyotype analysis revealed that all Micronucleus-injected embryos had

Somatic and genetic effects

International Nuclear Information System (INIS)

Broerse, J.J.; Barendsen, G.W.; Kal, H.B.; Kogel, A.J. van der

1983-01-01

This book contains the extended abstracts of the contributions of the poster workshop sessions on somatic and genetic effects of the 7th international congress of radiation research. They cover the following main topics: haematopoietic and immune systems, mechanisms of late effects in various tissues, endogenous and exogenous factors in radiation carcinogenesis, teratogenic effects, genetic effects, in vitro transformation, tumour induction in different tissues, carcinogenesis in incorporated tissues, cancer epidemology and risk assessment. refs.; figs.; tabs

Ballet as Somatic Practice: A Case Study Exploring the Integration of Somatic Practices in Ballet Pedagogy

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Berg, Tanya

2017-01-01

This case study explores one teacher's integration of Alexander Technique and the work of neuromuscular retrainer Irene Dowd in ballet pedagogy to establish a somatic approach to teaching, learning, and performing ballet technique. This case study highlights the teacher's unique teaching method called IMAGE TECH for dancers (ITD) and offers…

Somatic delusions and obsessive-compulsive disorder in ...

African Journals Online (AJOL)

2009-10-12

Oct 12, 2009 ... Case Study: Somatic delusions and obsessive-compulsive disorder in schizophrenia. 527. Vol 52 No 6 ... liver function, and urea and electrolytes), including an ... neurotransmitter systems (such as serotonin and dopamine).

Cellular and molecular changes associated with somatic embryogenesis induction in Agave tequilana.

Science.gov (United States)

Portillo, L; Olmedilla, A; Santacruz-Ruvalcaba, F

2012-10-01

In spite of the importance of somatic embryogenesis for basic research in plant embryology as well as for crop improvement and plant propagation, it is still unclear which mechanisms and cell signals are involved in acquiring embryogenic competence by a somatic cell. The aim of this work was to study cellular and molecular changes involved in the induction stage in calli of Agave tequilana Weber cultivar azul in order to gain more information on the initial stages of somatic embryogenesis in this species. Cytochemical and immunocytochemical techniques were used to identify differences between embryogenic and non-embryogenic cells from several genotypes. Presence of granular structures was detected after somatic embryogenesis induction in embryogenic cells; composition of these structures as well as changes in protein and polysaccharide distribution was studied using Coomassie brilliant blue and Periodic Acid-Schiff stains. Distribution of arabinogalactan proteins (AGPs) and pectins was investigated in embryogenic and non-embryogenic cells by immunolabelling using anti-AGP monoclonal antibodies (JIM4, JIM8 and JIM13) as well as an anti-methyl-esterified pectin-antibody (JIM7), in order to evaluate major modifications in cell wall composition in the initial stages of somatic embryogenesis. Our observations pointed out that induction of somatic embryogenesis produced accumulation of proteins and polysaccharides in embryogenic cells. Presence of JIM8, JIM13 and JIM7 epitopes were detected exclusively in embryogenic cells, which supports the idea that specific changes in cell wall are involved in the acquisition of embryogenic competence of A. tequilana.

Embodied Feeling and Reason in Decision-Making: Assessing the Somatic-Marker Hypothesis

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Warren TenHouten

2016-04-01

Full Text Available Whether or not reason and affect are complementary depends on the task at hand. In ordinary circumstances, problemsolving and decision-making involve both somatic feelings and limbic-structure-based emotions. Feelings, experienced as states of the body, can contribute to decision-making by triggering heuristic cues and rapidly eliminating negative behavioral alternatives, in part by providing what Damasio call somatic markers (Damasio, Tranel and Damasio, 1991; Damasio, 1994, 1999, 2003. However, if task-performance is motivated by potentially large rewards, with high demands on short-term memory and on concentration, the dorsolateral prefrontal cortexcan inhibit affects manifested in the medial prefrontal cortex in order to carry out the necessary cognitive operations. We interpret these two different mental task situations using dual process models. Although experimental evidence from studies of normal subjects and frontal-lobe-damaged patients performing the Iowa Gambling Task has been interpreted as supportive of the somatic-marker hypothesis (SMH, we show that this evidence has been called into question due to faulty study designs. However, studies of normal and psychopathic subjects playing the ultimatum game show that pulse-rate deceleration occurring during the brief period preceding decision-making constitutes a somatic marker. Compared to normal controls, psychopaths show less somatic (electro dermal activity and act with cool, economic rationality, accepting unfair (<50/50 offers that normal subjects reject on the basis of non-economic values of fairness. The somatic-marker hypothesis is discussed and criticized, and various theories based on this hypothesis are identified.

Detection of immunoglobulin M and immunoglobulin G antibodies to Mycoplasma pneumoniae in children with community-acquired lower respiratory tract infections

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Surinder Kumar

2018-01-01

Full Text Available Context: Mycoplasma pneumoniae (M. pneumoniae causes up to 40% of community-acquired pneumonia in children. It is impossible to identify M. pneumoniae infection on the basis of clinical signs, symptoms, and radiological features. Therefore, correct etiological diagnosis strongly depends on laboratory diagnosis. Aims: This study aims to investigate the role of M. pneumonia e in pediatric lower respiratory tract infections (LRTIs employing enzyme-linked immunosorbent assays (ELISA and particle agglutination (PA test. Settings and Design: Two hundred and eighty children, age 6 months to 12 years with community-acquired LRTIs were investigated for M. pneumoniae etiology. Materials and Methods: We investigated 280 children hospitalized for community-acquired LRTIs, using ELISA and PA test for detecting M. pneumoniae immunoglobulin M (IgM and immunoglobulin G antibodies. Statistical Analysis Used: The difference of proportion between the qualitative variables was tested using the Chi-square test and Fischer exact test. P ≤ 0.05 was considered as statistically significant. Kappa value was used to assess agreement between ELISA and PA test. Results: M. pneumoniae was positive in 51 (23.2% 5 years of age.

Health Anxiety in Panic Disorder, Somatization Disorder and Hypochondriasis

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Özgün Karaer KARAPIÇAK

2012-03-01

Full Text Available Objective: Health anxiety is the fear of being or getting seriously sick due to the misinterpretation of physical symptoms. Severe health anxiety is also named as hypochondriasis. Belief of having a disease due to the misinterpretation of physical symptoms is also seen in panic disorder and somatization disorder. The aim of this study is to search the health anxiety in panic disorder, somatization disorder and hypochondriasis and compare it with healthy volunteers. Method: SCID-I was used to determine psychiatric disorders in patient group. In order to assess the clinical state and disease severity of the patient group; Panic and Agoraphobia Scale, Hamilton Anxiety Rating Scale, Inventory of Depressive Symptomatology were used for patients with panic disorder and Symptom Interpretation Questionnaire, Hamilton Anxiety Rating Scale, Inventory of Depressive Symptomatology were used for patients with somatization disorder and hypochondriasis. Brief Symptom Inventory was used to assess psychopathology in healthy group. In order to evaluate health anxiety of both groups, Health Anxiety Inventory-Short Form was used. Results: Results of this study support that health anxiety is a significant major component of hypochondriasis. On the other hand, health anxiety seems to be common in panic disorder and somatization disorder. Health anxiety also may be a part of depression or present in healthy people. Conclusion: Further studies are needed in order to search how to manage health anxiety appropriately and which psychotherapeutic interventions are more effective.

An experience in the clinical use of specific immunoglobulin from horse blood serum for prophylaxis of Ebola haemorrhagic fever.

Science.gov (United States)

Borisevich, I V; Chemikova, Natalya K; Markov, V I; Krasnianskiy, V P; Borisevich, S V; Rozhdestvenskiy, E V

The aim of this work was to estimate the efficacy and safety of single intramuscular introduction of specific heterologous immunoglobulin as prophylactic drug against Ebola hemorrhagic fever. Materials and methods. The specific heterologous immunoglobulin was introduced as a special prophylactic drug to 28 patients in epidemic situations, after skin hurt with infectious materials or contact with infectious blood. Clinico-laboratory observation was performed in 24 subjects after single intramuscular introduction of heterologous immunoglobulin Ebola. The samples of blood serum were investigated for immunoglobulin Ebola and antibodies to horse gamma-globulin on the 30th and 60th days after prophylaxis. Results. None of the subjects of the study contracted Ebola fever. There were no anaphylactic reactions after special prophylaxis with specific heterologous immunoglobulin. Among the subjects with normal allergic state 31% responded with local reactions; 13%, with a general reaction (mild case of the serum disease). Almost no reaction was observed in patients with unfavorable allergic state subjected to desensitizing therapy; in the absence of desensitizing therapy, 50% of patients with unfavorable allergic state exhibited local reactions; 17%, mild cases of the serum disease; 33%, moderate cases of the serum disease. In summary, if the tactics of immunoglobulin application was right, the quantity of local allergic reactions was 28%; of wide spread reactions, 6%. Weak serum disease was observed in 11% of the subjects. The prognostic period of resistance to Ebola fever was less than 30 days. Conclusion. The prophylactic use of specific immunoglobulin from horse blood serum against hemorrhagic Ebola fever is effective and relatively safe in patients subjected to desensitizing therapy.

Somatic Embryos in Catharanthus roseus: A Scanning Electron Microscopic Study

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Junaid ASLAM

2014-06-01

Full Text Available Catharanthus roseus (L. G. Don is an important medicinal plant as it contains several anti-cancerous compounds, like vinblastine and vincristine. Plant tissue culture technology (organogenesis and embryogenesis has currently been used in fast mass propagating raw materials for secondary metabolite synthesis. In this present communication, scanning electron microscopic (SEM study of somatic embryos was conducted and discussed. The embryogenic callus was first induced from hypocotyls of in vitro germinated seeds on which somatic embryos, differentiated in numbers, particularly on 2,4-D (1.0 mg/L Murashige and Skoog (MS was medium. To understand more about the regeneration method and in vitro formed embryos SEM was performed. The SEM study revealed normal somatic embryo origin and development from globular to heart-, torpedo- and then into cotyledonary-stage of embryos. At early stage, the embryos were clustered together in a callus mass and could not easily be detached from the parental tissue. The embryos were often long cylindrical structure with or without typical notch at the tip. Secondary embryos were also formed on primary embryo structure. The advanced cotyledonary embryos showed prominent roots and shoot axis, which germinated into plantlets. The morphology, structure and other details of somatic embryos at various stages were presented.

Hypochondriasis and somatization in college women: a personal projects analysis.

Science.gov (United States)

Karoly, P; Lecci, L

1993-03-01

Although the descriptive features of hypochondriasis and somatization have been widely studied, the motivational correlates (goal representations) of individuals manifesting abnormal illness patterns have not been considered. The Personal Projects Analysis method (Little, 1983) was used to contrast the health and nonhealth goals of female undergraduates. Subjects selected 10 goals for evaluation along a series of dimensions. When health pursuits alone were examined, hypochondriasis on the Minnesota Multiphasic Personality Inventory was found to correlate directly with goal appraisal dimensions subsumed by an anxiety-absorption factor and inversely with dimensions characterizing rewardingness, thus suggesting a negativity of health goal construal. Somatizers also pursued more health-related projects than did nonsomatizers; nonhealth goal cognition did not relate as strongly to hypochondriasis. Finally, using discriminant function analysis, goal representations were shown to significantly and substantially differentiate somatizers from nonsomatizers.

Systematic review of measurement properties of questionnaires measuring somatization in primary care patients.

Science.gov (United States)

Sitnikova, Kate; Dijkstra-Kersten, Sandra M A; Mokkink, Lidwine B; Terluin, Berend; van Marwijk, Harm W J; Leone, Stephanie S; van der Horst, Henriëtte E; van der Wouden, Johannes C

2017-12-01

The aim of this review is to critically appraise the evidence on measurement properties of self-report questionnaires measuring somatization in adult primary care patients and to provide recommendations about which questionnaires are most useful for this purpose. We assessed the methodological quality of included studies using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. To draw overall conclusions about the quality of the questionnaires, we conducted an evidence synthesis using predefined criteria for judging the measurement properties. We found 24 articles on 9 questionnaires. Studies on the Patient Health Questionnaire-15 (PHQ-15) and the Four-Dimensional Symptom Questionnaire (4DSQ) somatization subscale prevailed and covered the broadest range of measurement properties. These questionnaires had the best internal consistency, test-retest reliability, structural validity, and construct validity. The PHQ-15 also had good criterion validity, whereas the 4DSQ somatization subscale was validated in several languages. The Bodily Distress Syndrome (BDS) checklist had good internal consistency and structural validity. Some evidence was found for good construct validity and criterion validity of the Physical Symptom Checklist (PSC-51) and good construct validity of the Symptom Check-List (SCL-90-R) somatization subscale. However, these three questionnaires were only studied in a small number of primary care studies. Based on our findings, we recommend the use of either the PHQ-15 or 4DSQ somatization subscale for somatization in primary care. Other questionnaires, such as the BDS checklist, PSC-51 and the SCL-90-R somatization subscale show promising results but have not been studied extensively in primary care. Copyright © 2017 Elsevier Inc. All rights reserved.

Somatic USP8 Gene Mutations Are a Common Cause of Pediatric Cushing Disease.

Science.gov (United States)

Faucz, Fabio R; Tirosh, Amit; Tatsi, Christina; Berthon, Annabel; Hernández-Ramírez, Laura C; Settas, Nikolaos; Angelousi, Anna; Correa, Ricardo; Papadakis, Georgios Z; Chittiboina, Prashant; Quezado, Martha; Pankratz, Nathan; Lane, John; Dimopoulos, Aggeliki; Mills, James L; Lodish, Maya; Stratakis, Constantine A

2017-08-01

Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have been recently identified as the most common genetic alteration in patients with Cushing disease (CD). However, the frequency of these mutations in the pediatric population has not been extensively assessed. We investigated the status of the USP8 gene at the somatic level in a cohort of pediatric patients with corticotroph adenomas. The USP8 gene was fully sequenced in both germline and tumor DNA samples from 42 pediatric patients with CD. Clinical, biochemical, and imaging data were compared between patients with and without somatic USP8 mutations. Five different USP8 mutations (three missense, one frameshift, and one in-frame deletion) were identified in 13 patients (31%), all of them located in exon 14 at the previously described mutational hotspot, affecting the 14-3-3 binding motif of the protein. Patients with somatic mutations were older at disease presentation [mean 5.1 ± 2.1 standard deviation (SD) vs 13.1 ± 3.6 years, P = 0.03]. Levels of urinary free cortisol, midnight serum cortisol, and adrenocorticotropic hormone, as well as tumor size and frequency of invasion of the cavernous sinus, were not significantly different between the two groups. However, patients harboring somatic USP8 mutations had a higher likelihood of recurrence compared with patients without mutations (46.2% vs 10.3%, P = 0.009). Somatic USP8 gene mutations are a common cause of pediatric CD. Patients harboring a somatic mutation had a higher likelihood of tumor recurrence, highlighting the potential importance of this molecular defect for the disease prognosis and the development of targeted therapeutic options. Copyright © 2017 Endocrine Society

Use of somatic cell banks in the conservation of wild felids.

Science.gov (United States)

Praxedes, Érika A; Borges, Alana A; Santos, Maria V O; Pereira, Alexsandra F

2018-05-03

The conservation of biological resources is an interesting strategy for the maintenance of biodiversity, especially for wild felids who are constantly threatened with extinction. For this purpose, cryopreservation techniques have been used for the long-term storage of gametes, embryos, gonadal tissues, and somatic cells and tissues. The establishment of these banks has been suggested as a practical approach to the preservation of species and, when done in tandem with assisted reproductive techniques, could provide the means for reproducing endangered species. Somatic cell banks have been shown remarkable for the conservation of genetic material of felids; by merely obtaining skin samples, it is possible to sample a large group of individuals without being limited by factors such as gender or age. Thus, techniques for somatic tissue recovery, cryopreservation, and in vitro culture of different wild felids have been developed, resulting in a viable method for the conservation of species. One of the most notable conservation programs for wild felines using somatic samples was the one carried out for the Iberian lynx, the most endangered feline in the world. Other wild felids have also been studied in other continents, such as the jaguar in South America. This review aims to present the technical progress achieved in the conservation of somatic cells and tissues in different wild felids, as well address the progress that has been achieved in a few species. © 2018 Wiley Periodicals, Inc.

Lethals induced by γ-radiation in drosophila somatic cells

International Nuclear Information System (INIS)

Ivanov, A.I.

1989-01-01

Exposure of 3-hour drosophila male embryos to γ-radiation during the topographic segregation of the germ anlage nuclei caused recessive sex-linked lethals in somatic cells only. The selectivity of the screening was determined by the ratio of mutation frequencies induced in embryos and adult males. Analysis of lethal mutations shows that a minimal rate of the divergence between germinal and somatic patterns of the cell development is observed in the embryogenesis, the 3d instar larva and prepupa, and maximal in the 1st and 2nd larva and pupa

Neuromyelitis Optica Immunoglobulin G in a Child

OpenAIRE

Hudson, Lynsee A.; Bernard, Timothy J.; Tseng, Brian S.; Miller, Bradford R.; Corboy, John R.

2006-01-01

Neuromyelitis optica or Devic’s syndrome is an uncommon demyelinating disorder that preferentially attacks the spinal cord and optic nerves. Although it is well described in adults, childhood neuromyelitis optica has rarely been reported in the literature and is frequently misdiagnosed as severe multiple sclerosis. Recently, a serum immunoglobulin G test for neuromyelitis optica has become available which may clarify and accelerate the diagnosis. This report describes a child with recurrent m...

Plant regeneration via direct somatic embryogenesis from leaf explants of Tolumnia Louise Elmore 'Elsa'.

Science.gov (United States)

Shen, Hui-Ju; Chen, Jen-Tsung; Chung, Hsiao-Hang; Chang, Wei-Chin

2018-01-22

Tolumnia genus (equitant Oncidium) is a group of small orchids with vivid flower color. Thousands of hybrids have been registered on Royal Horticulture Society and showed great potential for ornamental plant market. The aim of this study is to establish an efficient method for in vitro propagation. Leaf explants taken from in vitro-grown plants were used to induce direct somatic embryogenesis on a modified 1/2 MS medium supplemented with five kinds of cytokinins, 2iP, BA, kinetin, TDZ and zeatin at 0.3, 1 and 3 mg l -1 in darkness. TDZ at 3 mg l -1 gave the highest percentage of explants with somatic globular embryos after 90 days of culture. It was found that 2,4-D and light regime highly retarded direct somatic embryogenesis and showed 95-100% of explant browning. Histological observations revealed that the leaf cells divided into meristematic cells firstly, followed by somatic proembryos, and then somatic globular embryos. Eventually, somatic embryos developed a bipolar structure with the shoot apical meristem and the root meristem. Scanning electron microscopy observations showed that the direct somatic embryogenesis from leaf explants was asynchronously. The somatic embryos were found on the leaf tip, the adaxial surface and also the mesophyll through a cleft, and it reflected the heterogeneity of the explant. The 90-day-old globular embryos were detached from the parent explants and transferred onto a hormone-free 1/2 MS medium in light condition for about 1 month to obtain 1-cm-height plantlets. After another 3 months for growth, the plantlets were potted with Sphagnum moss and were acclimatized in a shaded greenhouse. After 1 month of culture, the survival rate was 100%. In this report, a protocol for efficient regenerating a Tolumnia orchid, Louise Elmore 'Elsa', was established via direct somatic embryogenesis and might reveal an alternative approach for mass propagation of Tolumnia genus in orchid industry.

Maturation and germination of somatic embryos of Sorghum bicolor (L. Moench cultivar 'CIAP 132R-05'

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Silvio de J Martínez

2017-03-01

Full Text Available In sorghum [Sorghum bicolor (L. Moench], developed protocols for plant regeneration via somatic embryogenesis do not include maturation stage. The present work was carried out with the aim of achieving the maturation and germination of sorghum somatic embryos in cultivar 'CIAP 132R-05'. It were studied four concentrations of sucrose (30, 50, 70 and 90 g l-1, two of abscisic acid (0.25 and 0.5 μM and a control without this growth regulator. Germination initiation (days and number of somatic embryos with complete germination were evaluated in three periods (1 - 7, 8 - 14 and 15 - 21 days of culture. In addition, the effect of 6-BAP (8.9, 17.8 and 26.6 μM on somatic embryo germination was determined. The germination start time (days and after 21 days the number of somatic embryos with complete germination and plants with malformations were determined. The addition of 70 g l-1 sucrose in the culture medium without abscisic acid increased the germination of the somatic embryos to 37.2 plants per embryo group (0.5 g of fresh mass. The highest number of somatic embryos germinated was obtained with 17.78 μM 6-BAP in the germination culture medium. It was demonstrated the need of a maturation stage in the sorghum somatic embryogenesis to increase the germination percentage.   Keywords: somatic embryogenesis, sorghum, sucrose, 6-BAP

Beneficial use of immunoglobulins in the treatment of Sydenham chorea

NARCIS (Netherlands)

T.D. van Immerzeel (Tabitha); R.M. van Gilst (Ruud); N.G. Hartwig (Nico)

2010-01-01

textabstractThis double case report indicates that treatment with intravenous immunoglobulins (IVIG) is effective in patients with Sydenham chorea (SC). SC is a rare but impressive clinical manifestation following streptococcal infection. This movement disorder characterised by chorea, emotional

Linking Anger Trait with Somatization in Low-Grade College Students: Moderating Roles of Family Cohesion and Adaptability.

Science.gov (United States)

Liu, Liang; Liu, Cuilian; Zhao, Xudong

2017-02-25

Between 22% and 58% of patients in primary care settings complain of somatic symptoms. Previous research has found that somatization was associated with anger traits and family functions. However, studies that specifically assess the moderating effect of family function in how anger traits become somatic complaints are lacking. This study was designed to examine whether the variances in family cohesion and family adaptability moderated the strength of the relationship between anger traits and somatization. A cross-section design was conducted and 2008 college students were recruited from a comprehensive university in Shanghai. All participants finished questionnaires including Symptom Check List- 90 (SCL-90), State-Trait Anger Expression Inventory 2 (STAXI-2, Chinese version) and Family Adaptability and Cohesion Scale, second edition (FACES II, Chinese Version) to assess their degree of current somatization, anger trait and family function. Hierarchical linear regression analysis (Enter) was conducted respectively for men and women to examine the moderation effect of family cohesion and family adaptability in the association between anger and somatization. Somatic symptoms were significantly linked in the expected directions with depression and anger trait for both genders. Family cohesion and family adaptability were negatively associated with somatic symptoms. For female college students family cohesion was found to moderate the link between anger trait and somatization, but for male college students the moderation effect of family cohesion was marginally significant. The moderating role of family adaptability was significant for neither male nor female after current depressive symptoms were accounted for. Proneness to anger is an independent predictor of somatization. For women, a high level of family cohesion was a protective factor which could reduce the influence of anger trait on somatic symptoms. Without comorbidity of current depression, family

Alexithymia and Somatosensory Amplification Link Perceived Psychosocial Stress and Somatic Symptoms in Outpatients with Psychosomatic Illness

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Mutsuhiro Nakao

2018-05-01

Full Text Available Background: Psychosomatic patients often complain of a variety of somatic symptoms. We sought to clarify the role of clinical predictors of complaints of somatic symptoms. Methods: We enrolled 604 patients visiting a psychosomatic outpatient clinic. The outcome was the total number of somatic symptoms, and the candidate clinical predictors were perceived psychosocial stress, alexithymia, somatosensory amplification, adaptation, anxiety, and depression. All participants completed questionnaires assessing the outcome and the predictors. Results: The average number of reported somatic symptoms was 4.8; the most frequent was fatigue (75.3%, followed by insomnia (56.1%, low-back pain (49.5%, headache (44.7%, and palpitations (43.1%. Multiple regression analysis showed that the total number of somatic symptoms was significantly associated with the degree of perceived psychosocial stress, alexithymia, somatosensory amplification, and depression. Also, structural equation models indicated links between excessive adaptation (via perceived psychosocial stress, alexithymia, and somatosensory amplification and the total number of somatic symptoms. Conclusion: The results suggested that the association between psychosocial stress and reported somatic symptoms is mediated by alexithymia and somatosensory amplification in psychosomatic patients.

Overexpression of the DNA mismatch repair factor, PMS2, confers hypermutability and DNA damage tolerance.

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Gibson, Shannon L; Narayanan, Latha; Hegan, Denise Campisi; Buermeyer, Andrew B; Liskay, R Michael; Glazer, Peter M

2006-12-08

Inherited defects in genes associated with DNA mismatch repair (MMR) have been linked to familial colorectal cancer. Cells deficient in MMR are genetically unstable and demonstrate a tolerance phenotype in response to certain classes of DNA damage. Some sporadic human cancers also show abnormalities in MMR gene function, typically due to diminished expression of one of the MutL homologs, MLH1. Here, we report that overexpression of the MutL homolog, human PMS2, can also cause a disruption of the MMR pathway in mammalian cells, resulting in hypermutability and DNA damage tolerance. A mouse fibroblast cell line carrying a recoverable lambda phage shuttle vector for mutation detection was transfected with either a vector designed to express hPMS2 or with an empty vector control. Cells overexpressing hPMS2 were found to have elevated spontaneous mutation frequencies at the cII reporter gene locus. They also showed an increase in the level of mutations induced by the alkylating agent, methynitrosourea (MNU). Clonogenic survival assays demonstrated increased survival of the PMS2-overexpressing cells following exposure to MNU, consistent with the induction of a damage tolerance phenotype. Similar results were seen in cells expressing a mutant PMS2 gene, containing a premature stop codon at position 134 and representing a variant found in an individual with familial colon cancer. These results show that dysregulation of PMS2 gene expression can disrupt MMR function in mammalian cells and establish an additional carcinogenic mechanism by which cells can develop genetic instability and acquire resistance to cytotoxic cancer therapies.

Enhancement of polymeric immunoglobulin receptor transcytosis by biparatopic VHH.

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Chris D Emmerson

Full Text Available The polymeric immunoglobulin receptor (pIgR ensures the transport of dimeric immunoglobulin A (dIgA and pentameric immunoglobulin M (pIgM across epithelia to the mucosal layer of for example the intestines and the lungs via transcytosis. Per day the human pIgR mediates the excretion of 2 to 5 grams of dIgA into the mucosa of luminal organs. This system could prove useful for therapies aiming at excretion of compounds into the mucosa. Here we investigated the use of the variable domain of camelid derived heavy chain only antibodies, also known as VHHs or Nanobodies®, targeting the human pIgR, as a transport system across epithelial cells. We show that VHHs directed against the human pIgR are able to bind the receptor with high affinity (∼1 nM and that they compete with the natural ligand, dIgA. In a transcytosis assay both native and phage-bound VHH were only able to get across polarized MDCK cells that express the human pIgR gene in a basolateral to apical fashion. Indicating that the VHHs are able to translocate across epithelia and to take along large particles of cargo. Furthermore, by making multivalent VHHs we were able to enhance the transport of the compounds both in a MDCK-hpIgR and Caco-2 cell system, probably by inducing receptor clustering. These results show that VHHs can be used as a carrier system to exploit the human pIgR transcytotic system and that multivalent compounds are able to significantly enhance the transport across epithelial monolayers.

Cross-cultural differences in somatic presentation in patients with generalized anxiety disorder.

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Hoge, Elizabeth A; Tamrakar, Sharad M; Christian, Kelly M; Mahara, Namrata; Nepal, Mahendra K; Pollack, Mark H; Simon, Naomi M

2006-12-01

Little is known about cultural differences in the expression of distress in anxiety disorders. Previous cross-cultural studies of depression have found a greater somatic focus in Asian populations. We examined anxiety symptoms in patients with generalized anxiety disorder (GAD) in urban mental health settings in Nepal (N = 30) and in the United States (N = 23). Participants completed the Beck Anxiety Inventory (BAI). The overall BAI score and somatic and psychological subscales were compared. While there was no difference in total BAI scores, the Nepali group scored higher on the somatic subscale (i.e. "dizziness" and "indigestion," t[df] = -2.63[50], p < 0.05), while the American group scored higher on the psychological subscale (i.e. "scared" and "nervous," t[df] = 3.27[50], p < 0.01). Nepali patients with GAD had higher levels of somatic symptoms and lower levels of psychological symptoms than American patients with GAD. Possible explanations include differences in cultural traditions of describing distress and the mind-body dichotomy.

Structure of filamin A immunoglobulin-like repeat 10 from Homo sapiens

International Nuclear Information System (INIS)

Page, Richard C.; Clark, Jeffrey G.; Misra, Saurav

2011-01-01

The structure of immunoglobulin-like repeat 10 from human filamin A solved at 2.44 Å resolution suggests the potential effects of mutations correlated with otopalatodigital syndrome spectrum disorders. Filamin A (FlnA) plays a critical role in cytoskeletal organization, cell motility and cellular signaling. FlnA utilizes different binding sites on a series of 24 immunoglobulin-like domains (Ig repeats) to interact with diverse cytosolic proteins and with cytoplasmic portions of membrane proteins. Mutations in a specific domain, Ig10 (FlnA-Ig10), are correlated with two severe forms of the otopalatodigital syndrome spectrum disorders Melnick–Needles syndrome and frontometaphyseal dysplasia. The crystal structure of FlnA-Ig10 determined at 2.44 Å resolution provides insight into the perturbations caused by these mutations

Grasping the nettle: A bacterial invasin that targets immunoglobulin variable domains.

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Barlow, Paul

2018-06-01

In a new paper, the protein InvD from Yersinia pseudotuberculosis , a zoonotic pathogen, is shown to assist late-stage invasion of intestinal epithelia. Remarkably, InvD acts by binding the Fab region of IgG or IgA. It straddles adjacent light-chain and heavy-chain variable domains, but its binding is different from that of antigens in that complementarity-determining regions do not participate. Structure determination revealed that its Fab-interacting domain adopts an immunoglobulin-like fold, fused to the preceding immunoglobulin-like domain and carried on a long stalk anchored to the bacterial outer membrane. Possible roles of this unusual host-pathogen interaction include avoidance of clearance from the intestine by secretory IgA. © 2018 Barlow.

[Value of intravenous immunoglobulins. A case of Guillain-Barré syndrome].

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Hidou, M; Olivier, J; Vivant, J F

1992-01-01

A case of severe Guillain-Barré syndrome (GBS) was treated with high dose intravenous immunoglobulin (IVIG), 400 mg.kg-1.days-1, over three consecutive days. The treatment was repeated once. We observed a time-related response between immunoglobulins administration and clinical improvement. The pathologic lesions of the GBS suggest that this syndrome has an immunologic basis: a humoral factor is probably not the only immunological mechanism and cellular mechanisms are also likely to be of importance. Specific mechanisms might also be present in GBS, such as anti-idiotypic suppression of autoantibodies, and elimination of circulating immune complexes. Treatment with IVIG might have several therapeutic advantages over plasmapheresis: IVIG is easily infused without any delay, is easily available and has been used widely without serious complications.

At the crossroads of fate - somatic cell lineage specification in the fetal gonad

DEFF Research Database (Denmark)

Rotgers, Emmi; Jørgensen, Anne; Yao, Humphrey Hung-Chang

2018-01-01

The reproductive endocrine systems are vastly different between male and female. This sexual dimorphism of endocrine milieu originates from sex-specific differentiation of the somatic cells in the gonads during fetal life. The majority of gonadal somatic cells arise from the adrenogonadal...... of the reproductive tracts. Impairment of lineage specification and function of gonadal somatic cells can lead to disorders of sexual development (DSDs) in humans. Human DSDs and processes for gonadal development have been successfully modelled using genetically modified mouse models. In this review, we focus...

Effects of Response Styles on the Report of Psychological and Somatic Distress.

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Linden, Wolfgang; And Others

1986-01-01

Assessed the impact of two major response style dimensions (self-deception and impression management) on the report of psychological and somatic symptoms. Results confirmed that response styles were more predictive of psychological than somatic symptoms. Both anxiety and depression were associated with a high rate of physical symptoms,…

Overlapping hotspots in CDRs are critical sites for V region diversification.

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Wei, Lirong; Chahwan, Richard; Wang, Shanzhi; Wang, Xiaohua; Pham, Phuong T; Goodman, Myron F; Bergman, Aviv; Scharff, Matthew D; MacCarthy, Thomas

2015-02-17

Activation-induced deaminase (AID) mediates the somatic hypermutation (SHM) of Ig variable (V) regions that is required for the affinity maturation of the antibody response. An intensive analysis of a published database of somatic hypermutations that arose in the IGHV3-23*01 human V region expressed in vivo by human memory B cells revealed that the focus of mutations in complementary determining region (CDR)1 and CDR2 coincided with a combination of overlapping AGCT hotspots, the absence of AID cold spots, and an abundance of polymerase eta hotspots. If the overlapping hotspots in the CDR1 or CDR2 did not undergo mutation, the frequency of mutations throughout the V region was reduced. To model this result, we examined the mutation of the human IGHV3-23*01 biochemically and in the endogenous heavy chain locus of Ramos B cells. Deep sequencing revealed that IGHV3-23*01 in Ramos cells accumulates AID-induced mutations primarily in the AGCT in CDR2, which was also the most frequent site of mutation in vivo. Replacing the overlapping hotspots in CDR1 and CDR2 with neutral or cold motifs resulted in a reduction in mutations within the modified motifs and, to some degree, throughout the V region. In addition, some of the overlapping hotspots in the CDRs were at sites in which replacement mutations could change the structure of the CDR loops. Our analysis suggests that the local sequence environment of the V region, and especially of the CDR1 and CDR2, is highly evolved to recruit mutations to key residues in the CDRs of the IgV region.

Clinical Efficiency of Application of Intravenous Immunoglobulin in Pregnant Women with Intrauterine Infection

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O.L. Ishchenko

2016-02-01

Full Text Available The problem of intrauterine infection (IUI is still relevant today. Ineffective treatment of this pathology is associated with physiological decline of the immunity in these patients. We have proposed the additional use of intravenous immunoglobulin for the treatment of pregnant women with IUI. There were examined 75 patients with IUI, which was diagnosed in the II trimester. The I group consisted of 40 individuals who received conventional treatment, the II group was formed from 35 women who additionally received intravenous immunoglobulin. On the background of IUI, pregnancy was characterized by an increased incidence of threatened miscarriage and premature labor, gestosis and placental dysfunction; during delivery, premature rupture of amniotic membrane and fetal distress were more common. These patients had placenta with both ultrasonic and histological signs of infection. Among newborns, there was a significant increase in the incidence of pathology associated with intrauterine infection. Additional use of intravenous immunoglobulin in the treatment of IUI during the II trimester of pregnancy in comparison with conventional therapy leads to a significant reduction in the incidence of both obstetric complications and perinatal pathology.

Dimensions of somatization and hypochondriasis.

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Ford, C V

1995-05-01

A significantly large group of patients who communicate their psychosocial distress in the form of physical symptoms are called somatizers. They tend to overuse medical services. The syndromes with which they present have indistinct boundaries, and there tends to be some fluidity of their symptomatic presentations. Underlying psychiatric disorders such as mood disorders, anxiety disorders (including obsessive compulsive disorder), and personality disorders are frequently present.

Induction and isolation of somatic mutations in vegetatively propagated plants

International Nuclear Information System (INIS)

Donini, B.

1975-01-01

Research carried out since 1963 concentrated on techniques of mutagenic treatment: problems of exposure, type of radiation (acute irradiation by x- and γ-rays, and chronic exposure in the gamma field), conditions during and after irradiation, mechanisms of mutation induction, and methodology of isolation of somatic mutations. Analyses of somatic mutations included studies on apple, pear, olive, peach, grape and cherry plants. Young trees, dormant and rooted scions, summer and floral buds or seeds were used

DIRECT AND INDIRECT SOMATIC EMBRYOGENESIS ON ARABICA COFFEE (Coffea arabica

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Meynarti Sari Dewi Ibrahim

2013-10-01

Full Text Available Propagation of Coffea arabica L. through direct and indirect somatic embryogenesis technique is promising for producing large number of coffee seedlings. The objectives of the research were to evaluate methods for direct and indirect somatic embryo-genesis induction of C. arabica var. Kartika. The explants were the youngest fully expanded leaves of arabica coffee. The evalu-ated medium was modified Murashige and Skoog (MS medium supplemented with a combination of 2.26 µM 2,4-D + 4.54 or 9.08 µM thidiazuron; 4.52 µM 2,4-D + 4.54 or 9.08 µM thidiazuron; or 9.04 µM 2,4-D + 9.08 µM thidiazuron. Both calli (100 mg and pre-embryos developed from the edge of leaf explants were subcultured into regeneration medium (half strength MS with modified vitamin, supplemented with kinetine 9.30 µM and adenine sulfate 40 mg L-1. The results showed coffee leaf explant cultured on medium containing 2.26 µM 2,4-D + 4.54 or 9.08 µM thidiazuron to induce direct somatic embriogenesis from explant, while that of 4.52 or 9.04 µM 2,4-D + 9.08 µM thidiazuron to induced indirect somatic embrio-genesis. The medium for calli induction from coffee by explants was medium supplemented with 4.52 or 9.04 µM 2,4-D in combination with 9.08 µM thidiazuron. On the other hand, the best medium for activation of induction of somatic embryos was MS medium supplemented with 9.04 µM 2,4-D + 9.08 µM thidiazuron. Based on this results, the first step for developing micropropagation for coffee has been resolved. The subsequent studies will be directed to evaluate agronomic performance of the derived planting materials.

Somatic Treatments in Treatment of Depression During Pregnancy

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Eylem Ozten

2015-09-01

Full Text Available Although some psychotropic drugs are known to be teratogenic no psychotropic drug is of proven safety for treatment of depression during pregnancy. Untreated mood disorders during pregnancy pose significant risks for mother and the newborn. This review focuses on the use of somatic tretments of depression during pregnancy.Electroconvulsive therapy, bright light therapy, transcranial magnetic stimulation and vagal nerve stimulation are relatively safe and effective treatments during pregnancy if steps are taken to decrease potential risks. A clear information related to the somatic treatment should be given to the patient and informed consent should be obtained. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(3.000: 244-254

The Association of Sensory Responsiveness with Somatic Symptoms and Illness Anxiety.

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Rodic, Donja; Meyer, Andrea Hans; Lieb, Roselind; Meinlschmidt, Gunther

2016-02-01

Somatoform Disorders or Somatic Symptom and Related Disorders are a major public health problem.The pathophysiology underlying these disorders is not yet understood. The aim of this study was to explore if sensory responsiveness could contribute to a better understanding of pathophysiological mechanisms underlying two key symptoms of Somatoform Disorders, namely somatic symptoms and illness anxiety. We measured vibrotactile perception thresholds with the HVLab Perception Meter and examined their association with somatic symptoms, illness anxiety and trait anxiety. A sample of 205 volunteers participated in the study. Sensory responsiveness was neither associated with somatic symptoms (β = -0.01; 95% confidence interval (CI), -0.37, 0.39) nor trait anxiety (β = -0.07; 95% CI, -0.30, 0.07). However, lower vibrotactile perception thresholds were associated with increased scores of the overall illness anxiety scale (β = -0.65; 95% CI, -1.21, -0.14) and its constituent subscale disease conviction (β = -2.07; 95% CI, -3.94, -0.43). Our results suggest that increased sensory responsiveness is associated with illness anxiety and hence should be examined further as potential target within the etiopathology of somatoform disorders.

Somatic Complaints in Adolescence and Labour Market Participation in Young Adulthood.

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Winding, Trine Nøhr; Andersen, Johan Hviid

2018-05-01

The primary aim was to investigate the association between somatic symptoms at ages 15 or 18 and reduced labour market participation at age 23, when socioeconomic, social, and mental health risk factors were taken into account. The study included 3223 participants from the West Jutland Cohort Study with questionnaire information on somatic symptoms at ages 15 or 18 and with register information on labour market participation at age 23, gathered from a national register on all public transfer benefits for a 52-week period. The analyses included additional information about socioeconomic background, number of negative life events, social climate in the family, social relations with friends, and depressive symptoms. Logistic regression analyses yielded odds ratios with 95% confidence intervals. Among the males, associations between reporting somatic symptoms at age 18 and low labour market participation was seen in both crude and adjusted analyses (odds ratio: 1.66; 95% confidence intervals: 1.01-2.75), whereas the association among the females disappeared after adjustments (odds ratio: 0.97; 95% confidence intervals: 0.63-1.52). The males that reported somatic symptoms in late adolescence appeared to be the most vulnerable to future reduced labour market participation.

The role of post-migration living difficulties on somatization among first-generation immigrants visited in a primary care service

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Massimiliano Aragona

2011-01-01

Full Text Available The role of post-migration living difficulties (PMLD on somatization was studied in 101 first generation immigrants visited in primary care. Premigratory traumas and post-traumatic stress disorder (PTSD were also assessed. About one third of patients somatized. Sociodemographic variables were similar in somatizers and non-somatizers. Premigratory traumas, PTSD and the likelihood to report at least one serious or very serious PMLD were higher in somatizers. Four kinds of PMLD were more frequent in somatizers: worries about unavailability of health assistance, working problems, discrimination and poor social help. Traumas and PTSD influenced the effect of PMLD on somatization. Findings suggest that in specific samples of primary care immigrants severe premigratory traumas increase the sensitivity to PMLD and in turn distress due to PMLD amplifies the tendency to somatize.

[Structure of childhood and adolescent invalidity in persons with chronic somatic diseases].

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Korenev, N M; Bogmat, L F; Tolmacheva, S R; Timofeeva, O N

2002-01-01

Based on the analysis of statistical data, prevalence is estimated of disorders with invalidism patterns outlined among those children and young adults under 40 years of age presenting with chronic somatic disorders in Kharkov. Both in children (52.4%) and in young adults (43.9%) diseases of the nervous system held the prominent place. Invalidity due to formed somatic disorders was identified in 10.9% of children and 24.3% of those persons less than 40 years old. There prevailed diseases of the circulation organs. The necessity is substantiated for the rehabilitation to be carried out of children with somatic disorders to prevent their disability.

Influence of column type and chromatographic conditions on the ion-exchange chromatography of immunoglobulins.

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Yang, Y B; Harrison, K

1996-08-30

Immunoglobulins are often purified by affinity chromatography. However, this technique is costly, can result in poor resolution for subclasses (or is only group specific), and leads to possible leaching of contaminants into the purified products. Ion-exchange chromatography has shown great potential and has found an increased usage in the purification of immunoglobulins. The aim of this study is to further understand the separation mechanism with emphasis on the influence of column type and chromatographic conditions on the peak shape, selectivity and changes in the elution patterns. Included are strong cation-exchange, strong anion-exchange and weak anion-exchange columns. Five immunoglobulin G antibodies were used as test probes. Some sera and ascites were also used in the study. Among the chromatographic conditions examined were mobile phase pH, buffer type, buffer concentration, gradient rate, and column temperature. Significant differences in the chromatographic behavior (elution pattern, peak shape and selectivity) of the test samples are discussed in regard to the column type and the chromatographic conditions.

Somatic Experiencing Treatment with Social Service Workers Following Hurricanes Katrina and Rita

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Leitch, M. Laurie; Vanslyke, Jan; Allen, Marisa

2009-01-01

In a disaster, social service workers are often survivors themselves. This study examines whether somatic intervention using a brief (one to two session) stabilization model now called the Trauma Resiliency Model[TM] (TRM), which uses the skills of Somatic Experiencing[R] (SE), can reduce the postdisaster symptoms of social service workers…

Higher Serum Levels of Free ĸ plus λ Immunoglobulin Light Chains Ameliorate Survival of Hemodialysis Patients

DEFF Research Database (Denmark)

Thilo, Florian; Caspari, Christina; Scholze, Alexandra

2011-01-01

Background/Aims: Impaired immune function is common in patients with chronic renal failure. Now, we determined whether serum levels of free immunoglobulin light chains predict mortality in patients with chronic kidney disease stage 5 on hemodialysis. Methods: We performed a prospective cohort study...... of 160 hemodialysis patients with a median follow-up of 15 months (interquartile range, 3-44 months). Serum levels of free κ and λ immunoglobulin light chains were measured at the start of the study. The primary end point was mortality from any cause. Results: In survivors, median serum levels of free κ...... plus λ immunoglobulin light chains were significantly higher compared with nonsurvivors (p light chains above the median compared with patients with serum levels below the median of 210 mg...

Reprogramming to pluripotency can conceal somatic cell chromosomal instability.

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Masakazu Hamada

Full Text Available The discovery that somatic cells are reprogrammable to pluripotency by ectopic expression of a small subset of transcription factors has created great potential for the development of broadly applicable stem-cell-based therapies. One of the concerns regarding the safe use of induced pluripotent stem cells (iPSCs in therapeutic applications is loss of genomic integrity, a hallmark of various human conditions and diseases, including cancer. Structural chromosome defects such as short telomeres and double-strand breaks are known to limit reprogramming of somatic cells into iPSCs, but whether defects that cause whole-chromosome instability (W-CIN preclude reprogramming is unknown. Here we demonstrate, using aneuploidy-prone mouse embryonic fibroblasts (MEFs in which chromosome missegregation is driven by BubR1 or RanBP2 insufficiency, that W-CIN is not a barrier to reprogramming. Unexpectedly, the two W-CIN defects had contrasting effects on iPSC genomic integrity, with BubR1 hypomorphic MEFs almost exclusively yielding aneuploid iPSC clones and RanBP2 hypomorphic MEFs karyotypically normal iPSC clones. Moreover, BubR1-insufficient iPSC clones were karyotypically unstable, whereas RanBP2-insufficient iPSC clones were rather stable. These findings suggest that aneuploid cells can be selected for or against during reprogramming depending on the W-CIN gene defect and present the novel concept that somatic cell W-CIN can be concealed in the pluripotent state. Thus, karyotypic analysis of somatic cells of origin in addition to iPSC lines is necessary for safe application of reprogramming technology.

A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types

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Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

2015-01-01

Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260

Effect of Cryopreservation and Post-Cryopreservation Somatic Embryogenesis on the Epigenetic Fidelity of Cocoa (Theobroma cacao L.).

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Adu-Gyamfi, Raphael; Wetten, Andy; Marcelino Rodríguez López, Carlos

2016-01-01

While cocoa plants regenerated from cryopreserved somatic embryos can demonstrate high levels of phenotypic variability, little is known about the sources of the observed variability. Previous studies have shown that the encapsulation-dehydration cryopreservation methodology imposes no significant extra mutational load since embryos carrying high levels of genetic variability are selected against during protracted culture. Also, the use of secondary rather than primary somatic embryos has been shown to further reduce the incidence of genetic somaclonal variation. Here, the effect of in vitro conservation, cryopreservation and post-cryopreservation generation of somatic embryos on the appearance of epigenetic somaclonal variation were comparatively assessed. To achieve this we compared the epigenetic profiles, generated using Methylation Sensitive Amplified Polymorphisms, of leaves collected from the ortet tree and from cocoa somatic embryos derived from three in vitro conditions: somatic embryos, somatic embryos cryopreserved in liquid nitrogen and somatic embryos generated from cryoproserved somatic embryos. Somatic embryos accumulated epigenetic changes but these were less extensive than in those regenerated after storage in LN. Furthermore, the passage of cryopreserved embryos through another embryogenic stage led to further increase in variation. Interestingly, this detected variability appears to be in some measure reversible. The outcome of this study indicates that the cryopreservation induced phenotypic variability could be, at least partially, due to DNA methylation changes. Phenotypic variability observed in cryostored cocoa somatic-embryos is epigenetic in nature. This variability is partially reversible, not stochastic in nature but a directed response to the in-vitro culture and cryopreservation.

Somatic mutations affect key pathways in lung adenocarcinoma

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Ding, Li; Getz, Gad; Wheeler, David A.; Mardis, Elaine R.; McLellan, Michael D.; Cibulskis, Kristian; Sougnez, Carrie; Greulich, Heidi; Muzny, Donna M.; Morgan, Margaret B.; Fulton, Lucinda; Fulton, Robert S.; Zhang, Qunyuan; Wendl, Michael C.; Lawrence, Michael S.; Larson, David E.; Chen, Ken; Dooling, David J.; Sabo, Aniko; Hawes, Alicia C.; Shen, Hua; Jhangiani, Shalini N.; Lewis, Lora R.; Hall, Otis; Zhu, Yiming; Mathew, Tittu; Ren, Yanru; Yao, Jiqiang; Scherer, Steven E.; Clerc, Kerstin; Metcalf, Ginger A.; Ng, Brian; Milosavljevic, Aleksandar; Gonzalez-Garay, Manuel L.; Osborne, John R.; Meyer, Rick; Shi, Xiaoqi; Tang, Yuzhu; Koboldt, Daniel C.; Lin, Ling; Abbott, Rachel; Miner, Tracie L.; Pohl, Craig; Fewell, Ginger; Haipek, Carrie; Schmidt, Heather; Dunford-Shore, Brian H.; Kraja, Aldi; Crosby, Seth D.; Sawyer, Christopher S.; Vickery, Tammi; Sander, Sacha; Robinson, Jody; Winckler, Wendy; Baldwin, Jennifer; Chirieac, Lucian R.; Dutt, Amit; Fennell, Tim; Hanna, Megan; Johnson, Bruce E.; Onofrio, Robert C.; Thomas, Roman K.; Tonon, Giovanni; Weir, Barbara A.; Zhao, Xiaojun; Ziaugra, Liuda; Zody, Michael C.; Giordano, Thomas; Orringer, Mark B.; Roth, Jack A.; Spitz, Margaret R.; Wistuba, Ignacio I.; Ozenberger, Bradley; Good, Peter J.; Chang, Andrew C.; Beer, David G.; Watson, Mark A.; Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William; Province, Michael A.; Weinstock, George M.; Varmus, Harold E.; Gabriel, Stacey B.; Lander, Eric S.; Gibbs, Richard A.; Meyerson, Matthew; Wilson, Richard K.

2009-01-01

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers—including NF1, APC, RB1 and ATM—and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment. PMID:18948947

Boron-Mediated Plant Somatic Embryogenesis: A Provocative Model

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Dhananjay K. Pandey

2012-01-01

Full Text Available A central question in plant regeneration biology concerns the primary driving forces invoking the acquisition of somatic embryogenesis. Recently, the role of micronutrient boron (B in the initiation and perpetuation of embryogenesis has drawn considerable attention within the scientific community. This interest may be due in part to the bewildering observation that the system-wide induction of embryogenic potential significantly varied in response to a minimal to optimal supply of B (minimal ≤ 0.1 mM, optimal = 0.1 mM. At the cellular level, certain channel proteins and cell wall-related proteins important for the induction of embryogenesis have been shown to be transcriptionally upregulated in response to minimal B supply suggesting the vital role of B in the induction of embryogenesis. At the molecular level, minimal to no B supply increased the endogenous level of auxin, which subsequently influenced the auxin-inducible somatic embryogenesis receptor kinases, suggesting the role of B in the induction of embryogenesis. Also, minimal B concentration may “turn on” other genetic and/or cellular transfactors reported earlier to be essential for cell-restructuring and induction of embryogenesis. In this paper, both the direct and indirect roles of B in the induction of somatic embryogenesis are highlighted and suggested for future validation.

Trauma exposure and the mediating role of posttraumatic stress on somatic symptoms in civilian war victims.

Science.gov (United States)

Morina, Naser; Schnyder, Ulrich; Klaghofer, Richard; Müller, Julia; Martin-Soelch, Chantal

2018-04-10

It has been well documented that the exposure to war has a negative effect on the psychological health of civilian. However, little is known on the impact of war exposure on the physical health of the civilian population. In addition, the link between trauma exposure and somatic symptoms remain poorly understood. This cross-sectional study examined levels of somatic symptoms in the aftermath of war, and the mediating role of posttraumatic stress symptoms in the relationship between trauma exposure and somatic symptoms. Civilian war survivors (N = 142) from Kosovo were assessed for potentially traumatic events, posttraumatic stress symptoms, and somatic symptoms. Data were analyzed using mediation analyses. Posttraumatic stress disorder (PTSD) symptoms were categorized based on King's four factor model (Psychol Assessment. 10: 90-96, 1998). Participants reported on average more than 5 types of traumatic exposure. The cut-off indicative for PTSD was exceeded by 26.1% of participants. Symptom levels of PTSD were associated with somatic symptoms. The relationship between trauma exposure and somatic symptoms was partly mediated by the active avoidance and hyperarousal symptom clusters of PTSD. Active avoidance and hyperarousal symptoms seem to play a key role in traumatized people suffering from somatic symptoms.

PECTIMORF and BIOBRAS-16 utilization in the potato somatic embryogenesis

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Jaime R. Hidrobo Luna

2002-01-01

Full Text Available With the application of PECTIMORF and BIOBRAS-16, somatic embryos were obtained in potato (Solanum tuberosum, L c.v. Desirèe, of 40 days old callus obtained from stem micropropagated plants. These were used as possible substitutes for crop regulators used in culture media for the induction of somatic embryos. The culture media was composed for 10ml.l-1 of Murashige and Skoog salt, 0.1mg.l-1 ANA, 0.1mg.l-1 kinetin, 0.5mg.l-1 thiamine, 2.5mg.l-1 cistein, 100mg.l-1 mioinositol, 20g.l-1 sucrose and 2.0g.l-1 agar. Four culture medias were tested in distinct combinations that contained different concentration of PECTIMOR and BIOBRAS-16 as substitute of auxins and cytokinins. After 90 days, the results obtained showed the possibility of substituting the auxins (0.5mg.l-1 ANA and the cytokinins (0.5mg.l-1 kinetin in the culture media, because the application of PECTIMORF at 3.2mg.l-1 and BIOBRAS-16 at 1.0mg.l-1, gave friable callus, high fresh weight (more than 1.4g and a brownish color at the end of the process, moment in which the somatic embryos of different phases, appeared at the surface of the callus. Keywords: brasinoesteroids, callus, oligopectate, somatic embryo

Somatic cell nuclear transfer cloning: practical applications and current legislation.

Science.gov (United States)

Niemann, H; Lucas-Hahn, A

2012-08-01

Somatic cloning is emerging as a new biotechnology by which the opportunities arising from the advances in molecular genetics and genome analysis can be implemented in animal breeding. Significant improvements have been made in SCNT protocols in the past years which now allow to embarking on practical applications. The main areas of application of SCNT are: Reproductive cloning, therapeutic cloning and basic research. A great application potential of SCNT based cloning is the production of genetically modified (transgenic) animals. Somatic cell nuclear transfer based transgenic animal production has significant advances over the previously employed microinjection of foreign DNA into pronuclei of zygotes. This cell based transgenesis is compatible with gene targeting and allows both, the addition of a specific gene and the deletion of an endogenous gene. Efficient transgenic animal production provides numerous opportunities for agriculture and biomedicine. Regulatory agencies around the world have agreed that food derived from cloned animals and their offspring is safe and there is no scientific basis for questioning this. Commercial application of somatic cloning within the EU is via the Novel Food regulation EC No. 258/97. Somatic cloning raises novel questions regarding the ethical and moral status of animals and their welfare which has prompted a controversial discussion in Europe which has not yet been resolved. © 2012 Blackwell Verlag GmbH.

Somatic diseases in patients with schizophrenia in general practice: their prevalence and health care.

Science.gov (United States)

Oud, Marian J T; Meyboom-de Jong, Betty

2009-05-09

Schizophrenia patients frequently develop somatic co-morbidity. Core tasks for GPs are the prevention and diagnosis of somatic diseases and the provision of care for patients with chronic diseases. Schizophrenia patients experience difficulties in recognizing and coping with their physical problems; however GPs have neither specific management policies nor guidelines for the diagnosis and treatment of somatic co-morbidity in schizophrenia patients. This paper systematically reviews the prevalence and treatment of somatic co-morbidity in schizophrenia patients in general practice. The MEDLINE, EMBASE, PsycINFO data-bases and the Cochrane Library were searched and original research articles on somatic diseases of schizophrenia patients and their treatment in the primary care setting were selected. The results of this search show that the incidence of a wide range of diseases, such as diabetes mellitus, the metabolic syndrome, coronary heart diseases, and COPD is significantly higher in schizophrenia patients than in the normal population. The health of schizophrenic patients is less than optimal in several areas, partly due to their inadequate help-seeking behaviour. Current GP management of such patients appears not to take this fact into account. However, when schizophrenic patients seek the GP's help, they value the care provided. Schizophrenia patients are at risk of undetected somatic co-morbidity. They present physical complaints at a late, more serious stage. GPs should take this into account by adopting proactive behaviour. The development of a set of guidelines with a clear description of the GP's responsibilities would facilitate the desired changes in the management of somatic diseases in these patients.

Circulating immune complexes, immunoglobulin classes (IgG, IgA ...

African Journals Online (AJOL)

Objective:- To evaluate serum levels of circulating immune complexes (CICs), immunoglobulin classes (IgG, IgA and IgM) and Complement Components (C3c, C4 and Factor B) in Nigerians with Type 1 or Type 2 diabetes mellitus. Design:- Case control study. Setting:- University College Hospital, Ibadan, Oyo State, Nigeria.

Effect of continuous milking on immunoglobulin concentrations in bovine colostrum

NARCIS (Netherlands)

Verweij, J.J.; Koets, A.P.; Eisenberg, S.W.F.

2014-01-01

Continuous milking is defined as a dairy cattle management system without a planned dry period for cows in late gestation. Continuous milking has been described to reduce health problems common in periparturient cattle, but may affect colostrum immunoglobulin (Ig) concentration and subsequently calf

Fungicidal activity of peptides encoded by immunoglobulin genes

OpenAIRE

Polonelli, Luciano; Ciociola, Tecla; Sperind?, Martina; Giovati, Laura; D?Adda, Tiziana; Galati, Serena; Travassos, Luiz R.; Magliani, Walter; Conti, Stefania

2017-01-01

Evidence from previous works disclosed the antimicrobial, antiviral, anti-tumour and/or immunomodulatory activity exerted, through different mechanisms of action, by peptides expressed in the complementarity-determining regions or even in the constant region of antibodies, independently from their specificity and isotype. Presently, we report the selection, from available databases, of peptide sequences encoded by immunoglobulin genes for the evaluation of their potential biological activitie...

Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming

NARCIS (Netherlands)

Krijger, Peter Hugo Lodewijk; Di Stefano, Bruno; de Wit, Elzo; Limone, Francesco; van Oevelen, Chris; de Laat, Wouter; Graf, Thomas

2016-01-01

Forced expression of reprogramming factors can convert somatic cells into induced pluripotent stem cells (iPSCs). Here we studied genome topology dynamics during reprogramming of different somatic cell types with highly distinct genome conformations. We find large-scale topologically associated

Migrants' utilization of somatic healthcare services in Europe - a systematic review

DEFF Research Database (Denmark)

Nørredam, Marie Louise; Nielsen, Signe Smith; Krasnik, Allan

2010-01-01

on the abstracts. Additional searches were conducted via the references of the selected articles. The final number of studies included was 21. Results: The results suggested a diverging picture regarding utilization of somatic healthcare services by migrants compared to non-migrants in Europe. Overall, migrants......Background: Utilization of services is an important aspect of migrants' access to healthcare. The aim was to review the European literature on utilization of somatic healthcare services related to screening, general practitioner, specialist, emergency room and hospital by adult first......-generation migrants. Our study question was: ‘Are there differences in migrants' utilization of somatic healthcare services compared to non-migrants?' Methods: Publications were identified by a systematic search of PUBMED and EMBASE. Appropriateness of the studies was judged independently by two researchers based...

Falsely Elevated Plasma Creatinine Due to an Immunoglobulin M Paraprotein.

Science.gov (United States)

McGill, Mitchell R; Vijayan, Anitha; Trulock, Elbert P; Witt, Chad A; Kohler, Giselle D; Scott, Mitchell G

2016-11-01

The most common method for measuring plasma creatinine is based on its reaction with picric acid. However, enzymatic methods are becoming more popular due to improved specificity. We present a case of falsely elevated plasma creatinine values obtained by an enzymatic method that turned out to be due to a monoclonal immunoglobulin M (IgM) paraprotein. A 63-year-old woman evaluated for lung transplantation had falsely increased plasma creatinine levels (1.54-1.71mg/dL; corresponding to estimated glomerular filtration rates of 32-36 mL/min/1.73m 2 ) as measured by the Roche Creatinine plus enzymatic assay when compared with the picric acid-based procedure and several other enzymatic methods, which gave plasma creatinine values of 0.7 to 0.8mg/dL. Serum protein electrophoresis revealed an IgM κ light chain paraprotein. Removal of high-molecular-weight (>30kDa) proteins by ultrafiltration reduced the patient's plasma creatinine level by the Roche enzymatic method to 0.7mg/dL. Addition of the patient's immunoglobulin fraction to plasma from other patients with normal plasma creatinine levels resulted in values that were increased by 0.58 to 0.62mg/dL. Furthermore, removal of non-IgM immunoglobulins with protein G-coupled beads did not eliminate the interference from the patient's plasma. Taken together, these studies demonstrate that falsely elevated plasma creatinine values by the Roche enzymatic method can be due to an IgM paraprotein. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Depression, disability and somatic diseases among elderly

NARCIS (Netherlands)

Verhaak, P.F.M.; Dekker, Janny; De Waal, M.W.M.; Van Marwijk, H.W.J.; Comijs, H.C.

2014-01-01

Objective: Depression among older adults is associated with both disability and somatic disease. We aimed to further understand this complicated relationship and to study the possible modifying effect of increasing age. Design: Cross sectional survey. Setting: Outpatient and inpatient clinics of

Somatic cancer variant curation and harmonization through consensus minimum variant level data

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Deborah I. Ritter

2016-11-01

Full Text Available Abstract Background To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG of the Clinical Genome Resource (ClinGen, in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD. MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice. Methods We developed MVLD through a consensus approach by i reviewing clinical actionability interpretations from institutions participating in the WG, ii conducting extensive literature search of clinical somatic interpretation schemas, and iii survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP, can be incorporated into MVLD. Results Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data. Conclusions We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of

The effects of Ostertagia occidentalis somatic antigens on ovine TLR2 and TLR4 expression

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Hassan BORJI

2015-10-01

Full Text Available Background: Recognition of helminth-derived pathogen associated molecular patterns (PAMPs by pattern recognition receptors (PRRs, including toll like recep­tors (TLRs is the first step towards initiating anti–helminth immune re­sponses.Methods: Using somatic antigens of Ostertagia occidentalis, an important abomasal parasite of ruminants, the expression of ovine TLR2 and TLR4 in peripheral blood mononuclear cells (PBMCs was analyzed by real-time quatitative reverse-transcrip­tion polymerase chain reaction (qRT-PCR. Somatic antigens of O. occidentalis were prepared to stimulate ovine PBMCs in a time and dose dependent manner.Results: A high expression of TLR2 and TLR4 was observed in PBMCs cultured with somatic antigens of the parasites specially when PBMCs were cultured with 100 µg/ml of somatic antigens and incubated for 2h. Up-regulation of TLR2 expres­sion was more pronounced and evident in our study.Conclsusion: Somatic antigens of O. occidentalis have immunostimulatory and domi­nant role on peripheral immune cells. This study provide for the first time evidence of induction of TLRs in ovine PBMCs by somatic antigen of O. occidentalis

Haemolytic anaemia as a complication to intravenous immunoglobulin infusion

DEFF Research Database (Denmark)

Markvardsen, Lars Høj; Harbo, Thomas; Christiansen, Ingelise

performed before and two weeks after infusion of IVIg. Following treatment blood haemoglobin declined from 8.6±0.8 to 8.1±1.3mmol/l, p... naive patients are susceptible to develop haemolysis. Haemolytic anaemia is a severe side effect that seems to be more frequent after immunoglobulin infusions than previously recognized....

Somatic and genetic radiation exposure of the patient in digital subtraction angiography (DSA)

International Nuclear Information System (INIS)

Neufang, K.F.R.; Ewen, K.

1986-01-01

The somatic and genetic radiation exposure of patients undergoing Digital Subtraction Angiography (DSA) and traditional Film Arteriography (FA) of cranial, cervical, thoracic and abdominal vascular territories are compared. The radiation doses absorbed within the critical organs - red bone marrow, lung, thyroid gland and female breast - and in the gonads were measured using an anthropomorphic Alderson phantom. A Somatic Dose Index was calculated in order to estimate the somatic radiation risk. The somatic radiation exposure depends upon the location of the critical organs with respect to the entrance site of the x-ray beam, and can be reduced by an appropriate choice of the angiographic projection. Under this condition, the radiation exposure of the patient during DSA can be lower than during FA. For renal DSA an a.p. projection, the use of an abdominal compression device and careful caudal shielding of the field are advocated. (orig.)

Somatic mutations in leafs of tobacco seedlings induced by ionizing radiation and pesticide

International Nuclear Information System (INIS)

Shin, H. S.; Kim, J. K.; Song, H. S.; Lee, Y. I.

2001-01-01

Somatic mutations induced by the combined treatment of pesticide and ionizing radiation were analyzed in the leaves of tobacco seedlings. The pesticide (1,5 and 10 ppm of parathion) was sprayed directly onto the seedlings. The seedlings, with or without pretreatment of pesticide, were irradiated with 0.1 ∼10 Gy of gamma ray. The difference in the somatic mutation frequencies were not significant among groups treated with different concentration of pesticide. The somatic mutations in tobacco seedlings irradiated with gamma-ray showed a clear dose-response relationship in a range of 0.1 to 10 Gy. However, the combined treatment of pesticide and radiation did not cause any synergistic enhancement in the mutation frequencies. The highest efficiency in the induction of somatic mutations could be obtained by irradiating the seedlings with 5 Gy, 12 hours after 1 ppm of pesticide treatment, or 24 hours after 5 ppm of pesticide treatment

Cancer treatment in childhood and testicular function: the importance of the somatic environment

Science.gov (United States)

Stukenborg, Jan-Bernd; Jahnukainen, Kirsi; Hutka, Marsida

2018-01-01

Testicular function and future fertility may be affected by cancer treatment during childhood. Whilst survival of the germ (stem) cells is critical for ensuring the potential for fertility in these patients, the somatic cell populations also play a crucial role in providing a suitable environment to support germ cell maintenance and subsequent development. Regulation of the spermatogonial germ-stem cell niche involves many signalling pathways with hormonal influence from the hypothalamo-pituitary-gonadal axis. In this review, we describe the somatic cell populations that comprise the testicular germ-stem cell niche in humans and how they may be affected by cancer treatment during childhood. We also discuss the experimental models that may be utilized to manipulate the somatic environment and report the results of studies that investigate the potential role of somatic cells in the protection of the germ cells in the testis from cancer treatment. PMID:29351905

Somatic Embryogenesis in Yam (Dioscorea rotundata

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Isidro Elías Suárez Padrón

2011-12-01

Full Text Available Embryogenic yam (Dioscorea rotundata cultures were induced from petioles of leaves of in vitro grown plants on medium supplemented with different 2.4-D concentrations. Cultures were maintained either on semisolid or in liquid MS medium supplemented with 4.52 µM 2.4-D. The effect of sucrose concentration on somatic embryo development was also evaluated and the effects of different BAP concentrations on somatic embryo conversion were determined. Treatments were distributed using a complete randomized design. The highest rate of induction occurred with 4.52 µM 2.4-D. Sucrose at 131.46 mM significantly enhanced somatic embryo development. The conversion rate was not affected by BAP.Cultivos embriogénicos de ñame (Dioscorea rotundata fueron inducidos a partir de explantes consistentes de hojas con peciolos, aisladas de plantas establecidas en condiciones in vitro, en presencia de diferentes concentraciones de 2,4-D. Los cultivos inducidos fueron mantenidos en medio MS líquido o semisólido suplido con 4,52 µM 2,4-D. El efecto de las concentraciones de sacarosa sobre el desarrollo de embriones somáticos y el efecto de varias concentraciones de BAP sobre la tasa de conversión de embriones somáticos en plantas también fueron evaluados. Todos los tratamientos fueron distribuidos usando un diseño completamente al azar. El mayor porcentaje de inducción de tejidos embriogénicos ocurrió con 4,52 µM de 2,4-D. La adición de 131,46 mM de sacarosa incrementó significativamente el desarrollo de embriones somáticos. La tasa de conversión de embriones somáticos en plantas no fue afectada por las concentraciones de BAP.

Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

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Danilo Santana Alessio Franceschi

2011-01-01

Full Text Available Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.

The Association of Sensory Responsiveness with Somatic Symptoms and Illness Anxiety.

OpenAIRE

Rodic Donja; Meyer Andrea Hans; Lieb Roselind; Meinlschmidt Gunther

2015-01-01

Somatoform Disorders or Somatic Symptom and Related Disorders are a major public health problem.The pathophysiology underlying these disorders is not yet understood. The aim of this study was to explore if sensory responsiveness could contribute to a better understanding of pathophysiological mechanisms underlying two key symptoms of Somatoform Disorders namely somatic symptoms and illness anxiety. We measured vibrotactile perception thresholds with the HVLab Perception Meter and examined the...

Long-Term Follow-Up of Individuals Undergoing Sex-Reassignment Surgery: Somatic Morbidity and Cause of Death

Directory of Open Access Journals (Sweden)

Rikke Kildevæld Simonsen, MA

2016-03-01

Conclusion: Of 98% of all Danish transsexuals who officially underwent SRS from 1978 through 2010, one in three had somatic morbidity and approximately 1 in 10 had died. No significant differences in somatic morbidity or mortality were found between male-to-female and female-to-male individuals. Despite the young average age at death and the relatively larger number of individuals with somatic morbidity, the present study design does not allow for determination of casual relations between, for example, specific types of hormonal or surgical treatment received and somatic morbidity and mortality.

Evaluation of salivary immunoglobulin A levels in tobacco smokers and patients with recurrent aphthous ulcers